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

Cohen, Kristen W.; Linderman, Susanne L.; Moodie, Zoe; Czartoski, Julie; Lai, Lilin; Mantus, Grace; Norwood, Carson; Nyhoff, Lindsay E.; Edara, Venkata Viswanadh; Floyd, Katharine; De Rosa, Stephen C.; Ahmed, Hasan; Whaley, Rachael; Patel, Shivan N.; Prigmore, Brittany; Lemos, Maria P.; Davis, Carl W.; Furth, Sarah; O’Keefe, James; Gharpure, Mohini P.; Gunisetty, Sivaram; Stephens, Kathy A.; Antia, Rustom; Zarnitsyna, Veronika I.; Stephens, David S.; Edupuganti, Srilatha; Rouphael, Nadine; Anderson, Evan J.; Mehta, Aneesh K.; Wrammert, Jens; Suthar, Mehul S.; Ahmed, Rafi; McElrath, M. Juliana

Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. We evaluated 254 COVID-19 patients longitudinally from early infection and for eight months thereafter and found a predominant broad-based immune memory response. SARS-CoV-2 spike binding and neutralizing antibodies exhibited a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. In addition, there was a sustained IgG+ memory B cell response, which bodes well for a rapid antibody response upon virus re-exposure. Polyfunctional virus-specific CD4+ and CD8+ T cells were also generated and maintained with an estimated half-life of 200 days. Interestingly, the CD4+ T cell response equally targeted several SARS-CoV-2 proteins, whereas the CD8+ T cell response preferentially targeted the nucleoprotein, highlighting the importance of including the nucleoprotein as a potential vaccine antigen. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.