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

  • Author(s): Neidleman, Jason
  • Luo, Xiaoyu
  • George, Ashley F
  • McGregor, Matthew
  • Yang, Junkai
  • Yun, Cassandra
  • Murray, Victoria
  • Gill, Gurjot
  • Greene, Warner C
  • Vasquez, Joshua
  • Lee, Sulggi A
  • Ghosn, Eliver
  • Lynch, Kara L
  • Roan, Nadia R
  • et al.

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.

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