Atypical response to bacterial co-infection and persistent neutrophilic broncho-alveolar inflammation distinguish critical COVID-19 from influenza.
Creators
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Cambier, Seppe1
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Metzemaekers, Mieke1
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de Carvalho, Ana Carolina2
- Nooyens, Amber1
- Jacobs, Cato1
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Vanderbeke, Lore1
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Malengier-Devlies, Bert1
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Gouwy, Mieke1
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Heylen, Elisabeth1
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Meersseman, Philippe1
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Hermans, Greet1
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Wauters, Els1
- Wilmer, Alexander1
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Schols, Dominique1
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Matthys, Patrick1
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Opdenakker, Ghislain1
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Marques, Rafael Elias2
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Wauters, Joost1
- Vandooren, Jennifer1
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Proost, Paul1
- and 10 more
- 1. Katholieke Universiteit Leuven
- 2. LNBio, CNPEM, Campinas, Brazil.
Description
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 broncho-alveolar 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 influenza patients, as a non-COVID-19 viral pneumonia cohort. Compared to influenza, BAL fluids of COVID-19 patients 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 (SLPI) and tissue inhibitor of metalloproteinases 1 (TIMP-1). In contrast, α-1 antitrypsin levels and net proteolytic activity were comparable in COVID-19 and influenza BAL fluids. During antibiotics treatment for bacterial co-infections, increased BAL fluid levels of several activating and chemotactic factors for monocytes, lymphocytes and NK cells were detected in COVID-19 patients whereas concentrations tended to decrease in influenza patients, highlighting the persistent immunological response to co-infections in COVID-19. Finally, the high proteolytic activity in COVID-19 lungs suggests considering protease inhibitors as a treatment option.
Open Access
Licence Attribution (CC BY)
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Publication Details
Journal article
Journal:
JCI insight
Publisher:
American Society for Clinical Investigation
ISSN:
23793708
Volume:
7
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Funding
Financial Support
Onderzoeksraad, KU Leuven — Grant: C16/17/010
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Fonds Wetenschappelijk Onderzoek — Grant: G0F7519N
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Fonds Wetenschappelijk Onderzoek — Grant: PhD fellowship to SC
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Fonds Wetenschappelijk Onderzoek — Grant: postdoctoral fellowship to JV
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Fonds Wetenschappelijk Onderzoek — Grant: postdoctoral clinical fellowship to JW
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FAPESP — Grant: 18/10990-1,PhD fellowship to ACdC
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L'Oréal UNESCO FWO — Grant: PhD fellowship for women in Science to MM
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References
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