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Gámiz Rejano A, López-Viñau T, López Martín C, Marín Moreno S, Machuca I, Rodríguez-Gómez J. Dual therapy with remdesivir plus extended nirmatrelvir/ritonavir in immunocompromised and critically ill patient with suspected persistent COVID-19 infection: Case report. Med Intensiva 2025; 49:174-177. [PMID: 39592344 DOI: 10.1016/j.medine.2024.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/08/2024] [Accepted: 10/11/2024] [Indexed: 11/28/2024]
Affiliation(s)
- Arturo Gámiz Rejano
- Servicio de Farmacia, Hospital Universitario Reina Sofía, Córdoba, Spain; Instituto Maimones de Investigación Biomédica de Córdoba, (IMIBIC), Córdoba, Spain
| | - Teresa López-Viñau
- Servicio de Farmacia, Hospital Universitario Reina Sofía, Córdoba, Spain; Instituto Maimones de Investigación Biomédica de Córdoba, (IMIBIC), Córdoba, Spain
| | | | | | - Isabel Machuca
- Servicio de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba, Spain; Instituto Maimones de Investigación Biomédica de Córdoba, (IMIBIC), Córdoba, Spain
| | - Jorge Rodríguez-Gómez
- Servicio de Medicina Intensiva, Hospital Universitario Reina Sofía, Córdoba, Spain; Instituto Maimones de Investigación Biomédica de Córdoba, (IMIBIC), Córdoba, Spain.
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Dequidt T, Richier Q, Louapre C, Ader F, Merad Y, Lauwerier N, Jacomet C, Carles M, Biron C, Gendrin V, Marlat C, Danion F, Lepage TM, Sotto A, Bourdellon L, Mania A, Martinot M, Falher GL, Ferre A, Pilmis B, Gondran G, Simeone P, Henry M, Kamel T, Ray S, Ancellin S, Mélé N, Camou F, Destremau M, Sellenet J, Zucman N, Le Maréchal M, Mellouki K, Langlois ME, Luque Paz D, Mousset M, Leclerc C, Sommet A, Lacombe K, Martin-Blondel G. Convalescent plasma in patients receiving rituximab or ocrelizumab for multiple sclerosis or neuromyelitis Optica spectrum disorder with Covid-19: A multicenter retrospective study. Int J Infect Dis 2025; 151:107323. [PMID: 39643155 DOI: 10.1016/j.ijid.2024.107323] [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: 09/10/2024] [Revised: 11/28/2024] [Accepted: 11/29/2024] [Indexed: 12/09/2024] Open
Abstract
BACKGROUND Despite vaccination, patients receiving anti-CD20 monoclonal antibodies (mAbs) for multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD) have an increased risk of developing severe or protracted COVID-19. The aim of this study was to describe the effect of COVID-19 convalescent plasma (CCP) in patients with MS or NMOSD exposed to anti-CD20 and infected by SARS-CoV-2. METHODS This French national, retrospective cohort study was conducted between November 2020 and June 2023. Patients with MS or NMOSD, under anti-CD20 mAbs, with symptomatic COVID-19 and treated by CCP were screened. Protracted COVID-19 was defined by a duration of symptoms >21 days. The primary endpoint was the overall survival 30 days after CCP administration. RESULTS Ninety-two patients from 34 hospitals were included, 84 (91%) with MS and 8 (9%) with NMOSD. Overall, 30-day survival was 97% (IC95%: 91-99). SARS-CoV-2 viremia was positive in 47/75 (61%) patients before CCP versus 9/59 (15%) seven days post-CCP. In the 52 patients (57%) with protracted COVID-19, the duration of symptoms before CCP was 51 [28-69] days, including fever in 75% of cases, which disappeared in 100% of patients 7 days post-CCP. CONCLUSIONS CCP could be a therapeutic option in patients exposed to anti-CD20 mAbs for inflammatory demyelinating disease, particularly in those with protracted COVID-19.
