Steroid initiation timing and outcome of coronavirus disease 2019 patients: A multicenter, retrospective, observational study

Objectives: Dexamethasone’s (DEXA) beneficial effect on survival when administered to critically ill patients with coronavirus disease 2019 (COVID-19) has been documented in randomized trials and meta-analyses. Here, we conducted this study to clarify the association between time from COVID-19 onset to steroid initiation and mortality and to examine the factors underlying these results. Methods: This was a multicenter, retrospective, observational study of patients enrolled in the Japanese COVID-19 Registry from January 1, 2020, to April 30, 2021. Demographic and clinical factors were extracted from patient records. Patients diagnosed with COVID-19 using polymerase chain reaction, loop-mediated isothermal amplification, or antigen tests were included. Patients aged <18 years, pregnant, with a history of chronic obstructive pulmonary disease or steroid or immunosuppressive drug use, transferred to another hospital, or with an unknown symptom onset were excluded. Results and Conclusion: The analysis included 3692 patients (men, 64.1%; median age, 68 years). Unadjusted comparisons of mortality groups showed significant differences in demographic and clinical characteristics; patients with early dexamethasone initiation had more risk factors for severe disease and significantly higher mortality than did patients with delayed initiation (13.3% vs 7.9%, p < .001). No significant differences were found in intubation rates or duration, length of hospitalization, or time from intubation to death. Multivariate analyses showed significant differences from symptom onset to steroid administration, with an adjusted odds ratio of 0.7 (p = .05) for patients who received steroids for ≥8 days. Early steroid administration to COVID-19 patients was associated with increased mortality, suggesting a subset with early severe disease and high mortality and/or adverse effects of early steroid administration.