Immunity
Volume 54, Issue 7, 13 July 2021, Pages 1578-1593.e5
Journal home page for Immunity

Article
Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

https://doi.org/10.1016/j.immuni.2021.05.002Get rights and content
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Highlights

  • GM-CSF+ T cells are a hallmark of severe respiratory syndrome independent of pathogen

  • T cell exhaustion and impaired early antiviral response are unique in severe COVID-19

  • Circulating CD56+T cell frequencies serve as a predictive biomarker for severe COVID-19

  • HLA profile links COVID-19 immunopathology to impaired virus recognition

Summary

Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2 peptides to the patients’ HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Toward clinical translation, circulating CD56+T cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19.

Keywords

COVID-19
SARS-CoV-2
high-dimensional single cell analysis
immune profiling
immunophenotyping
spectral flow cytometry
biomarker
GM-CSF
HLA typing
peptide binding strength

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These authors contributed equally

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These authors contributed equally

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