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

Jason Neidleman; Xiaoyu Luo; Ashley F George; Matthew McGregor; Junkai Yang; Cassandra Yun; Victoria Murray; Gurjot Gill; Warner C Greene; Joshua Vasquez; Sulggi A Lee; Eliver Ghosn; Kara L Lynch; Nadia R Roan

doi:10.1016/j.celrep.2021.109414

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

Cell Rep. 2021 Jul 20;36(3):109414. doi: 10.1016/j.celrep.2021.109414. Epub 2021 Jun 29.

Authors

Jason Neidleman¹, Xiaoyu Luo², Ashley F George¹, Matthew McGregor¹, Junkai Yang³, Cassandra Yun⁴, Victoria Murray⁵, Gurjot Gill⁵, Warner C Greene⁶, Joshua Vasquez⁷, Sulggi A Lee⁵, Eliver Ghosn⁸, Kara L Lynch⁹, Nadia R Roan¹⁰

Affiliations

¹ Gladstone Institutes, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, CA 94158, USA.
² Gladstone Institutes, San Francisco, CA 94158, USA.
³ Deptartments of Medicine and Pediatrics, Lowance Center for Human Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
⁴ Department of Laboratory Medicine, University of California, San Francisco, CA 94110, USA.
⁵ Zuckerberg San Francisco General Hospital and the University of California, San Francisco, CA 94110, USA.
⁶ Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, CA 94110, USA.
⁷ Department of Medicine, University of California, San Francisco, CA 94110, USA.
⁸ Deptartments of Medicine and Pediatrics, Lowance Center for Human Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA. Electronic address: eliver.ghosn@emory.edu.
⁹ Department of Laboratory Medicine, University of California, San Francisco, CA 94110, USA. Electronic address: kara.lynch@ucsf.edu.
¹⁰ Gladstone Institutes, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, CA 94158, USA. Electronic address: nadia.roan@gladstone.ucsf.edu.

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.

Keywords: CD127; COVID-19; CXCR4; SARS-CoV-2; T cells; lung.

Abstract

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