Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19

Author:

Hueso Thomas12ORCID,Pouderoux Cécile3,Péré Hélène45,Beaumont Anne-Lise6,Raillon Laure-Anne3,Ader Florence37,Chatenoud Lucienne89,Eshagh Déborah10,Szwebel Tali-Anne10,Martinot Martin11ORCID,Camou Fabrice12ORCID,Crickx Etienne13ORCID,Michel Marc13,Mahevas Matthieu13,Boutboul David1415,Azoulay Elie16,Joseph Adrien16ORCID,Hermine Olivier1718,Rouzaud Claire19,Faguer Stanislas20ORCID,Petua Philippe21ORCID,Pommeret Fanny22ORCID,Clerc Sébastien23,Planquette Benjamin23,Merabet Fatiha24,London Jonathan25ORCID,Zeller Valérie25,Ghez David1,Veyer David626ORCID,Ouedrani Amani89,Gallian Pierre2728,Pacanowski Jérôme6,Mékinian Arsène29ORCID,Garnier Marc30ORCID,Pirenne France2831,Tiberghien Pierre2832ORCID,Lacombe Karine633ORCID

Affiliation:

1. Hematology Department, Gustave Roussy, Villejuif, France;

2. Paris-Sud University, Paris-Saclay University, Le Kremlin-Bicêtre, France;

3. Infectious Diseases Department, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France;

4. Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;

5. Université de Paris, INSERM U970, Paris Cardiovascular Research Center, Paris, France;

6. Infectious Diseases Department, Saint-Antoine Hospital, AP-HP, Paris, France;

7. Université Claude Bernard Lyon 1, INSERM 1111, Centre International de Recherche en Infectiologie UCBL1, Lyon, France;

8. Paris University, Institut Necker-Enfants Malades, CNRS UMR 8253 and INSERM UMR1151, Hôpital Necker-Enfants Malades, Paris, France;

9. Laboratoire d’immunologie Biologique, Hôpital Necker-Enfants Malades, Paris, France;

10. Internal Medicine Department, Cochin Hospital, AP-HP, Paris, France;

11. Infectious Diseases Department, Hôpitaux Civils de Colmar, Colmar, France;

12. Intensive Care and Infectious Diseases Department, Saint-André Hospital, Bordeaux, France;

13. Internal Medicine Department, Centre National de Référence des Cytopénies Auto-Immunes de l’Adulte, Centre Hospitalier Universitaire Henri-Mondor, AP-HP, Université Paris Est Créteil, Créteil, France;

14. Department of Clinical Immunology, Hôpital Saint-Louis Hospital, AP-HP, Paris, France;

15. Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Imagine Institute, INSERM, Paris, France;

16. Intensive Care Unit, Hôpital Saint-Louis, AP-HP, Paris Diderot Sorbonne University, Paris, France;

17. Laboratory of Molecular Mechanisms of Hematologic Disorders and Therapeutic Implications, Imagine Institute, Paris, France;

18. Department of Clinical Hematology, Hôpital Necker-Enfants-Malades, Paris, France;

19. Infectious Diseases Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France;

20. Département de Néphrologie et Transplantation d’Organes, Centre de Référence des Maladies Rénales Rares, Centre Hospitalier Universitaire de Toulouse, Toulouse, France;

21. Intensive Care Unit, Tarbes Hospital, Tarbes, France;

22. Oncology Department, Gustave Roussy, Villejuif, France;

23. Respiratory Diseases Intensive Care Unit, Hôpital Européen Georges Pompidou, AP-HP, Paris, France;

24. Hematology Department, Versailles Hospital, Versailles, France;

25. Department of Internal Medicine and Infectious Diseases, Hôpital Diaconesses Croix Saint-Simon, Paris, France;

26. Université de Paris and Sorbonne Université, INSERM, Centre de Recherche des Cordeliers, Functional Genomics of Solid Tumors (FunGeST), Paris, France;

27. Unité des Virus Émergents (UVE) (Aix-Marseille Université-Institut de recherche pour le développement 190-INSERM 1207-IHU Méditerranée Infection), Marseille, France;

28. Etablissement Français du Sang, La Plaine St-Denis, France;

29. Sorbonne Université, Internal Medicine Department, Inflammation-Immunopathology-Biotherapy Department (DMU i3D), Saint-Antoine Hospital, AP-HP, Paris, France;

30. Sorbonne University, GRC 29, AP-HP, DMU DREAM, Anesthesiology and Intensive Care Department, Saint-Antoine Hospital, AP-HP, Paris, France;

31. Institut Mondor de Recherche Biomédicale, Unité 955, Equipe 2: Transfusion et Maladies du Globule Rouge, INSERM, Etablissement Français du Sang, Université Paris-Est Créteil, Créteil, France;

32. UMR 1098 RIGHT INSERM Université de Franche-Comté Etablissement Français du Sang, Besançon, France; and

33. Sorbonne University, INSERM IPLESP, AP-HP, Paris, France

Abstract

Abstract Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti–SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference25 articles.

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