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Affiliation(s)
- Tanguy Dequidt
- Department of Infectious Diseases, Guadeloupe University hospital, Pointe-à-Pitre, France.
| | - Quentin Richier
- Sorbonne University, Department of Infectious Diseases, Saint Antoine Hospital, APHP, Paris, France
| | - Céline Louapre
- Sorbonne University, Department of Neurology, Pitié Salpêtrière Hospital, APHP, CIC neurosciences, Paris Brain Institute, Paris, France
| | - Florence Ader
- Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France
| | - Yanis Merad
- Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France
| | - Nicolas Lauwerier
- Department of Infectious Diseases, Lille University Hospital, Lille, France
| | - Christine Jacomet
- Department of Infectious Diseases, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Michel Carles
- Department of Infectious Diseases, Nice University Hospital, Nice, France
| | - Charlotte Biron
- Department of Infectious Diseases, Nantes University Hospital, Nantes, France
| | - Vincent Gendrin
- Department of Infectious Diseases, Nord Franche-Comté Hospital, Belfort, France
| | - Clément Marlat
- Department of Infectious Diseases, Rouen University Hospital, Rouen, France
| | - François Danion
- Department of Infectious Diseases, Strasbourg University Hospital, Strasbourg, France
| | - Tristan M Lepage
- Department of Infectious Diseases, Montpellier University Hospital, Montpellier, France
| | - Albert Sotto
- Department of Infectious Diseases, Nimes University Hospital, Nimes, France
| | | | - Alexandre Mania
- Department of Internal Medicine, Henri Mondor Hospital, Aurillac, France
| | - Martin Martinot
- Department of Infectious Diseases, Colmar Hospital, Colmar, France
| | | | - Alexis Ferre
- Intensive Care Unit, Versailles Hospital, Le Chesnay, France
| | - Benoit Pilmis
- Antimicrobial Stewardship Team, Microbiology Unit, Groupe Hospitalier Paris Saint Joseph, Paris, France
| | - Guillaume Gondran
- Department of Internal Medicine, Limoges University Hospital, Limoges, France
| | - Pierre Simeone
- Department of Anesthesiology and Critical Care Medicine, University Hospital Timone, APHM, Marseille, France
| | - Matthieu Henry
- Medical-Surgical Intensive Care Unit, District Hospital Center, La Roche sur Yon, France
| | - Toufik Kamel
- Intensive Care Unit, Orléans University Hospital, Orléans, France
| | - Simon Ray
- Department of Infectious Diseases, Rodez Hospital, Rodez, France
| | - Sophie Ancellin
- Department of Infectious Diseases, Auch Hospital, Auch, France
| | - Nicolas Mélé
- Department of Neurology, GHU Paris Psychiatrie et Neurosciences, Sainte-Anne Hospital, Paris, France
| | - Fabrice Camou
- Intensive Care and Infectious Disease Unit, Groupe Saint-André, Bordeaux University Hospital, Bordeaux, France
| | - Marjolaine Destremau
- Intensive Care and Infectious Disease Unit, Groupe Saint-André, Bordeaux University Hospital, Bordeaux, France
| | - Jeremy Sellenet
- Department of Internal Medicine, Saint Jean Sud de France Clinic, Saint-Jean-de-Vedas, France
| | - Noémie Zucman
- Intensive Care Unit, CH Annecy Genevois, Epagny Metz-Tessy, France
| | - Marion Le Maréchal
- Univ. Grenoble Alpes, Infectious Diseases Department, CHU Grenoble Alpes, Grenoble, France
| | - Khawla Mellouki
- Department of Infectious Diseases, Claude Bernard University Lyon 1, Valence Hospital Center, Valence, France
| | - Marie-Elodie Langlois
- Department of Internal Medicine and Infectious Diseases, Saint Joseph Saint Luc Hospital, Lyon, France
| | - David Luque Paz
- Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France
| | - Maud Mousset
- Intensive Care Unit, Comminges Pyrénées Hospital, Saint-Gaudens, France
| | - Catherine Leclerc
- Department of Infectious Diseases, CHI Poissy - Saint-Germain-en-Laye, Saint-Germain-en-Laye, France
| | - Agnès Sommet
- Clinical Investigation Center, Toulouse University Hospital, Toulouse, France
| | - Karine Lacombe
- Sorbonne University, IPLESP Inserm, Infectious Diseases Department, Saint Antoine Hospital, APHP, Paris, France
| | - Guillaume Martin-Blondel
- Department of Infectious Diseases, Toulouse University Hospital, Toulouse, France; Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291 - CNRS UMR5051 - Toulouse III University, Toulouse, France
