Dexamethasone or hydrocortisone in COVID-19?
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* Chia Siang Kow
* Syed Shahzad Hasan

**To the Editor**: We read with interest the article by Chatterjee et al,1 who provided an overview of the use of corticosteroids in patients with novel coronavirus disease 2019 (COVID-19). The authors discussed the best available evidence at the time of their writing regarding the outcomes in hospitalized patients with COVID-19 who received corticosteroids. However, with the publication of more randomized trials plus a meta-analysis by the World Health Organization (WHO)2 on the use of corticosteroids in patients with COVID-19, we wish to complement the authors’ discussion to elaborate on the relationship between pharmacodynamic profiles of hydrocortisone and dexamethasone and their respective efficacy in patients with COVID-19.

From the subgroup pooled analysis by WHO to determine the association between corticosteroid use and 28-day all-cause mortality rates in COVID-19 patients, there were no mortality benefits detected from the use of hydrocortisone, whereas dexamethasone significantly reduced the odds of all-cause death at 28 days.2

This is consistent with pharmacodynamic observations. Hydrocortisone has a lower affinity for the glucocorticoid receptor compared with dexamethasone. The reported log relative receptor affinities for hydrocortisone and dexamethasone were 0.95 and 2.0, respectively.3 In addition, hydrocortisone demonstrates less inhibition of proinflammatory transcription factors than dexamethasone. For example, hydrocortisone inhibited tumor necrosis factor alpha-induced nuclear factor kappa B activation less than dexamethasone—the half-maximal inhibitory concentrations [IC50] for nuclear factor kappa inhibition were 15.52 nM and 2.93 nM, respectively.4 The same is observed for nongenomic activity, for which hydrocortisone demonstrates lower potency: hydrocortisone had less inhibition of the release of prostaglandin E2 (PGE2) compared with dexamethasone (the IC50s for PGE2 release were 750 nM and 20 nM, respectively).5 Both nuclear factor kappa B activation and PGE2 release play significant roles in the hyperinflammatory and immune responses in COVID-19.

For these reasons, along with its longer biological half-life and lesser mineralocorticoid activity, dexamethasone should be favored over hydrocortisone in patients with COVID-19 who need treatment with systemic corticosteroids.

*   Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.

## REFERENCES

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