|
1
|
Lin YQ, Li N, Wu YL, Ma JB, Gao HN, Zhang X. Clinical Features and Prognosis of Patients with COVID-19 and B-Cell Non-Hodgkin Lymphoma. Infect Drug Resist 2024; 17:4501-4510. [PMID: 39435457 PMCID: PMC11492921 DOI: 10.2147/idr.s477107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/28/2024] [Indexed: 10/23/2024] Open
Abstract
Purpose There is a lack of real-world data on the epidemiology, clinical manifestations, treatment effects, and prognosis of coronavirus disease 2019 (COVID-19) in patients with B-cell non-Hodgkin lymphoma (B-NHL). This study aimed to investigate the clinical features and prognostic factors of COVID-19 in patients with B-NHL. Patients and Methods This study included individuals diagnosed with B-NHL who were also diagnosed with COVID-19 and hospitalized. A retrospective analysis was conducted, and univariate and multivariate logistic regression were used to identify independent factors affecting the duration of the positive-to-negative transition of COVID-19 nucleic acid test results and prognoses. Receiver operating characteristic curves were used to assess diagnostic accuracy and determine the optimal threshold. Results Among 80 patients with COVID-19 and B-NHL, relapsed or refractory lymphoma and diffuse large B-cell lymphoma (DLBCL) accounted for 13.8% and 65% of cases, respectively. The mean age was 60.4 ± 13.0 years, and 50% of patients were women. The median duration of the positive-to-negative transition was 14 days (interquartile range [IQR], 17.2), and the median hospitalization duration was 12 days (IQR, 13). The rate of severe disease was 26.25%, and the 28-day mortality rate was 10.00%. Univariate and multivariate logistic regression analyses revealed that pathological classification of B-NHL, infection with COVID-19 within 3 months after the last dose of anti-CD20 monoclonal antibodies, and corticosteroid use were independent factors associated with a prolonged duration of the positive-to-negative transition. Compared with patients with DLBCL or FL and COVID-19, patients with B-NHL had longer nucleic acid test transition durations and higher rates of severe disease and mortality. Conclusion In patients with B-NHL, infection with COVID-19 within 3 months after treatment with anti-CD20 monoclonal antibodies prolonged the positive-to-negative transition of nucleic acid test results and increased the risks of severe disease and 28-day mortality. Treatment with corticosteroids further prolonged this transition.
Collapse
Affiliation(s)
- Ya-Qing Lin
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China
| | - Na Li
- Zhejiang Provincial General Hospital of the Chinese People’s Armed Police Force, Hangzhou, Zhejiang, People’s Republic of China
| | - Yan-Li Wu
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China
| | - Jin-Bao Ma
- Department of Drug-Resistance Tuberculosis, Xi’an Chest Hospital, Xi’an, People’s Republic of China
| | - Hai-Nv Gao
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China
| | - Xuan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| |
Collapse
|
|
2
|
Feuth E, Nieminen V, Palomäki A, Ranti J, Sucksdorff M, Finnilä T, Oksi J, Vuorinen T, Feuth T. Prolonged viral pneumonia and high mortality in COVID-19 patients on anti-CD20 monoclonal antibody therapy. Eur J Clin Microbiol Infect Dis 2024; 43:723-734. [PMID: 38358552 DOI: 10.1007/s10096-024-04776-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/05/2024] [Indexed: 02/16/2024]
Abstract
PURPOSE In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients. METHODS All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records. RESULTS Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy. CONCLUSION Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.
Collapse
Affiliation(s)
- Eeva Feuth
- Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland
| | - Valtteri Nieminen
- Department of Pulmonary Diseases and Clinical Allergology, Turku University Hospital and University of Turku, Turku, Finland
| | - Antti Palomäki
- Centre for Rheumatology and Clinical Immunology, and Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland
| | - Juha Ranti
- Department of Haematology, Turku University Hospital, Turku, Finland
| | - Marcus Sucksdorff
- Turku PET Centre, and Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland
| | - Taru Finnilä
- Department of Hospital Hygiene & Infection Control, Turku University Hospital, Turku, Finland
| | - Jarmo Oksi
- Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland
| | - Tytti Vuorinen
- Department of Clinical Microbiology, Turku University Hospital and Institute of Biomedicine, University of Turku, Turku, Finland
| | - Thijs Feuth
- Department of Pulmonary Diseases and Clinical Allergology, Turku University Hospital and University of Turku, Turku, Finland.
| |
Collapse
|
|
3
|
Stanevich OV, Alekseeva EI, Sergeeva M, Fadeev AV, Komissarova KS, Ivanova AA, Simakova TS, Vasilyev KA, Shurygina AP, Stukova MA, Safina KR, Nabieva ER, Garushyants SK, Klink GV, Bakin EA, Zabutova JV, Kholodnaia AN, Lukina OV, Skorokhod IA, Ryabchikova VV, Medvedeva NV, Lioznov DA, Danilenko DM, Chudakov DM, Komissarov AB, Bazykin GA. SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19. Nat Commun 2023; 14:149. [PMID: 36627290 PMCID: PMC9831376 DOI: 10.1038/s41467-022-34033-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 10/11/2022] [Indexed: 01/11/2023] Open
Abstract
Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin's lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.
Collapse
Affiliation(s)
| | | | - Maria Sergeeva
- Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia
| | - Artem V Fadeev
- Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia
| | | | - Anna A Ivanova
- Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia
| | | | - Kirill A Vasilyev
- Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia
| | | | - Marina A Stukova
- Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia
| | - Ksenia R Safina
- Skolkovo Institute of Science and Technology (Skoltech), Moscow, Russia
| | - Elena R Nabieva
- A.A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, Moscow, Russia
| | - Sofya K Garushyants
- A.A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, Moscow, Russia.,National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
| | - Galya V Klink
- A.A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, Moscow, Russia
| | - Evgeny A Bakin
- First Pavlov State Medical University, Saint-Petersburg, Russia.,Bioinformatics Institute, Saint Petersburg, Russia
| | | | - Anastasia N Kholodnaia
- First Pavlov State Medical University, Saint-Petersburg, Russia.,City Hospital 31, Saint-Petersburg, Russia
| | - Olga V Lukina
- First Pavlov State Medical University, Saint-Petersburg, Russia
| | | | | | | | - Dmitry A Lioznov
- Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia.,First Pavlov State Medical University, Saint-Petersburg, Russia
| | - Daria M Danilenko
- Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia
| | - Dmitriy M Chudakov
- Skolkovo Institute of Science and Technology (Skoltech), Moscow, Russia.,Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia
| | | | - Georgii A Bazykin
- Skolkovo Institute of Science and Technology (Skoltech), Moscow, Russia. .,A.A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, Moscow, Russia.
| |
Collapse
|
|
4
|
Senefeld JW, Franchini M, Mengoli C, Cruciani M, Zani M, Gorman EK, Focosi D, Casadevall A, Joyner MJ. COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis. JAMA Netw Open 2023; 6:e2250647. [PMID: 36633846 PMCID: PMC9857047 DOI: 10.1001/jamanetworkopen.2022.50647] [Citation(s) in RCA: 96] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 11/17/2022] [Indexed: 01/13/2023] Open
Abstract
Importance Patients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient. Objective To assess the growing number of reports of clinical experiences of patients with COVID-19 who are immunocompromised and treated with specific neutralizing antibodies via COVID-19 convalescent plasma transfusion. Data Sources On August 12, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma use in patients who are immunocompromised. Study Selection Randomized clinical trials, matched cohort studies, and case report or series on COVID-19 convalescent plasma use in patients who are immunocompromised were included. The electronic search yielded 462 unique records, of which 199 were considered for full-text screening. Data Extraction and Synthesis The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 3 independent reviewers in duplicate and pooled. Main Outcomes and Meaures The prespecified end point was all-cause mortality after COVID-19 convalescent plasma transfusion; exploratory subgroup analyses were performed based on putative factors associated with the potential mortality benefit of convalescent plasma. Results This systematic review and meta-analysis included 3 randomized clinical trials enrolling 1487 participants and 5 controlled studies. Additionally, 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included. Separate meta-analyses, using models both stratified and pooled by study type (ie, randomized clinical trials and matched cohort studies), demonstrated that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for the amalgam of both randomized clinical trials and matched cohort studies (risk ratio [RR], 0.63 [95% CI, 0.50-0.79]). Conclusions and Relevance These findings suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19.
