Citation: Mesland, J.-B.; Carlier, E.; François, B.; Serck, N.; Gerard, L.; Briat, C.; Piagnerelli, M.; Laterre, P.-F.; on behalf of the COVCORVAP Collaboration Group. Early Corticosteroid Therapy May Increase Ventilator-Associated Lower Respiratory Tract Infection in Critically Ill Patients with COVID-19: A Multicenter Retrospective Cohort Study. Microorganisms 2022, 10, 984. https://doi.org/10.3390/ microorganisms10050984 Academic Editor: Peré Domingo Received: 28 March 2022 Accepted: 6 May 2022 Published: 8 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). microorganisms Article Early Corticosteroid Therapy May Increase Ventilator-Associated Lower Respiratory Tract Infection in Critically Ill Patients with COVID-19: A Multicenter Retrospective Cohort Study Jean-Baptiste Mesland 1, * , Eric Carlier 2 , Bruno François 3 , Nicolas Serck 4 , Ludovic Gerard 1 , Charlotte Briat 3 , Michael Piagnerelli 2 , Pierre-François Laterre 1 and on behalf of the COVCORVAP Collaboration Group † 1 Critical Care Department, Cliniques Universitaires Saint-Luc, UCLouvain, 1200 Brussels, Belgium; ludovic.gerard@uclouvain.be (L.G.); pierre-francois.laterre@uclouvain.be (P.-F.L.) 2 Intensive Care, CHU-Charleroi Marie Curie, Université Libre de Bruxelles, 6042 Charleroi, Belgium; eric.carlier@chu-charleroi.be (E.C.); michael.piagnerelli@chu-charleroi.be (M.P.) 3 ICU Department and Inserm CIC 1435 & UMR 1092, CHU Dupuytren, 87000 Limoges, France; bruno.francois@chu-limoges.fr (B.F.); charlotte.briat@chu-limoges.fr (C.B.) 4 Unité de Soins Intensifs, Clinique Saint-Pierre, 1340 Ottignies, Belgium; nicolas.serck@cspo.be * Correspondence: jean-baptiste.mesland@saintluc.uclouvain.be † Collaborators/Membership of the COVCORVAP Collaboration Group is provided in the Acknowledgments. Abstract: Background: The coronavirus disease 2019 (COVID-19) pandemic has put significant pressure on hospitals and in particular on intensive care units (ICU). Some patients develop acute hypoxemic respiratory failure with profound hypoxia, which likely requires invasive mechanical ventilation during prolonged periods. Corticosteroids have become a cornerstone therapy for patients with severe COVID-19, though only little data are available regarding their potential harms and benefits, especially concerning the risk of a ventilator-associated lower respiratory tract infection (VA-LRTI). Methods: This retrospective multicenter study included patients admitted in four ICUs from Belgium and France for severe COVID-19, who required invasive mechanical ventilation (MV). We compared clinical and demographic variables between patients that received corticosteroids or not, using univariate, multivariate, and Fine and Gray analyses to identify factors influencing VA-LRTI occurrence. Results: From March 2020 to January 2021, 341 patients required MV for acute respiratory failure related to COVID-19, 322 of whom were included in the analysis, with 60.6% of them receiving corticosteroids. The proportion of VA-LRTI was significantly higher in the early corticosteroid group (63.1% vs. 48.8%, p = 0.011). Multivariable Fine and Gray modeling considering death and extubation as competing events revealed that the factors independently associated with VA-LRTI occurrence were male gender (adjusted sHR:1.7, p = 0.0022) and corticosteroids (adjusted sHR: 1.44, p = 0.022). Conclusions: in our multicenter retrospective cohort of COVID-19 patients undergoing MV, early corticosteroid therapy was independently associated with VA-LRTI. Keywords: COVID-19; SARS-CoV-2; ventilator-associated lower respiratory tract infection; corticosteroids; acute respiratory distress syndrome 1. Introduction Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading around the world. In 5–10% of cases, SARS-CoV-2 infection can trigger acute respiratory failure, which requires hospitalization, intensive care unit (ICU) admission, and invasive mechanical ventilation (MV), while being associated with high mortality [1]. Patients undergoing MV for severe SARS-CoV-2 pneumonia are particularly prone to develop ventilator-associated pneumonia (VAP), with an incidence rate as high as 58%, as Microorganisms 2022, 10, 984. https://doi.org/10.3390/microorganisms10050984 https://www.mdpi.com/journal/microorganisms