TY - JOUR AU - Cambier, Seppe AU - Metzemaekers, Mieke AU - de Carvalho, Ana Carolina AU - Nooyens, Amber AU - Jacobs, Cato AU - Vanderbeke, Lore AU - Malengier-Devlies, Bert AU - Gouwy, Mieke AU - Heylen, Elisabeth AU - Meersseman, Philippe AU - Hermans, Greet AU - Wauters, Els AU - Wilmer, Alexander AU - , AU - Schols, Dominique AU - Matthys, Patrick AU - Opdenakker, Ghislain AU - Marques, Rafael Elias AU - Wauters, Joost AU - Vandooren, Jennifer AU - Proost, Paul T1 - Atypical response to bacterial coinfection and persistent neutrophilic bronchoalveolar inflammation distinguish critical COVID-19 from influenza PY - 2022/01/11/ AB - Neutrophils are recognized as important circulating effector cells in the pathophysiology of severe coronavirus disease 2019 (COVID-19). However, their role within the inflamed lungs is incompletely understood. Here, we collected bronchoalveolar lavage (BAL) fluids and parallel blood samples of critically ill COVID-19 patients requiring invasive mechanical ventilation and compared BAL fluid parameters with those of mechanically ventilated patients with influenza, as a non–COVID-19 viral pneumonia cohort. Compared with those of patients with influenza, BAL fluids of patients with COVID-19 contained increased numbers of hyperactivated degranulating neutrophils and elevated concentrations of the cytokines IL-1β, IL-1RA, IL-17A, TNF-α, and G-CSF; the chemokines CCL7, CXCL1, CXCL8, CXCL11, and CXCL12α; and the protease inhibitors elafin, secretory leukocyte protease inhibitor, and tissue inhibitor of metalloproteinases 1. In contrast, α-1 antitrypsin levels and net proteolytic activity were comparable in COVID-19 and influenza BAL fluids. During antibiotic treatment for bacterial coinfections, increased BAL fluid levels of several activating and chemotactic factors for monocytes, lymphocytes, and NK cells were detected in patients with COVID-19 whereas concentrations tended to decrease in patients with influenza, highlighting the persistent immunological response to coinfections in COVID-19. Finally, the high proteolytic activity in COVID-19 lungs suggests considering protease inhibitors as a treatment option. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.155055 VL - 7 IS - 1 UR - https://doi.org/10.1172/jci.insight.155055 PB - The American Society for Clinical Investigation ER -