The dichotomous and incomplete adaptive immunity in COVID-19

The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is also not well studied. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 49 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 7) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and long-term humoral immunity, assessed by GC response indicators including follicular helper T (T_FH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific T_H1 and CD8⁺ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated T_FH responses; however, the virus-specific T_H1 and CD8⁺ T cells were minimally induced in these patients. These results therefore uncovered the protective immunity in COVID-19 patients and revealed the strikingly dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity, providing important insights into rational design of COVID-19 vaccines.