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

• Type of Material: Article
• Authors: Jason Neidleman, Gladstone Institutes; Xiaoyu Luo, Gladstone Institutes; Ashley F. George, Gladstone Institutes; Matthew McGregor, Gladstone Institutes; Junkai Yang, Emory University; Cassandra Yun, University of California San Francisco; Victoria Murray, University of California San Francisco; Gurjot Gill, University of California San Francisco; Warner C. Greene, Gladstone Institutes; Joshua Vasquez, University of California San Francisco; Sulggi A. Lee, University of California San Francisco; Eliver Ghosn, Emory University; Kara L. Lynch, University of California San Francisco; Nadia R. Roan, Gladstone Institutes
• Language: English
• Date: 2021-07-21
• Publisher: CELL PRESS
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2021.109414
• Title of Journal or Parent Work: CELL REPORTS
• Volume: 36
• Issue: 3
• Start Page: 109414
• End Page: 109414
• Grant/Funding Information: This work was supported by the Van Auken Private Foundation, David Henke, and Pamela and Edward Taft (to N.R.R.); the Program for Breakthrough Biomedical Research (to N.R.R., E.G., S.A.L., and J.V.), which is partly funded by the Sandler Foundation; philanthropic funds to Gladstone by The Roddenberry Foundation (to N.R.R.); awards 2164 (to N.R.R.), 2208 (to N.R.R.), and 2160 (to S.A.L.) from Fast Grants; and NIH R01 AI123126-05S1 (to E.G.). We acknowledge NIH DRC Center grant P30 DK063720 and S10 1S10OD018040 for use of CyTOF. We thank S. Tamaki, T. Peech, and C. Bispo for CyTOF assistance; H. Hartig for recruitment; N. Lazarus and E. Butcher for Act1; J. Carroll for graphics; F. Chanut for editorial assistance; and R. Givens for administrative assistance.
• Keywords: LUNG; Cell Biology; INFECTION; SPIKE; DISEASE SEVERITY; Life Sciences & Biomedicine; Science & Technology; CD8(+); IMMUNITY
• Research Categories: Health Sciences, Immunology; Biology, Cell

Abstract

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.