The association between early corticosteroid use and the risk of secondary infections in hospitalized patients with COVID-19: a double-edged sword. Results from the international SCCM discovery viral infection and respiratory illness universal study (VIRUS) COVID-19 registry

Vikas Bansal; Nitesh K Jain; Amos Lal; Anwar Khedr; Aysun Tekin; Abbas B Jama; Noura Attallah; Esraa Hassan; Hisham Ahmed Mushtaq; Sara Robinson; Marjan Jahani Kondori; Thoyaja Koritala; Donna Lee Armaignac; Amy B Christie; Umamaheswara Raju; Ashish Khanna; Rodrigo Cartin-Ceba; Devang K Sanghavi; Abigail La Nou; Karen Boman; Vishakha Kumar; Allan J Walkey; Juan Pablo Domecq; Rahul Kashyap; Syed Anjum Khan; Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group

doi:10.3389/fmed.2025.1466346

The association between early corticosteroid use and the risk of secondary infections in hospitalized patients with COVID-19: a double-edged sword. Results from the international SCCM discovery viral infection and respiratory illness universal study (VIRUS) COVID-19 registry

Front Med (Lausanne). 2025 Feb 14:12:1466346. doi: 10.3389/fmed.2025.1466346. eCollection 2025.

Authors

Vikas Bansal^#¹, Nitesh K Jain^#^{2

3}, Amos Lal³, Anwar Khedr², Aysun Tekin¹, Abbas B Jama², Noura Attallah², Esraa Hassan², Hisham Ahmed Mushtaq², Sara Robinson⁴, Marjan Jahani Kondori⁴, Thoyaja Koritala², Donna Lee Armaignac⁵, Amy B Christie⁶, Umamaheswara Raju⁷, Ashish Khanna⁸, Rodrigo Cartin-Ceba⁹, Devang K Sanghavi¹⁰, Abigail La Nou¹¹, Karen Boman¹², Vishakha Kumar¹², Allan J Walkey¹³, Juan Pablo Domecq^{1

2}, Rahul Kashyap^{14

15}, Syed Anjum Khan²; Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group

Affiliations

¹ Division of Nephrology and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States.
² Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States.
³ Department of Critical Care Medicine, North East Georgia Health System, Gainesville, GA, United States.
⁴ Department of Family Medicine, Mayo Clinic Health System, Mankato, MN, United States.
⁵ Center for Advanced Analytics, Baptist Health South Florida, Miami, FL, United States.
⁶ Department of Trauma Critical Care, The Medical Center Navicent Health, Mercer University School of Medicine, Macon, GA, United States.
⁷ Gandhi Medical College and Hospital, Hyderabad, India.
⁸ Section on Critical Care Medicine, Department of Anesthesiology, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, United States.
⁹ Division of Critical Care Medicine, Department of Pulmonary Medicine, Mayo Clinic, Scottsdale, AZ, United States.
¹⁰ Department of Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL, United States.
¹¹ Department of Critical Care Medicine, Mayo Clinic Health System, Eau Claire, WI, United States.
¹² Society of Critical Care Medicine, Mount Prospect, IL, United States.
¹³ Pulmonary Center, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
¹⁴ Division of Critical Care Medicine, Department of Anesthesiology and Perioperative Care, Mayo Clinic, Rochester, MN, United States.
¹⁵ Department of Medicine and Medical, Research, WellSpan Health, York, PA, United States.

^# Contributed equally.

Abstract

Background: Corticosteroids improve survival in hospitalized COVID-19 patients needing supplemental oxygen. However, concern exists about increased risk of secondary infections. This study investigated the impact of early corticosteroids use on these infections.

Methods: Data from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 registry were analyzed for adult patients, stratified by early corticosteroid use (within 48 h of admission). The primary outcome was documented secondary infections, including bacteremia, bacterial pneumonia, empyema, meningitis/encephalitis, septic shock, and ventilator-associated pneumonia. Univariate and multivariable logistic regression models were used to assess the association between early corticosteroids and these outcomes.

Results: Among 17,092 eligible patients, with 13.5% developed at least one secondary bacterial infection during hospitalization. Patients receiving early corticosteroids were older (median 63 years) compared to those who did not (median 60 years), with a similar gender distribution (42.5% vs. 44.2% female). Unadjusted analysis revealed a higher risk for any secondary infection (OR 1.93, 95% CI 1.76-2.12). This association persisted for specific infections including bacteremia (OR 2.0, 95% CI 1.58-2.54), bacterial pneumonia (OR 1.5, 95% CI 1.27-1.77), and septic shock (OR 1.67, 95% CI 1.44-1.93). However, the effect on meningitis/encephalitis (OR 0.62, 95% CI 0.24-1.57) and ventilator-associated pneumonia (VAP; OR 1.08, 95% CI 0.75-1.57) was non-significant. Adjusted analysis maintained significance for any secondary infection (OR 1.15, 95% CI 1.02-1.29), bacteremia (OR 1.43, 95% CI 1.09-1.88), and infections with unknown sources (OR 1.63, 95% CI 1.31-2.02). Notably, the association weakened and became non-significant for bacterial pneumonia (OR 0.98, 95% CI 0.81-1.20) and septic shock (OR 0.94, 95% CI 0.79-1.11), while it became significant for meningitis/encephalitis (OR 0.26, 95% CI 0.08-0.82). VAP remained non-significant (OR 0.87, 95% CI 0.56-1.34).

Conclusion: Early use of corticosteroids increased overall secondary infection risk in hospitalized COVID-19 patients, but the impact varied. Risk of bacteremia was notably increased, while the association with bacterial pneumonia and septic shock weakened after adjustment becoming non-significant and surprisingly reduced meningitis/encephalitis risk was noted suggesting the complexity of corticosteroid effects. Further research is needed to understand how corticosteroids influence specific secondary infections, and thereby optimize the treatment strategies.

Keywords: COVID-19; SARS-CoV-2; VIRUS COVID-19 registry; corticosteroids; early steroid treatment outcomes; hospitalized patients; risk factors; secondary infections.

Copyright © 2025 Bansal, Jain, Lal, Khedr, Tekin, Jama, Attallah, Hassan, Mushtaq, Robinson, Kondori, Koritala, Armaignac, Christie, Raju, Khanna, Cartin-Ceba, Sanghavi, La Nou, Boman, Kumar, Walkey, Domecq, Kashyap, Khan and the Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group.