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. 2023 Nov;38(11):1003-1014.
doi: 10.1177/08850666231177200. Epub 2023 May 24.

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019

Aysun Tekin  1 , Juan P Domecq  1 , Diana J Valencia Morales  2 , Krishna Mohan Surapeneni  3 , Igor B Zabolotskikh  4 , Rodrigo Cartin-Ceba  5 , Philippe Clevenbergh  6 , Jean-Baptiste Mesland  7 , Rolando Claure-Del Granado  8 , Oscar Y Gavidia  9 , Vishakha K Kumar  10 , Rahul Kashyap  2 , Allan J Walkey  11 , Ognjen Gajic  12 , Yewande Odeyemi  12   13 ; From the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group
Affiliations

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019

Aysun Tekin et al. J Intensive Care Med. 2023 Nov.

Abstract

Background: Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes.

Methods: This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels.

Results: Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased.

Conclusion: Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Keywords: C-reactive protein; anti-inflammatory therapy; biomarker-concordant; coronavirus disease-2019; corticosteroids.

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Conflict of interest statement

R.K. receives funding from the National Institutes of Health/National Heart, Lung and Blood Institute: R01HL 130881, UG3/UH3HL 141722; Gordon and Betty Moore Foundation, and Janssen Research & Development, LLC; and royalties from Ambient Clinical Analytics. Inc. They had no influence on the acquisition, analysis, interpretation, and reporting of pooled data for this manuscript. AJW receives funding from the National Institutes of Health/National Heart, Lung and Blood Institute grants R01HL151607, R01HL139751, Agency of Healthcare Research and Quality, R01HS026485, Department of Defense CP200036, and royalties from UpToDate. OG receives funding from the Agency of Healthcare Research and Quality R18HS 26609-2, National Institutes of Health/National Heart, Lung and Blood Institute: R01HL 130881, UG3/UH3HL 141722; Department of Defense DOD W81XWH; American Heart Association Rapid Response Grant—COVID-19; and royalties from Ambient Clinical Analytics. Inc. These funds had no influence on acquisition, analysis, interpretation and reporting of pooled data for this manuscript.

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