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Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection.
Graham, Jessica B; Swarts, Jessica L; Leist, Sarah R; Schäfer, Alexandra; Menachery, Vineet D; Gralinski, Lisa E; Jeng, Sophia; Miller, Darla R; Mooney, Michael A; McWeeney, Shannon K; Ferris, Martin T; de Villena, Fernando Pardo-Manuel; Heise, Mark T; Baric, Ralph S; Lund, Jennifer M.
  • Graham JB; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
  • Swarts JL; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Menachery VD; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Gralinski LE; Department of Microbiology and Immunology, University of Texas Medical Center, Galveston, TX.
  • Jeng S; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Miller DR; OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR.
  • Mooney MA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR.
  • McWeeney SK; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Ferris MT; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • de Villena FP; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR.
  • Heise MT; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR.
  • Baric RS; OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR.
  • Lund JM; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR.
bioRxiv ; 2020 Sep 21.
Article in English | MEDLINE | ID: covidwho-807105
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ABSTRACT
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.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines Language: English Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines Language: English Year: 2020 Document Type: Article