Molano, E. (Elvira)

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    Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients
    (Frontiers Research Foundation, 2021) Landecho, M.F. (Manuel F.); Zabaleta, A. (Aintzane); Vilas, A. (Amaia); Perez, C. (Cristina); Maia, C. (Catarina); Alegre, F. (Félix); Rua, M. (Marta); Sarvide, S. (Sarai); Lopez-Diaz-de-Cerio, A. (Ascensión); Marín-Oto, M. (Marta); Pineda, Í. (Íñigo); Molano, E. (Elvira); Fernández-Alonso, M. (Miriam); Carmona-Torre, F. (Francisco de A.); Botta, C. (Cirino); Inoges, S. (Susana); Garcés-Latre, J.J. (Juan José); Alcaide, A.B. (Ana Belén); Alignani, D. (Diego); Paiva, B. (Bruno); Yuste, J.R. (José Ramón); Martín-Sánchez, E. (Esperanza); Perez-Warnisher, M.T. (María Teresa); Argemí, J. (Josepmaria); Sogbe, M. (Miguel); Blanco-Fernández, L. (Laura); Moreno, C. (Cristina)
    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.