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

Sarah Beale (), Alexei Yavlinsky, Gemma Moncunill, Wing Lam Erica Fong, Vincent Grigori Nguyen, Jana Kovar, Andrew C. Hayward, Ibrahim Abubakar and Robert W. Aldridge
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Sarah Beale: University College London
Alexei Yavlinsky: University College London
Gemma Moncunill: ISGlobal
Wing Lam Erica Fong: University College London
Vincent Grigori Nguyen: University College London
Jana Kovar: University College London
Andrew C. Hayward: University College London
Ibrahim Abubakar: University College London
Robert W. Aldridge: University College London

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-58766-7

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