Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients. Scientific Publication

May 3, 2021 | Magazine: Frontiers in Immunology

Esperanza Martín-Sánchez 1 2 3 4 , Juan José Garcés 1 2 3 4 , Catarina Maia 1 2 3 4 , Susana Inogés 4 5 6 , Ascensión López-Díaz de Cerio 4 5 6 , Francisco Carmona-Torre 7 8 9 , Marta Marin-Oto 10 , Félix Alegre 7 , Elvira Molano 11 , Mirian Fernandez-Alonso 9 12 , Cristina Perez 2 3 4 , Cirino Botta 13 , Aintzane Zabaleta 1 2 3 4 , Ana Belen Alcaide 10 , Manuel F Landecho 7 , Marta Rua 12 , Teresa Pérez-Warnisher 14 , Laura Blanco 3 4 , Sarai Sarvide 2 3 4 , Amaia Vilas-Zornoza 2 3 4 , Diego Alignani 1 2 3 4 , Cristina Moreno 1 3 4 , Iñigo Pineda 7 , Miguel Sogbe 7 , Josepmaria Argemi 7 , Bruno Paiva 1 2 3 4 , José Ramón Yuste 7 8 9

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.

CITATION Front Immunol. 2021 May 3;12:659018. doi: 10.3389/fimmu.2021.659018. eCollection 2021.

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