Anti-Nucleocapsid and Anti-Spike Antibody Trajectories in People with Post-Covid Condition versus Acute-Only Infections: Results from the Virus Watch Prospective Cohort Study

Background Early evidence suggests that people with Post-Covid Condition (PCC) may demonstrate aberrant immune responses post-infection; however, serological follow-up studies are currently limited. We aimed to compare SARS-CoV-2 serological responses to primary infection and vaccination in people who developed PCC versus those with an acute infection only. Methods Participants ( n =2,010) were a sub-cohort of the Virus Watch community cohort study in England who experienced mild-moderate SARS-CoV-2 infections, completed surveys on persistent symptoms, and provided monthly finger-prick blood samples for serology. We compared the likelihood of post-infection seroconversion using logistic mixed models and the trajectories of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies using linear mixed models. Results Participants who developed PCC ( n =394) had 1.8x the odds of post-infection seroconversion for anti-N antibodies compared to those with an acute infection only ( n =1616) (adjusted odds ratio= 1.81 (95% confidence interval (CI) 1.16-2.90). Post-infection anti-N levels were persistently elevated in people with PCC (final log anti-N titres at 365 days 0.97, 95% CI 0.76-1.18) compared to those without (0.47, 95% CI 0.31-0.62). No differences were found in post-vaccination anti-S levels or trajectories before or after primary infection between participants with and without PCC; pre-vaccination anti-S responses could not be evaluated. Conclusion People with PCC demonstrated greater and more persistent anti-N antibody responses following primary infection compared to those with an acute infection only. Vaccination response pre- or post-infection did not systematically differ between groups. These findings extend emerging evidence around inflammatory and immune activation following infection in people with PCC.