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1
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Janoff EN, Shih MC, Donskey C, Belitskaya-Levy I, Brau N, Rodriguez-Barradas MC, Chan E, Zimmerman P, Miller EK, Vaughan LB, Daniel Markley J, Goldberg AM, Sriram P, Anzueto A, Uyeda L, Zehm L, Wills A, Hutchinson C, Jones L, Peterson D, Ringer RJ, Dumont L, Gleason T, Bonomo RA, Curtis JL, Brown ST. Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1). J Med Virol 2025; 97:e70349. [PMID: 40400480 DOI: 10.1002/jmv.70349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 01/26/2025] [Accepted: 03/27/2025] [Indexed: 05/23/2025]
Abstract
In the initial absence of proven therapies, empirical COVID-19 convalescent plasma (CCP) was rapidly introduced for individuals hospitalized for COVID-19. Seventy-five participants were randomized from November 2020 to June 2021 in a double-blind, multi-site, placebo-controlled, randomized trial (VA CURES-1) evaluating the impact of CCP vs. saline in Veterans hospitalized with COVID-19 with hypoxemia. The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 29. We analyzed clinical outcomes, nasal viral RNA, plasma cytokines and viral evolution over time. Among 40 participants receiving saline and 35 receiving CCP with high neutralizing titers (median 1:1420), the percent reaching the primary outcome was similar (10%), as were time to clinical recovery and to nasal viral clearance. By whole genome sequencing, viral molecular complexity evolved pre- to posttreatment more frequently in recipients of saline vs. CCP (4 of 7 (57.1%) vs. 1 of 4 (25%), respectively), based on numbers of mixed allele positions. Numbers of amino acid-changing, non-synonymous mutations in the spike protein were greater in saline vs. CCP recipients. Both outcomes suggested purifying selection (reduced overall viral infection complexity) following CCP. In conclusion, convalescent plasma showed no significant clinical impact but may influence SARS-CoV-2 complexity. Trial Registration: ClinicalTrials.gov Identifier: NCT04539275.
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Affiliation(s)
- Edward N Janoff
- Rocky Mountain Regional VA Medical Center, Aurora, Colorado, USA
- University of Colorado Denver School of Medicine, Aurora, Colorado, USA
| | - Mei-Chiung Shih
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, California, USA
- Stanford University School of Medicine, Stanford, California, USA
| | - Curtis Donskey
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
| | - Ilana Belitskaya-Levy
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, California, USA
| | - Norbert Brau
- James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
- Icahn School of Medicine at Mt. Sinai, New York, New York, USA
| | | | - Ernest Chan
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Peter Zimmerman
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Elliott K Miller
- Department of Veterans Affairs, Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico, USA
| | - Leroy B Vaughan
- Central Virginia VA Healthcare System, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - J Daniel Markley
- Central Virginia VA Healthcare System, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Alexa M Goldberg
- Department of Veterans Affairs, Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico, USA
| | - Peruvemba Sriram
- North Florida/South Georgia Veteran's Health System, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Antonio Anzueto
- South Texas Veterans Healthcare System, University of Texas Health San Antonio, San Antonio, Texas, USA
| | - Lauren Uyeda
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, California, USA
| | - Lisa Zehm
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, California, USA
| | - Ashlea Wills
- Rocky Mountain Regional VA Medical Center, Aurora, Colorado, USA
| | | | - Lucas Jones
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
| | - Dianne Peterson
- VA CSP Albuquerque Central Biorepository, Albuquerque, New Mexico, USA
| | - Robert J Ringer
- VA CSP Albuquerque Central Biorepository, Albuquerque, New Mexico, USA
| | - Larry Dumont
- Vitalant Research Institute, Aurora, Colorado, USA
| | - Theresa Gleason
- Department of Veterans Affairs, Cooperative Studies Program Clinical Science ResearcPharmacy Coordinating Center, Washington, DC, USA
| | - Robert A Bonomo
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
| | - Jeffrey L Curtis
- VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
- University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Sheldon T Brown
- James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
- Icahn School of Medicine at Mt. Sinai, New York, New York, USA
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Hoffmann S, Schrezenmeier E, Desmarets M, Halleck F, Durrbach A, Peters L, Tremmel AT, Seidel A, Führer M, Bachmann F, Schrezenmeier J, Greiner J, Körper S, Hofmann H, Ludwig C, Vieweg C, Jahrsdörfer B, Budde K, Schmidt M, Münch J, Joher N, Daguindau E, Grüner B, Brunotte G, Vauchy C, Seifried E, Bradshaw D, Estcourt LJ, Roberts DJ, Toussirot E, Rijnders B, Tiberghien P, Schrezenmeier H. Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19: an international, randomised, open-label trial. EBioMedicine 2025; 113:105613. [PMID: 40020259 PMCID: PMC11919330 DOI: 10.1016/j.ebiom.2025.105613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/05/2025] [Accepted: 02/08/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND COVID-19 convalescent plasma (CCP) is a treatment option for COVID-19. This study investigated the safety and efficacy of early, very high-titre CCP in immunocompromised individuals with mild COVID-19. METHODS This randomised, controlled, open-label trial assessed CCP in immunocompromised patients (n = 120) with mild COVID-19 in 10 clinical trial centres across Germany, France, and the Netherlands. Patients were randomised 1:1 to receive either standard of care (SoC) alone (SoC group) or SoC and 2 units of CCP. Most patients (89.7%) had received ≥3 SARS-CoV-2 vaccinations. The primary endpoint was hospitalisation for progressive COVID-19 symptoms or death by day 28 after randomisation, analysed on a modified intention-to-treat basis (117 patients). The safety analysis included the full analysis set. The trial is registered with EudraCT 2021-006621-22, and ClinicalTrials.gov, NCT05271929. FINDINGS Between April 11, 2022 and November 27, 2023, 120 patients were enrolled. Patients in the CCP group received a median of 559 ml CCP from convalescent, vaccinated donors with very high levels of SARS-CoV-2 antibodies (median 81,810 IU/ml) at a median 4 days after symptom onset. The primary outcome occurred in 5/58 patients (8.6%) in the SoC group and in 0/59 patients (0%) in the CCP group, difference -8.6% (95% confidence interval of difference -19% to -0.80%; p-value 0.027; Fisher's exact test). The course of SARS-CoV-2 antibodies in the patients demonstrated a passive transfer of antibodies by the CCP, in particular neutralising effects against new SARS-CoV-2 variants. Whole genome sequencing of SARS-CoV-2 in patients during follow-up showed significant intra-host viral evolution, but without differences between groups. CCP was well tolerated. INTERPRETATION Early administration of high-titre CCP can prevent hospitalisation or death in immunocompromised patients with mild COVID-19. FUNDING Support-e project (European Union's Horizon 2020 Programme), German Federal Ministry of Education and Research, ZonMw, the Netherlands Organisation for Health Research and Development.
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Affiliation(s)
- Simone Hoffmann
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Eva Schrezenmeier
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Maxime Desmarets
- Université Marie et Louis Pasteur, EFS, Inserm, RIGHT (UMR 1098), Besançon, France; CHU Besançon, Inserm, Centre d'Investigation Clinique (CIC 1431), Besançon, France
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Antoine Durrbach
- Department of Nephrology, AP-HP Hôpital Henri Mondor, Créteil, Île-de-France, France; INSERM UMR1186, Universite Paris Saclay, France
| | - Lynn Peters
- Division of Infectious Diseases, Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
| | | | - Alina Seidel
- Institute of Molecular Virology, Ulm University Medical Centre, Ulm, Germany
| | - Marita Führer
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Friederike Bachmann
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Jens Schrezenmeier
- Division of Haematology, Oncology, and Cancer Immunology, Medical Department, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Jochen Greiner
- Department of Internal Medicine, Diakonie Hospital Stuttgart, Stuttgart, Germany
| | - Sixten Körper
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Henrike Hofmann
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Carolin Ludwig
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Christiane Vieweg
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Bernd Jahrsdörfer
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Michael Schmidt
- Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen, Frankfurt, Germany
| | - Jan Münch
- Institute of Molecular Virology, Ulm University Medical Centre, Ulm, Germany
| | - Nizar Joher
- Department of Nephrology, AP-HP Hôpital Henri Mondor, Créteil, Île-de-France, France
| | - Etienne Daguindau
- Université Marie et Louis Pasteur, EFS, Inserm, RIGHT (UMR 1098), Besançon, France; Haematology Department, CHU Besançon, Besançon, France
| | - Beate Grüner
- Division of Infectious Diseases, Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
| | - Gaëlle Brunotte
- CHU Besançon, Inserm, Centre d'Investigation Clinique (CIC 1431), Besançon, France
| | - Charline Vauchy
- Université Marie et Louis Pasteur, EFS, Inserm, RIGHT (UMR 1098), Besançon, France; CHU Besançon, Inserm, Centre d'Investigation Clinique (CIC 1431), Besançon, France
| | - Erhard Seifried
- Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen, Frankfurt, Germany
| | - Daniel Bradshaw
- Virus Reference Department, UK Health Security Agency, London, UK
| | - Lise J Estcourt
- NHS Blood and Transplant, Oxford, Oxfordshire, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | - David J Roberts
- NHS Blood and Transplant, Oxford, Oxfordshire, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | - Eric Toussirot
- Université Marie et Louis Pasteur, EFS, Inserm, RIGHT (UMR 1098), Besançon, France; CHU Besançon, Inserm, Centre d'Investigation Clinique (CIC 1431), Besançon, France
| | - Bart Rijnders
- Department of Internal Medicine, Section of Infectious Diseases and Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Pierre Tiberghien
- Université Marie et Louis Pasteur, EFS, Inserm, RIGHT (UMR 1098), Besançon, France; Etablissement Francais du Sang, La Plaine Saint-Denis, Île-de-France, France
| | - Hubert Schrezenmeier
- Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
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3
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Sulaiman A, Sengsouk I, White JL, Marshall C, Fernandez RE, Redd AD, Eby Y, Casadevall A, Sullivan D, Gebo K, Shoham S, Laeyendecker O, Rai H, Bloch EM, Crowe EP, Tobian AAR. SARS-CoV-2 IgG antibodies in COVID-19 convalescent plasma and conventional plasma units. Transfusion 2025; 65:446-452. [PMID: 39844430 PMCID: PMC11925680 DOI: 10.1111/trf.18139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/09/2025] [Accepted: 01/09/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND The Association for the Advancement of Blood and Biotherapies guidelines recommend the use of high-titer COVID-19 convalescent plasma (CCP) for patients with SARS-CoV-2 at high risk of disease progression, including those who are immunocompromised. We hypothesized that conventional plasma units have comparable neutralizing antibody levels to CCP. STUDY DESIGN AND METHODS Conventional plasma and CCP units were obtained from blood suppliers. Quantitatively measured antibodies to SARS-CoV-2 were assessed using the MesoScale Discovery multiplex electrochemiluminescence immunoassay. Binding antibody distributions were compared with Wilcoxon rank-sum tests. SARS-CoV-2 neutralizing antibodies were analyzed using the GeneScript ELISA-based neutralization assay. The proportion of conventional and CCP units with a percent signal inhibition of ≥80% (as defined by the United States Food and Drug Administration for CCP in 2021) and exact binomial confidence intervals (CIs) were calculated. RESULTS Among 218 conventional plasma units and 74 CCP units collected between September 2023 and July 2024, the distribution of total antibody binding levels largely overlapped between conventional plasma and CCP, though statistically significant differences in median nucleocapsid and spike Omicron variant concentrations were observed. Median percent signal neutralization was 97.5% (range 3.4%-98.6%) among conventional plasma units and 97.7% (range 95.4%-98.6%) among CCP units. For conventional plasma, 95.0% (95% CI = 91.2%-97.5%) met the neutralization antibody threshold for high-titer CCP. For CCP, 100% (95% CI = 95.1%-100.0%) met the neutralization threshold for high-titer CCP. CONCLUSION Conventional plasma units demonstrate similar median antibody concentration to CCP units. In countries or regions where licensed CCP is unavailable and titers are unknown, transfusion of multiple conventional plasma units may be of clinical utility.
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Affiliation(s)
- Andrew Sulaiman
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Isabella Sengsouk
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Jodie L. White
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Christi Marshall
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | | | - Andrew D. Redd
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Yolanda Eby
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Arturo Casadevall
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - David Sullivan
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Kelly Gebo
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Shmuel Shoham
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Oliver Laeyendecker
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Herleen Rai
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Evan M. Bloch
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Elizabeth P. Crowe
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Aaron A. R. Tobian
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA
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Barbon S, Armellin F, Passerini V, De Angeli S, Primerano S, Del Pup L, Durante E, Macchi V, De Caro R, Parnigotto PP, Veronesi A, Porzionato A. Innate immune response in COVID-19: single-cell multi-omics profile of NK lymphocytes in a clinical case series. Cell Commun Signal 2024; 22:496. [PMID: 39407208 PMCID: PMC11476714 DOI: 10.1186/s12964-024-01867-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) represents the biggest global health emergency in recent decades. The host immune response to SARS-CoV-2 seems to play a key role in disease pathogenesis and clinical manifestations, with Natural Killer (NK) lymphocytes being among the targets of virus-induced regulation. METHODS This study performed a single-cell multi-omics analysis of transcripts and proteins of NK lymphocytes in COVID-19 patients, for the characterization of the innate immunological response to infection. NK cells were isolated from peripheral blood samples collected from adult subjects divided into 3 study groups: (1) non-infected subjects (Naïve group, n = 3), (2) post COVID-19 convalescent subjects (Healed group, n = 3) and (3) patients that were vaccinated against SARS-CoV-2 (Vaccine group, n = 3). Cells were then analysed by the BD Rhapsody System for the single-cell multi-omics investigation of transcriptome and membrane proteins. RESULTS The bioinformatic analysis identified 5 cell clusters which differentially expressed gene/protein markers, defining NK cell subsets as "Active NK cells" and "Mature NK cells". Calculating the relative proportion of each cluster within patient groups, more than 40% of the Naïve group cell population was found to belong to Mature NKs, whereas more than 75% of the Vaccine group cell population belonged to the cluster of Active NKs. Regarding the Healed group, it seemed to show intermediate phenotype between Active and Mature NK cells. Differential expression of specific genes, proteins and signaling pathways was detected comparing the profile of the 3 experimental groups, revealing a more activated NK cell phenotype in vaccinated patients versus recovered individuals. CONCLUSIONS The present study detected differential expression of NK cell markers in relation to SARS-CoV-2 infection and vaccine administration, suggesting the possibility to identify key molecular targets for clinical-diagnostic use of the individual response to viral infection and/or re-infection.
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Affiliation(s)
- Silvia Barbon
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy.
