Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

• Type of Material: Article
• Authors: Kristen W. Cohen, Fred Hutchinson Cancer Research Center; Susanne L. Linderman, Emory University; Zoe Moodie, Fred Hutchinson Cancer Research Center; Julie Czartoski, Fred Hutchinson Cancer Research Center; Lilin Lai, Emory University; Grace Mantus, Emory University; Carson Norwood, Emory University; Lindsay E. Nyhoff, Emory University; Venkata Viswanadh Edara, Emory University; Katherine Floyd, Emory University; Stephen C. De Rosa, Fred Hutchinson Cancer Research Center; Hasan Ahmed, Emory University; Rachael Whaley, Fred Hutchinson Cancer Research Center; Shivan N. Patel, Emory University; Brittany Prigmore, Fred Hutchinson Cancer Research Center; Maria P. Lemos, Fred Hutchinson Cancer Research Center; Carl Davis, Emory University; Sarah Furth, Fred Hutchinson Cancer Research Center; James O'Keefe, Emory University; Mohini P. Gharpure, Emory University; Sivaram Gunisetty, Emory University; Kathy Stephens, Emory University; Rustom Antia, Emory University; Veronika Zarnitsyna, Emory University; David Stephens, Emory University; Srilatha Edupuganti, Emory University; Nadine Rouphael, Emory University; Evan Anderson, Emory University; Aneesh Mehta, Emory University; Jens Wrammert, Emory University; Mehul Suthar, Emory University; Rafi Ahmed, Emory University; M. Juliana McElrath, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2021-07-21
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2021.100354
• Title of Journal or Parent Work: CELL REPORTS MEDICINE
• Volume: 2
• Issue: 7
• Start Page: 100354
• End Page: 100354
• Grant/Funding Information: The research reported in this publication was supported in part by COVID supplements from the National Institute of Allergy and Infectious Diseases and the Office of the Director of the National Institutes of Health under award numbers UM1AI068618-14S1 and UM1AI069481-14S1 (M.J.M.); UM1A057266-S1, U19AI057266-17S1, 1U54CA260563, and U19AI090023 (R. Ahmed); ORIP/OD P51OD011132 (M.S.S.); and T32AI074492 (L.E.N.). This work was also supported by grants from the Oliver S. and Jennie R. Donaldson Charitable Trust (R. Ahmed); Paul G. Allen Family Foundation Award #12931 (M.J.M.); Seattle COVID-19 Cohort Study (Fred Hutchinson Cancer Research Center, M.J.M.); the Joel D. Meyers Endowed Chair (M.J.M.); An Emory EVPHA Synergy Fund award (M.S.S. and J.W.); COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center (M.S.S.); the Center for Childhood Infections and Vaccines (M.S.S. and J.W.); Children’s Healthcare of Atlanta (M.S.S. and J.W.); a Woodruff Health Sciences Center 2020 COVID-19 CURE Award (M.S.S.); and the Vital Projects/Proteus funds. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.
• Keywords: HUMORAL IMMUNITY; Life Sciences & Biomedicine; Cell Biology; Medicine, Research & Experimental; Science & Technology; DURATION; Research & Experimental Medicine
• Research Categories: Health Sciences, Immunology; Biology, Cell

Abstract

Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 COVID-19 patients longitudinally up to 8 months and find durable broad-based immune responses. SARS-CoV-2 spike binding and neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. SARS-CoV-2 infection also boosts antibody titers to SARS-CoV-1 and common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist, which bodes well for a rapid antibody response upon virus re-exposure or vaccination. Virus-specific CD4+ and CD8+ T cells are polyfunctional and maintained with an estimated half-life of 200 days. Interestingly, CD4+ T cell responses equally target several SARS-CoV-2 proteins, whereas the CD8+ T cell responses preferentially target the nucleoprotein, highlighting the potential importance of including the nucleoprotein in future vaccines. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.