T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19

Author:

Zonozi Reza1ORCID,Walters Lucy C.234ORCID,Shulkin Aaron2ORCID,Naranbhai Vivek567ORCID,Nithagon Pravarut1ORCID,Sauvage Gabriel1ORCID,Kaeske Clarety2,Cosgrove Katherine1ORCID,Nathan Anusha28,Tano-Menka Rhoda2,Gayton Alton C.2ORCID,Getz Matthew A.2ORCID,Senjobe Fernando2ORCID,Worrall Daniel2ORCID,Iafrate A. John9ORCID,Fromson Caroline10,Montesi Sydney B.10,Rao Deepak A.11ORCID,Sparks Jeffrey A.11ORCID,Wallace Zachary S.12ORCID,Farmer Jocelyn R.213ORCID,Walker Bruce D.26141516ORCID,Charles Richelle C.17ORCID,Laliberte Karen1ORCID,Niles John L.1ORCID,Gaiha Gaurav D.218ORCID

Affiliation:

1. Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Boston, MA 02114, USA.

2. Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.

3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

4. Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.

5. Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.

6. Center for the AIDS Programme of Research in South Africa, Durban 4001, South Africa.

7. Monash University, Melbourne, VIC 3022, Australia.

8. Program in Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, Boston, MA 02115, USA.

9. Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.

10. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

11. Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

12. Division of Rheumatology, Massachusetts General Hospital, Boston, MA 02114, USA.

13. Division of Allergy and Inflammation, Beth Israel Lahey Health, Boston, MA 02215, USA.

14. Broad Institute, Cambridge, MA 02142, USA.

15. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

16. Institute for Medical Engineering and Science and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

17. Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.

18. Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract

Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease and mortality from coronavirus disease 2019 (COVID-19), but the immune responses and clinical outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have yet to be fully defined. Here, we evaluate the cellular immune responses after both SARS-CoV-2 infection and vaccination in patients receiving the anti-CD20 therapy rituximab (RTX) and those with low B cell counts due to common variable immune deficiency (CVID) disease. Assessment of effector and memory CD4 + and CD8 + T cell responses to SARS-CoV-2 revealed elevated reactivity and proliferative capacity after both infection and vaccination in B cell–deficient individuals, particularly within the CD8 + T cell compartment, in comparison with healthy controls. Evaluation of clinical outcomes demonstrates that vaccination of RTX-treated individuals was associated with about 4.8-fold reduced odds of moderate or severe COVID-19 in the absence of vaccine-induced antibodies. Analysis of T cell differentiation demonstrates that RTX administration increases the relative frequency of naïve CD8 + T cells, potentially by depletion of CD8 + CD20 dim T cells, which are primarily of an effector memory or terminal effector memory (TEMRA) phenotype. However, this also leads to a reduction in preexisting antiviral T cell immunity. Collectively, these data indicate that individuals with B cell deficiencies have enhanced T cell immunity after both SARS-CoV-2 infection and vaccination that potentially accounts for reduced hospitalization and severe disease from subsequent SARS-CoV-2 infection.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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