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Nature
. 2020 Jul 29.
doi: 10.1038/s41586-020-2600-6. Online ahead of print.
Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis
Julien Carvelli 1 2 , Olivier Demaria 3 , Fr?d?ric V?ly 4 5 , Luciana Batista 3 , Nassima Chouaki Benmansour 6 7 , Joanna Fares 3 , Sabrina Carpentier 3 , Marie-Laure Thibult 3 , Ariane Morel 3 , Romain Remark 3 , Pascale Andr? 3 , Agn?s Represa 3 , Christelle Piperoglou 4 5 , Explore COVID-19 IPH group; Pierre Yves Cordier 6 , Erwan Le Dault 6 , Christophe Guervilly 2 8 , Pierre Simeone 2 9 , Marc Gainnier 1 2 , Yannis Morel 3 , Mikael Ebbo 4 10 , Nicolas Schleinitz 4 10 , Eric Vivier 11 12 13 , Explore COVID-19 Marseille Immunopole group
Collaborators, Affiliations
- PMID: 32726800
- DOI: 10.1038/s41586-020-2600-6
Abstract
Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. The C5a anaphylatoxin and its receptor C5aR1 (CD88) play a key role in the initiation and maintenance of several inflammatory responses, by recruiting and activating neutrophils and monocytes in the lungs1. We provide a longitudinal analysis of immune responses, including immune cell phenotyping and assessments of the soluble factors present in the blood and broncho-alveolar lavage fluid (BALF) of patients at various stages of COVID-19 severity: paucisymptomatic, pneumonia and acute respiratory distress syndrome (ARDS). We report an increase in soluble C5a levels proportional to COVID-19 severity and high levels of C5aR1 expression in blood and pulmonary myeloid cells, supporting a role for the C5a-C5aR1 axis in the pathophysiology of ARDS. Anti-C5aR1 therapeutic monoclonal antibodies (mAbs) prevented C5a-mediated human myeloid cell recruitment and activation, and inhibited acute lung injury (ALI) in human C5aR1 knockin mice. These results suggest that C5a-C5aR1 axis blockade might be used as a means of limiting myeloid cell infiltration in damaged organs and preventing the excessive lung inflammation and endothelialitis associated with ARDS in COVID-19 patients.