Anti-nucleocapsid and anti-spike antibody trajectories in people with post-covid condition versus acute-only infections: a nested longitudinal case-control study within the Virus Watch prospective cohort

People with Post-Covid Condition (PCC) may demonstrate aberrant immune responses post-infection; however, serological follow-up studies are limited. We aim to compare SARS-CoV-2 serological responses to infection and vaccination in people who develop PCC versus those with an acute infection only. Participants (n = 2010) are a sub-cohort of the Virus Watch community cohort in England who provided monthly finger-prick serological samples. We compare 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. Participants who developed PCC (n = 394) have 1.8x the odds of post-infection seroconversion for anti-N antibodies compared to those with an acute infection only (n = 1616) (odds ratio= 1.81 (95% confidence interval (CI) 1.16-2.90); however, these results are moderated by vaccination status and variant - with differences observed in pre-Omicron, unvaccinated participants. Anti-N levels, however, were elevated within 200 days post-infection in people with PCC compared to those without, after accounting for variant and vaccination status. Vaccination response (anti-S) pre- or post-infection did not systematically differ between groups. People with PCC demonstrate persistently higher anti-N antibody levels following primary infection compared to those with an acute infection only. These findings extend emerging evidence around infection-related immune activation and PCC.