Collapse
Affiliation(s)
- Jonathon W. Senefeld
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Massimo Franchini
- Division of Transfusion Medicine, Carlo Poma Hospital, Mantua, Italy
| | - Carlo Mengoli
- Division of Transfusion Medicine, Carlo Poma Hospital, Mantua, Italy
| | - Mario Cruciani
- Division of Transfusion Medicine, Carlo Poma Hospital, Mantua, Italy
| | - Matteo Zani
- Division of Transfusion Medicine, Carlo Poma Hospital, Mantua, Italy
| | - Ellen K. Gorman
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Daniele Focosi
- North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy
| | - Arturo Casadevall
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Michael J. Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| |
Collapse
|
|
5
|
Shibeeb S, Ajaj I, Al-Jighefee H, Abdallah AM. Effectiveness of Convalescent Plasma Therapy in COVID-19 Patients with Hematological Malignancies: A Systematic Review. Hematol Rep 2022; 14:377-388. [PMID: 36547236 PMCID: PMC9778836 DOI: 10.3390/hematolrep14040052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/20/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Background: Immunocompromised patients, including those with hematological malignancies, are at a high risk of developing severe coronavirus disease 2019 (COVID-19) complications. Currently, there is a limited number of systematic reviews into the efficacy of convalescent plasma therapy (CPT) use in the treatment of COVID-19 patients with hematological malignancies. Therefore, the aim of this review was to systematically appraise the current evidence for the clinical benefits of this therapy in COVID-19 patients with hematological malignancies. Methods: A comprehensive search was conducted up to April 2022, using four databases: PubMed, Web of Science, Science Direct, and Scopus. Two reviewers independently assessed the quality of the included studies. Data collection analysis was performed using Microsoft Excel 365 and GraphPad Prism software. Results: 18 studies met the inclusion criteria; these records included 258 COVID-19 patients who had hematological malignancies and were treated with CPT. The main findings from the reviewed data suggest that CPT may be associated with improved clinical outcomes, including (a) higher survival rate, (b) improved SARS-CoV-2 clearance and presence of detectable anti-SARS-CoV-2 antibodies post CP transfusion, and (c) improved hospital discharge time and recovery after 1 month of CPT. Furthermore, treatment with convalescent plasma was not associated with the development of adverse events. Conclusions: CPT appears to be an effective supportive therapeutic option for hematological malignancy patients infected with COVID-19. To our knowledge, this is one of the first systematic reviews of the clinical benefits of CPT in COVID-19 patients with hematological malignancies.
Collapse
Affiliation(s)
- Sapha Shibeeb
- La Trobe College Australia, La Trobe University, Melbourne, VIC 3086, Australia
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar
| | - Ilham Ajaj
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar
| | - Hadeel Al-Jighefee
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar
| | - Atiyeh M. Abdallah
- La Trobe College Australia, La Trobe University, Melbourne, VIC 3086, Australia
- Correspondence: ; Tel.: +61-974-4403-6551
| |
Collapse
|
|
6
|
Dioverti V, Salto-Alejandre S, Haidar G. Immunocompromised Patients with Protracted COVID-19: a Review of "Long Persisters". CURRENT TRANSPLANTATION REPORTS 2022; 9:209-218. [PMID: 36407883 PMCID: PMC9660019 DOI: 10.1007/s40472-022-00385-y] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2022] [Indexed: 11/13/2022]
Abstract
Purpose of Review Certain immunocompromised individuals are at risk for protracted COVID-19, in which SARS-CoV-2 leads to a chronic viral infection. However, the pathogenesis, diagnosis, and management of this phenomenon remain ill-defined. Recent Findings Herein, we review key aspects of protracted SARS-CoV-2 infection in immunocompromised individuals, or the so-called long persisters, and describe the clinical presentation, risk factors, diagnosis, and treatment modalities of this condition, as well as intra-host viral evolution. Based on the available data, we also propose a framework of criteria with which to approach this syndrome. Summary Protracted COVID-19 is an uncharacterized syndrome affecting patients with B-cell depletion; our proposed diagnostic approach and definitions will inform much needed future research.
Collapse
Affiliation(s)
- Veronica Dioverti
- Division of Infectious Diseases, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287 USA
| | - Sonsoles Salto-Alejandre
- Division of Infectious Diseases, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287 USA
- Clinical Unit of Infectious Diseases and Microbiology, Institute of Biomedicine of Seville (IBiS)/Virgen del Rocío University Hospital/University of Seville/CSIC, Avda. Manuel Siurot s/n 41013, Seville, Spain
| | - Ghady Haidar
- Division of Infectious Diseases, University of Pittsburgh and UPMC, 3601 Fifth Ave, Falk Medical Building, Suite 5B, Pittsburgh, PA 15213 USA
| |
Collapse
|
|
7
|
Delgado-Fernández M, García-Gemar GM, Fuentes-López A, Muñoz-Pérez MI, Oyonarte-Gómez S, Ruíz-García I, Martín-Carmona J, Sanz-Cánovas J, Castaño-Carracedo MÁ, Reguera-Iglesias JM, Ruíz-Mesa JD. Treatment of COVID-19 with convalescent plasma in patients with humoral immunodeficiency - Three consecutive cases and review of the literature. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2022; 40:507-516. [PMID: 36336380 PMCID: PMC9631336 DOI: 10.1016/j.eimce.2021.01.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 01/20/2021] [Indexed: 06/16/2023]
Abstract
Patients lacking humoral response have been suggested to develop a less severe COVID-19, but there are some reports with a prolonged, relapsing or deadly course. From April 2020, there is growing evidence on the benefits of COVID-19 convalescent plasma (CCP) for patients with humoral immunodeficiency. Most of them had a congenital primary immunodeficiency or were on treatment with anti CD20 antibodies. We report on three patients treated in our hospital and review thirty-one more cases described in the literature. All patients but three resolved clinical picture with CCP. A dose from 200 to 800ml was enough in most cases. Antibody levels after transfusion were negative or low, suggesting consumption of them in SARS-CoV-2 neutralization. These patients have a protracted clinical course shortened after CCP. CCP could be helpful for patients with humoral immunodeficiency. It avoid relapses and chronification. CCP should be transfused as early as possible in patients with COVID-19 and humoral immunodeficiency.
