Immuno-Modulatory Effects of Dexamethasone in Severe COVID-19-A Swedish Cohort Study

Sana Asif; Robert Frithiof; Anders Larsson; Stephanie Franzén; Sara Bülow Anderberg; Bjarne Kristensen; Michael Hultström; Miklos Lipcsey

doi:10.3390/biomedicines11010164

Immuno-Modulatory Effects of Dexamethasone in Severe COVID-19-A Swedish Cohort Study

Biomedicines. 2023 Jan 9;11(1):164. doi: 10.3390/biomedicines11010164.

Authors

Sana Asif¹, Robert Frithiof¹, Anders Larsson², Stephanie Franzén¹, Sara Bülow Anderberg¹, Bjarne Kristensen³, Michael Hultström^{1

4}, Miklos Lipcsey^{1

5}

Affiliations

¹ Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
² Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden.
³ Thermo Fisher Scientific, DK-84 3450 Alleröd, Denmark.
⁴ Unit for Integrative Physiology, Department of Medical Cell Biology, Uppsala University, 751 85 Uppsala, Sweden.
⁵ Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden.

Abstract

Dexamethasone (Dex) has been shown to decrease mortality in severe coronavirus disease 2019 (COVID-19), but the mechanism is not fully elucidated. We aimed to investigate the physiological and immunological effects associated with Dex administration in patients admitted to intensive care with severe COVID-19. A total of 216 adult COVID-19 patients were included-102 (47%) received Dex, 6 mg/day for 10 days, and 114 (53%) did not. Standard laboratory parameters, plasma expression of cytokines, endothelial markers, immunoglobulin (Ig) IgA, IgM, and IgG against SARS-CoV-2 were analyzed post-admission to intensive care. Patients treated with Dex had higher blood glucose but lower blood lactate, plasma cortisol, IgA, IgM, IgG, D-dimer, cytokines, syndecan-1, and E-selectin and received less organ support than those who did not receive Dex (Without-Dex). There was an association between Dex treatment and IL-17A, macrophage inflammatory protein 1 alpha, syndecan-1 as well as E-selectin in predicting 30-day mortality. Among a subgroup of patients who received Dex early, within 14 days of COVID-19 debut, the adjusted mortality risk was 0.4 (95% CI 0.2-0.8), i.e., 40% compared with Without-Dex. Dex administration in a cohort of critically ill COVID-19 patients resulted in altered immunological and physiologic responses, some of which were associated with mortality.

Keywords: COVID-19; cytokines; dexamethasone; hypoxia; intensive care; treatment timing.

Grants and funding

The study was funded by the SciLifeLab/Knut and Alice Wallenberg national COVID-19 research program (M.H.: KAW 2020.0182, KAW 2020.0241), the Swedish Heart-Lung Foundation (M.H.: 20210089, 20190639, 20190637), the Swedish Research Council (R.F.: 2014-02569, 2014-07606), the Swedish Society of Medicine (M.H.:SLS-938101), and the Swedish Kidney Foundation (R.F.: F2020-0054). Funding bodies had no role in the design of the study, data collection, interpretation, or in the writing of the manuscript.