tetano
Editor, Senior Moderator
J Immunol Res
. 2026;2026(1):e7429749.
doi: 10.1155/jimr/7429749.
C3d Complement Activation and Antibody Immunity in Convalescent COVID-19: Insights From Adults and Children
Ratna Wijaya[SUP] 1 2 3 [/SUP], Jordan Stoddart[SUP] 1 [/SUP], Anurag Adhikari[SUP] 4 [/SUP], Arunasingam Abayasingam[SUP] 1 [/SUP], Adam W Bartlett[SUP] 1 5 [/SUP], William Rawlinson[SUP] 2 6 [/SUP], Michael M Mina[SUP] 7 [/SUP], Jeffrey J Post[SUP] 8 9 [/SUP], Bernard Hudson[SUP] 10 [/SUP], Nicky Gilroy[SUP] 11 [/SUP], Pam Konecny[SUP] 9 12 [/SUP], Golo Ahlenstiel[SUP] 13 14 15 [/SUP], Marianne Martinello[SUP] 1 8 [/SUP], Andrew R Lloyd[SUP] 1 [/SUP], Nicodemus Tedla[SUP] 2 [/SUP], Rowena A Bull[SUP] 1 2 [/SUP], Melanie R Walker[SUP] 1 2 [/SUP]
Affiliations
Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the complement pathway becomes activated, generating the stable split product C3d. Although C3d can modulate B cell responses through complement receptor 2 (CR2) in experimental systems, it remains unclear how circulating C3d relates to antibody responses after SARS-CoV-2 infection in humans. Here, we examined plasma C3d levels and their associations with SARS-CoV-2-specific antibody responses and clinical characteristics in convalescent adults and children. In adults, older age, male sex, and a history of severe COVID-19 were independently associated with higher C3d levels. C3d concentrations positively correlated with receptor-binding domain (RBD)-specific antibody-dependent cellular phagocytosis (ADCP), neutralizing antibody (nAb) titer, and anti-spike IgM, IgG, IgG1, and IgG3 levels. In children, C3d levels were significantly lower than in adults and correlated with anti-spike and anti-RBD IgG titers. These findings demonstrate that systemic complement activation, reflected by circulating C3d, is positively associated with SARS-CoV-2 antibody responses in both age groups. As this cross-sectional study cannot determine causality, further mechanistic and longitudinal studies are needed to define the role, if any, of C3d in shaping adaptive immunity to SARS-CoV-2.
. 2026;2026(1):e7429749.
doi: 10.1155/jimr/7429749.
C3d Complement Activation and Antibody Immunity in Convalescent COVID-19: Insights From Adults and Children
Ratna Wijaya[SUP] 1 2 3 [/SUP], Jordan Stoddart[SUP] 1 [/SUP], Anurag Adhikari[SUP] 4 [/SUP], Arunasingam Abayasingam[SUP] 1 [/SUP], Adam W Bartlett[SUP] 1 5 [/SUP], William Rawlinson[SUP] 2 6 [/SUP], Michael M Mina[SUP] 7 [/SUP], Jeffrey J Post[SUP] 8 9 [/SUP], Bernard Hudson[SUP] 10 [/SUP], Nicky Gilroy[SUP] 11 [/SUP], Pam Konecny[SUP] 9 12 [/SUP], Golo Ahlenstiel[SUP] 13 14 15 [/SUP], Marianne Martinello[SUP] 1 8 [/SUP], Andrew R Lloyd[SUP] 1 [/SUP], Nicodemus Tedla[SUP] 2 [/SUP], Rowena A Bull[SUP] 1 2 [/SUP], Melanie R Walker[SUP] 1 2 [/SUP]
Affiliations
- PMID: 41968603
- DOI: 10.1155/jimr/7429749
Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the complement pathway becomes activated, generating the stable split product C3d. Although C3d can modulate B cell responses through complement receptor 2 (CR2) in experimental systems, it remains unclear how circulating C3d relates to antibody responses after SARS-CoV-2 infection in humans. Here, we examined plasma C3d levels and their associations with SARS-CoV-2-specific antibody responses and clinical characteristics in convalescent adults and children. In adults, older age, male sex, and a history of severe COVID-19 were independently associated with higher C3d levels. C3d concentrations positively correlated with receptor-binding domain (RBD)-specific antibody-dependent cellular phagocytosis (ADCP), neutralizing antibody (nAb) titer, and anti-spike IgM, IgG, IgG1, and IgG3 levels. In children, C3d levels were significantly lower than in adults and correlated with anti-spike and anti-RBD IgG titers. These findings demonstrate that systemic complement activation, reflected by circulating C3d, is positively associated with SARS-CoV-2 antibody responses in both age groups. As this cross-sectional study cannot determine causality, further mechanistic and longitudinal studies are needed to define the role, if any, of C3d in shaping adaptive immunity to SARS-CoV-2.