Collapse
Affiliation(s)
| | | | - Ana Fuentes-López
- Microbiology Department, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | | | - Salvador Oyonarte-Gómez
- Director of "Red andaluza de Medicina transfusional, tejidos y células" del Sistema Sanitario Público de Andalucía, Spain
| | | | | | - Jaime Sanz-Cánovas
- Internal Medicine Department, Hospital Regional Universitario de Málaga, Spain
| | | | | | - Juan Diego Ruíz-Mesa
- Infectious Diseases Department, Hospital Regional Universitario de Málaga, Spain
| |
Collapse
|
|
8
|
Focosi D, Franchini M. Potential use of convalescent plasma for SARS-CoV-2 prophylaxis and treatment in immunocompromised and vulnerable populations. Expert Rev Vaccines 2022; 21:877-884. [PMID: 34015243 PMCID: PMC8171015 DOI: 10.1080/14760584.2021.1932475] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/17/2021] [Indexed: 12/21/2022]
Abstract
INTRODUCTION : The ongoing SARS-CoV-2 pandemic is a serious threat for the health of immunocompromised patients. Among neutralizing antibody-based therapeutics, convalescent plasma containing polyclonal anti-SARS-CoV-2 immunoglobulins has promising results in both congenital and iatrogenic immunodeficiencies in oncohematological and transplant patients. AREAS COVERED : This article discusses case reports, case series and controlled studies detailing the efficacy of convalescent plasma in immunocompromised patients. EXPERT OPINION : Convalescent plasma, when administered at high neutralizing antibody titers, is a safe and effective treatment for frail immunocompromised patients. Genetic monitoring of refractory patients is recommended to intercept intra-host emergence of SARS-CoV-2 variants.
Collapse
Affiliation(s)
- Daniele Focosi
- North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy
| | - Massimo Franchini
- Department of Hematology and Transfusion Medicine, Carlo Poma Hospital, Mantua, Italy
| |
Collapse
|
|
9
|
Naimi A, Yashmi I, Jebeleh R, Imani Mofrad M, Azimian Abhar S, Jannesar Y, Heidary M, Pakzad R. Comorbidities and mortality rate in COVID-19 patients with hematological malignancies: A systematic review and meta-analysis. J Clin Lab Anal 2022; 36:e24387. [PMID: 35385130 PMCID: PMC9102765 DOI: 10.1002/jcla.24387] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/15/2022] [Accepted: 03/18/2022] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION The global pandemic of coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It seems that there is an association between blood cancer and an increased risk of severe COVID-19. This study aimed to review the literature reporting the COVID-19 outcomes in patients with hematological malignancies. MATERIAL AND METHODS In this systematic review and meta-analysis, Pubmed, Embase, and Web of Science databases were searched using the following keywords: COVID-19, SARS-CoV-2, blood cancer, myeloma, lymphoma, and leukemia. All the published articles in English from January 1, 2019, until March 10, 2021 were collected and evaluated. RESULTS In total, 53 studies with 2395 patients were included based on inclusion criteria. Most of these studies took place in Spain (14.81%), followed by the USA (11.11%), China (9.26%), and the UK (9.26%). More than half of COVID-19 patients with hematological malignancy were male (56.73%). Oxygen therapy played an important role in COVID-19 treatment. Moreover, anticoagulant therapies such as enoxaparin and heparin were two great assists for these patients. Fever (74.24%), cough (67.64%), and fatigue (53.19%) were the most reported clinical manifestations. In addition, hypertension and dyslipidemia were the most common comorbidities. The mortality rate due to COVID-19 in patients with hematological malignancies was 21.34%. CONCLUSION This study demonstrated that hematologic cancer patients were more susceptible to a severe COVID-19 than patients without blood cancer. Thus, the management of COVID-19 in these patients requires much more attention, and their screening should perform regularly.
Collapse
Affiliation(s)
- Adel Naimi
- Cellular and Molecular Research CenterSabzevar University of Medical SciencesSabzevarIran
| | - Ilya Yashmi
- Student Research CommitteeSabzevar University of Medical SciencesSabzevarIran
| | - Reza Jebeleh
- Student Research CommitteeSabzevar University of Medical SciencesSabzevarIran
| | | | | | - Yasaman Jannesar
- Student Research CommitteeSabzevar University of Medical SciencesSabzevarIran
| | - Mohsen Heidary
- Cellular and Molecular Research CenterSabzevar University of Medical SciencesSabzevarIran
- Department of Laboratory SciencesSchool of Paramedical SciencesSabzevar University of Medical SciencesSabzevarIran
| | - Reza Pakzad
- Department of EpidemiologyFaculty of HealthIlam University of Medical SciencesIlamIran
| |
Collapse
|
|
10
|
Bansal N, Raturi M, Bansal Y. SARS-CoV-2 variants in immunocompromised COVID-19 patients: The underlying causes and the way forward. Transfus Clin Biol 2022; 29:161-163. [PMID: 34973463 PMCID: PMC8714679 DOI: 10.1016/j.tracli.2021.12.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 12/20/2021] [Accepted: 12/26/2021] [Indexed: 01/25/2023]
Affiliation(s)
- N. Bansal
- Department of Transfusion Medicine, VCSG Government Institute of Medical Science and Research, Srinagar, Uttarakhand, India,Corresponding author
| | - M. Raturi
- Department of Immunohematology and Blood Transfusion, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, India
| | - Y. Bansal
- Department of Microbiology, VCSG Government Institute of Medical Science and Research, Srinagar, Uttarakhand, India
| |
Collapse
|
|
11
|
Visco C, Marcheselli L, Mina R, Sassone M, Guidetti A, Penna D, Cattaneo C, Bonuomo V, Busca A, Ferreri AJM, Bruna R, Petrucci L, Cairoli R, Salvini M, Bertù L, Ladetto M, Pilerci S, Pinto A, Ramadan S, Marchesi F, Cavo M, Arcaini L, Coviello E, Romano A, Musto P, Massaia M, Fracchiolla N, Marchetti M, Scattolin A, Tisi MC, Cuneo A, Della Porta M, Trentin L, Turrini M, Gherlinzoni F, Tafuri A, Galimberti S, Bocchia M, Cardinali V, Cilloni D, Corso A, Armiento D, Rigacci L, La Barbera EO, Gambacorti-Passerini C, Visani G, Vallisa D, Venditti A, Selleri C, Conconi A, Tosi P, Lanza F, Candoni A, Krampera M, Corradini P, Passamonti F, Merli F, on behalf of the ITA-HEMA-COV investigators. A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study. Blood Adv 2022; 6:327-338. [PMID: 34644385 PMCID: PMC8516438 DOI: 10.1182/bloodadvances.2021005691] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/08/2021] [Indexed: 11/20/2022] Open
Abstract
Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin's lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.