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Seki M, Kubosawa C, Ono M, Kamoshita F, Shimizu A, Mitsutake K. Clinical Features of Patients with COVID-19 Recurrence During Hospitalization in the Omicron Variant Surge. Infect Drug Resist 2024; 17:5011-5015. [PMID: 39554473 PMCID: PMC11568766 DOI: 10.2147/idr.s485976] [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: 07/07/2024] [Accepted: 11/07/2024] [Indexed: 11/19/2024] Open
Abstract
Background Repeat positive results for SARS-CoV-2 by antigen detection test/RT-PCR in recovered COVID-19 patients were not very rare even when omicron variants became dominant, but the clinical features of patients with recurrent COVID-19 during hospitalization are still unclear. Methods The clinical characteristics of patients with recurrent COVID-19 during hospitalization were retrospectively investigated from January 2023 to December 2023. Results Recurrence of COVID-19 was found in 7 of 275 (2.5%) patients during hospitalization. Their mean age was 80.3 (74-89) years, and 4 of 7 (57.1%) patients were hospitalized on the hematology ward with B cell/non-Hodgkin lymphoma. These 4 lymphoma patients had been vaccinated, but the other 3 patients hospitalized on the emergency ward and the neurology ward had not been vaccinated. Of the 7 patients, 6 (85.7%) were initially treated with remdesivir (RDV), but only 3 patients were re-treated with RDV, and the other 4 patients were successfully re-treated with oral 3C-like protease inhibitors, such as ensitrelvir (ESV) and nirmatrelvir/ritonavir (N/R). Conclusion These data suggest that COVID-19 recurrence was found in patients with hematological disorders, such as lymphoma, and/or patients with no vaccination history. However, these patients were treated successfully by re-administration of anti-SARS-CoV-2 agents, including ESV and N/R.
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Affiliation(s)
- Masafumi Seki
- Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, Japan
| | - Chie Kubosawa
- Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, Japan
| | - Makoto Ono
- Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, Japan
| | - Fumitaka Kamoshita
- Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, Japan
| | - Atsuko Shimizu
- Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, Japan
| | - Kotaro Mitsutake
- Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, Japan
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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: 0] [Impact Index Per Article: 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.
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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.
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Lindahl AL, Ahava MJ, Haukipää M, Kreivi HR, Lipponen A, Kortela E. Successful treatment of persisting SARS-CoV-2 infection in an immunocompromised patient with repeated nirmatrelvir/ritonavir courses: a case report. Infect Dis (Lond) 2023; 55:585-589. [PMID: 37334428 DOI: 10.1080/23744235.2023.2223274] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 05/30/2023] [Accepted: 06/05/2023] [Indexed: 06/20/2023] Open
Abstract
BACKGROUND In immunocompromised patients, persistent SARS-CoV-2 viral shedding and relapsing COVID-19 pneumonia have been described. Currently, little is known about the management of persisting COVID-19, and immunocompromised patients are recommended to be treated using antivirals and immunomodulatory therapies at similar doses and durations as the general population. Previous case reports have described treatment with repeated and prolonged courses of remdesivir and some evidence is emerging in the use of nirmatrelvir/ritonavir combination (NMV/r). METHODS We describe a patient with recent chemotherapy including rituximab for follicular lymphoma with persisting SARS-CoV-2 infection. Polymerase chain reaction tests (PCR), cycle threshold values and blood SARS-CoV-2 antigen levels were evaluated. RESULTS The patient presented with persisting SARS-CoV-2 with relapsing COVID-19 pneumonia. The patient was treated successfully with repeated courses of NMV/r without any observed adverse effects. After the third, prolonged course, the patient remained afebrile and PCR negative, and no relapses have been observed four months after the third NMV/r course. CONCLUSIONS Nirmatrelvir-ritonavir could offer a more accessible alternative to remdesivir. Further research and guidelines for persisting SARS-CoV-2 infection in immunocompromised patients are urgently needed.
