Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells
Kristen W. Cohen, Susanne L. Linderman, Zoe Moodie, Julie Czartoski, Lilin Lai, Grace Mantus, Carson Norwood, Lindsay E. Nyhoff, Venkata Viswanadh Edara, Katharine Floyd, Stephen C. De Rosa, Hasan Ahmed, Rachael E. Whaley, Shivan Patel, Brittany Prigmore, Maria P. Lemos, Carl W. Davis, Sarah Furth, James B. O’Keefe, Mohini P. Gharpure, Sivaram Gunisetty, Kathy Stephens, Rustom Antia, Veronika I. Zarnitsyna, David S. Stephens, Srilatha Edupuganti, Nadine Rouphael, Evan J. Anderson, Aneesh K. Mehta, Jens Wrammert, Mehul S. Suthar, Rafi Ahmed, M. Juliana McElrath
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.