Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19

摘要

Although T?cells are likely players in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity, little is known about the phenotypic features of SARS-CoV-2-specific T?cells associated with recovery from severe coronavirus disease 2019 (COVID-19). We analyze T?cells from 34 individuals with COVID-19 with severity ranging from mild (outpatient) to critical, culminating in death. Relative to individuals who succumbed, individuals who recovered from severe COVID-19 harbor elevated and increasing numbers of SARS-CoV-2-specific T?cells capable of homeostatic proliferation. In contrast, fatal COVID-19 cases display elevated numbers of SARS-CoV-2-specific regulatory T?cells and a time-dependent escalation in activated bystander CXCR4 T?cells, as assessed by longitudinal sampling. Together with the demonstration of increased proportions of inflammatory CXCR4 T?cells in the lungs of individuals with severe COVID-19, these results support a model where lung-homing T?cells activated through bystander effects contribute to immunopathology, whereas a robust, non-suppressive SARS-CoV-2-specific T?cell response limits pathogenesis and promotes recovery from severe COVID-19.