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Affiliation(s)
- Anna L Lindahl
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Finland
| | - Maarit J Ahava
- Diagnostic Center, Helsinki University Hospital and University of Helsinki, Finland
| | - Mia Haukipää
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Finland
| | - Hanna-Riikka Kreivi
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Finland
| | - Anne Lipponen
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Finland
| | - Elisa Kortela
- Inflammation Center, Helsinki University Hospital and University of Helsinki, Finland
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Nelson MC, Manos CK, Flanagan E, Prahalad S. COVID-19 after rituximab therapy in cSLE patients. Ther Adv Vaccines Immunother 2023; 11:25151355231181242. [PMID: 37362155 PMCID: PMC10285438 DOI: 10.1177/25151355231181242] [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: 02/17/2023] [Accepted: 05/18/2023] [Indexed: 06/28/2023] Open
Abstract
Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease associated with significant morbidity and mortality. Rituximab is a B-cell depleting therapy utilized in the treatment of SLE. In adults, rituximab has been associated with increased risk of adverse outcomes in patients who develop coronavirus disease 2019 (COVID-19). We aimed to assess the impact of prior rituximab treatment on clinical outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in children with SLE. To describe the impact of rituximab on outcomes from SARS-CoV-2 infection, we conducted a retrospective study of pediatric SLE patients in our center diagnosed with COVID-19 who had previously received rituximab between February 2019 and October 2022. Patients' clinical characteristics, disease activity, and outcomes were assessed. Of the eight subjects assessed, five required hospitalizations for COVID-19, four required ICU admission, and two were seen in the emergency department for their symptoms. One patient ultimately expired from her illness. The median time between rituximab administration and COVID-19 diagnosis was 3 months. We assessed the clinical outcomes, including the need of ICU admission and fatal outcome, of COVID-19 in our cSLE patient population after rituximab administration. Approximately 60% of our patients required hospitalization for their illness, and seven out of eight patients required healthcare utilization to include hospitalization and/or emergency department visits.
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Affiliation(s)
| | - Cynthia K. Manos
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USAChildren’s Healthcare of Atlanta, Atlanta, GA, USA
| | - Elaine Flanagan
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USAChildren’s Healthcare of Atlanta, Atlanta, GA, USA
| | - Sampath Prahalad
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USAChildren’s Healthcare of Atlanta, Atlanta, GA, USADepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA
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Tomisti L, Angelotti F, Lenzi M, Amadori F, Sarteschi G, Porcu A, Capria AL, Bertacca G, Lombardi S, Bianchini G, Vincenti A, Cesta N. Efficacy of Convalescent Plasma to Treat Long-Standing COVID-19 in Patients with B-Cell Depletion. Life (Basel) 2023; 13:1266. [PMID: 37374049 DOI: 10.3390/life13061266] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/21/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
The use of antivirals, corticosteroids, and IL-6 inhibitors has been recommended by the WHO to treat COVID-19. CP has also been considered for severe and critical cases. Clinical trials on CP have shown contradictory results, but an increasing number of patients, including immunocompromised ones, have shown benefits from this treatment. We reported two clinical cases of patients with prolonged COVID-19 infection and B-cell depletion who showed rapid clinical and virological recovery after the administration of CP. The first patient in this study was a 73-year-old female with a history of follicular non-Hodgkin lymphoma previously treated with bendamustine followed by maintenance therapy with rituximab. The second patient was a 68-year-old male with chronic obstructive pulmonary disease, bipolar disorder, alcoholic liver disease, and a history of mantellar non-Hodgkin lymphoma treated with rituximab and radiotherapy. After the administration of CP, both patients showed a resolution of symptoms, improvement of their clinical conditions, and a negative result of the nasopharyngeal swab test. The administration of CP might be effective in resolving symptoms and improving clinical and virological outcomes in patients with B-cell depletion and prolonged SARS-CoV2 infections.
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Affiliation(s)
- Luca Tomisti
- ASL Toscana Nord-Ovest, Internal Medicine Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Francesca Angelotti
- ASL Toscana Nord-Ovest, Internal Medicine Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Mirco Lenzi
- ASL Toscana Nord-Ovest, Infectious Diseases Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Francesco Amadori
- ASL Toscana Nord-Ovest, Infectious Diseases Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Giovanni Sarteschi
- ASL Toscana Nord-Ovest, Infectious Diseases Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Anna Porcu
- ASL Toscana Nord-Ovest, Pneumology Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Anna-Lisa Capria
- UOC Virologia, Dipartimento di Medicina di Laboratorio, AOUP Azienda Ospedaliero Universitaria Pisana, 56100 Pisa, Italy
| | - Gloria Bertacca
- ASL Toscana Nord-Ovest, SSD Clinical Chemistry Analyses and Molecular Biology, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Stefania Lombardi
- ASL Toscana Nord-Ovest, SSD Clinical Chemistry Analyses and Molecular Biology, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Guido Bianchini
- ASL Toscana Nord-Ovest, Internal Medicine Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Antonella Vincenti
- ASL Toscana Nord-Ovest, Infectious Diseases Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
| | - Novella Cesta
- ASL Toscana Nord-Ovest, Infectious Diseases Department, Nuovo Ospedale Apuano, 54100 Massa, Italy
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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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9
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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: 95] [Impact Index Per Article: 47.5] [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.
