1. Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients.
- Author
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Martín-Sánchez E, Garcés JJ, Maia C, Inogés S, López-Díaz de Cerio A, Carmona-Torre F, Marin-Oto M, Alegre F, Molano E, Fernandez-Alonso M, Perez C, Botta C, Zabaleta A, Alcaide AB, Landecho MF, Rua M, Pérez-Warnisher T, Blanco L, Sarvide S, Vilas-Zornoza A, Alignani D, Moreno C, Pineda I, Sogbe M, Argemi J, Paiva B, and Yuste JR
- Subjects
- Adaptive Immunity, Adult, Aged, Aged, 80 and over, B-Lymphocytes immunology, Biomarkers, COVID-19 pathology, Female, Humans, Immunity, Innate, Lymphopenia immunology, Lymphopenia mortality, Lymphopenia pathology, Male, Middle Aged, Monocytes immunology, Prognosis, SARS-CoV-2, Survival Analysis, Young Adult, COVID-19 immunology, COVID-19 mortality
- 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martín-Sánchez, Garcés, Maia, Inogés, López-Díaz de Cerio, Carmona-Torre, Marin-Oto, Alegre, Molano, Fernandez-Alonso, Perez, Botta, Zabaleta, Alcaide, Landecho, Rua, Pérez-Warnisher, Blanco, Sarvide, Vilas-Zornoza, Alignani, Moreno, Pineda, Sogbe, Argemi, Paiva and Yuste.)
- Published
- 2021
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