Impairment of T cells’ antiviral and anti-inflammation immunities dominates death from COVID-19

Abstract

Clarifying key factors dominating the immune heterogeneity from non-survivors to survivors is crucial for therapeutics and vaccine developments against COVID-19. The main difficulty is to quantitatively analyze the multi-level clinical data of viral dynamics, immune response, and tissue damages. Here, we adopt top-down modeling to quantify key functional aspects and their dynamical interplays in the virus-immune system battle, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses demonstrates T cells' dominant role in the virus clearance relative to antibodies, especially for mild patients(96.5%). Moreover, the anti-inflammatory responses, namely cytokine inhibition rate and tissue repair rate also have positive correlations with T cell number, and are significantly suppressed in non-survivors. Simulations show that impaired immune functions of T cells leads to greater inflammation (thus dominates the death), explaining the monotonous increase of COVID-19 mortality with age and higher mortality for males. We conclude that T cells play the role of crucial immunity that saves the death from COVID-19, which points out a new direction to advance current prevention and treatment by incorporating the vaccines, drugs and health care activities that aim to improve T cells' number and functions.