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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
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10
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Ljungquist O, Lundgren M, Iliachenko E, Månsson F, Böttiger B, Landin-Olsson M, Wikén C, Rosendal E, Överby AK, Wigren BJ, Forsell MNE, Kjeldsen-Kragh J, Rasmussen M, Kahn F, Holm K. Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19: an observational study of 28 cases. Infect Dis (Lond) 2022; 54:283-291. [PMID: 34878955 PMCID: PMC8726003 DOI: 10.1080/23744235.2021.2013528] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/25/2021] [Accepted: 11/28/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment. METHODS We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28). RESULTS In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged. CONCLUSION As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.
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Affiliation(s)
- Oskar Ljungquist
- Department of Translational Medicine, Clinical Infection Medicine, Faculty of Medicine, Lund University, Malmö, Sweden
- Department of Infectious Diseases, Helsingborg Hospital, Helsingborg, Sweden
| | - Maria Lundgren
- Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services, Lund, Sweden
| | - Elena Iliachenko
- Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services, Lund, Sweden
| | - Fredrik Månsson
- Department of Translational Medicine, Clinical Infection Medicine, Faculty of Medicine, Lund University, Malmö, Sweden
- Skåne University Hospital, Malmö, Sweden
| | - Blenda Böttiger
- Department of Clinical Microbiology, University and Regional Laboratories, Lund, Sweden
| | - Mona Landin-Olsson
- Skåne University Hospital, Malmö, Sweden
- Department of Clinical Science, Division of Internal Medicine, Lund University, Lund, Sweden
| | - Christian Wikén
- Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden
| | - Ebba Rosendal
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
| | - Anna K. Överby
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
| | | | | | - Jens Kjeldsen-Kragh
- Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services, Lund, Sweden
| | - Magnus Rasmussen
- Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden
| | - Fredrik Kahn
- Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden
| | - Karin Holm
- Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden
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11
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Kajova M, Kekäläinen E, Anttila VJ, Paajanen J. Successful treatment with a short course of remdesivir in a case of prolonged COVID-19 in a lymphoma patient. Infect Dis (Lond) 2022; 54:455-459. [PMID: 35086417 DOI: 10.1080/23744235.2022.2028896] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Patients with haematological malignancies have an increased susceptibility for COVID-19 and higher mortality. They may also have prolonged symptoms and viral shedding. Clinical trials have not specifically addressed the management of this patient group. We present a lymphoma patient with COVID-19 who was treated with remdesivir, and a literature review of similar cases. METHODS SARS-CoV-2 RT-PCR, virus culture and whole-genome sequencing were performed from nasopharyngeal swabs and antibody testing from serum. In addition, SARS-CoV-2 nucleocapsid antigen was tested from serum. Medline was searched for reported cases of lymphoma and COVID-19 treated with remdesivir. RESULTS The patient was undergoing lymphoma treatment including chemotherapy, rituximab and prednisolone. After diagnosis of COVID-19, broad-spectrum antibiotics were administered due to neutropenia and fever. After 20 d of fever with no signs of co-infection, remdesivir was initiated with rapid response. The treatment was continued for 4 d. Serum SARS-CoV-2 antibody tests were negative 20, 30 and 66 d from symptom onset. Before starting remdesivir, the SARS-CoV-2 PCR and virus culture from the nasopharynx and serum antigen test were positive. From earlier reports, we identified a total of eleven cases of lymphoma and COVID-19 treated with remdesivir accompanied by other antivirals and anti-inflammatory agents. CONCLUSIONS As shown in this and earlier reports on lymphoma patients, the clinical course of COVID-19 may be protracted and a humoral immune response may remain absent. In addition, optimal management remains undecided. The presented patient responded well to a short course of remdesivir.
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Affiliation(s)
- Mikael Kajova
- Department of Infectious Diseases, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Eliisa Kekäläinen
- HUS Diagnostic Center, HUSLAB, Clinical Microbiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.,Translational Immunology Research Program and Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
| | - Veli-Jukka Anttila
- Department of Infectious Diseases, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Juuso Paajanen
- Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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12
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Furlan A, Forner G, Cipriani L, Vian E, Rigoli R, Gherlinzoni F, Scotton P. COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge. Front Immunol 2021; 12:763412. [PMID: 34804051 PMCID: PMC8595333 DOI: 10.3389/fimmu.2021.763412] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 10/14/2021] [Indexed: 12/15/2022] Open
Abstract
B cell-targeting strategies such as rituximab are widely used in B cell hematologic malignancies, rheumatologic and musculoskeletal diseases and a variety of autoimmune disorders. The purpose of this paper is to illustrate how exposure to anti-CD20 treatment profoundly affects B cell functions involved in anti-SARS-CoV-2 immunity and significantly impacts on the clinical and serological course of SARS-CoV-2 infection, long term immunity and vaccine responses. The data presented here suggest that the effects of B cell-depleting agents on adaptive immunity should be taken into account for the proper selection and interpretation of SARS-CoV-2 diagnostics and to guide appropriate therapeutic approaches and protective measures. Combination therapeutic strategies including immunotherapy in association with prolonged antiviral treatment may play a decisive role in the setting of B cell immune deficiencies.
