Loss expansion of SARS-CoV-2 specific immunity is a key risk factor in fatal patients with COVID-19

The dynamic immunological characteristics of COVID-19 patients are essential for clinicians to understand the disease progression. Our data showed that the immune system and function have gradually remodeled and declined with age from 16-91 years old in 25,239 healthy controls. Analyzing the relationship between the number of lymphocytes and age showed that lymphocytes and subsets tended to decline with age significantly, whereas, the number of natural killer cells tended to increase with age significantly. SARS-CoV-2 specific immunity has declined with age in fatal cases. Furthermore, SARS-CoV-2 specific immunity is associated with survival time in fatal cases. The loss expansion of SARS-CoV-2 specific immunity could be expanded in vitro. A concurrent decline in SARS-CoV-2 specific cellular and humoral immunity and prolonged SARS-CoV-2 exposure predicted fatal outcomes. Our findings have provided a basis for further analysis of SARS-CoV-2 specific immunity and understanding the pathogenesis of fatal COVID-19 patients.