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

Knowledge of the dynamic immunological characteristics of patients with coronavirus disease 2019 (COVID-19) is essential for clinicians to understand the progression of the disease. Our data showed that the immune system and function gradually remodeled and declined with age, starting from age 16 until age 91 in 25,239 healthy controls. An analysis of the relationship between the number of lymphocytes and age revealed that the lymphocyte and subset counts tended to decline with age significantly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity declined with age and was associated with survival time in fatal cases. Loss in the expansion of SARS-CoV-2-specific immunity could be expanded in vitro . The concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and prolonged SARS-CoV-2 exposure predicted fatal outcomes. Our findings provide a basis for further analysis of SARS-CoV-2-specific immunity and understanding of the pathogenesis of fatal COVID-19 cases.

Highlights

• The immune system and function gradually remodeled and declined with age .

• SARS-CoV-2-specific immunity declined with age in fatal cases .

• SARS-CoV-2-specific immunity was associated with survival time in fatal cases .

• Loss in the expansion of SARS-CoV-2-specific immunity could be expanded in vitro .

• A concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and prolonged SARS-CoV-2 exposure predicted fatal outcomes .