Collapse
Affiliation(s)
- Carlo Visco
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
| | | | - Roberto Mina
- Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliera Universitaria Citta’della Salute e della Scienza, Turin, Italy
| | - Marianna Sassone
- Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Anna Guidetti
- Hematology and Bone Marrow Transplantation, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, University of Milano, Milano, Italy
| | - Domenico Penna
- Hematology, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Reggio Emilia, Reggio Emilia, Italy
| | - Chiara Cattaneo
- Hematology, Azienda Socio-Sanitaria Territoriale-Spedali Civili, Brescia, Italy
| | - Valentina Bonuomo
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
| | - Alessandro Busca
- Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliera Universitaria Citta’della Salute e della Scienza, Turin, Italy
| | - Andrés José María Ferreri
- Lymphoma Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Riccardo Bruna
- Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Ospedale Maggiore della Carità, Novara, Italy
| | - Luigi Petrucci
- Hematology, Department of Translational and Precision Medicine, Sapienza, University of Rome, Rome, Italy
| | - Roberto Cairoli
- Hematology, Azienda Socio-Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marco Salvini
- Department of Medicine and Surgery, University of Insubria and Azienda Socio-Sanitaria Territoriale Sette Laghi, Ospedale di Circolo of Varese, Varese, Italy
| | - Lorenza Bertù
- Department of Medicine and Surgery, University of Insubria and Azienda Socio-Sanitaria Territoriale Sette Laghi, Ospedale di Circolo of Varese, Varese, Italy
| | - Marco Ladetto
- Hematology, Azienda Ospedaliera Santissimi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | - Sofia Pilerci
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Antonello Pinto
- Hematology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico “Fondazione G Pascale,” Naples, Italy
| | - Safaa Ramadan
- Division of Onco-Hematology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
| | - Francesco Marchesi
- Hematology and Stem Cell Transplant Unit, Istituto di Ricovero e Cura a Carattere Scientifico Regina Elena National Cancer Institute, Rome, Italy
| | - Michele Cavo
- Seràgnoli Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine, Bologna University School of Medicine, Bologna, Italy
| | - Luca Arcaini
- Division of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo & Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Elisa Coviello
- Hematology and bone marrow transplant, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino, Genova, Italy
| | - Alessandra Romano
- Hematology, Dipartimento di Chirurgia e Specialità Medico Chirurgiche, Università degli Studi di Catania, Catania, Italy
| | - Pellegrino Musto
- Department of Emergency and Organ Transplantation, Aldo Moro” University School of Medicine and Unit of Hematology and Stem Cell Transplantation, Azienda Ospedaliera Universitaria Consorziale Policlinico, Bari, Italy
| | | | - Nicola Fracchiolla
- Oncoematologia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
| | - Monia Marchetti
- Hematology, Azienda Ospedaliera Santissimi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | | | | | - Antonio Cuneo
- Hematology, Azienda Ospedaliero Universitaria Sant’Anna, Ferrara, Italy
| | - Matteo Della Porta
- Humanitas Clinical and Research Hospital Istituto di Ricovero e Cura a Carattere Scientifico and Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Livio Trentin
- Hematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Padua, Italy
| | | | | | - Agostino Tafuri
- Hematology, University Hospital Sant’Andrea, Sapienza, Rome, Italy
| | - Sara Galimberti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Monica Bocchia
- Hematology Unit, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
| | | | - Daniela Cilloni
- Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Turin, Italy
| | | | - Daniele Armiento
- Unit of Hematology, Stem Cell Transplantation, University Campus Bio-Medico, Rome, Italy
| | | | - Elettra Ortu La Barbera
- Unità Operativa Complessa Ematologia con Trapianto, Ospedale Santa Maria Goretti, Latina, Italy
| | | | - Giuseppe Visani
- Dipartimento di OncoEmatologia, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy
| | | | - Adriano Venditti
- Department of Biomedicine and Prevention, University Tor Vergata Rome, Rome, Italy
| | - Carmine Selleri
- Department of Medicine, Hematology, University of Salerno, Ospedale San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy
| | | | - Patrizia Tosi
- Hematology, Ospedale degli Infermi di Rimini, Rimini, Italy
| | | | - Anna Candoni
- Hematology and Stem Cell Transplant Unit, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | - Mauro Krampera
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
| | - Paolo Corradini
- Hematology and Bone Marrow Transplantation, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, University of Milano, Milano, Italy
| | - Francesco Passamonti
- Department of Medicine and Surgery, University of Insubria and Azienda Socio-Sanitaria Territoriale Sette Laghi, Ospedale di Circolo of Varese, Varese, Italy
| | - Francesco Merli
- Hematology, Azienda Unità Sanitaria Locale-Istituto di Ricovero e Cura a Carattere Scientifico Reggio Emilia, Reggio Emilia, Italy
| | | |
Collapse
|
|
12
|
Dhillon RA, Qamar MA, Gilani JA, Irfan O, Waqar U, Sajid MI, Mahmood SF. The mystery of COVID-19 reinfections: A global systematic review and meta-analysis. Ann Med Surg (Lond) 2021; 72:103130. [PMID: 34900250 PMCID: PMC8642249 DOI: 10.1016/j.amsu.2021.103130] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/22/2021] [Accepted: 11/30/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND As the COVID-19 pandemic rages on, reports on disparities in vaccine roll out alongside COVID-19 reinfection have been emerging. We conducted a systematic review to assess the determinants and disease spectrum of COVID-19 reinfection. MATERIALS AND METHODS A comprehensive search covering relevant databases was conducted for observational studies reporting Polymerase Chain Reaction (PCR) confirmed infection and reinfection cases. A quality assessment tool developed by the National Institute of Health (NIH) for the assessment of case series was utilized. Meta-analyses were performed using RevMan 5.3 for pooled proportions of findings in first infection and reinfection with a 95% confidence interval (CI). RESULTS Eighty-one studies reporting 577 cases were included from 22 countries. The mean age of patients was 46.2 ± 18.9 years and 179 (31.0%) cases of comorbidities were reported. The average time duration between first infection and reinfection was 63.6 ± 48.9 days. During first infection and reinfection, fever was the most common symptom (41.4% and 36.4%, respectively) whilst anti-viral therapy was the most common treatment regimen administered (44.5% and 43.0%, respectively). Comparable odds of symptomatic presentation and management were reported for the two infections. However, a higher Intensive Care Unit (ICU) admission rate was observed in reinfection compared to first infection (10 vs 3). Ten deaths were reported with respiratory failure being the most common cause of death (7/10 deaths). CONCLUSION Our findings support immunization practices given increased ICU admissions and mortality in reinfections. Our cohort serves as a guide for clinicians and authorities in devising an optimal strategy for controlling the pandemic. (249 words).
Collapse
Affiliation(s)
| | | | | | - Omar Irfan
- Amaris Consulting, Toronto, Ontario, Canada
| | - Usama Waqar
- Medical College, Aga Khan University, Karachi, Sindh, Pakistan
| | | | - Syed Faisal Mahmood
- Section of Infectious Diseases, Aga Khan University, Karachi, Sindh, Pakistan
| |
Collapse
|
|
13
|
Bonuomo V, Ferrarini I, Dell'Eva M, Sbisà E, Krampera M, Visco C. COVID-19 (SARS-CoV-2 infection) in lymphoma patients: A review. World J Virol 2021; 10:312-325. [PMID: 34909405 PMCID: PMC8641038 DOI: 10.5501/wjv.v10.i6.312] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 07/16/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection now has a global resonance and represents a major threat for several patient populations. Observations from initial case series suggested that cancer patients in general might have an unfavorable outcome following coronavirus disease 2019 (COVID-19), due to their underlying conditions and cytotoxic treatments. More recently, data regarding the incidence and clinical evolution of COVID-19 in lymphomas have been reported with the aim to identify those more frequently associated with severe complications and death. Patients with lymphoma appear particularly vulnerable to SARS-CoV-2 infection, only partly because of the detrimental effects of the anti-neoplastic regimens (chemotherapy, pathway inhibitors, monoclonal antibodies) on the immune system. Here, we systematically reviewed the current literature on COVID-19 in adult patients with lymphoma, with particular emphasis on disease course and prognostic factors. We also highlighted the potential differences in COVID-19 clinical picture according to lymphoma subtype, delivered treatment for the hematological disease and its relationship on how these patients have been managed thus far.
