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Regular and young investigator award abstracts
COVID and Immunotherapy
483 Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis
  1. Olivier Demaria1,
  2. Julien Carvelli2,
  3. Nassima Chouaki Benmansour3,
  4. Joanna Fares1,
  5. Luciana Batista1,
  6. Marie-Laure Thibult1,
  7. Ariane Morel1,
  8. Sabrina Carpentier1,
  9. Romain Remark1,
  10. Agnes Represa1,
  11. Frederic Vely2,
  12. Mikael Ebbo2,
  13. Nicolas Schleinitz2,
  14. Robert Zerbib1,
  15. Yannis Morel1,
  16. Eric Vivier1 and
  17. Olivier Demaria1
  1. 1Innate Pharma, marseille, France
  2. 2Hôpital de la TIMONE, Marseille Cedex 5, France
  3. 3Hôpital d’Instruction des Armées Laveran, Marseille, France

Abstract

Background 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.

Methods 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)

Results 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. Avdoralimab, an 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.

Conclusions These results support the evaluation of avdoralimab to block C5a-C5aR1 axis as a mean of limiting myeloid cell infiltration in damaged organs and preventing the excessive lung inflammation and endothelialitis associated with ARDS in COVID-19 patients

Acknowledgements The Explore COVID-19 IPH group, the Explore COVID-19 Marseille Immunopole group.

Ethics Approval Human study protocol was approved by the Committee for the Protection of Persons Ile-de-France III – France (#2020-A00757-32). Animal experiments were approved by the ministere de l’enseignement superieur, de la recherche et de l’innovation – France (APAFIS#25418-2020051512242806 v2).

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/jitc-2020-SITC2020.0483

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