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy.
| | - Fabrizio Armellin
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Verena Passerini
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
| | - Sergio De Angeli
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Simona Primerano
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Laura Del Pup
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Elisabetta Durante
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy
| | - Veronica Macchi
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy
| | - Raffaele De Caro
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
| | - Pier Paolo Parnigotto
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
| | - Arianna Veronesi
- Complex Operative Unit of Transfusion Medicine - Marca Trevigiana Local Unit of Health and Social Services 2, Treviso Hospital, Piazzale dell'Ospedale 1, 31100, Treviso, Italy.
| | - Andrea Porzionato
- Section of Human Anatomy, Department of Neuroscience, University of Padova, Via Gabelli 65, 35121, Padova, Italy
- Foundation for Biology and Regenerative Medicine, Tissue Engineering and Signaling - T.E.S. Onlus, Padova, Italy
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5
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Klassen SA, Senefeld JW. Evidence for the Efficacy of COVID-19 Convalescent Plasma. Curr Top Microbiol Immunol 2024. [PMID: 39192049 DOI: 10.1007/82_2024_280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
During the global health emergency caused by the coronavirus disease 2019 (COVID-19), evidence relating to the efficacy of convalescent plasma therapy-evidence critically needed for both public policy and clinical practice-came from multiple levels of the epistemic hierarchy. The challenges of conducting clinical research during a pandemic, combined with the biological complexities of convalescent plasma treatment, required the use of observational data to fully assess the impact of convalescent plasma therapy on COVID symptomatology, hospitalization rates, and mortality rates. Observational studies showing the mortality benefits of convalescent plasma emerged early during the COVID-19 pandemic from multiple continents and were substantiated by real-time pragmatic meta-analyses. Although many randomized clinical trials (RCTs) were initiated at the onset of the pandemic and were designed to provide high-quality evidence, the relative inflexibility in the design of clinical trials meant that findings generally lagged behind other forms of emerging information and ultimately provided inconsistent results on the efficacy of COVID-19 convalescent plasma. In the pandemic framework, it is necessary to emphasize more flexible analytic strategies in clinical trials, including secondary, subgroup, and exploratory analyses. We conclude that in totality, observational studies and clinical trials taken together provide strong evidence of a mortality benefit conferred by COVID-19 convalescent plasma, while acknowledging that some randomized clinical trials examined suboptimal uses of convalescent plasma.
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Affiliation(s)
- Stephen A Klassen
- Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, Canada.
| | - Jonathon W Senefeld
- Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana, IL, USA
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6
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Voss WN, Mallory MA, Byrne PO, Marchioni JM, Knudson SA, Powers JM, Leist SR, Dadonaite B, Townsend DR, Kain J, Huang Y, Satterwhite E, Castillo IN, Mattocks M, Paresi C, Munt JE, Scobey T, Seeger A, Premkumar L, Bloom JD, Georgiou G, McLellan JS, Baric RS, Lavinder JJ, Ippolito GC. Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination. Cell Rep Med 2024; 5:101668. [PMID: 39094579 PMCID: PMC11384961 DOI: 10.1016/j.xcrm.2024.101668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 05/15/2024] [Accepted: 07/09/2024] [Indexed: 08/04/2024]
Abstract
We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC50] ∼0.1-1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [KD] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.
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Affiliation(s)
- William N Voss
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
| | - Michael A Mallory
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Patrick O Byrne
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
| | - Jeffrey M Marchioni
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA
| | - Sean A Knudson
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
| | - John M Powers
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Sarah R Leist
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Bernadeta Dadonaite
- Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Douglas R Townsend
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
| | - Jessica Kain
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
| | - Yimin Huang
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
| | - Ed Satterwhite
- Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA
| | - Izabella N Castillo
- Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Melissa Mattocks
- Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Chelsea Paresi
- Department of Chemistry, The University of Texas at Austin, Austin, TX, USA
| | - Jennifer E Munt
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Trevor Scobey
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Allison Seeger
- Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA
| | - Lakshmanane Premkumar
- Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jesse D Bloom
- Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA, USA
| | - George Georgiou
- Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA
| | - Jason S McLellan
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
| | - Ralph S Baric
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jason J Lavinder
- Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
| | - Gregory C Ippolito
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
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7
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Maličev E, Žiberna K, Jazbec K, Kolenc A, Mali P, Potokar UR, Rožman P. Cytokine, Anti-SARS-CoV-2 Antibody, and Neutralizing Antibody Levels in Conventional Blood Donors Who Have Recovered from COVID-19. Transfus Med Hemother 2024; 51:175-184. [PMID: 38867805 PMCID: PMC11166906 DOI: 10.1159/000531942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 07/02/2023] [Indexed: 06/14/2024] Open
Abstract
Background At the beginning of the pandemic, COVID-19 convalescent plasma (CCP) containing anti-SARS-CoV-2 antibodies was suggested as a source of therapy. In the last 3 years, many trials have demonstrated the limited usefulness of CCP therapy. This led us to the hypothesis that CCP could contain other elements, along with the desired neutralizing antibodies, which could potentially prevent it from having a therapeutic effect, among them cytokines, chemokines, growth factors, clotting factors, and autoantibodies. Methods In total, 39 cytokines were analyzed in the plasma of 190 blood donors, and further research focused on the levels of 23 different cytokines in CCP (sCD40L, eotaxin, FGF-2, FLT-3L, ractalkine, GRO-α, IFNα2, IL-1β, IL-1RA, IL-5, IL-6, IL-8, IL-12, IL-13, IL-15, IL-17E, IP-10, MCP-1, MIP-1b, PDGF-AA, TGFα, TNFα, and TRAIL). Anti-SARS-CoV-2 antibodies and neutralizing antibodies were detected in CCP. Results We found no significant differences between CCP taken within a maximum of 180 days from the onset of the first COVID-19 symptoms and the controls. We also made a comparison of the cytokine levels between the low neutralizing antibodies (<160) group and the high neutralizing antibodies (≥160) group and found there were no differences between the groups. Our research also showed no correlation either to levels of anti-SARS-CoV-2 IgG Ab or to the levels of neutralizing antibodies. There were also no significant changes in cytokine levels based on the period after the start of COVID-19 symptoms. Conclusions No elements which could potentially be responsible for preventing CCP from having a therapeutic effect were found.
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Affiliation(s)
- Elvira Maličev
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
- Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Klemen Žiberna
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
| | | | - Ana Kolenc
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
| | - Polonca Mali
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
| | | | - Primož Rožman
- Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
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8
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Voss WN, Mallory MA, Byrne PO, Marchioni JM, Knudson SA, Powers JM, Leist SR, Dadonaite B, Townsend DR, Kain J, Huang Y, Satterwhite E, Castillo IN, Mattocks M, Paresi C, Munt JE, Scobey T, Seeger A, Premkumar L, Bloom JD, Georgiou G, McLellan JS, Baric RS, Lavinder JJ, Ippolito GC. Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.22.576742. [PMID: 38545622 PMCID: PMC10970720 DOI: 10.1101/2024.01.22.576742] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/07/2024]
Abstract
We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (K D < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC 50 ∼0.1-1.75 nM) and provided robust protection in vivo . Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization. HIGHLIGHTS ▪ Infection and vaccination elicit unique IgG antibody profiles at the molecular level▪ Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)▪ Hybrid immunity maintains the imprint of first infection or first vaccination▪ Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth.
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9
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Terada M, Saito S, Kutsuna S, Kinoshita-Iwamoto N, Togano T, Hangaishi A, Shiratori K, Takamatsu Y, Maeda K, Ishizaka Y, Ohtsu H, Satake M, Mitsuya H, Ohmagari N. Efficacy and Safety of Treatment with Plasma from COVID-19-Recovered Individuals. Life (Basel) 2023; 13:2184. [PMID: 38004324 PMCID: PMC10671928 DOI: 10.3390/life13112184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/14/2023] [Accepted: 10/31/2023] [Indexed: 11/26/2023] Open
Abstract
Convalescent plasma therapy, which involves administering plasma from recovered coronavirus disease 2019 (COVID-19) patients to infected individuals, is being explored as a potential treatment for severe cases of COVID-19. This study aims to evaluate the efficacy and safety of convalescent plasma therapy in COVID-19 patients with moderate to severe illness. An open-label, single-arm intervention study was conducted without a control group. Plasma collected from recovered COVID-19 patients was administered to eligible participants. The primary endpoint was the proportion of patients who were placed on artificial ventilation or died within 14 days of transfusion. Secondary endpoints included clinical improvement, viral load measurements, and adverse event monitoring. A total of 59 cases were included in the study. The primary endpoint was evaluated by comparing the rate obtained in the study to an existing rate of 25%. The study also assessed clinical improvement, viral load changes, and safety endpoints through adverse event monitoring. Convalescent plasma therapy shows potential as a treatment option for COVID-19. This study aimed to provide evidence for the efficacy and safety of this therapy and may contribute to its future use in treating severe cases of COVID-19.
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Affiliation(s)
- Mari Terada
- Center for Clinical Sciences, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Sho Saito
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Satoshi Kutsuna
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Noriko Kinoshita-Iwamoto
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
| | - Tomiteru Togano
- Department of Hematology, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Akira Hangaishi
- Department of Hematology, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Katsuyuki Shiratori
- Laboratory Testing Department, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Yuki Takamatsu
- Department of Refractory Viral Infections, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Kenji Maeda
- Division of Antiviral Therapy Joint Research Center for Human Retrovirus Infection, Kagoshima University, Sakuragaoka, Kagoshima 890-8544, Japan
| | - Yukihito Ishizaka
- Department of Intractable Diseases, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Hiroshi Ohtsu
- Faculty of Health Data Science, Juntendo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Masahiro Satake
- Central Blood Institute, Japanese Red Cross, Tatsumi, Koto-ku, Tokyo 135-8521, Japan
| | - Hiroaki Mitsuya
- Department of Intractable Diseases, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
| | - Norio Ohmagari
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan (S.K.)
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10
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Ahmed SMJ, Miskeen E, Awadelgeed BA, Al Faifi JA. The psychological impact of the ongoing COVID-19 pandemic on health-care workers in primary health-care centers in resource-poor settings. J Family Med Prim Care 2023; 12:2840-2847. [PMID: 38186781 PMCID: PMC10771213 DOI: 10.4103/jfmpc.jfmpc_2416_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 03/07/2023] [Accepted: 03/22/2023] [Indexed: 01/09/2024] Open
Abstract
Background Health-care workers' psychological status is essential to Preventive control measures in a weak and unstable health system with poor infrastructural constraints. This study examines the psychological impact of the ongoing coronavirus disease 2019 (COVID-19) pandemic on the health-care providers working in primary health-care settings in Sudan. Materials and Methods This is a health facility-based cross-sectional study conducted in primary health-care units in White Nile State, Sudan. The psychological impact of stress and anxiety was determined using the Depression Anxiety Stress Scale 21 (DASS-21). A self-administered questionnaire measured depression, anxiety, and stress. The population of this study included health professionals working in health centers, including physicians, nurses, technicians, pharmacists, and other support staff. Results A total of 167 health professionals were systematically recruited. The mean anxiety score in the study population was 8.26 & 9.0 (corresponding to mild anxiety). Participants without anxiety constituted 26.35% (n = 44) of the participants. Women were significantly more likely to be affected than men (P = 0.0). Age (21-40 years), female nurses, and other health-care workers (anesthesiology, public health, health education, occupational health, psychiatry, etc.) could be strong predictors of psychological disorders (P-value of 0.0). Conclusion This study provided evidence for primary health care at its preparatory levels, as they are the first line of protection against the COVID-19 pandemic. Addressing the high-risk population is a high priority in the preliminary phase.
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Affiliation(s)
| | - Elhadi Miskeen
- Department of Obstetrics and Gynaecology, College of Medicine, University of Bisha, Bisha, Saudi Arabia
- Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Gezira, Sudan
| | | | - Jaber Ahmed Al Faifi
- Department of Paediatrics, College of Medicine, University of Bisha, Bisha, Saudi Arabia
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11
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Janoff EN, Brown ST, Belitskaya-Levy I, Curtis JL, Bonomo RA, Miller EK, Goldberg AM, Zehm L, Wills A, Hutchinson C, Dumont LJ, Gleason T, Shih MC, ADD Caitlin MS in CCTC website. Design of VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1): A double-blind, randomized placebo-controlled trial of COVID-19 convalescent plasma in hospitalized patients with early respiratory compromise. Contemp Clin Trials Commun 2023; 35:101190. [PMID: 37560085 PMCID: PMC10407261 DOI: 10.1016/j.conctc.2023.101190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 07/07/2023] [Accepted: 07/15/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Effective therapeutics for severe acute respiratory syndrome CoronaVirus-2 (SARS-CoV-2) infection are evolving. Under Emergency Use Authorization, COVID-19 convalescent plasma (CCP) was widely used in individuals hospitalized for COVID-19, but few randomized controlled trials supported its efficacy to limit respiratory failure or death. METHODS VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1) was a double-blind, multi-site, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of CCP with conventional therapy in hospitalized Veterans with SARS-CoV-2 infection and early respiratory compromise (requirement for oxygen). Participants (planned sample size 702) were randomized 1:1 to receive CCP with high titer neutralizing activity or 0.9% saline, stratified by site and age (≥65 versus <65 years old). Participants were followed daily during initial hospitalization and at Days 15, 22 and 28. OUTCOMES The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 28. Secondary outcomes by day 28 included time-to-recovery, clinical severity, mortality, rehospitalization for COVID-19, and adverse events. Serial respiratory and blood samples were collected for safety, virologic and immunologic analyses and future studies. Key variables in predicting the success of CURES-1 were: (1) enrollment early in the course of severe infection; (2) use of plasma with high neutralizing activity; (3) reliance on unambiguous, clinically meaningful outcomes. CURES-1 was terminated for futility due to perceived inability to enroll in the lull between the Alpha and Delta waves of the SARS CoV-2 epidemic. CONCLUSIONS VA CURES-1 was a large multi-site trial designed to provide conclusive information about the efficacy of CCP in well-characterized patients at risk for progression of COVID-19. It utilized a rigorous study design with relevant initial timing, quality of product and outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04539275.
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Affiliation(s)
- Edward N. Janoff
- Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
- University of Colorado Denver School of Medicine, Aurora, CO, USA
| | - Sheldon T. Brown
- James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, USA
- Icahn School of Medicine at Mt. Sinai, New York, NY, USA
| | - Ilana Belitskaya-Levy
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, CA, USA
| | - Jeffrey L. Curtis
- VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
- University of Michigan Medical School, Ann Arbor, MI, USA
| | - Robert A. Bonomo
- Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA
- Case VA CARES, Case Western Reserve University School of Medicine, USA
| | - Elliott K. Miller
- Department of Veterans Affairs, Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, USA
| | - Alexa M. Goldberg
- Department of Veterans Affairs, Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, USA
| | - Lisa Zehm
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, CA, USA
| | - Ashlea Wills
- Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
| | | | - Larry J. Dumont
- University of Colorado Denver School of Medicine, Aurora, CO, USA
- Vitalant Research Institute, Denver, CO, USA
| | - Theresa Gleason
- Department of Veterans Affairs, Clinical Science Research and Development Service, Washington, DC, USA
| | - Mei-Chiung Shih
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, CA, USA
- Stanford University School of Medicine, Palo Alto, CA, USA
| | - ADD Caitlin MS in CCTC website
- Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
- University of Colorado Denver School of Medicine, Aurora, CO, USA
- James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, USA
- Icahn School of Medicine at Mt. Sinai, New York, NY, USA
- Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, CA, USA
- VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
- University of Michigan Medical School, Ann Arbor, MI, USA
- Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA
- Case VA CARES, Case Western Reserve University School of Medicine, USA
- Department of Veterans Affairs, Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, USA
- Vitalant Research Institute, Denver, CO, USA
- Department of Veterans Affairs, Clinical Science Research and Development Service, Washington, DC, USA
- Stanford University School of Medicine, Palo Alto, CA, USA
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12
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Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev 2023; 5:CD013600. [PMID: 37162745 PMCID: PMC10171886 DOI: 10.1002/14651858.cd013600.pub6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
BACKGROUND Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required. OBJECTIVES To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS In this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease 29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text. Convalescent plasma versus placebo or standard care alone Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus human immunoglobulin Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma. Convalescent plasma versus placebo or standard care alone We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence. AUTHORS' CONCLUSIONS For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have very-low to low certainty evidence for most primary outcomes and moderate certainty for hospital admission or death. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.