Collapse
Affiliation(s)
- Valentina Bonuomo
- Section of Haematology, Department of Medicine, University of Verona, Verona 37134, Italy
| | - Isacco Ferrarini
- Section of Haematology, Department of Medicine, University of Verona, Verona 37134, Italy
| | - Michele Dell'Eva
- Section of Haematology, Department of Medicine, University of Verona, Verona 37134, Italy
| | - Eugenio Sbisà
- Section of Haematology, Department of Medicine, University of Verona, Verona 37134, Italy
| | - Mauro Krampera
- Section of Haematology, Department of Medicine, University of Verona, Verona 37134, Italy
| | - Carlo Visco
- Section of Haematology, Department of Medicine, University of Verona, Verona 37134, Italy
| |
Collapse
|
|
14
|
Chamblain M, Dawkins E, Lane J, Ghany R, Tamariz L, Palacio A, Guzman-Suarez B. A case of COVID-19 Reinfection and Systematic Review of Patterns of Reinfection. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2021; 29:e409-e411. [PMID: 34803348 PMCID: PMC8594394 DOI: 10.1097/ipc.0000000000001055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
We present a case of a middle age Hispanic patient with COVID-19 reinfection. We conducted a systematic review of the literature of reinfection cases and found that women represent the majority of the cases and that reinfection usually presents with more severe disease, particularly among healthcare workers.
Collapse
|
|
15
|
Gaspar-Rodríguez A, Padilla-González A, Rivera-Toledo E. Coronavirus persistence in human respiratory tract and cell culture: An overview. Braz J Infect Dis 2021; 25:101632. [PMID: 34627782 PMCID: PMC8486621 DOI: 10.1016/j.bjid.2021.101632] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/13/2021] [Accepted: 09/13/2021] [Indexed: 01/12/2023] Open
Abstract
Emerging human coronaviruses, including the recently identified SARS-CoV-2, are relevant respiratory pathogens due to their potential to cause epidemics with high case fatality rates, although endemic coronaviruses are also important for immunocompromised patients. Long-term coronavirus infections had been described mainly in experimental models, but it is currently evident that SARS-CoV-2 genomic-RNA can persist for many weeks in the respiratory tract of some individuals clinically recovered from coronavirus infectious disease-19 (COVID-19), despite a lack of isolation of infectious virus. It is still not clear whether persistence of such viral RNA may be pathogenic for the host and related to long-term sequelae. In this review, we summarize evidence of SARS-CoV-2 RNA persistence in respiratory samples besides results obtained from cell culture and histopathology describing long-term coronavirus infection. We also comment on potential mechanisms of coronavirus persistence and relevance for pathogenesis.
Collapse
Affiliation(s)
- Adriana Gaspar-Rodríguez
- Universidad Nacional Autonoma de Mexico, Facultad de Medicina, Departamento de Microbiología y Parasitología, Coyoacan, Mexico
| | - Ana Padilla-González
- Universidad Nacional Autonoma de Mexico, Facultad de Medicina, Departamento de Microbiología y Parasitología, Coyoacan, Mexico.
| | - Evelyn Rivera-Toledo
- Universidad Nacional Autonoma de Mexico, Facultad de Medicina, Departamento de Microbiología y Parasitología, Coyoacan, Mexico.
| |
Collapse
|
|
16
|
Moutinho-Pereira S, Calisto R, Sabio F, Guerreiro L. High-titre convalescent plasma therapy for an immunocompromised patient with systemic lupus erythematosus with protracted SARS-CoV-2 infection. BMJ Case Rep 2021; 14:14/8/e244853. [PMID: 34433539 PMCID: PMC8388267 DOI: 10.1136/bcr-2021-244853] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
A 39-year-old woman with systemic lupus erythematosus treated with anti-CD20 monoclonal antibody rituximab was admitted to our hospital with COVID-19 pneumonia. Despite receiving dexamethasone, she developed hypoxaemia and persistent lung opacities. As bronchoalveolar lavage was suggestive of cryptogenic organising pneumonia, high-dose corticosteroid was administered, and she received antimicrobial therapy for opportunistic infections without improvement. Reverse transcription PCR was repeatedly positive for SARS-CoV-2, and virus replication was confirmed in cell cultures. As no anti-SARS-CoV-2 antibodies were detected more than 100 days after symptom onset, she was treated with convalescent plasma with fast clinical improvement, returning home days later. Our case shows that persistent SARS-CoV-2 infection in an immunocompromised patient may be overturned with the appropriate treatment.
Collapse
Affiliation(s)
- Sara Moutinho-Pereira
- Departmento de Medicina, Serviço de Medicina Interna, Unidade Local de Saúde de Matosinhos EPE, Senhora da Hora, Portugal
| | - Raquel Calisto
- Departmento de Medicina, Serviço de Medicina Interna, Unidade Local de Saúde de Matosinhos EPE, Senhora da Hora, Portugal
| | - Federico Sabio
- Departmento de Medicina, Serviço de Imunohemoterapia, Unidade Local de Saúde de Matosinhos EPE, Senhora da Hora, Portugal
| | - Luísa Guerreiro
- Departmento de Medicina, Serviço de Medicina Interna, Unidade Local de Saúde de Matosinhos EPE, Senhora da Hora, Portugal
| |
Collapse
|
|
17
|
Duléry R, Lamure S, Delord M, Di Blasi R, Chauchet A, Hueso T, Rossi C, Drenou B, Deau Fischer B, Soussain C, Feugier P, Noël N, Choquet S, Bologna S, Joly B, Philippe L, Kohn M, Malak S, Fouquet G, Daguindau E, Taoufik Y, Lacombe K, Cartron G, Thiéblemont C, Besson C. Prolonged in-hospital stay and higher mortality after Covid-19 among patients with non-Hodgkin lymphoma treated with B-cell depleting immunotherapy. Am J Hematol 2021; 96:934-944. [PMID: 33909916 PMCID: PMC8212109 DOI: 10.1002/ajh.26209] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 04/23/2021] [Accepted: 04/23/2021] [Indexed: 12/19/2022]
Abstract
Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19-92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1-235). After a median follow-up of 191 days (3-260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42-3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04-4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
Collapse
Affiliation(s)
- Rémy Duléry
- Service d'Hématologie Clinique et de Thérapie Cellulaire Hôpital Saint Antoine, Assistance Publique—Hôpitaux de Paris, Sorbonne Université, Inserm UMRs Paris France
| | - Sylvain Lamure
- Département d'Hématologie Clinique, CHU de Montpellier, UMR‐CNRS 5535 Université de Montpellier Montpellier France
| | - Marc Delord
- Clinical Research Center Centre Hospitalier de Versailles Le Chesnay France
| | - Roberta Di Blasi
- Service d'Hématologie‐Oncologie Hôpital Saint Louis, Assistance Publique—Hôpitaux de Paris; Université de Paris – Diderot Paris France
| | | | - Thomas Hueso
- Service d'Hématologie Adulte Institut Gustave Roussy, Université Paris‐Sud, Université Paris‐Saclay Villejuif France
