Comparative effectiveness of dexamethasone in treatment of hospitalized COVID-19 patients in the United States during the first year of the pandemic: Findings from the National COVID Cohort Collaborative (N3C) data repository.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

COVID-19*/epidemiology ; Vaccines*; Humans ; United States/epidemiology ; Pandemics ; Hospital Mortality ; COVID-19 Drug Treatment ; Inpatients ; Dexamethasone/therapeutic use

Background: Dexamethasone was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial, but evidence is still needed to support its real-world effectiveness in heterogeneous populations of patients with a wide range of comorbidities.
Methods: COVID-19 inpatients represented within the National COVID Cohort Collaborative (N3C) Data Enclave, prior to vaccine availability, were studied. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome defined by use of ECMO or mechanical ventilation. Missing data were imputed with single imputation. Dexamethasone-treated patients were propensity score (PS) matched to non-dexamethasone-treated controls, stratified by remdesivir treatment and based on demographics, baseline laboratory values, comorbidities, and amount of missing data before imputation. Treatment benefit was quantified using logistic regression. Further sensitivity analyses were performed using clinical adjusters in matched groups and in strata defined by quartiles of PS.
Results: Dexamethasone treatment was associated with reduced risk of in-hospital mortality for n = 1,263 treated, matched 1:3 to untreated, patients not receiving remdesivir (OR = 0.77, 95% CI: 0.62 to 0.95, p = 0.017), and for n = 804 treated, matched 1:1 to untreated, patients receiving remdesivir (OR = 0.74, 95% CI: 0.53 to 1.02, p = 0.054). Treatment showed secondary outcome benefit. In sensitivity analyses, treatment effect generally remained similar with some heterogeneity of benefit across quartiles of PS, possibly reflecting concentration of benefit among the more severely affected.
Conclusions: We add evidence that dexamethasone provides benefit with respect to mortality and severe outcomes in a diverse, national hospitalized sample, prior to vaccine availability.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Update of: medRxiv. 2022 Oct 24;:. (PMID: 36324806)

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R01 AI151176 United States AI NIAID NIH HHS; U01 IP001136 United States IP NCIRD CDC HHS; U01IP001136 United States ACL ACL HHS; U24 TR002306 United States TR NCATS NIH HHS

0 (Vaccines)
7S5I7G3JQL (Dexamethasone)

Date Created: 20240321 Date Completed: 20240325 Latest Revision: 20240401

20240402

PMC10956822

10.1371/journal.pone.0294892

38512832