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Affiliation(s)
- Claire Iannizzi
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Khai Li Chai
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Vanessa Piechotta
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Sarah J Valk
- Jon J van Rood Center for Clinical Transfusion Research, Sanquin/Leiden University Medical Center, Leiden, Netherlands
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
| | - Catherine Kimber
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Ina Monsef
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Erica M Wood
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | | | - David J Roberts
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Zoe McQuilten
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Cynthia So-Osman
- Sanquin Blood Bank, Amsterdam, Netherlands
- Erasmus Medical Centre, Rotterdam, Netherlands
| | - Aikaj Jindal
- Department of Transfusion Medicine, SPS Hospitals, Ludhiana (Punjab), India
| | - Nora Cryns
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Lise J Estcourt
- Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK
| | - Nina Kreuzberger
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Nicole Skoetz
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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13
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Kumar NR, Karanam VC, Kumar S, Kumar SD. Convalescent Plasma Therapy in Late-State, Severe COVID-19 Infection. South Med J 2023; 116:427-433. [PMID: 37137479 PMCID: PMC10143395 DOI: 10.14423/smj.0000000000001546] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
OBJECTIVES Current evidence favors plasma to be effective against coronavirus disease 2019 (COVID-19) in critically ill patients in the early stages of infection. We investigated the safety and efficacy of convalescent plasma in specifically late-stage (designated as after 2 weeks of hospital admission) severe COVID-19 infection. We also conducted a literature review on the late-stage use of plasma in COVID-19. METHODS This case series examined eight COVID-19 patients admitted to the intensive care unit (ICU) who met criteria for severe or life-threatening complications. Each patient received one dose (200 mL) of plasma. Clinical information was gathered in intervals of 1 day pretransfusion and 1 hour, 3 days, and 7 days posttransfusion. The primary outcome was effectiveness of plasma transfusion, measured by clinical improvement, laboratory parameters, and all-cause mortality. RESULTS Eight ICU patients received plasma late in the course of COVID-19 infection, on average at 16.13 days postadmission. On the day before transfusion, the averaged initial Sequential Organ Failure Assessment (SOFA) score, PaO2:FiO2 ratio, Glasgow Coma Scale (GCS), and lymphocyte count were 6.5, 228.03, 8.63, and 1.19, respectively. Three days after plasma treatment, the group averages for the SOFA score (4.86), PaO2:FiO2 ratio (302.73), GCS (9.29), and lymphocyte count (1.75) improved. Although the mean GCS improved to 10.14 by posttransfusion day 7, the other means marginally worsened with an SOFA score of 5.43, a PaO2:FiO2 ratio of 280.44, and a lymphocyte count of 1.71. Clinical improvement was noted in six patients who were discharged from the ICU. CONCLUSIONS This case series provides evidence that convalescent plasma may be safe and effective in late-stage, severe COVID-19 infection. Results showed clinical improvement posttransfusion as well as decreased all-cause mortality in comparison to pretransfusion predicted mortality. Randomized controlled trials are needed to conclusively determine benefits, dosage, and timing of treatment.
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Affiliation(s)
- Neil R Kumar
- From Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, Florida
| | - Veena C Karanam
- the University of Miami Miller School of Medicine, Miami, Florida
| | - Shari Kumar
- Columbia University College of Dental Medicine, New York, New York
| | - Sunil D Kumar
- the Pulmonary/Critical Care, Broward Health Medical Center, Ft Lauderdale, Florida
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14
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Desmarets M, Hoffmann S, Vauchy C, Rijnders BJA, Toussirot E, Durrbach A, Körper S, Schrezenmeier E, van der Schoot CE, Harvala H, Brunotte G, Appl T, Seifried E, Tiberghien P, Bradshaw D, Roberts DJ, Estcourt LJ, Schrezenmeier H. Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial. BMJ Open 2023; 13:e071277. [PMID: 37105693 PMCID: PMC10151238 DOI: 10.1136/bmjopen-2022-071277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/29/2023] Open
Abstract
INTRODUCTION COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients. METHODS AND ANALYSIS COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle. ETHICS AND DISSEMINATION Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. TRIAL REGISTRATION Clinical Trials.gov (NCT05271929), EudraCT (2021-006621-22).
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Affiliation(s)
- Maxime Desmarets
- Centre d'Investigation Clinique Inserm CIC1431, CHU Besançon, Besançon, Bourgogne Franche-Comté, France
- UMR 1098 Right, Inserm, Établissement Français du Sang, Université de Franche-Comté, Besançon, Bourgogne Franche-Comté, France
| | - Simone Hoffmann
- Blood Transfusion Service Baden-Württemberg-Hessen, German Red Cross, Ulm, Baden-Württemberg, Germany
| | - Charline Vauchy
- Centre d'Investigation Clinique Inserm CIC1431, CHU Besançon, Besançon, Bourgogne Franche-Comté, France
- UMR 1098 Right, Inserm, Établissement Français du Sang, Université de Franche-Comté, Besançon, Bourgogne Franche-Comté, France
| | - Bart J A Rijnders
- University Medical Center, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
| | - Eric Toussirot
- Centre d'Investigation Clinique Inserm CIC1431, CHU Besançon, Besançon, Bourgogne Franche-Comté, France
- UMR 1098 Right, Inserm, Établissement Français du Sang, Université de Franche-Comté, Besançon, Bourgogne Franche-Comté, France
| | - Antoine Durrbach
- Department of Nephrology, AP-HP Hôpital Henri Mondor, Créteil, Île-de-France, France
| | - Sixten Körper
- Blood Transfusion Service Baden-Württemberg-Hessen, German Red Cross, Ulm, Baden-Württemberg, Germany
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, Ulm, Baden-Württemberg, Germany
| | - Eva Schrezenmeier
- Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - C Ellen van der Schoot
- Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Noord-Holland, Netherlands
| | - Heli Harvala
- Microbiology Services, NHS Blood and Transplant, Colindale, London, UK
| | - Gaëlle Brunotte
- Centre d'investigation clinique Inserm CIC1431, CHU Besançon, Besançon, France
| | - Thomas Appl
- Blood Transfusion Service Baden-Württemberg-Hessen, German Red Cross, Ulm, Baden-Württemberg, Germany
| | - Erhard Seifried
- Blood Transfusion Service Baden-Württemberg-Hessen, German Red Cross, Ulm, Baden-Württemberg, Germany
| | - Pierre Tiberghien
- UMR 1098 Right, Inserm, Établissement Français du Sang, Université de Franche-Comté, Besançon, Bourgogne Franche-Comté, France
- Etablissement Francais du Sang, La Plaine Saint-Denis, Île-de-France, France
| | - Daniel Bradshaw
- Virus Reference Department, UK Health Security Agency, London, UK
| | - David J Roberts
- NHS Blood and Transplant, Oxford, Oxfordshire, UK
- Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | - Lise J Estcourt
- NHS Blood and Transplant, Oxford, Oxfordshire, UK
- Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK
| | - Hubert Schrezenmeier
- Blood Transfusion Service Baden-Württemberg-Hessen, German Red Cross, Ulm, Baden-Württemberg, Germany
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, Ulm, Baden-Württemberg, Germany
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15
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Seidel A, Hoffmann S, Jahrsdörfer B, Körper S, Ludwig C, Vieweg C, Albers D, von Maltitz P, Müller R, Lotfi R, Wuchter P, Klüter H, Kirchhoff F, Schmidt M, Münch J, Schrezenmeier H. SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against Omicron subvariants BA.1, BA.2 and BA.5 and can be predicted by anti-S antibody concentrations in serological assays. Front Immunol 2023; 14:1170759. [PMID: 37180152 PMCID: PMC10166809 DOI: 10.3389/fimmu.2023.1170759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 04/10/2023] [Indexed: 05/15/2023] Open
Abstract
Background Recent data on immune evasion of new SARS-CoV-2 variants raise concerns about the efficacy of antibody-based COVID-19 therapies. Therefore, in this study the in-vitro neutralization capacity against SARS-CoV-2 variant B.1 and the Omicron subvariants BA.1, BA.2 and BA.5 of sera from convalescent individuals with and without boost by vaccination was assessed. Methods and findings The study included 313 serum samples from 155 individuals with a history of SARS-CoV-2 infection, divided into subgroups without (n=25) and with SARS-CoV-2 vaccination (n=130). We measured anti-SARS-CoV-2 antibody concentrations by serological assays (anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S) and neutralizing titers against B.1, BA.1, BA.2 and BA.5 in a pseudovirus neutralization assay. Sera of the majority of unvaccinated convalescents did not effectively neutralize Omicron sublineages BA.1, BA.2 and BA.5 (51.7%, 24.1% and 51.7%, resp.). In contrast, 99.3% of the sera of superimmunized individuals (vaccinated convalescents) neutralized the Omicron subvariants BA.1 and BA.5 and 99.6% neutralized BA.2. Neutralizing titers against B.1, BA.1, BA.2 and BA.5 were significantly higher in vaccinated compared to unvaccinated convalescents (p<0.0001) with 52.7-, 210.7-, 141.3- and 105.4-fold higher geometric mean of 50% neutralizing titers (NT50) in vaccinated compared to unvaccinated convalescents. 91.4% of the superimmunized individuals showed neutralization of BA.1, 97.2% of BA.2 and 91.5% of BA.5 with a titer ≥ 640. The increase in neutralizing titers was already achieved by one vaccination dose. Neutralizing titers were highest in the first 3 months after the last immunization event. Concentrations of anti-S antibodies in the anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S assays predicted neutralization capacity against B.1 and Omicron subvariants BA.1, BA.2 and BA.5. Conclusions These findings confirm substantial immune evasion of the Omicron sublineages, which can be overcome by vaccination of convalescents. This informs strategies for choosing of plasma donors in COVID-19 convalescent plasma programs that shall select specifically vaccinated convalescents with very high titers of anti-S antibodies.
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Affiliation(s)
- Alina Seidel
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Simone Hoffmann
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden- Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Bernd Jahrsdörfer
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden- Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Sixten Körper
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden- Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Carolin Ludwig
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden- Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Christiane Vieweg
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden- Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Dan Albers
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Pascal von Maltitz
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Rebecca Müller
- Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University; German Red Cross Blood Service Baden-Württemberg– Hessen, Mannheim, Germany
| | - Ramin Lotfi
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden- Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Patrick Wuchter
- Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University; German Red Cross Blood Service Baden-Württemberg– Hessen, Mannheim, Germany
| | - Harald Klüter
- Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University; German Red Cross Blood Service Baden-Württemberg– Hessen, Mannheim, Germany
| | - Frank Kirchhoff
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Michael Schmidt
- Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg – Hessen, Frankfurt, Germany
| | - Jan Münch
- Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
| | - Hubert Schrezenmeier
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden- Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
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16
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Ioannou P, Katsigiannis A, Papakitsou I, Kopidakis I, Makraki E, Milonas D, Filippatos TD, Sourvinos G, Papadogiannaki M, Lydaki E, Chamilos G, Kofteridis DP. Convalescent Plasma Treatment of Patients Previously Treated with B-Cell-Depleting Monoclonal Antibodies Suffering COVID-19 Is Associated with Reduced Re-Admission Rates. Viruses 2023; 15:756. [PMID: 36992465 PMCID: PMC10059055 DOI: 10.3390/v15030756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/12/2023] [Accepted: 03/12/2023] [Indexed: 03/17/2023] Open
Abstract
Patients receiving treatment with B-cell-depleting monoclonal antibodies, such as anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, either for hematological disease or another diagnosis, such as a rheumatological disease, are at an increased risk for medical complications and mortality from COVID-19. Since inconsistencies persist regarding the use of convalescent plasma (CP), especially in the vulnerable patient population that has received previous treatment with B-cell-depleting monoclonal antibodies, further studies should be performed in thisdirection. The aim of the present study was to describe the characteristics of patients with previous use of B-cell-depleting monoclonal antibodies and describe the potential beneficial effects of CP use in terms of mortality, ICU admission and disease relapse. In this retrospective cohort study, 39 patients with previous use of B-cell-depleting monoclonal antibodies hospitalized in the COVID-19 department of a tertiary hospital in Greece were recorded and evaluated. The mean age was 66.3 years and 51.3% were male. Regarding treatment for COVID-19, remdesivir was used in 89.7%, corticosteroids in 94.9% and CP in 53.8%. In-hospital mortality was 15.4%. Patients who died were more likely to need ICU admission and also had a trend towards a longer hospital stay, even though the last did not reach statistical significance. Patients treated with CP had a lower re-admission rate for COVID-19 after discharge. Further studies should be performed to identify the role of CP in patients with treatment with B-cell-depleting monoclonal antibodies suffering from COVID-19.
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Affiliation(s)
- Petros Ioannou
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.C.)
- COVID-19 Department, University Hospital of Heraklion, 71110 Heraklion, Greece
| | | | - Ioanna Papakitsou
- COVID-19 Department, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - Ioannis Kopidakis
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.C.)
| | - Eirini Makraki
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.C.)
| | - Dimitris Milonas
- COVID-19 Department, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - Theodosios D. Filippatos
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.C.)
- COVID-19 Department, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - George Sourvinos
- Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece;
| | - Marina Papadogiannaki
- Department of Blood Transfusion, University Hospital of Heraklion, 71110 Heraklion, Greece; (M.P.)
| | - Evaggelia Lydaki
- Department of Blood Transfusion, University Hospital of Heraklion, 71110 Heraklion, Greece; (M.P.)
| | - Georgios Chamilos
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.C.)
- Microbiology Department, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - Diamantis P. Kofteridis
- School of Medicine, University of Crete, 71003 Heraklion, Greece (G.C.)
- COVID-19 Department, University Hospital of Heraklion, 71110 Heraklion, Greece
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17
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Schrezenmeier H, Hoffmann S, Hofmann H, Appl T, Jahrsdörfer B, Seifried E, Körper S. Immune Plasma for the Treatment of COVID-19: Lessons Learned so far. Hamostaseologie 2023; 43:67-74. [PMID: 36807822 DOI: 10.1055/a-1987-3682] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023] Open
Abstract
COVID-19 convalescent plasma (CCP) has been explored as one of the treatment options for COVID-19. Results of many cohort studies and clinical trials have been recently published. At first glance, the results of the CCP studies appear to be inconsistent. However, it became clear that CCP is not beneficial if CCP with low anti-SARS-CoV-2 antibody concentrations is used, if it is administered late in advanced disease stages, and to patients who already mounted an antibody response against SARS-CoV-2 at the time of CCP transfusion. On the other hand, CCP may prevent progression to severe COVID-19 when very high-titer CCP is given early in vulnerable patients. Immune escape of new variants is a challenge for passive immunotherapy. While new variants of concern developed resistance to most clinically used monoclonal antibodies very rapidly, immune plasma from individuals immunized by both a natural SARS-CoV-2 infection and SARS-CoV-2 vaccination retained neutralizing activity against variants. This review briefly summarizes the evidence on CCP treatment to date and identifies further research needs. Ongoing research on passive immunotherapy is not only relevant for improving care for vulnerable patients in the ongoing SARS-CoV-2 pandemic, but even more as a model for passive immunotherapy in case of future pandemics with a newly evolving pathogen. Compared to other drugs, which must be newly developed in a pandemic (e.g., monoclonal antibodies, antiviral drugs), convalescent plasma is rapidly available, inexpensive to produce, and can be adaptive to viral evolution by selection of contemporary convalescent donors.
