Brian Imbiakha, Julie M. Sahler, David W. Buchholz, Shahrzad Ezzatpour, Mason Jager, Annette Choi, Isaac A. Monreal, Haewon Byun, Richard Ayomide Adeleke, Justin Leach, Gary Whittaker, Stephen Dewhurst, Brian D. Rudd, Hector C. Aguilar, Avery August

Adaptive immune cells are necessary for SARS-CoV-2–induced pathology

  • Multidisciplinary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic associated with morbidity and mortality in humans. Although disease severity correlates with immune dysregulation, the cellular mechanisms of inflammation and pathogenesis of COVID-19 remain relatively poorly understood. Here, we used mouse-adapted SARS-CoV-2 strain MA10 to investigate the role of adaptive immune cells in disease. We found that while infected wild-type mice lost ~10% weight by 3 to 4 days postinfection, rag −/− mice lacking B and T lymphocytes did not lose weight. Infected lungs at peak weight loss revealed lower pathology scores, fewer neutrophils, and lower interleukin-6 and tumor necrosis factor–α in rag −/− mice. Mice lacking αβ T cells also had less severe weight loss, but adoptive transfer of T and B cells into rag −/− mice did not significantly change the response. Collectively, these findings suggest that while adaptive immune cells are important for clearing SARS-CoV-2 infection, this comes at the expense of increased inflammation and pathology.

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