Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients
Keywords: 
COVID-19
SARS-CoV-2
Biomarkers
Flow cytometry
Lymphopenia
Outcome
Survival
Issue Date: 
2021
Publisher: 
Frontiers Research Foundation
ISSN: 
1664-3224
Note: 
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Citation: 
Martín-Sánchez, E. (Esperanza); Garcés-Latre, J.J. (Juan José); Maia, C. (Catarina); et al. "Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients". Frontiers in immunology. (12), 2021, 659018
Abstract
Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.

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