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Affiliation(s)
- Anna Furlan
- Hematology Unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Gabriella Forner
- Infectious Disease Unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Ludovica Cipriani
- Infectious Disease Unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Elisa Vian
- Microbiology Unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Roberto Rigoli
- Microbiology Unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
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13
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Hanssen JLJ, Stienstra J, Boers SA, Pothast CR, Zaaijer HL, Tjon JM, Heemskerk MHM, Feltkamp MCW, Arend SM. Convalescent Plasma in a Patient with Protracted COVID-19 and Secondary Hypogammaglobulinemia Due to Chronic Lymphocytic Leukemia: Buying Time to Develop Immunity? Infect Dis Rep 2021; 13:855-864. [PMID: 34698153 PMCID: PMC8544405 DOI: 10.3390/idr13040077] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/22/2021] [Accepted: 09/24/2021] [Indexed: 12/15/2022] Open
Abstract
It is not exactly clear yet which type of immune response prevails to accomplish viral clearance in coronavirus disease 2019 (COVID-19). Studying a patient with chronic lymphocytic leukemia and hypogammaglobulinemia who suffered from COVID-19 provided insight in the immunological responses after treatment with COVID-19 convalescent plasma (CCP). Treatment consisted of oxygen, repeated glucocorticosteroids and multiple dosages of CCP guided by antibody levels. Retrospectively performed humoral and cellular immunity analysis made clear that not every serological test for COVID-19 is appropriate for follow-up of sufficient neutralizing antibodies after CCP. In retrospect, we think that CCP merely bought time for this patient to develop an adequate cellular immune response which led to viral clearance and ultimately clinical recovery.
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Affiliation(s)
- Jaap L. J. Hanssen
- Department of Infectious Diseases, Leiden University Medical Center, C5-P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
- Correspondence: ; Tel.: +31-71-5262620
| | - Johan Stienstra
- Department of Internal Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
| | - Stefan A. Boers
- Department of Medical Microbiology, Leiden University Medical Center, E4-P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; (S.A.B.); (M.C.W.F.)
| | - Cilia R. Pothast
- Department of Hematology, Leiden University Medical Center, C2-R, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; (C.R.P.); (J.M.T.); (M.H.M.H.)
| | - Hans L. Zaaijer
- Sanquin Blood Supply Foundation, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands;
| | - Jennifer M. Tjon
- Department of Hematology, Leiden University Medical Center, C2-R, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; (C.R.P.); (J.M.T.); (M.H.M.H.)
| | - Mirjam H. M. Heemskerk
- Department of Hematology, Leiden University Medical Center, C2-R, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; (C.R.P.); (J.M.T.); (M.H.M.H.)
| | - Mariet C. W. Feltkamp
- Department of Medical Microbiology, Leiden University Medical Center, E4-P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; (S.A.B.); (M.C.W.F.)
| | - Sandra M. Arend
- Department of Infectious Diseases, Leiden University Medical Center, C5-P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;
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14
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García-Erce JA, Jericó C, Abad-Motos A, Rodríguez García J, Antelo Caamaño ML, Domingo Morera JM, Sola Lapeña C, Arroyo JL, Fernández Fuertes F, Zalba Marcos S, Cerdán Rodríguez G, Laso Morales MJ, Bueno Cabrera JL, Chica E, Recasens V, Zabalegui A, Balen E, Urrechaga E, Abad-Gurrumenta A, Quintana Díaz M. PBM: Now more than ever necessary. REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION 2021; 69:S0034-9356(21)00181-X. [PMID: 34563367 PMCID: PMC8486592 DOI: 10.1016/j.redar.2021.03.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/24/2021] [Accepted: 03/30/2021] [Indexed: 01/12/2023]
Affiliation(s)
- J A García-Erce
- Banco de Sangre y Tejidos de Navarra, Servicio Navarro de Salud, Osasunbidea, Pamplona, España; Grupo Español de Rehabilitación Multimodal (GERM), Instituto Aragonés de Ciencias de la Salud, Zaragoza, España; PBM Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, España.
