Research ArticleCORONAVIRUS

Comprehensive mapping of immune perturbations associated with severe COVID-19

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Science Immunology  15 Jul 2020:
Vol. 5, Issue 49, eabd7114
DOI: 10.1126/sciimmunol.abd7114

Immune system fallout in severe COVID-19

The immune response to SARS-CoV-2 infection ranges from modest responses after asymptomatic infection all the way to life-threatening cytokine storms in severe COVID-19. To capture the full range of immunophenotypic changes elicited in white blood cells from infected patients, Kuri-Cervantes et al. used multiparametric flow cytometry and antibody gene sequencing to compare peripheral blood samples from patients with COVID-19 with different degrees of severity, recovered individuals, and healthy donors. Severe COVID-19 was associated with perturbation of multiple lymphocyte and myeloid subsets and notable oligoclonal expansions of plasmablasts. By contributing to the establishment of an immune atlas defining the full range of perturbations in severe COVID-19, this study will guide future efforts to detect early warning signs of impending immune decompensation in recently diagnosed patients with COVID-19.


Although critical illness has been associated with SARS-CoV-2–induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2–infected and –recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2–recovered or moderate severity patients. We found the neutrophil-to-lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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