Fc-mediated antibody functions are associated with disease severity in COVID-19

IntroductionFc-mediated antibody effector functions play key roles in both antiviral immunity and immunopathology in COVID-19. While antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) contribute to pathogen clearance, they may also be associated with inflammatory responses.

The contribution of these pathways—particularly antibody-dependent enhancement (ADE)—to severe COVID-19 remains incompletely understood. We prospectively investigated relationships among ADE, ADCC, and ADCP across multiple SARS-CoV-2 variants from 64 patients with laboratory-confirmed SARS-CoV-2 infection.MethodsPatient Fc-mediated effector activities were profiled.

Disease severity was classified using National Institutes of Health criteria. ADE was assessed using pseudotyped SARS-CoV-2 entry into THP-1 cells, whereas Fc gamma receptors (FcγR)IIIa- and FcγRIIa-mediated reporter activities (reflecting ADCC and ADCP surrogate responses, respectively) were assessed using spike-expressing A549 target cells and FcγR-expressing Jurkat-Lucia reporter cells.

Functional responses were measured against wild-type SARS-CoV-2 and Omicron sublineages (B.1.1.529, BA.4/BA.5, XBB.1.5).ResultsAmong 64 participants (40 with mild, 24 with severe COVID-19; median age, 58 years [interquartile range, 45–71], 56% men), anti-spike IgG binding did not differ by severity.