tetano
Editor, Senior Moderator
Nature
. 2020 Jul 29.
doi: 10.1038/s41586-020-2600-6. Online ahead of print.
Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis
Julien Carvelli[SUP] 1 2 [/SUP], Olivier Demaria[SUP] 3 [/SUP], Fr?d?ric V?ly[SUP] 4 5 [/SUP], Luciana Batista[SUP] 3 [/SUP], Nassima Chouaki Benmansour[SUP] 6 7 [/SUP], Joanna Fares[SUP] 3 [/SUP], Sabrina Carpentier[SUP] 3 [/SUP], Marie-Laure Thibult[SUP] 3 [/SUP], Ariane Morel[SUP] 3 [/SUP], Romain Remark[SUP] 3 [/SUP], Pascale Andr?[SUP] 3 [/SUP], Agn?s Represa[SUP] 3 [/SUP], Christelle Piperoglou[SUP] 4 5 [/SUP], Explore COVID-19 IPH group; Pierre Yves Cordier[SUP] 6 [/SUP], Erwan Le Dault[SUP] 6 [/SUP], Christophe Guervilly[SUP] 2 8 [/SUP], Pierre Simeone[SUP] 2 9 [/SUP], Marc Gainnier[SUP] 1 2 [/SUP], Yannis Morel[SUP] 3 [/SUP], Mikael Ebbo[SUP] 4 10 [/SUP], Nicolas Schleinitz[SUP] 4 10 [/SUP], Eric Vivier[SUP] 11 12 13 [/SUP], Explore COVID-19 Marseille Immunopole group
Collaborators, Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[SUP]1[/SUP]. 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[SUP]1[/SUP]. 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.
. 2020 Jul 29.
doi: 10.1038/s41586-020-2600-6. Online ahead of print.
Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis
Julien Carvelli[SUP] 1 2 [/SUP], Olivier Demaria[SUP] 3 [/SUP], Fr?d?ric V?ly[SUP] 4 5 [/SUP], Luciana Batista[SUP] 3 [/SUP], Nassima Chouaki Benmansour[SUP] 6 7 [/SUP], Joanna Fares[SUP] 3 [/SUP], Sabrina Carpentier[SUP] 3 [/SUP], Marie-Laure Thibult[SUP] 3 [/SUP], Ariane Morel[SUP] 3 [/SUP], Romain Remark[SUP] 3 [/SUP], Pascale Andr?[SUP] 3 [/SUP], Agn?s Represa[SUP] 3 [/SUP], Christelle Piperoglou[SUP] 4 5 [/SUP], Explore COVID-19 IPH group; Pierre Yves Cordier[SUP] 6 [/SUP], Erwan Le Dault[SUP] 6 [/SUP], Christophe Guervilly[SUP] 2 8 [/SUP], Pierre Simeone[SUP] 2 9 [/SUP], Marc Gainnier[SUP] 1 2 [/SUP], Yannis Morel[SUP] 3 [/SUP], Mikael Ebbo[SUP] 4 10 [/SUP], Nicolas Schleinitz[SUP] 4 10 [/SUP], Eric Vivier[SUP] 11 12 13 [/SUP], Explore COVID-19 Marseille Immunopole group
Collaborators, Affiliations
- PMID: 32726800
- DOI: 10.1038/s41586-020-2600-6
Abstract
Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[SUP]1[/SUP]. 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[SUP]1[/SUP]. 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.