HIGHLIGHTSd Cross-sectional study of 44 hospitalized COVID-19 patients d RBD-specific IgG responses detectable in all patients 6 days after PCR confirmation d Neutralizing titers are detectable in all patients 6 days after PCR confirmation d RBD-specific IgG titers correlate with the neutralizing potency

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.

28SARS-CoV-2 is currently causing a devastating pandemic and there is a pressing need to 29 understand the dynamics, specificity, and neutralizing potency of the humoral immune response 30 during acute infection. Herein, we report the dynamics of antibody responses to the receptor-31 binding domain (RBD) of the spike protein and virus neutralization activity in 44 COVID-19 32 patients. RBD-specific IgG responses were detectable in all patients 6 days after PCR 33 confirmation. Using a clinical isolate of SARS-CoV-2, neutralizing antibody titers were also 34 detectable in all patients 6 days after PCR confirmation. The magnitude of RBD-specific IgG 35 binding titers correlated strongly with viral neutralization. In a clinical setting, the initial analysis of 36 the dynamics of RBD-specific IgG titers was corroborated in a larger cohort of PCR-confirmed 37 patients (n=231). These findings have important implications for our understanding of protective 38 immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of 39 much-needed vaccines. 40 41