| | - Cédric Rossi
- Service d'Hématologie Clinique CHU de Dijon Bourgogne Dijon France
| | - Bernard Drenou
- Département d'Hématologie Groupe Hospitalier de Mulhouse Sud Alsace Mulhouse France
| | - Bénédicte Deau Fischer
- Service d'Hématologie Clinique Hôpital Cochin, Assistance Publique ‐ Hôpitaux de Paris Paris France
| | - Carole Soussain
- Département d'Oncologie Médicale ‐ Hématologie Institut Curie Saint Cloud France
| | | | - Nicolas Noël
- Service de Médecine Interne – Immunologie Hôpital Bicêtre, Assistance Publique ‐ Hôpitaux de Paris Le Kremlin‐Bicêtre France
| | - Sylvain Choquet
- Service d'Hématologie Clinique Hôpital Pitié‐Salpêtrière, Assistance Publique ‐ Hôpitaux de Paris Paris France
| | - Serge Bologna
- Service d'Hématologie Centre d'Oncologie de Gentilly Nancy France
| | - Bertrand Joly
- Service d'Hématologie Centre Hospitalier Sud Francilien Corbeil‐Essonnes France
| | - Laure Philippe
- Service d'Hématologie Centre Hospitalier d'Annecy Annecy France
| | - Milena Kohn
- Service d'Hématologie Oncologie Centre Hospitalier de Versailles Le Chesnay France
| | - Sandra Malak
- Département d'Oncologie Médicale ‐ Hématologie Institut Curie Saint Cloud France
| | - Guillemette Fouquet
- Service d'Hématologie Clinique Hôpital Cochin, Assistance Publique ‐ Hôpitaux de Paris Paris France
| | | | - Yassine Taoufik
- Service d'Hématologie et Immunologie Biologique Hôpital Bicêtre, Assistance Publique‐Hôpitaux de Paris, INSERM 1186, Institut Gustave Roussy Villejuif France
| | - Karine Lacombe
- Service des Maladies Infectieuses et Tropicales Sorbonne Université, Inserm IPLESP, Hôpital Saint Antoine, Assistance Publique—Hôpitaux de Paris Paris France
| | - Guillaume Cartron
- Département d'Hématologie Clinique, CHU de Montpellier, UMR‐CNRS 5535 Université de Montpellier Montpellier France
| | - Catherine Thiéblemont
- Service d'Hématologie‐Oncologie Hôpital Saint Louis, Assistance Publique—Hôpitaux de Paris; Université de Paris – Diderot Paris France
| | - Caroline Besson
- Service d'Hématologie Oncologie Centre Hospitalier de Versailles Le Chesnay France
- Centre de recherche en Epidémiologie et Santé des Populations (CESP), INSERM U1018 Université Paris‐Saclay, UVSQ, Inserm, Équipe Villejuif France
| |
Collapse
|
|
18
|
Senefeld JW, Klassen SA, Ford SK, Senese KA, Wiggins CC, Bostrom BC, Thompson MA, Baker SE, Nicholson WT, Johnson PW, Carter RE, Henderson JP, Hartman WR, Pirofski L, Wright RS, Fairweather DL, Bruno KA, Paneth NS, Casadevall A, Joyner MJ. Use of convalescent plasma in COVID-19 patients with immunosuppression. Transfusion 2021; 61:2503-2511. [PMID: 34036587 PMCID: PMC8242637 DOI: 10.1111/trf.16525] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/05/2021] [Accepted: 05/05/2021] [Indexed: 12/24/2022]
Abstract
In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID-19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune-deficient and immune-suppressed patients with COVID-19 warrants further investigation.
Collapse
Affiliation(s)
- Jonathon W. Senefeld
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| | - Stephen A. Klassen
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| | - Shane K. Ford
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| | - Katherine A. Senese
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| | - Chad C. Wiggins
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| | - Bruce C. Bostrom
- Pediatric Oncology and Hematology, Children's Hospital of MinnesotaMinneapolisMinnesotaUSA
| | | | - Sarah E. Baker
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| | - Wayne T. Nicholson
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| | - Patrick W. Johnson
- Department of Health Sciences Research, Mayo ClinicJacksonvilleFloridaUSA
| | - Rickey E. Carter
- Department of Health Sciences Research, Mayo ClinicJacksonvilleFloridaUSA
| | - Jeffrey P. Henderson
- Division of Infectious Diseases, Department of MedicineWashington University School of MedicineSt. LouisMissouriUSA
| | - William R. Hartman
- Department of AnesthesiologyUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Liise‐anne Pirofski
- Division of Infectious Diseases, Department of MedicineAlbert Einstein College of MedicineBronxNew YorkUSA
| | - R. Scott Wright
- Department of Cardiovascular Medicine and Director Human Research Protection ProgramMayo ClinicRochesterMinnesotaUSA
| | | | - Katelyn A. Bruno
- Department of Cardiovascular MedicineMayo ClinicJacksonvilleFloridaUSA
| | - Nigel S. Paneth
- Department of Epidemiology and Biostatistics and Department of Pediatrics and Human DevelopmentMichigan State UniversityEast LansingMichiganUSA
| | - Arturo Casadevall
- Department of Molecular Microbiology and ImmunologyJohns Hopkins Bloomberg School of Public HealthBaltimoreMarylandUSA
| | - Michael J. Joyner
- Department of Anesthesiology and Perioperative MedicineMayo ClinicRochesterMinnesotaUSA
| |
Collapse
|
|
19
|
Yasuda H, Mori Y, Chiba A, Bai J, Murayama G, Matsushita Y, Miyake S, Komatsu N. Resolution of One-Year Persisting COVID-19 Pneumonia and Development of Immune Thrombocytopenia in a Follicular Lymphoma Patient With Preceding Rituximab Maintenance Therapy: A follow-up Report and Literature Review of Cases With Prolonged Infections. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2021; 21:e810-e816. [PMID: 34393077 PMCID: PMC8286809 DOI: 10.1016/j.clml.2021.07.004] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 07/02/2021] [Indexed: 11/22/2022]
Abstract
Background We previously reported elsewhere of a follicular lymphoma patient suffering from persistent COVID-19 pneumonia that was still ongoing at 2 months after onset. Materials and Methods We provide a follow-up report of the case along with a literature review of immunocompromised lymphoma patients experiencing prolonged COVID-19 infections. Results Although requiring a full 1 year, the presented case eventually achieved spontaneous resolution of COVID-19 pneumonia. Anti-SARS-CoV-2 antibodies could not be detected throughout the disease course, but COVID-19-directed T-cell response was found to be intact. The patient also developed secondary immune thrombocytopenia subsequent to COVID-19 pneumonia. We found 19 case reports of immunocompromised lymphoma patients with prolonged COVID-19 infections in the literature. All 5 patients who died did not receive convalescent plasma therapy, whereas resolution of COVID-19 infection was achieved in 8 out of 9 patients who received convalescent plasma therapy. Conclusions We demonstrate through the presented case that while time-consuming, resolution of COVID-19 infections may be achieved without aid from humoral immunity if cellular immunity is intact. Immunocompromised lymphoma patients are at risk of a prolonged disease course of COVID-19, and convalescent plasma therapy may be a promising approach in such patients.