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Affiliation(s)
- Hubert Schrezenmeier
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany.,Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Simone Hoffmann
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany.,Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Henrike Hofmann
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany.,Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Thomas Appl
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany.,Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Bernd Jahrsdörfer
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany.,Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Erhard Seifried
- Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen, Frankfurt, Germany
| | - Sixten Körper
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany.,Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
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18
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Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev 2023; 2:CD013600. [PMID: 36734509 PMCID: PMC9891348 DOI: 10.1002/14651858.cd013600.pub5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required. OBJECTIVES To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS In this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease 29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text. Convalescent plasma versus placebo or standard care alone Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus human immunoglobulin Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma. Convalescent plasma versus placebo or standard care alone We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence. AUTHORS' CONCLUSIONS For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have low certainty evidence for our primary outcomes. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.
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Affiliation(s)
- Claire Iannizzi
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Khai Li Chai
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Vanessa Piechotta
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Sarah J Valk
- Jon J van Rood Center for Clinical Transfusion Research, Sanquin/Leiden University Medical Center, Leiden, Netherlands
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
| | - Catherine Kimber
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Ina Monsef
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Erica M Wood
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | | | - David J Roberts
- Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK
| | - Zoe McQuilten
- Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Cynthia So-Osman
- Sanquin Blood Bank, Amsterdam, Netherlands
- Erasmus Medical Centre, Rotterdam, Netherlands
| | - Aikaj Jindal
- Department of Transfusion Medicine, SPS Hospitals, Ludhiana (Punjab), India
| | - Nora Cryns
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Lise J Estcourt
- Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK
| | - Nina Kreuzberger
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Nicole Skoetz
- Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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State of the art in epitope mapping and opportunities in COVID-19. Future Sci OA 2023; 16:FSO832. [PMID: 36897962 PMCID: PMC9987558 DOI: 10.2144/fsoa-2022-0048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 02/15/2023] [Indexed: 03/08/2023] Open
Abstract
The understanding of any disease calls for studying specific biological structures called epitopes. One important tool recently drawing attention and proving efficiency in both diagnosis and vaccine development is epitope mapping. Several techniques have been developed with the urge to provide precise epitope mapping for use in designing sensitive diagnostic tools and developing rpitope-based vaccines (EBVs) as well as therapeutics. In this review, we will discuss the state of the art in epitope mapping with a special emphasis on accomplishments and opportunities in combating COVID-19. These comprise SARS-CoV-2 variant analysis versus the currently available immune-based diagnostic tools and vaccines, immunological profile-based patient stratification, and finally, exploring novel epitope targets for potential prophylactic, therapeutic or diagnostic agents for COVID-19.
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Körper S, Grüner B, Zickler D, Wiesmann T, Wuchter P, Blasczyk R, Zacharowski K, Spieth P, Tonn T, Rosenberger P, Paul G, Pilch J, Schwäble J, Bakchoul T, Thiele T, Knörlein J, Dollinger MM, Krebs J, Bentz M, Corman VM, Kilalic D, Schmidtke-Schrezenmeier G, Lepper PM, Ernst L, Wulf H, Ulrich A, Weiss M, Kruse JM, Burkhardt T, Müller R, Klüter H, Schmidt M, Jahrsdörfer B, Lotfi R, Rojewski M, Appl T, Mayer B, Schnecko P, Seifried E, Schrezenmeier H. One-year follow-up of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients. J Clin Invest 2022; 132:e163657. [PMID: 36326824 PMCID: PMC9753994 DOI: 10.1172/jci163657] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 10/18/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTSThe median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSIONThe trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registrationEudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health).
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Affiliation(s)
- Sixten Körper
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Beate Grüner
- Division of Infectious Diseases, University Hospital and Medical Center Ulm, Ulm, Germany
| | - Daniel Zickler
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, corporate member of Free University Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Thomas Wiesmann
- Department of Anesthesiology and Intensive Care Medicine, Phillips-University Marburg, Marburg, Germany
| | - Patrick Wuchter
- Institute of Transfusion Medicine and Immunology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, Germany
| | - Rainer Blasczyk
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Kai Zacharowski
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University, Germany
| | - Peter Spieth
- Department of Anesthesiology and Critical Care Medicine, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany
| | - Torsten Tonn
- Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden and German Red Cross Blood Donation Service North-East gGmbH, Dresden, Germany
| | - Peter Rosenberger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Gregor Paul
- Department of Gastroenterology, Hepatology, Pneumology and Infectious Diseases, Klinikum Stuttgart, Stuttgart, Germany
| | - Jan Pilch
- Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University Hospital, Homburg/Saar, Germany
| | - Joachim Schwäble
- Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg – Hessen, Frankfurt, Germany
| | - Tamam Bakchoul
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Thomas Thiele
- Institute of Transfusion Medicine, University Hospital Greifswald, Greifswald, Germany
| | - Julian Knörlein
- Clinic of Anesthesiology and Intensive Care Medicine, University Medical Center of Freiburg, Freiburg, Germany
| | | | - Jörg Krebs
- Clinic for Anesthesiology and Surgical Intensive Care Medicine, University of Mannheim, Mannheim, Germany
| | - Martin Bentz
- Department of Internal Medicine III, Hospital of Karlsruhe, Karlsruhe, Germany
| | - Victor M. Corman
- Institute of Virology, Charité - University Medicine Berlin, corporate member of Free University Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and German Centre for Infection Research, Berlin, Germany
| | - Dzenan Kilalic
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | | | - Philipp M. Lepper
- Department of Internal Medicine V – Pneumology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany
| | - Lucas Ernst
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, corporate member of Free University Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Hinnerk Wulf
- Department of Anesthesiology and Intensive Care Medicine, Phillips-University Marburg, Marburg, Germany
| | - Alexandra Ulrich
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Manfred Weiss
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Ulm University, Ulm, Germany
| | - Jan Matthias Kruse
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, corporate member of Free University Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Thomas Burkhardt
- Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden and German Red Cross Blood Donation Service North-East gGmbH, Dresden, Germany
| | - Rebecca Müller
- Institute of Transfusion Medicine and Immunology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, Germany
| | - Harald Klüter
- Institute of Transfusion Medicine and Immunology, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, Germany
| | - Michael Schmidt
- Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg – Hessen, Frankfurt, Germany
| | - Bernd Jahrsdörfer
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Ramin Lotfi
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Markus Rojewski
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Thomas Appl
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
| | - Benjamin Mayer
- Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany
| | | | - Erhard Seifried
- Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg – Hessen, Frankfurt, Germany
| | - Hubert Schrezenmeier
- Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm and Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
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Evaluation of a COVID-19 convalescent plasma program at a U.S. academic medical center. PLoS One 2022; 17:e0277707. [PMID: 36480499 PMCID: PMC9731422 DOI: 10.1371/journal.pone.0277707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 11/01/2022] [Indexed: 12/13/2022] Open
Abstract
Amidst the therapeutic void at the onset of the COVID-19 pandemic, a critical mass of scientific and clinical interest coalesced around COVID-19 convalescent plasma (CCP). To date, the CCP literature has focused largely on safety and efficacy outcomes, but little on implementation outcomes or experience. Expert opinion suggests that if CCP has a role in COVID-19 treatment, it is early in the disease course, and it must deliver a sufficiently high titer of neutralizing antibodies (nAb). Missing in the literature are comprehensive evaluations of how local CCP programs were implemented as part of pandemic preparedness and response, including considerations of the core components and personnel required to meet demand with adequately qualified CCP in a timely and sustained manner. To address this gap, we conducted an evaluation of a local CCP program at a large U.S. academic medical center, the University of North Carolina Medical Center (UNCMC), and patterned our evaluation around the dimensions of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to systematically describe key implementation-relevant metrics. We aligned our evaluation with program goals of reaching the target population with severe or critical COVID-19, integrating into the structure of the hospital-wide pandemic response, adapting to shifting landscapes, and sustaining the program over time during a compassionate use expanded access program (EAP) era and a randomized controlled trial (RCT) era. During the EAP era, the UNCMC CCP program was associated with faster CCP infusion after admission compared with contemporaneous affiliate hospitals without a local program: median 29.6 hours (interquartile range, IQR: 21.2-48.1) for the UNCMC CCP program versus 47.6 hours (IQR 32.6-71.6) for affiliate hospitals; (P<0.0001). Sixty-eight of 87 CCP recipients in the EAP (78.2%) received CCP containing the FDA recommended minimum nAb titer of ≥1:160. CCP delivery to hospitalized patients operated with equal efficiency regardless of receiving treatment via a RCT or a compassionate-use mechanism. It was found that in a highly resourced academic medical center, rapid implementation of a local CCP collection, treatment, and clinical trial program could be achieved through re-deployment of highly trained laboratory and clinical personnel. These data provide important pragmatic considerations critical for health systems considering the use of CCP as part of an integrated pandemic response.
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22
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Nontawong N, Siripongboonsitti T, Tawinprai K, Boonpratoom M, Krailassiri N, Boonkhum C, Soonklang K, Poovorawan Y, Mahanonda N. The clinical outcomes of high neutralizing antibodies titer convalescent plasma therapy in early developed severe COVID-19 patients; a case-control study. Ann Clin Microbiol Antimicrob 2022; 21:51. [PMID: 36403020 PMCID: PMC9675119 DOI: 10.1186/s12941-022-00542-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 11/08/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) causes life-threatening pneumonia. Convalescent plasma therapy (CPT) is expected to be the effective COVID-19 treatment for passive immunity. The high neutralizing antibodies titer of CPT is needed to prove the benefit in early developed severe COVID-19. OBJECTIVE This case-control study evaluated transfusion efficacy and adverse events with high-titer (≥ 1:320) COVID-19 convalescent plasma compared with standard care alone in severe COVID-19 pneumonia. RESULTS Among 107 severe COVID-19 patients, 55 received CPT plus standard care, and 52 received standard care alone. All-cause mortality was 15.3% in the CPT group compared with 85.4% in the standard care group (p < 0.001). Univariate and multivariate analyses revealed reduced mortality with CPT (HR 0.14; 95% CI 0.07-0.31; p < 0.001 and HR 0.26; 95% CI 0.08-0.79; p = 0.018, respectively). CPT resulted in decreased use of mechanical ventilation, duration of supplemental oxygen, and high-flow oxygen requirement. Clinical and radiological outcomes improved. CONCLUSIONS Immediate high neutralizing antibody titer CPT is safe and reduces mortality in early developed severe COVID-19 patients. The benefit of CPT in the early course of illness is challenging and requires additional study. Trial registration Thai clinical trials registry (TCTR) no. 20220101003.
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Affiliation(s)
| | - Taweegrit Siripongboonsitti
- Division of Infectious Diseases, Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand.
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand.
| | - Kriangkrai Tawinprai
- Division of Infectious Diseases, Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
| | | | | | | | - Kamonwan Soonklang
- Center of Learning and Research in Celebration of HRH Princess Chulabhorn 60th Birthday Anniversary, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Nithi Mahanonda
- Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
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Impact of Convalescent Plasma Therapy in Hospitalized Patients With Severe COVID-19. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2022. [DOI: 10.1097/ipc.0000000000001161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Grubovic Rastvorceva RM, Useini S, Stevanovic M, Demiri I, Petkovic E, Franchini M, Focosi D. Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients-An Open-Label Phase II Clinical Trial. Life (Basel) 2022; 12:1565. [PMID: 36295001 PMCID: PMC9605182 DOI: 10.3390/life12101565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/14/2022] [Accepted: 09/27/2022] [Indexed: 01/24/2023] Open
Abstract
Background: COVID-19 convalescent plasma (CCP) is an important antiviral option for selected patients with COVID-19. Materials and Methods: In this open-label, phase 2, clinical trial conducted from 30 April 2020 till 10 May 2021 in the Republic of North Macedonia, we evaluated the efficacy and safety of CCP in hospitalized patients. Treatment was with a single unit of CCP having an anti-RBD IgG concentration higher than 5 AU/mL. Results: There were 189 patients that completed the study, of which 65 (34.4%) had WHO 8-point clinical progression scale score of 3 (requiring hospital care but not oxygen support), 65 (34.4%) had a score of 4 (hospitalized and requiring supplemental oxygen by mask or nasal prongs), and 59 (31.2%) had a score of 5 (hospitalized and requiring supplemental oxygen by non-invasive ventilation or high-flow oxygen). Mean age was 57 years (range 22−94), 78.5% were males, 80.4% had elevated body mass index, and 70.9% had comorbidity. Following CCP transfusion, we observed clinical improvement with increase rates in oxygenation-free days of 32.3% and 58.5% at 24 h and seven days after CCP transfusion, a decline in WHO scores, and reduced progression to severe disease (only one patient was admitted to ICU after CCP transfusion). Mortality in the entire cohort was 11.6% (22/189). We recorded 0% mortality in WHO score 3 (0/65) and in patients that received CCP transfusion in the first seven days of disease, 4.6% mortality in WHO score 4 (3/65), and 30.5% mortality in WHO score 5 (18/59). Mortality correlated with WHO score (Chi-square 19.3, p < 0.001) and with stay in the ICU (Chi-square 55.526, p ≤ 0.001). No severe adverse events were reported. Conclusions: This study showed that early administration of CCP to patients with moderate disease was a safe and potentially effective treatment for hospitalized COVID-19 patients. The trial was registered at clinicaltrials.gov (NCT04397523).
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Affiliation(s)
- Rada M. Grubovic Rastvorceva
- Institute for Transfusion Medicine of RNM, 1000 Skopje, North Macedonia
- Faculty of Medical Sciences, University Goce Delcev, 2000 Stip, North Macedonia
| | - Sedula Useini
- Institute for Transfusion Medicine of RNM, 1000 Skopje, North Macedonia
| | - Milena Stevanovic
- University Clinic for Infectious Diseases, 1000 Skopje, North Macedonia
| | - Ilir Demiri
- University Clinic for Infectious Diseases, 1000 Skopje, North Macedonia
| | - Elena Petkovic
- Institute for Transfusion Medicine of RNM, 1000 Skopje, North Macedonia
| | | | - Daniele Focosi
- North-Western Tuscany Blood Bank, Pisa University Hospital, 56124 Pisa, Italy
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Targeted therapy in Coronavirus disease 2019 (COVID-19): Implication from cell and gene therapy to immunotherapy and vaccine. Int Immunopharmacol 2022; 111:109161. [PMID: 35998506 PMCID: PMC9385778 DOI: 10.1016/j.intimp.2022.109161] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/27/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
Abstract
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19.
