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

Martín-Sánchez, Esperanza ; Garcés, Juan José ; Maia, Catarina ; Inogés, Susana ; López-Díaz de Cerio, Ascensión ; Carmona-Torre, Francisco ; Marin-Oto, Marta ; Alegre, Félix ; Molano, Elvira ; Fernández-Alonso, Mirian ; Pérez, Cristina ; Botta, Cirino ; Zabaleta, Aintzane ; Alcaide, Ana Belén ; Landecho, Manuel F. ; Rua, Marta ; Pérez-Warnisher, Teresa ; Blanco, Laura ; Sarvide, Sarai ; Vilas-Zornoza, Amaia ; Alignani, Diego ; Moreno, Cristina ; Pineda, Iñigo ; Sogbe, Miguel ; Argemi, Josepmaria ; Paiva, Bruno ; Yuste, José Ramón

Resumen: 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.

Idioma: Inglés

DOI: 10.3389/fimmu.2021.659018

Año: 2021

Publicado en: Frontiers in Immunology 12 (2021), 659018 [13 pp.]
ISSN: 1664-3224

Factor impacto JCR: 8.787 (2021)

Categ. JCR: IMMUNOLOGY rank: 35 / 162 = 0.216 (2021) - Q1 - T1

Factor impacto CITESCORE: 9.8 - Immunology and Microbiology (Q1) - Medicine (Q1)

Factor impacto SCIMAGO: 2.331 - Immunology and Allergy (Q1) - Immunology (Q1)

Tipo y forma: Article (Published version)