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Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis

Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The C5a anaphylatoxin and its receptor C5aR1 (CD88) play a key role in the initiation and maintenance of several inflammatory responses, by recruiting...

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Detalles Bibliográficos
Autores principales: Carvelli, Julien, Demaria, Olivier, Vély, Frédéric, Batista, Luciana, Benmansour, Nassima Chouaki, Fares, Joanna, Carpentier, Sabrina, Thibult, Marie-Laure, Morel, Ariane, Remark, Romain, André, Pascale, Represa, Agnès, Piperoglou, Christelle, Cordier, Pierre Yves, Le Dault, Erwan, Guervilly, Christophe, Simeone, Pierre, Gainnier, Marc, Morel, Yannis, Ebbo, Mikael, Schleinitz, Nicolas, Vivier, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116884/
https://www.ncbi.nlm.nih.gov/pubmed/32726800
http://dx.doi.org/10.1038/s41586-020-2600-6
Descripción
Sumario:Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 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 lungs(1). 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.