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Prolonged ICU Stay in Severe and Critically-Ill COVID-19 Patients Who Received Convalescent Plasma Therapy. Crit Care Res Pract 2022; 2022:1594342. [PMID: 36118915 PMCID: PMC9473920 DOI: 10.1155/2022/1594342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 07/22/2022] [Accepted: 08/05/2022] [Indexed: 11/26/2022] Open
Abstract
Background Convalescent plasma administration in severe and critically-ill COVID-19 patients have been proven to not provide improvement in patients' outcome, yet it is still widely used in countries with limited resources due to its high availability and safety. This study aims to investigate its effects on ICU mortality, ICU length of stay (LoS), and improvement of oxygen support requirements. Methods Data of all severe and critically-ill patients in our COVID-19 ICU was collected retrospectively between May and November 2020. We dichotomized the variables and compared outcome data of 48 patients, who received convalescent plasma to 131 patients, receiving standard of care. Data were analyzed using multiple logistic regression to make prediction models of mortality, length of stay, and oxygen support device requirement. Result Overall mortality rate in our COVID-19 ICU was 55.3%, with a median overall length of stay of 8 (4–11) days. Less patients that received convalescent plasma presented with the need for mechanical ventilation on ICU admission (p < 0.001), but with comparable PaO2 to FiO2 (P/F) ratio (p=0.95). Factors that confounded mortality were obesity (aOR = 14.1; 95% CI (1.25, 166.7); p=0.032), mechanical ventilation (aOR = 333; 95% CI (4.5,1,000); p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (aOR = 7.32; 95% CI (1.82, 29.4); p=0.005), and lower P/F ratio (aOR = 7.70; 95% CI (2.04, 29.4); p=0.003). ICU LoS was longer in patients, who had prior history of hypertension (aOR = 2.14; 95% CI (1.05, 4.35); p=0.036) and received convalescent plasma (aOR = 3.88; 95% CI (1.77, 8.05); p < 0.001). Deceased patients, who received convalescent plasma, stayed longer in the ICU with a mean length of stay of 12.87 ± 5.7 days versus 8.13 ± 4.8 days with a significant difference (U = 434; p < 0.000). The chance of improved oxygen support requirements was lower in obese patients (aOR = 9.18; 95%CI (2.0, 42.1); p < 0.004), mechanically ventilated patients (aOR = 13.15; 95% CI (3.75, 46.09); p < 0.001), patients with higher NLR (aOR = 2.5; 95% CI (1.07, 5.85); p=0.034), and lower P/F ratio (aOR = 2.76; 95% CI (1.1, 6.91); p=0.031). Conclusion The length of stay of patients in the convalescent plasma group was significantly longer than the control group. There was no effect of convalescent plasma in ICU mortality and no improvement was observed in terms of oxygen support requirements.
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27
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Birschmann I, von Bargen K, Teune M, Flottmann C, Knüttgen F, Knabbe C. Retrospective study shows that early administration of convalescent plasma in hospitalized COVID-19 patients may have a positive effect on disease progression. Health Sci Rep 2022; 5:e714. [PMID: 35957967 PMCID: PMC9362730 DOI: 10.1002/hsr2.714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 05/16/2022] [Accepted: 06/14/2022] [Indexed: 12/02/2022] Open
Affiliation(s)
- Ingvild Birschmann
- Herz‐ und Diabeteszentrum Nordrhein‐Westfalen, Universitätsklinik der Ruhr‐Universität BochumInstitut für Laboratoriums‐ und TransfusionsmedizinBad OeynhausenGermany
| | - Katharina von Bargen
- Herz‐ und Diabeteszentrum Nordrhein‐Westfalen, Universitätsklinik der Ruhr‐Universität BochumInstitut für Laboratoriums‐ und TransfusionsmedizinBad OeynhausenGermany
| | - Michelle Teune
- Herz‐ und Diabeteszentrum Nordrhein‐Westfalen, Universitätsklinik der Ruhr‐Universität BochumInstitut für Laboratoriums‐ und TransfusionsmedizinBad OeynhausenGermany
| | - Christian Flottmann
- Lukas Krankenhaus BündeMedizinische Klinik II – Innere Medizin und KardiologieBündeGermany
| | - Franziska Knüttgen
- Herz‐ und Diabeteszentrum Nordrhein‐Westfalen, Universitätsklinik der Ruhr‐Universität BochumInstitut für Laboratoriums‐ und TransfusionsmedizinBad OeynhausenGermany
| | - Cornelius Knabbe
- Herz‐ und Diabeteszentrum Nordrhein‐Westfalen, Universitätsklinik der Ruhr‐Universität BochumInstitut für Laboratoriums‐ und TransfusionsmedizinBad OeynhausenGermany
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Iranijam E, Ghobadi H, Matin S, Habibzadeh S, Zandian H, Mohammadshahi J, Fooladi S, Dargahi A, Safarzadeh E, Negaresh M, Hosseini J, Samadi AH, Hoseininia S, salehzadeh H, Dezhkam S. The effect of convalescent plasma on the treatment of COVID-19 patients in Ardabil, Iran. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2022; 11:266. [PMID: 36325204 PMCID: PMC9621377 DOI: 10.4103/jehp.jehp_1439_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/20/2021] [Indexed: 06/16/2023]
Abstract
BACKGROUND Infection with COVID-19 has resulted in considerable mortality all around the world. This study aimed to investigate the effect of convalescent plasma on the treatment of hospitalized patients with COVID-19 in Imam Khomeini Hospital at Ardabil, Iran. MATERIALS AND METHODS In this quasi-experimental clinical trial, patients over 18 years of age with polymerase chain reaction-positive COVID-19 were admitted based on the clinical criteria of respiratory distress with hypoxia (O2 saturation <90) and tachypnea (R Relative Risk (RR) >24) with moderate-to-severe lung involvement and in the 1st week of respiratory disease who were not intubated were nonrandomly assigned to two groups: convalescent plasma therapy (CPT) group (197 cases) and control group (200 cases). We used the Chi-square, t-test, Fisher's exact test, and Pearson's correlation coefficient for statistical analysis. RESULTS Analyses revealed that length of stay in hospital was significantly lower in the CPT group as compared to the control group (P = 0.001). Twenty-four cases (22.0%) in the CPT group and 85 cases (78.0%) in the control group needed intubation. Furthermore, mortality was 17 cases (18.3%) in the CPT group and 76 cases (81.7%) in the control group, the difference of which was also found to be statistically significant (P < 0.05). CONCLUSIONS It seems that CPT can be used as an alternative treatment at the early stages of COVID-19 to prevent the progress of the disease, reduce the need for intubation and consequently the length of stay in hospital, and finally, decrease mortality.
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Affiliation(s)
- Effat Iranijam
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hassan Ghobadi
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Somaieh Matin
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Shahram Habibzadeh
- Department of Infectious Disease and Tropical Medicine, Ardabil University of Medical Science, Ardabil, Iran
| | - Hamed Zandian
- Social Determinants of Health Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Jafar Mohammadshahi
- Department of Infectious Disease and Tropical Medicine, Ardabil University of Medical Science, Ardabil, Iran
| | - Shahnaz Fooladi
- Department of Anesthesiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Abdollah Dargahi
- Social Determinants of Health Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Department of Microbiology and Immunology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Negaresh
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Javad Hosseini
- Department of Biostatistics, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ali Hossein Samadi
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Saeed Hoseininia
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hossein salehzadeh
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sharareh Dezhkam
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
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29
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Weisser M, Khanna N, Hedstueck A, Tschudin Sutter S, Roesch S, Stehle G, Sava M, Deigendesch N, Battegay M, Infanti L, Holbro A, Bassetti S, Pargger H, Hirsch HH, Leuzinger K, Kaiser L, Vu D, Baur K, Massaro N, Busch MP, Simmons G, Stone M, Felgner PL, de Assis RR, Khan S, Tsai C, Robinson PV, Seftel D, Irsch J, Bagri A, Buser AS, Corash L. Characterization of Pathogen Inactivated
COVID
‐19 Convalescent Plasma and Responses in Transfused Patients. Transfusion 2022; 62:1997-2011. [PMID: 36054476 PMCID: PMC9538076 DOI: 10.1111/trf.17083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 07/31/2022] [Accepted: 07/31/2022] [Indexed: 12/15/2022]
Abstract
Background Efficacy of donated COVID‐19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. Study Design and Methods In a single‐center hypothesis‐generating prospective case–control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID‐19 pneumonia received 2 × 200 ml pathogen‐reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies in COVID‐19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28‐day mortality, and dCCP ‐related adverse events in recipients. Results Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP‐related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV‐2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS‐CoV‐2 antigens over 14–21 days post dCCP in all except 4 immunosuppressed recipients. Discussion PRT did not impact dCCP anti‐virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post‐transfusion antibody responses indicate the need for controlled trials using well‐characterized dCCP with informative assays.
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Affiliation(s)
- Maja Weisser
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Nina Khanna
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Anemone Hedstueck
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
| | - Sarah Tschudin Sutter
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Sandra Roesch
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
| | - Gregor Stehle
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Mihaela Sava
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
| | | | - Manuel Battegay
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
| | - Laura Infanti
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Andreas Holbro
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Stefano Bassetti
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Department of Internal Medicine University Hospital Basel Basel Switzerland
| | - Hans Pargger
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Department of Intensive Care University Hospital Basel Basel Switzerland
| | - Hans H. Hirsch
- Division of Infectious Diseases & Hospital Epidemiology University and University Hospital of Basel Basel Switzerland
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Transplantation & Clinical Virology, Department of Biomedicine University of Basel Basel Switzerland
| | - Karoline Leuzinger
- Transplantation & Clinical Virology, Department of Biomedicine University of Basel Basel Switzerland
| | - Laurent Kaiser
- Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, 1205 Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals & Faculty of Medicine University of Geneva Geneva Switzerland
| | - Diem‐Lan Vu
- Division of Infectious Diseases Geneva University Hospitals Geneva Switzerland
| | - Katharina Baur
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Nadine Massaro
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
| | - Michael Paul Busch
- Department of Laboratory Medicine University of California, San Francisco San Francisco CA USA
- Vitalant Research Institute San Francisco CA
| | - Graham Simmons
- Department of Laboratory Medicine University of California, San Francisco San Francisco CA USA
- Vitalant Research Institute San Francisco CA
| | - Mars Stone
- Department of Laboratory Medicine University of California, San Francisco San Francisco CA USA
- Vitalant Research Institute San Francisco CA
| | - Philip L. Felgner
- Department of Physiology and Biophysics, Vaccine Research and Development Laboratory University of California, Irvine Irvine CA USA
| | - Rafael R. de Assis
- Department of Physiology and Biophysics, Vaccine Research and Development Laboratory University of California, Irvine Irvine CA USA
| | - Saahir Khan
- Division of Infectious Diseases, Department of Medicine, Keck School of Medicine University of Southern California Los Angeles CA USA
| | | | | | | | | | | | - Andreas S. Buser
- Department of Clinical Research University Hospital Basel Basel Switzerland
- Regional Blood Transfusion Service, Swiss Red Cross, Basel Basel Switzerland
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Exercise in Cold Weather for COVID-19-Recovered Individuals (CRI). Asian J Sports Med 2022. [DOI: 10.5812/asjsm-127151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: The sedentary lifestyle caused by the COVID-19 quarantine has resulted in a devastating threat to human health due to stress and anxiety. Although infected individuals must stop exercising, exercise is not prohibited when without symptoms and complications. Whereas exercise can be effective in immune system reinforcement during the prevention, recovery, and post-recovery stages, COVID-19-recovered Individuals (CRI) must exercise under accurate considerations. Objectives: This study aimed to study exercise in cold weather for the CRI. Methods: This article overviews how different exercises affect the immune system. PubMed, Science Direct, and Google Scholar Databases and keywords including cold weather, COVID-19, immune system, and combined exercise were used to access scientific articles. Results: Recent reports show that different sports and exercises significantly improve COVID-19 symptoms, although there are many discrepancies among researchers in prescribing exercise programs (various training protocols, duration, and intensity). Also, CRI should avoid exercise in cold weather due to breathing complications Conclusions: Based on the present study, regular exercises (aerobic, resistance, and combined) with moderate intensity improve COVID-19 symptoms and the immune system.
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Marconato M, Abela IA, Hauser A, Schwarzmüller M, Katzensteiner R, Braun DL, Epp S, Audigé A, Weber J, Rusert P, Schindler E, Pasin C, West E, Böni J, Kufner V, Huber M, Zaheri M, Schmutz S, Frey BM, Kouyos RD, Günthard HF, Manz MG, Trkola A. Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response. J Clin Invest 2022; 132:e158190. [PMID: 35482408 PMCID: PMC9197521 DOI: 10.1172/jci158190] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 04/26/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUNDNeutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated.METHODSWe conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7-11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends.RESULTSIn this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1-8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1-11; P = 0.034).CONCLUSIONOur data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies.TRIAL REGISTRATIONClinicalTrials.gov NCT04869072.FUNDINGThis study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program "Comprehensive Genomic Pathogen Detection" of the University of Zurich.
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Affiliation(s)
- Maddalena Marconato
- Department of Medical Oncology and Haematology; University Hospital Zurich and University of Zurich; Comprehensive Cancer Center Zurich; Switzerland
| | - Irene A. Abela
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Anthony Hauser
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| | | | - Rheliana Katzensteiner
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| | - Dominique L. Braun
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| | - Selina Epp
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Annette Audigé
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Jacqueline Weber
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Peter Rusert
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Eméry Schindler
- Blood Transfusion Service Zurich, Swiss Red Cross, Zurich, Switzerland
| | - Chloé Pasin
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Emily West
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| | - Jürg Böni
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Verena Kufner
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Michael Huber
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Maryam Zaheri
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Stefan Schmutz
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Beat M. Frey
- Blood Transfusion Service Zurich, Swiss Red Cross, Zurich, Switzerland
| | - Roger D. Kouyos
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Huldrych F. Günthard
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Markus G. Manz
- Department of Medical Oncology and Haematology; University Hospital Zurich and University of Zurich; Comprehensive Cancer Center Zurich; Switzerland
| | - Alexandra Trkola
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
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Beraud M, Goodhue Meyer E, Lozano M, Bah A, Vassallo R, Brown BL. Lessons learned from the use of convalescent plasma for the treatment of COVID-19 and specific considerations for immunocompromised patients. Transfus Apher Sci 2022; 61:103355. [PMID: 35063360 PMCID: PMC8757642 DOI: 10.1016/j.transci.2022.103355] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/10/2022] [Indexed: 12/11/2022]
Abstract
Coronavirus disease 2019 (COVID-19) convalescent plasma (CovCP) infusions have been widely used for the treatment of hospitalized patients with COVID-19. The aims of this narrative review were to analyze the safety and efficacy of CovCP infusions in the overall population and in immunocompromised patients with COVID-19 and to identify the lessons learned concerning the use of convalescent plasma (CP) to fill treatment gaps for emerging viruses. Systematic searches (PubMed, Scopus, and COVID-19 Research) were conducted to identify peer-reviewed articles and pre-prints published between March 1, 2020 and May 1, 2021 on the use of CovCP for the treatment of patients with COVID-19. From 261 retrieved articles, 37 articles reporting robust controlled studies in the overall population of patients with COVID-19 and 9 articles in immunocompromised patients with COVID-19 were selected. While CovCP infusions are well tolerated in both populations, they do not seem to improve clinical outcomes in critically-ill patients with COVID-19 and no conclusion could be drawn concerning their potential benefits in immunocompromised patients with COVID-19. To be better prepared for future epidemics/pandemics and to evaluate potential benefits of CP treatment, only CP units with high neutralizing antibodies (NAbs) titers should be infused in patients with low NAb titers, patient eligibility criteria should be based on the disease pathophysiology, and measured clinical outcomes and methods should be comparable across studies. Even if CovCP infusions did not improve clinical outcomes in patients with COVID-19, NAb-containing CP infusions remain a safe, widely available and potentially beneficial treatment option for future epidemics/pandemics.