Collapse
Affiliation(s)
- Hajime Yasuda
- Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.
| | - Yosuke Mori
- Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
| | - Asako Chiba
- Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
| | - Jie Bai
- Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
| | - Goh Murayama
- Department of Internal Medicine and Rheumatology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Yasushi Matsushita
- Department of Internal Medicine and Rheumatology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Sachiko Miyake
- Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
| | - Norio Komatsu
- Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan; Laboratory for the Development of Therapies Against MPN, Juntendo University School of Medicine, Tokyo, Japan; Department of Advanced Hematology, Juntendo University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
20
|
Jones JM, Faruqi AJ, Sullivan JK, Calabrese C, Calabrese LH. COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those with Humoral Immunodeficiency States: A Scoping Review. Pathog Immun 2021; 6:76-103. [PMID: 34056149 PMCID: PMC8150936 DOI: 10.20411/pai.v6i1.435] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 04/26/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The role of humoral immunity has been well established in reducing infection risk and facilitating viral clearance in patients with COVID-19. However, the relationship between specific antibody responses and severity of COVID-19 is less well understood. METHODS To address this question and identify gaps in knowledge, we utilized the methodology of a scoping review to interrogate risk of infection and clinical outcomes of COVID-19 in patients with iatrogenic and inborn humoral immunodeficiency states based on existing literature. RESULTS Among patients with iatrogenic B-cell depletion, particularly with agents targeting CD20, our analysis found increased risk of severe COVID-19 and death across a range of underlying disease states. Among patients with humoral inborn errors of immunity with COVID-19, our synthesis found that patients with dysregulated humoral immunity, predominantly common variable immunodeficiency (CVID), may be more susceptible to severe COVID-19 than patients with humoral immunodeficiency states due to X-linked agammaglobulinemia and other miscellaneous forms of humoral immunodeficiency. There were insufficient data to appraise the risk of COVID-19 infection in both populations of patients. CONCLUSIONS Our work identifies potentially significant predictors of COVID-19 severity in patients with humoral immunodeficiency states and highlights the need for larger studies to control for clinical and biologic confounders of disease severity.
Collapse
Affiliation(s)
- Jessica M. Jones
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
| | - Aiman J. Faruqi
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
| | - James K. Sullivan
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
| | - Cassandra Calabrese
- Cleveland Clinic, Department of Rheumatic and Immunologic Diseases, Cleveland, Ohio
| | - Leonard H. Calabrese
- Cleveland Clinic, Department of Rheumatic and Immunologic Diseases, Cleveland, Ohio
| |
Collapse
|
|
21
|
Klassen SA, Senefeld JW, Johnson PW, Carter RE, Wiggins CC, Shoham S, Grossman BJ, Henderson JP, Musser J, Salazar E, Hartman WR, Bouvier NM, Liu STH, Pirofski LA, Baker SE, van Helmond N, Wright RS, Fairweather D, Bruno KA, Wang Z, Paneth NS, Casadevall A, Joyner MJ. The Effect of Convalescent Plasma Therapy on Mortality Among Patients With COVID-19: Systematic Review and Meta-analysis. Mayo Clin Proc 2021; 96:1262-1275. [PMID: 33958057 PMCID: PMC7888247 DOI: 10.1016/j.mayocp.2021.02.008] [Citation(s) in RCA: 115] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 02/01/2021] [Accepted: 02/11/2021] [Indexed: 02/07/2023]
Abstract
To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments. Additional analyses showed that early transfusion (within 3 days of hospital admission) of higher titer plasma is associated with lower patient mortality. These data provide evidence favoring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized patients with COVID-19.
Collapse
Affiliation(s)
- Stephen A Klassen
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Jonathon W Senefeld
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Patrick W Johnson
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | - Rickey E Carter
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | - Chad C Wiggins
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Shmuel Shoham
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Brenda J Grossman
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO
| | - Jeffrey P Henderson
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO
| | - James Musser
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX; Center for Molecular and Translational Human Infectious Diseases, Houston Methodist Research Institute, Houston, TX; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY
| | - Eric Salazar
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY
| | - William R Hartman
- Department of Anesthesiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Nicole M Bouvier
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Sean T H Liu
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Liise-Anne Pirofski
- Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY
| | - Sarah E Baker
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Noud van Helmond
- Department of Anesthesiology, Cooper Medical School of Rowan University, Cooper University Health Care, Camden, NJ
| | - R Scott Wright
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN; Director, Human Research Protection Program, Mayo Clinic, Rochester, MN
| | | | - Katelyn A Bruno
- Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL
| | - Zhen Wang
- Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Nigel S Paneth
- Department of Epidemiology and Biostatistics, Michigan State University, East Lansing; Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing
| | - Arturo Casadevall
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN.
| |
Collapse
|
|
22
|
Rnjak D, Ravlić S, Šola AM, Halassy B, Šemnički J, Šuperba M, Hećimović A, Kurolt IC, Kurtović T, Mačak Šafranko Ž, Polančec D, Bendelja K, Mušlin T, Jukić I, Vuk T, Zenić L, Artuković M. COVID-19 convalescent plasma as long-term therapy in immunodeficient patients? Transfus Clin Biol 2021; 28:264-270. [PMID: 33901641 PMCID: PMC8064810 DOI: 10.1016/j.tracli.2021.04.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 04/16/2021] [Indexed: 02/07/2023]
Abstract
Objectives The patients with hematological malignancies are a vulnerable group to COVID-19, due to the immunodeficiency resulting from the underlying disease and oncological treatment that significantly impair cellular and humoral immunity. Here we report on a beneficial impact of a passive immunotherapy with convalescent plasma to treat a prolonged, active COVID-19 infection in a patient with a history of nasopharyngeal diffuse large B-cell lymphoma treated with the therapy inducing substantial impairment of particularly humoral arm of immune system. The specific aim was to quantify SARS-CoV2 neutralizing antibodies in a patient plasma during the course of therapy. Materials and methods Besides the standard of care treatment and monitoring, neutralizing antibody titers in patient's serum samples, calibrated according to the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human), were quantified in a time-dependent manner. During the immunotherapy period peripheral blood flow cytometry immunophenotyping was conducted to characterize lymphocyte subpopulations. Results The waves of clinical improvements and worsening coincided with transfused neutralizing antibodies rises and drops in the patient's systemic circulation, proving their contribution in controlling the disease progress. Besides the patient's lack of own humoral immune system, immunophenotyping analysis revealed also the reduced level of helper T-lymphocytes and immune exhaustion of monocytes. Conclusion Therapeutic approach based on convalescent plasma transfusion transformed a prolonged, active COVID-19 infection into a manageable chronic disease.
Collapse
Affiliation(s)
- D Rnjak
- Special Hospital for Pulmonary Diseases, Rockefellerova 3, 10000 Zagreb, Croatia.
| | - S Ravlić
- University of Zagreb, Centre for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia; Centre of Excellence for Virus Immunology and Vaccines, Zagreb, Croatia.
