RT Journal Article
SR Electronic
T1 Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.21.306837
DO 10.1101/2020.09.21.306837
A1 Jessica B. Graham
A1 Jessica L. Swarts
A1 Sarah R. Leist
A1 Alexandra Schäfer
A1 Vineet D. Menachery
A1 Lisa E. Gralinski
A1 Sophia Jeng
A1 Darla R. Miller
A1 Michael A. Mooney
A1 Shannon K. McWeeney
A1 Martin T. Ferris
A1 Fernando Pardo-Manuel de Villena
A1 Mark T. Heise
A1 Ralph S. Baric
A1 Jennifer M. Lund
YR 2020
UL http://biorxiv.org/content/early/2020/09/21/2020.09.21.306837.abstract
AB The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans, from asymptomatic or mild disease to severe disease that can require mechanical ventilation. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from indiviuals that go on to become infected with SARS-CoV-2. Here, we utilized data from a screen of genetically diverse mice from the Collaborative Cross (CC) infected with SARS-CoV to determine whether circulating baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Further, early control of virus in the lung correlates with an increased abundance of activated CD4 and CD8 T cells and regulatory T cells prior to infections across strains. A basal propensity of T cells to express IFNg and IL17 over TNFa also correlated with early viral control. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. While future studies of human samples prior to infection with SARS-CoV-2 are required, our studies in mice with SARS-CoV serve as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.Summary We used a screen of genetically diverse mice from the Collaborative Cross infected with mouse-adapted SARS-CoV in combination with comprehensive pre-infection immunophenotyping to identify baseline circulating immune correlates of severe virologic and clinical outcomes upon SARS-CoV infection.Competing Interest StatementThe authors have declared no competing interest.