p Atypical response to bacterial coinfection and persistent neutrophilic bronchoalveolar inflammation distinguish critical COVID-19 from influenza

Author(s):Show less -

Cambier, Seppe ^[1] ; Metzemaekers, Mieke ^[1] ; de Carvalho, Ana Carolina ^{[2, 1, 3]} ; Nooyens, Amber ^[1] ; Jacobs, Cato ^[4] ; Vanderbeke, Lore ^[5] ; Malengier-Devlies, Bert ^[6] ; Gouwy, Mieke ^[1] ; Heylen, Elisabeth ^[7] ; Meersseman, Philippe ^[4] ; Hermans, Greet ^[8] ; Wauters, Els ^{[9, 10]} ; Wilmer, Alexander ^[4] ; Schols, Dominique ^[7] ; Matthys, Patrick ^[6] ; Opdenakker, Ghislain ^[6] ; Marques, Rafael Elias ^[2] ; Wauters, Joost ^[4] ; Vandooren, Jennifer ^[6] ; Proost, Paul ^[1] ; Consortium, CONTAGIOUS

Affiliation

^[1] Katholieke Univ Leuven, Lab Mol Immunol, Dept Microbiol Immunol & Transplantat, Rega Inst, Leuven - Belgium

^[2] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas - Brazil

^[3] Univ Campinas UNICAMP, Inst Biol, Dept Genet Microbiol & Immunol, Campinas - Brazil

^[4] Katholieke Univ Leuven, Lab Clin Infect & Inflammatory Disorders, Dept Microbiol Immunol Transplantat, Leuven - Belgium

^[5] Katholieke Univ Leuven, Lab Clin Bacteriol & Mycol, Dept Microbiol Immunol Transplantat, Leuven - Belgium

^[6] Katholieke Univ Leuven, Rega Inst, Dept Microbiol Immunol & Transplantat, Lab Immunobiol, Leuven - Belgium

^[7] Katholieke Univ Leuven, Rega Inst, Dept Microbiol Immunol & Transplantat, Lab Virol & Chemotherapy, Leuven - Belgium

^[8] Katholieke Univ Leuven, Lab Intens Care Med, Dept Cellular & Mol Med, Leuven - Belgium

^[9] Katholieke Univ Leuven, Lab Resp Dis & Thorac Surg BREATHE, Dept Chron Dis & Metab, Leuven - Belgium

^[10] Univ Hosp Leuven, Dept Pneumol, Leuven - Belgium

• Document type: Journal article
• Source: JCI INSIGHT; v. 7, n. 1 JAN 11 2022.
• Web of Science Citations: 1

Abstract

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-1 beta, IL-1RA, IL-17A, TNF-alpha, and G-CSF; the chemokines CCL7, CXCL1, CXCL8, CXCL11, and CXCL12 alpha; and the protease inhibitors elafin, secretory leukocyte protease inhibitor, and tissue inhibitor of metalloproteinases 1. In contrast, alpha-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. (AU)

• FAPESP's process: 18/10990-1 - Characterization and therapeutic potential of chemokine action in sepsis and Flavivirus-induced encephalitis
• Grantee: Rafael Elias Marques Pereira Silva
• Support Opportunities: Regular Research Grants