Abstract
Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro interferon gamma (IFNγ) production correlates with infection risk and mortality. This prospective, monocentric, observational study included adult patients consecutively admitted with radiologic evidence of COVID-19 pneumonia and respiratory failure. MR-proADM and in vitro IFNγ production were measured at T0 (day 1 from admission) and T1 (day 7 from enrollment). One hundred patients were enrolled. Thirty-six percent were females, median age 65 (Q1-Q3 54.5-75) years, and 58% had ≥1 comorbidity. Only 16 patients had received COVID-19 vaccination before hospitalization. At admission, the median PaO2:FiO2 ratio was 241 (157-309) mmHg. In-hospital mortality was 13%. MR-proADM levels differed significantly between deceased and survivors both at T0 (1.41 (1.12-1.77) nmol/L vs. 0.79 (0.63-1.03) nmol/L, p < 0.001) and T1 (1.67 (1.08-1.96) nmol/L vs. 0.66 (0.53-0.95) nmol/L, p < 0.001). In vitro IFNγ production at T0 and T1 did not vary between groups. When only the subset of non-vaccinated patients was considered, both biomarkers at T1 resulted significantly associated with in-hospital mortality. AUROC for MR-proADM at T0 to predict in-hospital mortality was 0.87 (95%CI 0.79-0.94), with the best cut-off point at 1.04 nmol/L (92% sensitivity, 75% specificity and 98% negative predictive value). In patients with COVID-19 pneumonia and different degrees of respiratory failure, MR-proADM at admission and during hospitalization resulted strongly associated with in-hospital mortality. Low in vitro IFNγ production after the first week of hospitalization was associated with mortality in non-vaccinated patients possibly identifying the subgroup characterized by a higher degree of immune suppression.
Keywords: MR-proADM; SARS-CoV-2; interferon gamma; mid-region proadrenomedullin; quantiferon monitor.
【저자키워드】 SARS-CoV-2, MR-proADM, interferon gamma, mid-region proadrenomedullin, quantiferon monitor., 【초록키워드】 COVID-19, coronavirus disease, coronavirus, COVID-19 pneumonia, Biomarker, Respiratory failure, Mortality, Hospitalization, Pneumonia, interferon, Immunocompromised patients, Comorbidity, endothelial damage, in vitro, observational study, adverse outcomes, Predictive value, Coagulopathy, adverse outcome, sensitivity, specificity, Hospital mortality, COVID-19 vaccination, Patient, infection risk, Admission, predict, in-hospital mortality, Immune suppression, MR-proADM, interferon gamma, Evidence, Deceased, Negative predictive value, immune dysregulation, Prognostic factor, evidence of, with infection, dysregulation, best, cut-off point, Non-COVID-19, Enrollment, predictive value), 95%CI, Adult patients, median age, IFNγ, AUROC, cut-off, MONITOR, survivor, females, PaO2:FiO2, enrolled, radiologic, significantly, characterized, cause, groups, subset, were measured, patients with COVID-19, the median, 【제목키워드】 Production, Prospective, Gamma, respiratory, value, with COVID-19,