Dexamethasone chronotherapy of COVID-19 patients admitted to intensive care unit: an exploratory study

Background: Dexamethasone has been demonstrated to be a potential treatment approach preventing COVID-19 related fatalities by managing the cytokine release storm (CRS). The expression of the inflammatory mediators involved in the CRS is regulated by the circadian biology of the immune response and it peaks during the evening. Accordingly, it has been hypothesized that the administration of anti-inflammatory medications in the evening could help better manage the CRS. Therefore, we investigated the association between dexamethasone administration time and COVID-19 mortality. Methods: A retrospective cohort study was conducted using electronic health records of COVID-19 patients hospitalized in the State of Qatar between March 2020 and April 2021. The exposure group received dexamethasone between 16:00 h and 04:00 h, while the control group received dexamethasone between 04:00 h and 16:00 h. Results: From the 875 COVID-19 patients included in the study, 161 received dexamethasone treatments between 16:00 h and 04:00 h while 714 received it between 04:00 h and 16:00 h. After adjusting for confounding variables, dexamethasone given between 16:00 h and 04:00 h was associated with lower odds of COVID-19 mortality (OR: 0.22, CI 95%: 0.06, 0.84). Conclusion: Dexamethasone administration tailored to the circadian rhythm was associated with lower odds of mortality in hospitalized COVID-19 patients.