| | - A-M Šola
- Special Hospital for Pulmonary Diseases, Rockefellerova 3, 10000 Zagreb, Croatia
| | - B Halassy
- University of Zagreb, Centre for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia; Centre of Excellence for Virus Immunology and Vaccines, Zagreb, Croatia
| | - J Šemnički
- Special Hospital for Pulmonary Diseases, Rockefellerova 3, 10000 Zagreb, Croatia
| | - M Šuperba
- Special Hospital for Pulmonary Diseases, Rockefellerova 3, 10000 Zagreb, Croatia
| | - A Hećimović
- Croatian Institute of Transfusion Medicine, Zagreb, Croatia
| | - I-C Kurolt
- University Hospital for Infectious Diseases Dr. Fran Mihaljević, Zagreb, Croatia; Centre of Excellence for Virus Immunology and Vaccines, Zagreb, Croatia
| | - T Kurtović
- University of Zagreb, Centre for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia; Centre of Excellence for Virus Immunology and Vaccines, Zagreb, Croatia
| | - Ž Mačak Šafranko
- University Hospital for Infectious Diseases Dr. Fran Mihaljević, Zagreb, Croatia; Centre of Excellence for Virus Immunology and Vaccines, Zagreb, Croatia
| | - D Polančec
- Srebrnjak Children's Hospital, Zagreb, Croatia
| | - K Bendelja
- University of Zagreb, Centre for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia
| | - T Mušlin
- Croatian Institute of Transfusion Medicine, Zagreb, Croatia
| | - I Jukić
- Croatian Institute of Transfusion Medicine, Zagreb, Croatia
| | - T Vuk
- Croatian Institute of Transfusion Medicine, Zagreb, Croatia
| | - L Zenić
- Srebrnjak Children's Hospital, Zagreb, Croatia
| | - M Artuković
- Special Hospital for Pulmonary Diseases, Rockefellerova 3, 10000 Zagreb, Croatia
| |
Collapse
|
|
23
|
Machhi J, Shahjin F, Das S, Patel M, Abdelmoaty MM, Cohen JD, Singh PA, Baldi A, Bajwa N, Kumar R, Vora LK, Patel TA, Oleynikov MD, Soni D, Yeapuri P, Mukadam I, Chakraborty R, Saksena CG, Herskovitz J, Hasan M, Oupicky D, Das S, Donnelly RF, Hettie KS, Chang L, Gendelman HE, Kevadiya BD. Nanocarrier vaccines for SARS-CoV-2. Adv Drug Deliv Rev 2021; 171:215-239. [PMID: 33428995 PMCID: PMC7794055 DOI: 10.1016/j.addr.2021.01.002] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 12/18/2020] [Accepted: 01/01/2021] [Indexed: 02/07/2023]
Abstract
The SARS-CoV-2 global pandemic has seen rapid spread, disease morbidities and death associated with substantive social, economic and societal impacts. Treatments rely on re-purposed antivirals and immune modulatory agents focusing on attenuating the acute respiratory distress syndrome. No curative therapies exist. Vaccines remain the best hope for disease control and the principal global effort to end the pandemic. Herein, we summarize those developments with a focus on the role played by nanocarrier delivery.
Collapse
Affiliation(s)
- Jatin Machhi
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Farah Shahjin
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Srijanee Das
- Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Milankumar Patel
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Mai Mohamed Abdelmoaty
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, NE 68198, USA; Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza, Egypt
| | - Jacob D Cohen
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Preet Amol Singh
- Department of Pharmaceutical Sciences & Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India
| | - Ashish Baldi
- Department of Pharmaceutical Sciences & Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India
| | - Neha Bajwa
- Department of Pharmaceutical Sciences & Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India
| | - Raj Kumar
- Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Lalit K Vora
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Tapan A Patel
- Department of Biological Sciences, P. D. Patel Institute of Applied Sciences (PDPIAS), Charotar University of Science and Technology (CHARUSAT), Changa, Anand 388421, Gujarat, India
| | - Maxim D Oleynikov
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Dhruvkumar Soni
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, NE 68198, USA
| | - Pravin Yeapuri
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Insiya Mukadam
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, NE 68198, USA
| | - Rajashree Chakraborty
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Caroline G Saksena
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Jonathan Herskovitz
- Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| | - Mahmudul Hasan
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, NE 68198, USA
| | - David Oupicky
- Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Suvarthi Das
- Department of Medicine, Stanford Medical School, Stanford University, Palo Alto, CA 94304, USA
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
| | - Kenneth S Hettie
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Department of Otolaryngology - Head & Neck Surgery, Stanford University, Palo Alto, CA 94304, USA
| | - Linda Chang
- Departments of Diagnostic Radiology & Nuclear Medicine, and Neurology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA
| | - Howard E Gendelman
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA; Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, NE 68198, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, NE 68198, USA.
| | - Bhavesh D Kevadiya
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE 68198, USA
| |
Collapse
|
|
24
|
Early Administration of Convalescent Plasma Improves Survival in Patients with Hematological Malignancies and COVID-19. Viruses 2021; 13:v13030436. [PMID: 33800528 PMCID: PMC8001057 DOI: 10.3390/v13030436] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/02/2021] [Accepted: 03/05/2021] [Indexed: 02/06/2023] Open
Abstract
The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48-72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0.03460). The plasma-treated group also showed a significantly milder course of infection (p = 0.03807), characterized by less severe symptoms and faster recovery (p = 0.00001). In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19. To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies.
Collapse
|
|
25
|
Delgado-Fernández M, García-Gemar GM, Fuentes-López A, Muñoz-Pérez MI, Oyonarte-Gómez S, Ruíz-García I, Martín-Carmona J, Sanz-Cánovas J, Castaño-Carracedo MÁ, Reguera-Iglesias JM, Ruíz-Mesa JD. Treatment of COVID-19 with convalescent plasma in patients with humoral immunodeficiency - Three consecutive cases and review of the literature. Enferm Infecc Microbiol Clin 2021; 40:S0213-005X(21)00035-5. [PMID: 33741148 PMCID: PMC7877207 DOI: 10.1016/j.eimc.2021.01.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/19/2021] [Accepted: 01/20/2021] [Indexed: 12/31/2022]
Abstract
Patients lacking humoral response have been suggested to develop a less severe COVID-19, but there are some reports with a prolonged, relapsing or deadly course. From April 2020, there is growing evidence on the benefits of COVID-19 convalescent plasma (CCP) for patients with humoral immunodeficiency. Most of them had a congenital primary immunodeficiency or were on treatment with anti CD20 antibodies. We report on three patients treated in our hospital and review thirty-one more cases described in the literature. All patients but three resolved clinical picture with CCP. A dose from 200 to 800ml was enough in most cases. Antibody levels after transfusion were negative or low, suggesting consumption of them in SARS-CoV-2 neutralization. These patients have a protracted clinical course shortened after CCP. CCP could be helpful for patients with humoral immunodeficiency. It avoid relapses and chronification. CCP should be transfused as early as possible in patients with COVID-19 and humoral immunodeficiency.
Collapse
Affiliation(s)
| | | | - Ana Fuentes-López
- Microbiology Department, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | | | - Salvador Oyonarte-Gómez
- Director of "Red andaluza de Medicina transfusional, tejidos y células" del Sistema Sanitario Público de Andalucía, Spain
| | | | | | - Jaime Sanz-Cánovas
- Internal Medicine Department, Hospital Regional Universitario de Málaga, Spain
| | | | | | - Juan Diego Ruíz-Mesa
- Infectious Diseases Department, Hospital Regional Universitario de Málaga, Spain
| |
Collapse
|
|
26
|
Syal K. Guidelines on newly identified limitations of diagnostic tools for COVID-19 and consequences. J Med Virol 2020; 93:1837-1842. [PMID: 33200414 PMCID: PMC7753543 DOI: 10.1002/jmv.26673] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/05/2020] [Accepted: 11/12/2020] [Indexed: 01/07/2023]
Abstract
Coronavirus disease 2019 (COVID-19) caused by coronavirus has spread worldwide and has become the deadliest pandemic of the 21st century. Such rapid spread is predominantly attributed to the poor diagnosis and its asymptomatic transmission. In the absence of treatment regime, timely diagnosis is the best available remedy that can restrict its spread. An early diagnosis of COVID-19 is critical for determining the line of treatment and preventing long term complications in the infected subject. Unfortunately, available rapid antigen and antibody kits are known to be erroneous whereas reverse transcription polymerase chain reaction based tests are expensive, viral load dependent and at times inconclusive. In current scenario, the false-negative results imposed a major risk to the individual patient care and also to the efforts for containing the spread at the population level, where as false positives are traumatic for families and can lead to improper treatment resulting in severe complications. In this article, the limitations of available diagnostic procedures have been elaborated and plausible combination approach has been advised.
Collapse
Affiliation(s)
- Kirtimaan Syal
- Department of Biological Sciences, BITS-Pilani, Telangana, India
| |
Collapse
|