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, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Susanne L Linderman, Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.; Zoe Moodie, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Julie Czartoski, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Lilin Lai, Emory University; Grace Mantus, Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Emory University Department of Pediatrics Department of Medicine, Atlanta, GA 30322, USA.; Carson Norwood, Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Emory University Department of Pediatrics Department of Medicine, Atlanta, GA 30322, USA.; Lindsay E Nyhoff, Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Emory University Department of Pediatrics Department of Medicine, Atlanta, GA 30322, USA.; Venkata Viswanadh Edara, Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Emory University Department of Pediatrics Department of Medicine, Atlanta, GA 30322, USA.; Katharine Floyd, Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Emory University Department of Pediatrics Department of Medicine, Atlanta, GA 30322, USA.; Stephen C De Rosa, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Hasan Ahmed, Emory University; Rachael Whaley, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Shivan N Patel, Department of Medicine, Division of Infectious Diseases, Hope Clinic of Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.; Brittany Prigmore, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Maria P Lemos, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; Carl Davis, Emory University; Sarah Furth, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.; James O'Keefe, Emory University; Mohini P Gharpure, Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.; Sivaram Gunisetty, Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.; Kathy A Stephens, No affiliation; Rustom Antia, Department of Biology, Emory University, Atlanta, GA 30322, USA.; Veronika I Zarnitsyna, Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.; David Stephens, Emory University; Srilatha Edupuganti, Emory University; Nadine Rouphael, Emory University; Evan Anderson, Emory University; Aneesh K Mehta, Emory University School of Medicine, Department of Medicine, Atlanta, GA 30322, USA.; Jens Wrammert, Emory University; Mehul Suthar, Emory University; Rafi Ahmed, Emory University; MJ McElrath, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
• Language: English
• Date: 2021-06-18
• Publisher: medRxiv
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2021.04.19.21255739
• Title of Journal or Parent Work: medRxiv
• 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 (MJM); UM1A057266-S1, U19AI057266-17S1, 1U54CA260563, and U19AI090023 (R. Ahmed); ORIP/OD P51OD011132 (MSS); and T32AI074492 (LEN). 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 (MJM); Seattle COVID-19 Cohort Study (Fred Hutchinson Cancer Research Center, MJM); the Joel D. Meyers Endowed Chair (MJM); An Emory EVPHA Synergy Fund award (MSS and JW); COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center (MSS); the Center for Childhood Infections and Vaccines (MSS and JW); Children’s Healthcare of Atlanta (MSS and JW), a Woodruff Health Sciences Center 2020 COVID-19 CURE Award (MSS) 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: RBD; CD8+ T cells; Spike; B cells; SARS-CoV-2; Antibody; CD4+ T cells; Immune memory; COVID-19; Endemic coronaviruses; Kinetics; Neutralization

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 eight 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.