2. Academic Validation
  3. Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis

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

  • Nature. 2020 Dec;588(7836):146-150. doi: 10.1038/s41586-020-2600-6.
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,  Explore COVID-19 Marseille Immunopole 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
Affiliations

Affiliations

  • 1 Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Réanimation des Urgences, Marseilles, France.
  • 2 Aix Marseille Université, Marseilles, France.
  • 3 Innate Pharma, Marseilles, France.
  • 4 Aix Marseille Université, CNRS, INSERM, CIML, Marseilles, France.
  • 5 Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Immunology, Marseille Immunopole, Marseilles, France.
  • 6 Hôpital d'Instruction des Armées Laveran, Marseilles, France.
  • 7 Assistance Publique des Hôpitaux de Marseille, Marseilles, France.
  • 8 Assistance Publique des Hôpitaux de Marseille, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Aix-Marseille Université, Marseilles, France.
  • 9 Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Réanimation Polyvalente, Aix-Marseille Université, Marseilles, France.
  • 10 Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Internal Medicine, Marseilles, France.
  • 11 Innate Pharma, Marseilles, France. [email protected].
  • 12 Aix Marseille Université, CNRS, INSERM, CIML, Marseilles, France. [email protected].
  • 13 Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Immunology, Marseille Immunopole, Marseilles, France. [email protected].
  • # Contributed equally.
PMID: 32726800 DOI: 10.1038/s41586-020-2600-6
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.

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