PT  - JOURNAL ARTICLE
AU  - Bruna M. Silva
AU  - Flavio P. Veras
AU  - Giovanni F. Gomes
AU  - Seppe Cambier
AU  - Gabriel V. L. Silva
AU  - Andreza U. Quadros
AU  - Diego B. Caetité
AU  - Daniele C. Nascimento
AU  - Camilla M. Silva
AU  - Juliana C. Silva
AU  - Samara Damasceno
AU  - Ayda H. Schneider
AU  - Fabio Beretta
AU  - Sabrina S. Batah
AU  - Icaro M. S. Castro
AU  - Isadora M. Paiva
AU  - Tamara Rodrigues
AU  - Ana Salina
AU  - Ronaldo Martins
AU  - Guilherme C.M. Cebinelli
AU  - Naira L. Bibo
AU  - Daniel M. Jorge
AU  - Helder I. Nakaya
AU  - Dario S. Zamboni
AU  - Luiz O. Leiria
AU  - Alexandre T. Fabro
AU  - José C. Alves-Filho
AU  - Eurico Arruda
AU  - Paulo Louzada-Junior
AU  - Renê D. Oliveira
AU  - Larissa D. Cunha
AU  - Pierre Van Mol
AU  - Lore Vanderbeke
AU  - Simon Feys
AU  - Els Wauters
AU  - Laura Brandolini
AU  - Fernando Q. Cunha
AU  - Jörg Köhl
AU  - Marcello Allegretti
AU  - Diether Lambrechts
AU  - Joost Wauters
AU  - Paul Proost
AU  - Thiago M. Cunha
TI  - Targeting C5aR1 signaling reduced neutrophil extracellular traps and ameliorates COVID-19 pathology
AID  - 10.1101/2022.07.03.498624
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.07.03.498624
4099  - http://biorxiv.org/content/early/2022/07/06/2022.07.03.498624.short
4100  - http://biorxiv.org/content/early/2022/07/06/2022.07.03.498624.full
AB  - Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonist of C5aR1 could be useful for COVID-19 treatment.Competing Interest StatementThe authors have declared no competing interest.