Authors: Julien Carvelli 1 2, Olivier Demaria 3, Frédéric Vély 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 André 3, Agnès 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
Issue: Nature. 2020 Jul 29. doi: 10.1038/s41586-020-2600-6.
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.