biostudies-literatureEllsworth CRAmerican Heart AssociationAmerican Heart Association-American Stroke AssociationNHLBI NIH HHSNIHU.S. Department of Veterans AffairsNIH HHS405https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405604biostudies-literatureUnknown81(1)Emerging evidence indicates that activation of complement system leading to the formation of the membrane attack complex (MAC) plays a detrimental role in COVID-19. However, their pathogenic roles have never been experimentally investigated before. We used three knock out mice strains (1. C3^-/-; 2. C7^-/-; and 3. Cd59ab^-/-) to evaluate the role of complement in severe COVID-19 pathogenesis. C3 deficient mice lack a key common component of all three complement activation pathways and are unable to generate C3 and C5 convertases. C7 deficient mice lack a complement protein needed for MAC formation. Cd59ab deficient mice lack an important inhibitor of MAC formation. We also used anti-C5 antibody to block and evaluate the therapeutic potential of inhibiting MAC Cellular and molecular life sciences : CMLSEnhanced complement activation and MAC formation accelerates severe COVID-19.PMC11405604R01 HL165265P51 OD011104R01HL165265HL139930AHA962950R01DK129881IK6BX005235962950P51OD011104-62Qian CKhatun MSWang CManess NJIslamuddin MHalperin JAQin XLiu SKolls JKXiao MTBlair RVChen ZTomlinson SEllsworth CRfalseEnhanced complement activation and MAC formation accelerates severe COVID-19.Emerging evidence indicates that activation of complement system leading to the formation of the membrane attack complex (MAC) plays a detrimental role in COVID-19. However, their pathogenic roles have never been experimentally investigated before. We used three knock out mice strains (1. C3^-/-; 2. C7^-/-; and 3. Cd59ab^-/-) to evaluate the role of complement in severe COVID-19 pathogenesis. C3 deficient mice lack a key common component of all three complement activation pathways and are unable to generate C3 and C5 convertases. C7 deficient mice lack a complement protein needed for MAC formation. Cd59ab deficient mice lack an important inhibitor of MAC formation. We also used anti-C5 antibody to block and evaluate the therapeutic potential of inhibiting MAC 2024-01-01T00:00:00Z2024 Sep2026-06-02T23:16:51.024Z2025-04-04T12:09:25.372ZS-EPMC114056043928494410.1007/s00018-024-05430-w