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Affiliation(s)
- Mickael Beraud
- Terumo Blood and Cell Technologies Europe NV, Ikaroslaan 41, 1930, Zaventem, Belgium.
| | - Erin Goodhue Meyer
- Terumo Blood and Cell Technologies, 10811 W Collins Ave, Lakewood, CO, 80215, United States.
| | - Miquel Lozano
- Department of Hemotherapy and Hemostasis, ICMHO, University Clinic Hospital, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Catalonia, Spain.
| | - Aicha Bah
- Terumo Blood and Cell Technologies Europe NV, Ikaroslaan 41, 1930, Zaventem, Belgium.
| | - Ralph Vassallo
- Vitalant, 6210 E Oak St, Scottsdale, AZ, 85257, United States.
| | - Bethany L Brown
- American Red Cross, Biomedical Services, Holland Laboratory for the Biomedical Sciences, 15601 Crabbs Branch Way, Rockville, MD, 20855, United States.
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Reinforcement of the Standard Therapy with Two Infusions of Convalescent Plasma for Patients with COVID-19: A Randomized Clinical Trial. J Clin Med 2022; 11:jcm11113039. [PMID: 35683427 PMCID: PMC9181298 DOI: 10.3390/jcm11113039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/25/2022] [Accepted: 05/25/2022] [Indexed: 12/10/2022] Open
Abstract
Background: The aim was to evaluate the reinforcement of the standard therapy with hyperimmune plasma (HP) in Coronavirus-19 disease (COVID-19) patients. Methods: Open-label, multicenter, randomized clinical trial performed in three hospitals in the Balearic Islands. Non-severe COVID-19 hospitalized patients with clinical time evolution equal to/less than 7 days were included, and randomized in: plasma group (PG) (n = 37), receiving 600 mL divided into two doses from convalescent plasma donor, administered on days 1 and 2 after the enrollment; and control group (CG) (n = 17). Primary outcome was the time for clinical improvement within 21 days, defined as patient achievement of categories 8, 7, and 6 in the Adaptive COVID-19 Treatment Trial scale (ACTT). The trial was terminated early due to the impossibility of recruitment due to the pandemic. Results: PG presented better scores on the ACTT scale at 7 days after HP infusion, whereas CG was needed 14 days to achieve similar results. The plasma infusion was safe. Conclusions: Despite the tendency observed in the plasma group to achieve slightly earlier better physical condition compared with the standard treatment alone. The administration of HP has been shown to be a safe therapy. No robust evidence was found to affirm a therapeutic effect of the early administration of two infusions of HP for non-severe COVID-19 infected patients. The interpretation is limited by the early termination of the trial, which resulted in a small sample size.
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Yang S, Tong Y, Chen L, Yu W. Human Identical Sequences, hyaluronan, and hymecromone ─ the new mechanism and management of COVID-19. MOLECULAR BIOMEDICINE 2022; 3:15. [PMID: 35593963 PMCID: PMC9120813 DOI: 10.1186/s43556-022-00077-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 05/04/2022] [Indexed: 02/08/2023] Open
Abstract
COVID-19 caused by SARS-CoV-2 has created formidable damage to public health and market economy. Currently, SARS-CoV-2 variants has exacerbated the transmission from person-to-person. Even after a great deal of investigation on COVID-19, SARS-CoV-2 is still rampaging globally, emphasizing the urgent need to reformulate effective prevention and treatment strategies. Here, we review the latest research progress of COVID-19 and provide distinct perspectives on the mechanism and management of COVID-19. Specially, we highlight the significance of Human Identical Sequences (HIS), hyaluronan, and hymecromone ("Three-H") for the understanding and intervention of COVID-19. Firstly, HIS activate inflammation-related genes to influence COVID-19 progress through NamiRNA-Enhancer network. Accumulation of hyaluronan induced by HIS-mediated HAS2 upregulation is a substantial basis for clinical manifestations of COVID-19, especially in lymphocytopenia and pulmonary ground-glass opacity. Secondly, detection of plasma hyaluronan can be effective for evaluating the progression and severity of COVID-19. Thirdly, spike glycoprotein of SARS-CoV-2 may bind to hyaluronan and further serve as an allergen to stimulate allergic reaction, causing sudden adverse effects after vaccination or the aggravation of COVID-19. Finally, antisense oligonucleotides of HIS or inhibitors of hyaluronan synthesis (hymecromone) or antiallergic agents could be promising therapeutic agents for COVID-19. Collectively, Three-H could hold the key to understand the pathogenic mechanism and create effective therapeutic strategies for COVID-19.
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Affiliation(s)
- Shuai Yang
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China
| | - Ying Tong
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China
| | - Lu Chen
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China
| | - Wenqiang Yu
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China.
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Jacobs JL, Bain W, Naqvi A, Staines B, Castanha PMS, Yang H, Boltz VF, Barratt-Boyes S, Marques ETA, Mitchell SL, Methé B, Olonisakin TF, Haidar G, Burke TW, Petzold E, Denny T, Woods CW, McVerry BJ, Lee JS, Watkins SC, St Croix CM, Morris A, Kearney MF, Ladinsky MS, Bjorkman PJ, Kitsios GD, Mellors JW. Severe Acute Respiratory Syndrome Coronavirus 2 Viremia Is Associated With Coronavirus Disease 2019 Severity and Predicts Clinical Outcomes. Clin Infect Dis 2022; 74:1525-1533. [PMID: 34374761 PMCID: PMC9070832 DOI: 10.1093/cid/ciab686] [Citation(s) in RCA: 97] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with coronavirus disease 2019 (COVID-19), but it is not clear whether this RNAemia reflects viremia (ie, virus particles) and how it relates to host immune responses and outcomes. METHODS SARS-CoV-2 vRNA was quantified in plasma samples from observational cohorts of 51 COVID-19 patients including 9 outpatients, 19 hospitalized (non-intensive care unit [ICU]), and 23 ICU patients. vRNA levels were compared with cross-sectional indices of COVID-19 severity and prospective clinical outcomes. We used multiple imaging methods to visualize virions in plasma. RESULTS SARS-CoV-2 vRNA was detected in plasma of 100%, 52.6%, and 11.1% of ICU, non-ICU, and outpatients, respectively. Virions were detected in plasma pellets using electron tomography and immunostaining. Plasma vRNA levels were significantly higher in ICU > non-ICU > outpatients (P < .0001); for inpatients, plasma vRNA levels were strongly associated with higher World Health Organization (WHO) score at admission (P = .01), maximum WHO score (P = .002), and discharge disposition (P = .004). A plasma vRNA level >6000 copies/mL was strongly associated with mortality (hazard ratio, 10.7). Levels of vRNA were significantly associated with several inflammatory biomarkers (P < .01) but not with plasma neutralizing antibody titers (P = .8). CONCLUSIONS Visualization of virus particles in plasma indicates that SARS-CoV-2 RNAemia is due, at least in part, to viremia. The levels of SARS-CoV-2 RNAemia correlate strongly with disease severity, patient outcome, and specific inflammatory biomarkers but not with neutralizing antibody titers.
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Affiliation(s)
- Jana L Jacobs
- Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - William Bain
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Veteran’s Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
| | - Asma Naqvi
- Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Brittany Staines
- Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Priscila M S Castanha
- Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
| | - Haopu Yang
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Center for Medicine and the Microbiome, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- School of Medicine, Tsinghua University, Beijing, China
| | - Valerie F Boltz
- HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA
| | - Simon Barratt-Boyes
- Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
| | - Ernesto T A Marques
- Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
| | - Stephanie L Mitchell
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Barbara Methé
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Center for Medicine and the Microbiome, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Tolani F Olonisakin
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Ghady Haidar
- Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Thomas W Burke
- Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina, USA
| | - Elizabeth Petzold
- Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina, USA
| | - Thomas Denny
- Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA
| | - Chris W Woods
- Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina, USA
- Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA
| | - Bryan J McVerry
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Janet S Lee
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Simon C Watkins
- Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Claudette M St Croix
- Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alison Morris
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Center for Medicine and the Microbiome, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Mary F Kearney
- HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA
| | - Mark S Ladinsky
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
| | - Pamela J Bjorkman
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
| | - Georgios D Kitsios
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Medicine and the Microbiome, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - John W Mellors
- Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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Sanz C, Nomdedeu M, Pereira A, Sauleda S, Alonso R, Bes M, Brillembourg H, García‐Vidal C, Millan A, Martínez‐Llonch N, Pirón M, Puerta‐Alcalde P, Puig L, Rico V, Soriano A. Efficacy of early transfusion of convalescent plasma with high-titer SARS-CoV-2 neutralizing antibodies in hospitalized patients with COVID-19. Transfusion 2022; 62:974-981. [PMID: 35338710 PMCID: PMC9115410 DOI: 10.1111/trf.16863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 03/03/2022] [Accepted: 03/03/2022] [Indexed: 12/16/2022]
Abstract
BACKGROUND Despite most controlled trials have shown no measurable benefit of COVID-19 convalescent plasma (CCP) in patients with COVID-19, some studies suggest that early administration of CCP with high-titer anti-SARS-CoV-2 can be beneficial in selected patients. We investigated the efficacy of early administration of high-titer CCP to patients with COVID-19 who required hospitalization, STUDY DESIGN AND METHODS: Observational, propensity score (PS) matched case-control study of COVID-19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti-SARS-CoV-2 sample-to-cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high-standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. RESULTS A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56-79), and 953 (60%) were men. Presenting factors independently associated with higher 30-day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d-dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30-day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91-0.98; p = .001) that extended to the 60th day after COVID-19 diagnosis (OR: 0.95; 95% CI: 0.92-0.99; p = .01). CONCLUSION Our results suggest that CCP can still be helpful in selected patients with COVID-19 and call for further studies before withdrawing CCP from the COVID-19 therapeutic armamentarium.
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Affiliation(s)
- Cristina Sanz
- Blood Bank and Transfusion ServiceHospital Clínic de BarcelonaBarcelonaSpain
| | - Meritxell Nomdedeu
- Hemathology and Hemotherapy ServiceHospital Clínic de BarcelonaBarcelonaSpain
| | - Arturo Pereira
- Blood Bank and Transfusion ServiceHospital Clínic de BarcelonaBarcelonaSpain
| | | | - Rodrigo Alonso
- Infectious Diseases DepartmentHospital Clínic‐IDIBAPS, University of BarcelonaBarcelonaSpain
| | - Marta Bes
- Banc de Sang i TeixitsBarcelonaSpain
| | - Helena Brillembourg
- Blood Bank and Transfusion ServiceHospital Clínic de BarcelonaBarcelonaSpain
| | - Carolina García‐Vidal
- Infectious Diseases DepartmentHospital Clínic‐IDIBAPS, University of BarcelonaBarcelonaSpain
| | | | | | | | - Pedro Puerta‐Alcalde
- Infectious Diseases DepartmentHospital Clínic‐IDIBAPS, University of BarcelonaBarcelonaSpain
| | | | - Veronica Rico
- Infectious Diseases DepartmentHospital Clínic‐IDIBAPS, University of BarcelonaBarcelonaSpain
| | - Alex Soriano
- Infectious Diseases DepartmentHospital Clínic‐IDIBAPS, University of BarcelonaBarcelonaSpain
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Preservation of anti-SARS-CoV-2 neutralising antibodies in convalescent plasma after pathogen reduction with methylene blue and visible light. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2022; 20:206-212. [PMID: 34369870 PMCID: PMC9068354 DOI: 10.2450/2021.0136-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 06/14/2021] [Indexed: 01/24/2023]
Abstract
BACKGROUND COVID-19 convalescent plasma (CCP) is an experimental treatment against SARS-CoV-2. Although there has so far been no evidence of transmission through transfusion, pathogen reduction technologies (PRT) have been applied to CCP to mitigate risk of infectious disease. This study aims to assess the impact of methylene blue (MB) plus visible light PRT on the virus-neutralising activity of the specific antibodies against SARS-CoV-2. MATERIAL AND METHODS Thirty-five plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to MB plus visible light PRT. Anti-SARS-CoV-2 RBD S1 epitope IgGs antibodies were quantified by ELISA. Titres of SARS-CoV-2 neutralising antibodies (NtAbs) were measured before and after the PRT process. A Spearman's correlation was run to determine the relationship between antibody neutralisation ability and SARS-CoV-2 IgG ELISA ratio. Pre- and post-inactivation neutralising antibody titres were evaluated using a Wilcoxon test. RESULTS The plasma pathogen reduction procedure did not diminish NtAbS titres and so did not cause a change in the viral neutralisation capacity of CCP. There was a strong correlation between pre-and post-PRT NtAbs and anti-SARS-CoV-2 IgGs titres. DISCUSSION Our results showed PRT with MB did not impair the CCP passive immunity preserving its potential therapeutic potency. Therefore, PRT of CCP should be recommended to mitigate the risk for transmission of transfusion-associated infectious disease. There is a good correlation between SARS-CoV-2 IgG titres determined by ELISA and the neutralising capacity. This allows blood centres to select CCP donors based on IgG ELISA titres avoiding the much more labour-intensive laboratory processes for determining neutralising antibodies.
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Bajpai M, Maheshwari A, Dogra V, Kumar S, Gupta E, Kale P, Saluja V, Thomas SS, Trehanpati N, Bihari C, Agarwal R, Bharti P, Shankar P, Hussain J, Chhabra K, Gupta A, Narayanan A, Agarwal S, Jain S, Bhardwaj A, Kumar G, Yadav BK, Sarin SK. Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial). BMJ Open 2022; 12:e055189. [PMID: 35387813 PMCID: PMC8987237 DOI: 10.1136/bmjopen-2021-055189] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
IMPORTANCE No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. INTERVENTION One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. CONCLUSION AND RELEVANCE Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. TRIAL REGISTRATION NUMBER NCT04425915.
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Affiliation(s)
- Meenu Bajpai
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashish Maheshwari
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikas Dogra
- Department of Pulmonology, Rajiv Gandhi Super Speciality Hospital, New Delhi, India
| | - Suresh Kumar
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Pratibha Kale
- Department of Clinical Microbiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vandana Saluja
- Department of Anesthesia, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sherin S Thomas
- Department of Clinical Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nirupama Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Reshu Agarwal
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Praveen Bharti
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Prabha Shankar
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Javid Hussain
- Department of Pulmonology, Rajiv Gandhi Super Speciality Hospital, New Delhi, India
| | - Karan Chhabra
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Amita Gupta
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashad Narayanan
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sarika Agarwal
- Department of Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shruti Jain
- Department of Pulmonology, Rajiv Gandhi Super Speciality Hospital, New Delhi, India
| | - Ankit Bhardwaj
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Birendra Kumar Yadav
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Gille T, Sivapalan P, Kaltsakas G, Kolekar SB, Armstrong M, Tuffnell R, Evans RA, Vagheggini G, Degani-Costa LH, Vicente C, Das N, Poberezhets V, Rolland-Debord C, Bayat S, Vogiatzis I, Franssen FM, Pinnock H, Vanfleteren LE. ERS International Congress 2021: highlights from the Respiratory Clinical Care and Physiology Assembly. ERJ Open Res 2022; 8:00710-2021. [PMID: 35615417 PMCID: PMC9125042 DOI: 10.1183/23120541.00710-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 04/06/2022] [Indexed: 11/05/2022] Open
Abstract
It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, randomised controlled trials and qualitative research that were presented during the 2021 European Respiratory Society International Congress within the sessions from the five groups of the Assembly 1 - Respiratory clinical care and physiology. Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.
