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

Julien Carvelli, Olivier Demaria, Frédéric Vély, Luciana Batista, Nassima Chouaki Benmansour, Joanna Fares, Sabrina Carpentier, Marie-Laure Thibult, Ariane Morel, Romain Remark, Pascale André, Agnès Represa, Christelle Piperoglou, Pierre Yves Cordier, Erwan Le Dault, Christophe Guervilly, Pierre Simeone, Marc Gainnier, Yannis Morel, Mikael Ebbo, Nicolas Schleinitz and Eric Vivier ()
Additional contact information
Julien Carvelli: Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Réanimation des Urgences
Olivier Demaria: Innate Pharma
Frédéric Vély: Aix Marseille Université, CNRS, INSERM, CIML
Luciana Batista: Innate Pharma
Nassima Chouaki Benmansour: Hôpital d’Instruction des Armées Laveran
Joanna Fares: Innate Pharma
Sabrina Carpentier: Innate Pharma
Marie-Laure Thibult: Innate Pharma
Ariane Morel: Innate Pharma
Romain Remark: Innate Pharma
Pascale André: Innate Pharma
Agnès Represa: Innate Pharma
Christelle Piperoglou: Aix Marseille Université, CNRS, INSERM, CIML
Pierre Yves Cordier: Hôpital d’Instruction des Armées Laveran
Erwan Le Dault: Hôpital d’Instruction des Armées Laveran
Christophe Guervilly: Aix Marseille Université
Pierre Simeone: Aix Marseille Université
Marc Gainnier: Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Réanimation des Urgences
Yannis Morel: Innate Pharma
Mikael Ebbo: Aix Marseille Université, CNRS, INSERM, CIML
Nicolas Schleinitz: Aix Marseille Université, CNRS, INSERM, CIML
Eric Vivier: Innate Pharma

Nature, 2020, vol. 588, issue 7836, 146-150

Abstract: Abstract Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes1. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a–C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a–C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.

Date: 2020
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DOI: 10.1038/s41586-020-2600-6

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