Journal Article

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

Fares, Joanna, André, Pascale, Demaria, Olivier, Gainnier, Marc, Schleinitz, Nicolas, Vély, Frédéric, Represa, Agnès, Piperoglou, Christelle, Ebbo, Mikael, Remark, Romain, Carpentier, Sabrina, Le Dault, Erwan, Simeone, Pierre, Thibult, Marie-Laure, Batista, Luciana, Chouaki Benmansour, Nassima, Vivier, Eric, Guervilly, Christophe, Carvelli, Julien, Morel, Ariane, Morel, Yannis, Cordier, Pierre Yves

2020

Overview

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 pandemic 1 . 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 monocytes 1 . 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. Blockade of the C5a–C5aR1 axis using anti-C5aR1 monoclonal antibodies prevented inflammation associated with COVID-19.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/21 / 13/31 / 13/51 / 14 / 14/19 / 38 / 38/1 / 38/39 / 631/250/2501 / 631/250/255 / 631/326/596/4130 / Acute Lung Injury - drug therapy / Acute Lung Injury - immunology / Acute Lung Injury - prevention & control / Alveoli / Animals / Blood / Bronchoalveolar Lavage Fluid - chemistry / Bronchoalveolar Lavage Fluid - immunology / Bronchus / CD11b Antigen - immunology / CD11b Antigen - metabolism / Cell activation / Complement C5a - antagonists & inhibitors / Complement C5a - biosynthesis / Complement C5a - immunology / Complement component C5a / Coronaviruses / COVID-19 / COVID-19 - blood / COVID-19 - complications / COVID-19 - immunology / COVID-19 - pathology / Cytokine Release Syndrome - drug therapy / Cytokine Release Syndrome - immunology / Cytokine Release Syndrome - prevention & control / Disease Models, Animal / Female / Humanities and Social Sciences / Humans / Immune response / Immune system / Inflammation / Inflammation - complications / Inflammation - drug therapy / Inflammation - immunology / Inflammation - pathology / Leukocytes (neutrophilic) / Lung - drug effects / Lung - immunology / Lung - pathology / Lungs / Mice / Mice, Inbred C57BL / Monoclonal antibodies / multidisciplinary / Myeloid cells / Myeloid Cells - drug effects / Myeloid Cells - immunology / Myeloid Cells - pathology / Organs / Pathophysiology / Receptor, Anaphylatoxin C5a - antagonists & inhibitors / Receptor, Anaphylatoxin C5a - blood / Receptor, Anaphylatoxin C5a - immunology / Receptors / Recruitment / Respiratory diseases / Respiratory distress syndrome / Respiratory Distress Syndrome - drug therapy / Respiratory Distress Syndrome - immunology / Respiratory Distress Syndrome - prevention & control / SARS-CoV-2 - drug effects / SARS-CoV-2 - immunology / SARS-CoV-2 - pathogenicity / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Smoke inhalation / Viral diseases