| | - C Jericó
- Servicio de Medicina Interna, Hospital Sant Joan Despí Barcelona, España
| | - A Abad-Motos
- Servicio de Anestesiología, Hospital Universitario Infanta Leonor de Madrid; Grupo Español de Rehabilitación Multimodal (GERM), Instituto Aragonés de Ciencias de la Salud, Zaragoza, España
| | - J Rodríguez García
- Servicio de Medicina Preventiva, Hospital Universitario Son Espases, Palma de Mallorca, España
| | - M L Antelo Caamaño
- Servicio de Apoyo a la Gestión Clínica y Continuidad Asistencial, Complejo Hospitalario de Navarra, Pamplona, España
| | | | | | - J L Arroyo
- Banco de Sangre y Tejidos de Cantabria, Santander, España
| | - F Fernández Fuertes
- Servicio Hematología y Hemoterapia, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, España
| | - S Zalba Marcos
- Servicio de Hematología y Hemoterapia, Hospital García Orcoyen, Estella (Navarra), España
| | - G Cerdán Rodríguez
- Servicio de Anestesiología, Hospital García Orcoyen, Estella (Navarra), España
| | - M J Laso Morales
- Servicio de Anestesiología, Hospital Universitario Parc Taulí, Sabadell, Barcelona, España
| | - J L Bueno Cabrera
- Servicio de Hematología y Hemoterapia, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, España
| | - E Chica
- Servicio de Hematología y Hemoterapia, Hospital Universitario de Getafe, Getafe, España
| | - V Recasens
- Servicio de Hematología y Hemoterapia, Hospital Universitario Miguel Servet, Zaragoza, España
| | - A Zabalegui
- Servicio de Análisis Clínico, Complejo Hospitalario de Navarra, Pamplona, España
| | - E Balen
- Servicio de Cirugía General, Complejo Hospitalario de Navarra, Pamplona, España
| | - E Urrechaga
- Biocruces Bizkaia Research Institute, Bilbao, España
| | - A Abad-Gurrumenta
- Servicio de Anestesiología, Hospital Universitario Infanta Leonor de Madrid; Grupo Español de Rehabilitación Multimodal (GERM), Instituto Aragonés de Ciencias de la Salud, Zaragoza, España
| | - M Quintana Díaz
- Servicio de Cuidados Intensivos, Hospital Universitario La Paz; PBM Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, España
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15
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Calderón-Parra J, Múñez-Rubio E, Fernández-Cruz A, García Sánchez MC, Maderuelo-González E, López-Dosil M, Calvo-Salvador M, Baños-Pérez I, Valle-Falcones M, Ramos-Martínez A. Incidence, clinical presentation, relapses and outcome of SARS-CoV-2 infection in patients treated with anti-CD20 monoclonal antibodies. Clin Infect Dis 2021; 74:1786-1794. [PMID: 34383032 DOI: 10.1093/cid/ciab700] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Our objective is to describe the presentation and complications, including relapses, of COVID-19 in patients under anti-CD20 treatments. In addition, to describe viral clearance and determine the safety of reintroducing anti-CD20 treatment. METHODS Retrospective cohort study of 422 patients under anti-CD20 treatment that was administered from January 1, 2019, to December 31, 2020. RESULTS Fifty-seven patients were diagnosed of COVID-19 (13.5%). 25 patients (43.9%) required hospital admission. 5 patients died (8.8%), 10 developed severe COVID-19 and acute respiratory distress syndrome. Mortality rate was higher among patients infected during the first 3 months following the last dose of anti-CD20 (14.7% vs 0%, p=0,046).The median time of persistence of positive RT-PCR was 22 days (IQR 13-40). Nine out of 52 survivors (17.3%) presented relapses. All of them received the last dose of anti-CD20 less than 6 months before the COVID-19 episode. Clinical presentation was fever (n=8; 88.9%), dyspnea (n=7; 77.8%), cough (n=7; 77.8%), worsening of previous infiltrates (n=5; 55.6%) and new pulmonary infiltrates (n=8; 88.9%). An increase in lymphocytes with CD4/CD8 ratio inversion was observed in all cases. Among the 25 patients who resumed anti-CD20 drug, 4 (16.0%) presented relapses vs 5/28 among those who did not (17.9%), (p=0.857). CONCLUSION Patients infected with SARS-CoV-2 during the 6 months after anti-CD20 administration had a worse outcome and a higher mortality rate. The duration of infectivity may be longer. Relapses of COVID-19 occurred in more than 15% and were associated with viral replication. Once the infection is resolved, it is safe to restart treatment with anti-CD20.