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Affiliation(s)
- Thomas Gille
- Service de Physiologie et Explorations Fonctionnelles, Centre Hospitalier Universitaire Avicenne, Hôpitaux Universitaires de Paris Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris, Bobigny, France
- Inserm U1272 “Hypoxia and the Lung”, UFR Santé – Médecine – Biologie Humaine Léonard de Vinci, Université Sorbonne Paris Nord, Bobigny, France
| | - Pradeesh Sivapalan
- Section of Respiratory Medicine, Herlev-Gentofte University Hospital, Hellerup, Denmark
| | - Georgios Kaltsakas
- Lane Fox Respiratory Service, Guy's and St Thomas’ NHS Foundation Trust, London, UK
- Centre of Human and Applied Physiological Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
- 1st Respiratory Medicine Dept, “Sotiria” Hospital for Diseases of the Chest, National and Kapodistrian University of Athens, Athens, Greece
| | - Shailesh B. Kolekar
- Dept of Internal Medicine, Zealand University Hospital, Roskilde, Denmark
- Dept of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Matthew Armstrong
- Dept of Rehabilitation and Sport Sciences, Bournemouth University, Poole, UK
| | - Rachel Tuffnell
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Rachael A. Evans
- NIHR Leicester Biomedical Research Centre – Respiratory, University Hospitals of Leicester NHS Trust, Leicester, UK
- Dept of Respiratory Sciences, University of Leicester, Leicester, UK
| | - Guido Vagheggini
- Dept of Medical Specialties, Chronic Respiratory Failure Care Pathway, Azienda USL Toscana Nordovest, Volterra, Italy
- Fondazione Volterra Ricerche Onlus, Volterra, Italy
| | | | | | - Nilakash Das
- Laboratory of Respiratory Diseases and Thoracic Surgery, Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Vitalii Poberezhets
- Dept of Propedeutics of Internal Medicine, National Pirogov Memorial Medical University, Vinnytsya, Ukraine
| | - Camille Rolland-Debord
- Service de Pneumologie, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Sam Bayat
- Service de Pneumologie et de Physiologie, CS10217, CHU Grenoble, Grenoble, France
- Univ. Grenoble Alpes, Inserm UA07 STROBE, Grenoble, France
| | - Ioannis Vogiatzis
- Dept of Sport, Exercise and Rehabilitation, Northumbria University Newcastle, Newcastle upon Tyne, UK
| | - Frits M.E. Franssen
- Dept of Research and Development, Ciro, Horn, the Netherlands
- Dept of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands
| | - Hilary Pinnock
- Allergy and Respiratory Research Group, Usher Institute, The University of Edinburgh, Edinburgh, UK
| | - Lowie E.G.W. Vanfleteren
- COPD Center, Dept of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Dept of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Shaik FB, Swarnalatha K, Mohan M, Thomas A, Chikati R, Sandeep G, Maddu N. Novel antiviral effects of chloroquine, hydroxychloroquine, and green tea catechins against SARS CoV-2 main protease (Mpro) and 3C-like protease for COVID-19 treatment. CLINICAL NUTRITION OPEN SCIENCE 2022; 42:62-72. [PMID: 35106518 PMCID: PMC8795779 DOI: 10.1016/j.nutos.2021.12.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 12/30/2021] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVES Coronaviruses are globally emerging viruses that threaten our health care systems and have become a popular pandemic around the world. This causes a sudden rise in positive coronavirus cases and related deaths to occur worldwide, representing a significant health hazard to humans and the economy. METHODS We examined predominantly catechins of green tea include epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), and drugs of chloroquine (CQ), and hydroxychloroquine (HCQ) appearing to reveal anti-viral activities. Data were collected from PubMed, Google Scholar, and Science Direct databases. To investigate the role of antiviral effects (CQ and HCQ), green tea catechins, beneficial use of convalescent plasma; covaxin in COVID-19 patients faced a dangerous healthiness issue. Computational docking analysis has been used for this purpose. RESULTS The lead compounds are EGCG and ECG act as potential inhibitors bind to the active site region of the HKU4-CoV 3CL protease and M-Pro protease enzymes of coronavirus. Conclusions: SARS-COV-2 is a pathogen of substantial vigour concern and the review unveils the role of catechins associated with many viral diseases. We suggested that the function of green tea catechins, novel drugs of CQ, and HCQ exhibit antiviral activities against positive-sense single-stranded RNA viruses (CoVs).
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Affiliation(s)
- Fareeda Begum Shaik
- Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515003, A.P. India
| | - K. Swarnalatha
- Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515003, A.P. India
| | | | - Anu Thomas
- Department of Nursing, Banaswadi College of Nursing, Bangalore, Karnataka, India
| | - Rajasekhar Chikati
- Department of Biochemistry, Yogivemana University, Kadapa, 516005, A.P. India
| | - G. Sandeep
- Division of Molecular Biology, Department of Zoology, Sri Venkateswara University, Tirupati, 517502, A.P, India
| | - Narendra Maddu
- Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515003, A.P. India,Corresponding author. Department of Biochemistry, Sri Krishnadevaraya University, Ananthapuramu, 515003, Andhra Pradesh, India. Tel.: +91 9441983797
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Abstract
COVID-19 infection is a global health issue, and vaccination is the main strategy to control this pandemic. In this study, 189 participants received BNT162b2 or CoronaVac vaccine, and 133 of them recorded adverse events (AEs) daily for 4 weeks after vaccination. Their neutralizing antibody against SARS-CoV-2 was determined with live virus microneutralization (vMN) assay. The vMN geometric mean titer (GMT) on day 56 was 129.9 (95% confidence interval [CI],108.6 to 155.2) in the BNT162b2 group and 13.1 (95% CI, 11.2 to 15.3) in the CoronaVac group. Day 56 vMN GMT was 147.9 (95% CI, 118.9 to 184.1) in females and 129.9 (95% CI, 108.6 to 155.2) in males receiving BNT162b2, while it was 14.0 (95% CI, 11.6 to 17.0) in females and 11.4 (95% CI, 8.7 to 15.0) in males receiving CoronaVac. Injection site pain (88.8%) and redness (77.5%) were the most commonly BNT162b2-related AEs, and injection site pain (37.7%) and tiredness (26.4%) were more frequent in the CoronaVac group. Women showed a higher frequency of headache (45.7% versus 29.4%) and joint pain (26.1 versus 14.7%) than men in BTN162b2 group. Headache (26.5% versus 0%) and tiredness (38.2% versus 5.3%) were more common in women than in men vaccinated with CoronaVac. No correlation between any AE and antibody response was observed in BNT162b2 or CoronaVac platforms. After taking the gender factor into account, in the BNT162b2 group, a low correlation between day 21 vMN titer and redness (rho = 0.34) or itching (rho = 0.32) was presented in females, and a low correlation between day 56 vMN titer and fever (rho = 0.35) was presented in males. Taken together, AEs could have a low correlation with BNT162b2 vaccine response. IMPORTANCE Effective vaccines against SARS-CoV-2 are vital tools for containing the COVID-19 pandemic by increasing population immunity. While currently available vaccines can elicit antibody response against SARS-CoV-2 with high efficacy, the associated side effects may cause vaccine hesitancy. Our work is important in that we have thoroughly analyzed the correlation between immunogenicity and reactogenicity of two COVID-19 vaccines (BNT162b2 and CoronaVac) in the study. Our results showed that women had higher levels of neutralizing antibodies than men after receiving BNT162b2 or CoronaVac. Furthermore, a low correlation was observed between day 21 vMN titer and local reactions (redness and itching) in females, as well as between day 56 vMN titer and fever in males receiving BNT162b2. Thus, common side effects are not always a negative impact of vaccination but may serve as an indicator of immunogenicity of vaccines. Our study may help in increasing the public’s acceptance and confidence over COVID-19 vaccination and ultimately achieving the goal of containing COVID-19 pandemic.
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Traboulsi H, Khedr MA, Elgorashe R, Al-Faiyz Y, Negm A. Development of superior antibodies against the S-protein of SARS-Cov-2 using macrocyclic epitopes. ARAB J CHEM 2022; 15:103631. [PMID: 34909055 PMCID: PMC8662835 DOI: 10.1016/j.arabjc.2021.103631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 12/06/2021] [Indexed: 11/29/2022] Open
Abstract
One of the proven methods to prevent and inhibit viral infections is to use antibodies to block the initial Receptor Binding Domain (RBD) of SARS-CoV-2 S protein and avoid its binding with the host cells. Thus, developing these RBD-targeting antibodies would be a promising approach for treating the SARS-CoV-2 infectious disease and stop virus replication. Macrocyclic epitopes constitute closer mimics of the receptor's actual topology and, as such, are expected to be superior epitopes for antibody generation. This work demonstrated the vital effect of the three-dimensional shape of epitopes on the developed antibodies' activity against RBD protein of SARS-CoV-2. The molecular dynamics studies showed the greater stability of the cyclic epitopes in comparison with the linear counterpart, which was reflected in the activity of their produced antibodies. Indeed, the antibodies we developed using macrocyclic epitopes showed superiority with respect to binding to RBD proteins compared to antibodies formed from a linear peptide. The results of the present work constitute a roadmap for developing superior antibodies that could be used to inhibit the activity of the SARS-CoV-2 and prevent its reproduction.
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Affiliation(s)
- Hassan Traboulsi
- Department of Chemistry, College of Science, King Faisal University, P.O Box 400, Al-Ahsa 31982, Saudi Arabia
| | - Mohammed A Khedr
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-AHasa 31982, Saudi Arabia
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, P.O. Box 11795, Cairo, Egypt
| | - Rafea Elgorashe
- Department of Chemistry, College of Science, King Faisal University, P.O Box 400, Al-Ahsa 31982, Saudi Arabia
| | - Yasair Al-Faiyz
- Department of Chemistry, College of Science, King Faisal University, P.O Box 400, Al-Ahsa 31982, Saudi Arabia
| | - Amr Negm
- Department of Chemistry, College of Science, King Faisal University, P.O Box 400, Al-Ahsa 31982, Saudi Arabia
- Biochemistry Division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt
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Al-Hajeri H, Baroun F, Abutiban F, Al-Mutairi M, Ali Y, Alawadhi A, Albasri A, Aldei A, AlEnizi A, Alhadhood N, Al-Herz A, Alkadi A, Alkanderi W, Almathkoori A, Almutairi N, Alsayegh S, Alturki A, Bahbahani H, Dehrab A, Ghanem A, Haji Hasan E, Hayat S, Saleh K, Tarakmeh H. Therapeutic role of immunomodulators during the COVID-19 pandemic- a narrative review. Postgrad Med 2022; 134:160-179. [PMID: 35086413 PMCID: PMC8862162 DOI: 10.1080/00325481.2022.2033563] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/18/2022] [Indexed: 02/07/2023]
Abstract
The emergency state caused by COVID-19 saw the use of immunomodulators despite the absence of robust research. To date, the results of relatively few randomized controlled trials have been published, and methodological approaches are riddled with bias and heterogeneity. Anti-SARS-CoV-2 antibodies, convalescent plasma and the JAK inhibitor baricitinib have gained Emergency Use Authorizations and tentative recommendations for their use in clinical practice alone or in combination with other therapies. Anti-SARS-CoV-2 antibodies are predominating the management of non-hospitalized patients, while the inpatient setting is seeing the use of convalescent plasma, baricitinib, tofacitinib, tocilizumab, sarilumab, and corticosteroids, as applicable. Available clinical data also suggest the potential clinical benefit of the early administration of blood-derived products (e.g. convalescent plasma, non-SARS-CoV-2-specific immunoglobins) and the blockade of factors implicated in the hyperinflammatory state of severe COVID-19 (Interleukin 1 and 6; Janus Kinase). Immune therapies seem to have a protective effect and using immunomodulators alone or in combination with viral replication inhibitors and other treatment modalities might prevent progression into severe COVID-19 disease, cytokine storm and death. Future trials should address existing gaps and reshape the landscape of COVID-19 management.
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Affiliation(s)
- Hebah Al-Hajeri
- Department of Rheumatology and Internal Medicine, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
| | - Fatemah Baroun
- Department of Rheumatology and Internal Medicine, AlJahra Hospital, Al-Jahra, Kuwait
| | - Fatemah Abutiban
- Department of Rheumatology and Internal Medicine, Jaber Al-Ahmad Hospital, South Surra, Kuwait
| | | | - Yasser Ali
- Rheumatology Unit, Department of Internal Medicine, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
| | - Adel Alawadhi
- Rheumatology Unit, Department of Internal Medicine, Al-Amiri Hospital, Kuwait City, Kuwait
| | - Anwar Albasri
- Rheumatology Unit, Department of Internal Medicine, Jaber Al-Ahmad Hospital, South Surra, Kuwait
| | - Ali Aldei
- Rheumatology Unit, Department of Internal Medicine, Al-Amiri Hospital, Kuwait City, Kuwait
| | - Ahmad AlEnizi
- Rheumatology Unit, Department of Internal Medicine, AlJahra Hospital, AlJahra, Kuwait
| | - Naser Alhadhood
- Rheumatology Unit, Department of Internal Medicine, Farwaneyah Hospital, AlFarwaniya, Kuwait
| | - Adeeba Al-Herz
- Rheumatology Unit, Department of Internal Medicine, Al-Amiri Hospital, Kuwait City, Kuwait
| | - Amjad Alkadi
- Rheumatology Unit, Department of Internal Medicine, Al-Sabah Hospital, Alsabah, Kuwait
| | - Waleed Alkanderi
- Rheumatology Unit, Department of Internal Medicine, Farwaneyah Hospital, AlFarwaniya, Kuwait
| | - Ammar Almathkoori
- Rheumatology Unit, Department of Internal Medicine, Al-Adan Hospital, Hadiya, Kuwait
| | - Nora Almutairi
- Rheumatology Unit, Department of Internal Medicine, Al-Sabah Hospital, Alsabah, Kuwait
| | - Saud Alsayegh
- Rheumatology Unit, Department of Internal Medicine, Jaber Al-Ahmad Armed Forces, Kuwait City, Kuwait
| | - Ali Alturki
- Rheumatology Unit, Department of Internal Medicine, Al-Adan Hospital, Hadiya, Kuwait
| | - Husain Bahbahani
- Rheumatology Unit, Department of Internal Medicine, Farwaneyah Hospital, AlFarwaniya, Kuwait
| | - Ahmad Dehrab
- Rheumatology Unit, Department of Internal Medicine, Al-Amiri Hospital, Kuwait City, Kuwait
| | - Aqeel Ghanem
- Rheumatology Unit, Department of Internal Medicine, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
| | - Eman Haji Hasan
- Rheumatology Unit, Department of Internal Medicine, Al-Amiri Hospital, Kuwait City, Kuwait
| | - Sawsan Hayat
- Rheumatology Unit, Department of Internal Medicine, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
| | - Khuloud Saleh
- Rheumatology Unit, Department of Internal Medicine, Farwaneyah Hospital, AlFarwaniya, Kuwait
| | - Hoda Tarakmeh
- Rheumatology Unit, Department of Internal Medicine, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
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The “Invisible Enemy” SARS-CoV-2: Viral Spread and Drug Treatment. Medicina (B Aires) 2022; 58:medicina58020261. [PMID: 35208584 PMCID: PMC8875987 DOI: 10.3390/medicina58020261] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/05/2022] [Accepted: 02/07/2022] [Indexed: 12/15/2022] Open
Abstract
Nowadays, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become the main subject of the scientific medical world and all World Organizations, causing millions of deaths worldwide. In this review, we have highlighted the context of the Coronavirus disease 2019 (COVID-19) pandemic, how the virus spreads, the symptoms and complications that may occur, and, especially, the drug treatment of viral infection, with emphasis on monoclonal antibodies. While well-known strains such as Alpha, Beta, Gamma, and, especially, Delta have shown an accelerated transmission among the population, the new Omicron variant (discovered on 24 November 2021) indicates more significant infectiousness and the poor efficacy of monoclonal antibody therapy due to mutations on the spike protein receptor-binding domain. With these discoveries, the experiments began, the first being in silico and in vitro, but these are not enough, and in vivo experiments are needed to see exactly the cause of neutralization of the action of these drugs. Following the documentation of the latest medical and scientific research, it has been concluded that there are many chemical molecules that have the potential to treat SARS-CoV-2 infection, but more detailed clinical trials are needed for their use in therapy. In addition, it is important to consider the structure of the viral strain in the administration of treatment.
