IUIS Webinar: Involvement of C5a-C5aR1 axis in COVID-19 pathology


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In a recent IUIS Webinar, Eric Vivier presented data on longitudinal analysis of immune responses in the blood and bronchoalveolar lavage fluid (BALF) of patients at various stages of COVID-19 severity: paucisymptomatic, pneumonia and acute respiratory distress syndrome (ARDS). Highlights of his webinar include:

  • Description of how SARS-CoV-2 (as well as SARS-CoV, MERS-CoV) N proteins bind to MASP-2, which leads to activation of complement component 5a (C5a) and aggravated lung damage. C5a has also been shown to drive pathogenesis of several viral-induced pneumonia and ARDS, and he specifically showed that levels of C5a increased with COVID-19 disease severity.
  • C5a can bind to C5a receptor 1 (C5aR1) which is expressed on neutrophils and myeloid cells. He presented data that demonstrated upregulation of C5aR1+ cells in BALF from COVID-19 patients.
  • Anti-C5aR1 therapeutic monoclonal antibodies, Avdoralimab, prevented C5a-mediated human myeloid cell recruitment and activation and inhibited acute lung injury (ALI) in human C5aR1 knockin mice. These results support C5a-C5aR1 axis blockade 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. (Proposed mechanism is described in the figure below)

 

 

Summary by Cheleka AM Mpande

 
 
 
 
 
 
International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation