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.
【저자키워드】 COVID-19, SARS-CoV-2, Biomarkers, outcome, flow cytometry, lymphopenia, survival, 【초록키워드】 coronavirus disease, Neutrophils, Monocytes, Coronavirus disease 2019, immune response, Biomarker, SARS-COV-2 infection, neutrophil, Infection, Comorbidities, severe acute respiratory syndrome coronavirus-2, severe acute respiratory syndrome Coronavirus, immune, monocyte, Peripheral blood, Non-classical monocytes, infections, immune responses, Patient, age, respiratory, patients, COVID-19 patients, B-cell, Plasma cells, Coronavirus-2, Multivariate analysis, Analysis, severe disease, B-cells, COVID-19 patient, Prognostic factor, Predictive, risk of death, acute respiratory syndrome, acute respiratory syndrome coronavirus, healthy donors, profile, acute respiratory syndrome coronavirus-2, cohorts, circulating, immunotype, peripheral blood samples, significantly lower, Unsupervised clustering, feature, independent, healthy donor, identify, significantly, conducted, reduced, characterized, presenting, multidimensional, non-classical monocyte, percentage,