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Huang HJ, Yi SG, Mobley CM, Saharia A, Bhimaraj A, Moore LW, Kloc M, Adrogue HE, Graviss EA, Nguyen DT, Eagar TN, Jones SL, Ankoma-Sey V, MacGillivray TE, Knight RJ, Gaber AO, Ghobrial RM. Early humoral immune response to two doses of severe acute respiratory syndrome coronavirus 2 vaccine in a diverse group of solid organ transplant candidates and recipients. Clin Transplant 2022; 36:e14600. [PMID: 35083796 DOI: 10.1111/ctr.14600] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/17/2022] [Accepted: 01/18/2022] [Indexed: 11/27/2022]
Abstract
Response to two doses of a nucleoside-modified messenger ribonucleic acid (mRNA) vaccine was evaluated in a large solid-organ transplant program. mRNA COVID-19 vaccine was administered to transplant candidates and recipients who met study inclusion criteria. Qualitative anti-SARS-CoV-2 Spike Total Immunoglobulin (Ig) and IgG-specific assays, and a semi-quantitative test for anti-SARS-CoV-2 Spike protein IgG were measured in 241 (17.2%) transplant candidates and 1,163 (82.8%) transplant recipients; 55.2% of whom were non-Hispanic White and 44.8% identified as another race. Transplant recipients were a median (IQR) of 3.2 (1.1, 6.8) years from transplantation. Response differed by transplant status: 96.0% vs 43.2% by the anti-SARS-CoV-2 Total Ig (candidates vs recipients, respectively), 93.5% vs 11.6% by the anti-SARS-CoV-2 IgG assay, and 91.9% vs 30.1% by anti-spike titers after two doses of vaccine. Multivariable analysis revealed candidates had higher likelihood of response vs recipients (odds ratio [OR], 14.6; 95 %CI 2.19, 98.11; p = 0.02). A slightly lower response was demonstrated in older patients (OR 0.96; 95 %CI 0.94, 0.99; p = 0.002), patients taking antimetabolites (OR, 0.21; 95% CI 0.08, 0.51; p = 0.001). Vaccination prior to transplantation should be encouraged. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Howard J Huang
- Department of Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Stephanie G Yi
- Department of Surgery, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Constance M Mobley
- Department of Surgery, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Ashish Saharia
- Department of Surgery, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Arvind Bhimaraj
- Department of Cardiology, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Linda W Moore
- Department of Surgery, Houston Methodist Hospital, Houston, TX, 77030, USA.,Center for Outcomes Research, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Malgorzata Kloc
- Transplant Immunobiology, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Horacio E Adrogue
- Department of Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Edward A Graviss
- Department of Surgery, Houston Methodist Hospital, Houston, TX, 77030, USA.,Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Duc T Nguyen
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Todd N Eagar
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - Stephen L Jones
- Center for Outcomes Research, Houston Methodist Hospital, Houston, TX, 77030, USA
| | | | | | - Richard J Knight
- Department of Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - A Osama Gaber
- Department of Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
| | - R Mark Ghobrial
- Department of Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA
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46
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Chan CW, Yi X, Lenza M, Baldwin AD, Jakalski J, Tesic V, Yeo KTJ. Analytical and Clinical Evaluation of the Semiquantitative Elecsys Anti-SARS-CoV-2 Spike Protein Receptor Binding Domain Antibody Assay on the Roche cobas e602 Analyzer. Am J Clin Pathol 2022; 157:109-118. [PMID: 34463315 PMCID: PMC8499855 DOI: 10.1093/ajcp/aqab092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/22/2021] [Indexed: 01/15/2023] Open
Abstract
Objectives To analytically and clinically evaluate the semiquantitative Elecsys anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody (S-Ab) assay on the Roche cobas e602 analyzer. Methods The S-Ab assay is a 1-step, double-antigen sandwich electrochemiluminescent immunoassay that semiquantitatively measures total IgG, IgM, and IgA antibodies specific for the receptor binding domain of SARS-CoV-2 spike protein in serum or plasma. The S-Ab assay was evaluated for precision, linearity, interference (by hemoglobin, bilirubin, triglycerides, and biotin), cross-reactivity, and clinical performance, and was compared to the qualitative Elecsys anti-nucleocapsid (N-Ab) immunoassay, a lateral flow device that qualitatively detects S-Ab and N-Ab, and an anti-spike enzyme-linked immunosorbent assay (ELISA). Results S-Ab assay is precise, exhibits linearity from 0.4 to 250 U/mL, is unaffected by significant cross-reactivity or interferences, and qualitatively demonstrates greater than 90% concordance with N-Ab assay and lateral flow device. Readouts of S-Ab assay correlate with ELISA, which in turn correlates strongly with SARS-CoV-2 virus neutralization assay, and exhibit 100% sensitivity and specificity for COVID-19 patient samples obtained at or more than 14 days after PCR positivity. Conclusions The S-Ab assay is a robust clinical test for qualitative and semiquantitative detection of seropositivity following SARS-CoV-2 infection or spike-encoding mRNA COVID-19 vaccination.
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Affiliation(s)
- Clarence W Chan
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - Xin Yi
- Department of Pathology and Genomic Medicine, Weill Cornell Medical College, New York, NY, USA
- Houston Methodist Hospital and Research Institute, Houston, TX, USA
| | - Michael Lenza
- Clinical Chemistry Laboratory, University of Chicago Hospital, Chicago, IL, USA
| | - Angel D Baldwin
- Clinical Chemistry Laboratory, University of Chicago Hospital, Chicago, IL, USA
| | - Jennifer Jakalski
- Clinical Chemistry Laboratory, University of Chicago Hospital, Chicago, IL, USA
| | - Vera Tesic
- Department of Pathology, University of Chicago, Chicago, IL, USA
- Pritzker School of Medicine, University of Chicago, Chicago, IL, USA
| | - Kiang-Teck J Yeo
- Department of Pathology, University of Chicago, Chicago, IL, USA
- Clinical Chemistry Laboratory, University of Chicago Hospital, Chicago, IL, USA
- Pritzker School of Medicine, University of Chicago, Chicago, IL, USA
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47
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Joyce MG, Chen WH, Sankhala RS, Hajduczki A, Thomas PV, Choe M, Martinez EJ, Chang WC, Peterson CE, Morrison EB, Smith C, Chen RE, Ahmed A, Wieczorek L, Anderson A, Case JB, Li Y, Oertel T, Rosado L, Ganesh A, Whalen C, Carmen JM, Mendez-Rivera L, Karch CP, Gohain N, Villar Z, McCurdy D, Beck Z, Kim J, Shrivastava S, Jobe O, Dussupt V, Molnar S, Tran U, Kannadka CB, Soman S, Kuklis C, Zemil M, Khanh H, Wu W, Cole MA, Duso DK, Kummer LW, Lang TJ, Muncil SE, Currier JR, Krebs SJ, Polonis VR, Rajan S, McTamney PM, Esser MT, Reiley WW, Rolland M, de Val N, Diamond MS, Gromowski GD, Matyas GR, Rao M, Michael NL, Modjarrad K. SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity. Cell Rep 2021; 37:110143. [PMID: 34919799 PMCID: PMC8651551 DOI: 10.1016/j.celrep.2021.110143] [Citation(s) in RCA: 111] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/19/2021] [Accepted: 11/29/2021] [Indexed: 12/30/2022] Open
Abstract
The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID50 > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID50 neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.
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Affiliation(s)
- M Gordon Joyce
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
| | - Wei-Hung Chen
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Rajeshwer S Sankhala
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Agnes Hajduczki
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Paul V Thomas
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Misook Choe
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Elizabeth J Martinez
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - William C Chang
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Caroline E Peterson
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
| | - Elaine B Morrison
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Clayton Smith
- Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA
| | - Rita E Chen
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Aslaa Ahmed
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Lindsay Wieczorek
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Alexander Anderson
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Oak Ridge Institute of Science and Education, Oak Ridge, TN, USA
| | - James Brett Case
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Yifan Li
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Therese Oertel
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Oak Ridge Institute of Science and Education, Oak Ridge, TN, USA
| | - Lorean Rosado
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Akshaya Ganesh
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Oak Ridge Institute of Science and Education, Oak Ridge, TN, USA
| | - Connor Whalen
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Oak Ridge Institute of Science and Education, Oak Ridge, TN, USA
| | - Joshua M Carmen
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Letzibeth Mendez-Rivera
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Christopher P Karch
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Neelakshi Gohain
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Zuzana Villar
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - David McCurdy
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Zoltan Beck
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Jiae Kim
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Shikha Shrivastava
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Ousman Jobe
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Vincent Dussupt
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Sebastian Molnar
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Ursula Tran
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Chandrika B Kannadka
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Sandrine Soman
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Caitlin Kuklis
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Michelle Zemil
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Htet Khanh
- Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA
| | - Weimin Wu
- Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA
| | | | | | | | | | | | - Jeffrey R Currier
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Shelly J Krebs
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Victoria R Polonis
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Saravanan Rajan
- Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
| | - Patrick M McTamney
- Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
| | - Mark T Esser
- Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
| | | | - Morgane Rolland
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Natalia de Val
- Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA
| | - Michael S Diamond
- Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Gregory D Gromowski
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Gary R Matyas
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Mangala Rao
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Nelson L Michael
- Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Kayvon Modjarrad
- Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
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Risk Factors Associated With an Impaired Antibody Response in Kidney Transplant Recipients Following 2 Doses of the SARS-CoV-2 mRNA Vaccine. Transplant Direct 2021; 8:e1257. [PMID: 34912946 PMCID: PMC8670582 DOI: 10.1097/txd.0000000000001257] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 09/13/2021] [Indexed: 01/10/2023] Open
Abstract
Background. Data about vaccine efficacy in solid organ transplant patients are limited. We previously reported our initial observation of a 6.2% immunogenicity rate in kidney transplant recipients (KTRs) after administration of 1 dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. We sought to report our observations of anti-SARS-CoV-2 antibody in KTRs after 2 doses of the SARS-CoV-2 mRNA vaccine. Methods. We identified 105 KTRs who received 2 doses of the Pfizer-BioNTech or Moderna mRNA-1273 vaccine per availability and had anti-SARS-CoV-2 labs obtained at least 2 wk following administration of the second dose. Antibody testing was performed using 3 clinically validated qualitative and semiquantitative assays. Results. KTRs had a 36.2% antibody response rate, whereas an age ≥68 years and a longer time from transplant were factors associated with antibody response. Conclusions. The low antibody response in KTRs may be associated with the immunosuppressive state. More data are needed to evaluate if KTRs may require higher vaccine doses or an additional booster dose to increase their ability to mount an immune response to the SARS-CoV-2 vaccine.
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Rehan MA, Waheed A, Iqbal M, Javed A, Khalid SR, Shabbir A. Charismatic Trends in COVID-19 Patients in Pakistan: A Case Series. Cureus 2021; 13:e19345. [PMID: 34909306 PMCID: PMC8653918 DOI: 10.7759/cureus.19345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/08/2021] [Indexed: 11/15/2022] Open
Abstract
Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2), the novel coronavirus causing the coronavirus disease (COVID-19), spread across the world, resulting in a global crisis. This pandemic has caused consequences that are beyond the boundaries of a single discipline of life, but it is healthcare that is under the most stress. As we received COVID-19 cases in our hospital (a private tertiary care facility in Sialkot, Pakistan), we geared up to accommodate these cases, since the government sector was already overburdened. The purpose of this study is to report the trends observed in 80 COVID-19 patients admitted at our facility from May 16 to July 14, 2020.
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Affiliation(s)
- Muhammad Awais Rehan
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Amir Waheed
- Pulmonology Department, Sialkot Medical College, Sialkot, PAK
| | - Momin Iqbal
- Molecular Imaging and Neuropathology Department, New York State Psychiatric Institute, New York, USA
| | - Ali Javed
- Medicine, Abdul Sattar Lab, Sialkot, PAK
| | | | - Adnan Shabbir
- Gastroenterology, Lahore General Hospital, Lahore, PAK
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Dhala A, Gotur D, Hsu SHL, Uppalapati A, Hernandez M, Alegria J, Masud F. A Year of Critical Care: The Changing Face of the ICU During COVID-19. Methodist Debakey Cardiovasc J 2021; 17:31-42. [PMID: 35855452 PMCID: PMC9244858 DOI: 10.14797/mdcvj.1041] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 09/17/2021] [Indexed: 11/10/2022] Open
Abstract
During the SARS-CoV-2 pandemic, admissions to hospital intensive care units (ICUs) surged, exerting unprecedented stress on ICU resources and operations. The novelty of the highly infectious coronavirus disease 2019 (COVID-19) required significant changes to the way critically ill patients were managed. Houston Methodist’s incident command center team navigated this health crisis by ramping up its bed capacity, streamlining treatment algorithms, and optimizing ICU staffing while ensuring adequate supplies of personal protective equipment (PPE), ventilators, and other ICU essentials. A tele–critical-care program and its infrastructure were deployed to meet the demands of the pandemic. Community hospitals played a vital role in creating a collaborative ecosystem for the treatment and referral of critically ill patients. Overall, the healthcare industry’s response to COVID-19 forced ICUs to become more efficient and dynamic, with improved patient safety and better resource utilization. This article provides an experiential account of Houston Methodist’s response to the pandemic and discusses the resulting impact on the function of ICUs.
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Affiliation(s)
- Atiya Dhala
- Houston Methodist Hospital, Houston, Texas, US
| | - Deepa Gotur
- Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas, US
| | - Steven Huan-Ling Hsu
- Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas, US
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