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.
Subject(s)
COVID-19/immunology , COVID-19/mortality , 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 AdultSubject(s)
Erythema/microbiology , Klebsiella Infections/complications , Klebsiella pneumoniae , Pneumonia, Bacterial/complications , Vasculitis, Leukocytoclastic, Cutaneous/microbiology , Adult , Biopsy , Cough/microbiology , Erythema/pathology , Female , Fever/microbiology , Humans , Klebsiella Infections/diagnosis , Klebsiella Infections/drug therapy , Leg , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/drug therapy , Vasculitis, Leukocytoclastic, Cutaneous/pathologyABSTRACT
Skin popping refers to the practice of injecting drugs beneath the skin without concern for vascular access. We describe a male HIV seropositive injecting-drug user with chronic cutaneous ulcerations on the legs at sites of skin popping. Treatment with antiretroviral drugs and stanozolol was associated with a striking clinical improvement of the ulcer in two weeks. The mechanism of action, improvement of immune function by the antiretroviral treatment or activity of stanozolol on collagen and transforming growth factor-beta1 synthesis, remains unknown.
