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

• Type of Material: Article
• Authors: Jason Neidleman, Gladstone Institutes, San Francisco, CA, USA.; Xiaoyu Luo, Gladstone Institutes, San Francisco, CA, USA.; Ashley F. George, Gladstone Institutes, San Francisco, CA, USA.; Matthew McGregor, Gladstone Institutes, San Francisco, CA, USA.; Junkai Yang, Department of Medicine, Lowance Center for Human Immunology, Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Cassandra Yun, Department of Laboratory Medicine, University of California, San Francisco, CA USA.; Victoria Murray, Zuckerberg San Francisco General Hospital and the University of California, San Francisco, CA, USA.; Gurjot Gill, Zuckerberg San Francisco General Hospital and the University of California, San Francisco, CA, USA.; Warner C. Greene, Gladstone Institutes, San Francisco, CA, USA.; Joshua Vasquez, Department of Medicine, University of California, San Francisco, CA, USA.; Sulggi Lee, Zuckerberg San Francisco General Hospital and the University of California, San Francisco, CA, USA.; Eliver Ghosn, Emory University; Kara Lynch, Department of Laboratory Medicine, University of California, San Francisco, CA USA.; Nadia R. Roan, Gladstone Institutes, San Francisco, CA, USA.
• Language: English
• Date: 2021-02-05
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2021.01.22.21250054
• Title of Journal or Parent Work: medRxiv
• Grant/Funding Information: Awards #2164 (N.R.R.), #2208 (N.R.R.), and #2160 (to S.L.) from Fast Grants, a part of Emergent Ventures at the Mercatus Center, George Mason University; and NIH R01 AI123126-05S1 (E.G.).; This work was supported by the Van Auken Private Foundation and David Henke (N.R.R.);; We acknowledge the NIH DRC Center Grant P30 DK063720 and the S10 1S10OD018040-01 for use of the CyTOF instrument.; Program for Breakthrough Biomedical Research (N.R.R., E.G., S.L., J.V., which is partly funded by the Sandler Foundation;; philanthropic funds donated to Gladstone Institutes by The Roddenberry Foundation and individual donors devoted to COVID-19 research (N.R.R.)
• Keywords: Recovery; SARS-CoV-2; Laboratory medicine; Pediatrics; T cells; Prediction; Urology & Nephrology
• Research Categories: Health Sciences, Epidemiology; Biology, Cell; Health Sciences, Public Health; Health Sciences, Health Care Management

Abstract

Although T cells are likely players in SARS-CoV-2 immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe COVID-19. We analyzed T cells from longitudinal specimens of 34 COVID-19 patients with severities ranging from mild (outpatient) to critical culminating in death. Relative to patients that succumbed, individuals that recovered from severe COVID-19 harbored elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 displayed elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of severe COVID-19 patients, these results support a model whereby lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.