The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity
Hamid Bolouri, … , Jane H. Buckner, the Benaroya Research Institute COVID-19 Research Team
Hamid Bolouri, … , Jane H. Buckner, the Benaroya Research Institute COVID-19 Research Team
Published February 1, 2021
Citation Information: J Clin Invest. 2021;131(3):e143648. https://doi.org/10.1172/JCI143648.
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Clinical Research and Public Health

The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity

Abstract

BACKGROUND Despite a rapidly growing body of literature on coronavirus disease 2019 (COVID-19), our understanding of the immune correlates of disease severity, course, and outcome remains poor.METHODS Using mass cytometry, we assessed the immune landscape in longitudinal whole-blood specimens from 59 patients presenting with acute COVID-19 and classified based on maximal disease severity. Hospitalized patients negative for SARS-CoV-2 were used as controls.RESULTS We found that the immune landscape in COVID-19 formed 3 dominant clusters, which correlated with disease severity. Longitudinal analysis identified a pattern of productive innate and adaptive immune responses in individuals who had a moderate disease course, whereas those with severe disease had features suggestive of a protracted and dysregulated immune response. Further, we identified coordinate immune alterations accompanying clinical improvement and decline that were also seen in patients who received IL-6 pathway blockade.CONCLUSION The hospitalized COVID-19 negative cohort allowed us to identify immune alterations that were shared between severe COVID-19 and other critically ill patients. Collectively, our findings indicate that selection of immune interventions should be based in part on disease presentation and early disease trajectory due to the profound differences in the immune response in those with mild to moderate disease and those with the most severe disease.FUNDING Benaroya Family Foundation, the Leonard and Norma Klorfine Foundation, Glenn and Mary Lynn Mounger, and the National Institutes of Health.

Authors

Hamid Bolouri, Cate Speake, David Skibinski, S. Alice Long, Anne M. Hocking, Daniel J. Campbell, Jessica A. Hamerman, Uma Malhotra, Jane H. Buckner, the Benaroya Research Institute COVID-19 Research Team

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Figure 10

Early immune responses to tocilizumab but not convalescent plasma in severe COVID-19.

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Early immune responses to tocilizumab but not convalescent plasma in sev...
(A) Serum CRP in patients receiving tocilizumab (top; n = 7) or convalescent plasma (bottom; n = 7) measured in clinical labs relative to day of treatment. Each line represents an individual patient. (B and C) Change in blood immune populations measured by CyTOF after treatment with tocilizumab (B) or convalescent plasma (C). The fold change in each population for each subject was determined by dividing the percentage of each population in the first posttreatment sample at day +2 or more after treatment with the closest pretreatment sample available as detailed in Supplemental Table 3. All are shown as percentage of CD45+ cells unless otherwise indicated. (D) Plots showing the percent of the indicated populations in tocilizumab-treated patients before and after treatment, using the time points used for analysis in B and Supplemental Table 3. (E) Plots showing all the data points available for tocilizumab-treated patients for the indicated populations shown in D and Supplemental Table 3. Each line represents an individual patient and the color of the line reflects the clinical ordinal score at the time of sampling. *P < 0.05 Wilcoxon matched pairs test, adjusted for multiple comparisons.