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Publications

Journal Article Ppublish

PubMed: 41968603 DOI: 10.1155/jimr/7429749

C3d Complement Activation and Antibody Immunity in Convalescent COVID-19: Insights From Adults and Children.

J Immunol Res 2026(1):e7429749

Authors: Ratna Wijaya, Jordan Stoddart, Anurag Adhikari, Arunasingam Abayasingam, Adam W Bartlett, William Rawlinson, Michael M Mina, Jeffrey J Post, Bernard Hudson, Nicky Gilroy, Pam Konecny, Golo Ahlenstiel, Marianne Martinello, Andrew R Lloyd, Nicodemus Tedla, Rowena A Bull, Melanie R Walker

Affiliations

  • The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia, unsw.edu.au. School of Biomedical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia, unsw.edu.au. Faculty of Medicine, University of Pelita Harapan, Tangerang, Indonesia.
  • The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia, unsw.edu.au.
  • Department of Infection and Immunology, Kathmandu Research Institute for Biological Sciences, Lalitpur, Nepal, kribs.org.np.
  • Sydney Children's Hospital Randwick, Sydney, New South Wales, Australia, schn.health.nsw.gov.au.
  • School of Biomedical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia, unsw.edu.au.
  • Serology and Virology Division, Department of Microbiology, NSW Health Pathology, Prince of Wales Hospital, Sydney, New South Wales, Australia, princeofwalesprivatehospital.com.au.
  • Northern Beaches Hospital, Sydney, New South Wales, Australia, northernbeacheshospital.com.au.
  • Department of Infectious Diseases, Prince of Wales Hospital, Sydney, New South Wales, Australia, princeofwalesprivatehospital.com.au.
  • School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia, unsw.edu.au.
  • Royal North Shore Hospital, Sydney, New South Wales, Australia, nsw.gov.au.
  • Westmead Hospital, Sydney, New South Wales, Australia, nsw.gov.au.
  • School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia, unsw.edu.au. St George Hospital, Sydney, New South Wales, Australia, nhs.uk.
  • Blacktown Clinical School, School of Medicine, Western Sydney University, Blacktown, New South Wales, Australia, westernsydney.edu.au.
  • Blacktown Hospital, Western Sydney Local Health District, Blacktown, New South Wales, Australia, nsw.gov.au.
  • Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia, sydney.edu.au.

Abstract

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.

MeSH

Cells, Antibody Formation, Complement C3D, Sars-Cov-2, Covid-19, Immunity, Complement System Proteins, Complement Activation, Infections, Child