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Affiliation(s)
- Jorge Calderón-Parra
- Infectious Diseases Unit, Department of Internal Medicine. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain).,Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid (Spain)
| | - Elena Múñez-Rubio
- Infectious Diseases Unit, Department of Internal Medicine. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain).,Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid (Spain)
| | - Ana Fernández-Cruz
- Infectious Diseases Unit, Department of Internal Medicine. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain).,Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid (Spain)
| | - María Cristina García Sánchez
- Infectious Diseases Unit, Department of Internal Medicine. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain)
| | - Esther Maderuelo-González
- Infectious Diseases Unit, Department of Internal Medicine. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain)
| | - Marcos López-Dosil
- Department of Microbiology. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain)
| | - Marina Calvo-Salvador
- Department of Pharmacy. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain)
| | - Isolina Baños-Pérez
- Department of Internal Medicine. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain)
| | - Manuel Valle-Falcones
- Department of Neumology. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain)
| | - Antonio Ramos-Martínez
- Infectious Diseases Unit, Department of Internal Medicine. Hospital Universitario Puerta de Hierro, Majadahonda, Madrid (Spain).,Medicine Department. Universidad Autónoma de Madrid, Madrid (Spain)
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16
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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.
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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
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17
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Riches JC. Impact of COVID-19 in patients with lymphoid malignancies. World J Virol 2021; 10:97-110. [PMID: 34079692 PMCID: PMC8152455 DOI: 10.5501/wjv.v10.i3.97] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/08/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
The first cases of coronavirus disease 2019 (COVID-19) were detected in Wuhan, China, in December 2019. Since this time a concerted global effort of research and observational data gathering has meant that a great deal has been learnt about the impact of COVID-19 in patients with lymphoid malignancies. Approximately one-third of patients with lymphoid malignancies who acquire COVID-19 and have it severely enough to require hospital assessment will die from this infection. Major risk factors for a poor outcome are age and co-morbidities, but when these are taken into account lymphoma patients have a slightly greater than 2-fold increased risk compared to the general population. Notably, despite early concerns regarding the particular vulnerability of lymphoma patients due to the immunosuppressive effects of therapy, active treatment, including B-cell depleting agents such as rituximab, do not appear to be associated with an increased risk of a poorer outcome. Indeed, some treatments such as ibrutinib may be beneficial due to their modulation of the potential fatal hyperinflammatory phase of infection. There are risks associated with hemopoietic stem cell transplantation, but the collective experience is that these can be minimized by preventive strategies and that the majority of transplant recipients with COVID-19 infection will survive. Many questions remain including those regarding the outcome of COVID-19 infection in the rarer lymphoid malignancies and the efficacy of COVID-19 vaccines in lymphoma patients. This review aims to discuss these issues and present a summary of the current knowledge of the impact of COVID-19 in lymphoid malignancies.
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Affiliation(s)
- John Charles Riches
- Centre for Haemato-Oncology, Barts Cancer Institute - a Cancer Research UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom
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Furukawa Y, Ando M, Azusawa Y, Kinoshita S, Harada S, Ochiai T, Honda T, Sugimoto K, Tabe Y, Komatsu N, Ando J. Persistent immune thrombocytopaenic purpura associated with SARS-CoV-2 infection. ACTA ACUST UNITED AC 2021; 2:530-533. [PMID: 34226897 PMCID: PMC8242397 DOI: 10.1002/jha2.201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/08/2021] [Indexed: 01/31/2023]
Affiliation(s)
- Yoshiki Furukawa
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Miki Ando
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Yoko Azusawa
- Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University School of Medicine Tokyo Japan
| | - Shintaro Kinoshita
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Sakiko Harada
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Tomonori Ochiai
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Tadahiro Honda
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Kazuya Sugimoto
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Yoko Tabe
- Department of Next Generation Hematological Laboratory Medicine Juntendo University School of Medicine Tokyo Japan
| | - Norio Komatsu
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan
| | - Jun Ando
- Department of Hematology, Juntendo University School of Medicine Tokyo Japan.,Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University School of Medicine Tokyo Japan
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