Serological outcomes of SARS-CoV-2 infection by vaccination status and variant in England

BACKGROUND: Throughout the SARS-CoV-2 pandemic, several vaccines have been rolled out and distinct variants with different severity and immune profiles emerged in England. Using data from enhanced surveillance of COVID-19 in vaccine eligible individuals we investigated the antibody response following SARS-CoV-2 infection according to vaccination status and variant. METHODS: SARS-CoV-2 PCR-positive eligible individuals were identified from community PCR testing data in England between February 2021 and April 2022 and contacted by nurses to complete questionnaires at recruitment and 21 days post recruitment. Individuals were sent self-sampling kits and self-sampled nasal/oropharyngeal swabs were taken day 1, day 3 and day 7 post-recruitment as well as acute (day 1), convalescent (follow-up) serum and oral fluid samples. Regression analyses were used to investigate how N antibody seroconversion differs by vaccine status, and to investigate how N and S antibody levels differ by vaccine status overall and stratified by variants. Interval-censored analyses and regression analyses were used to investigate the effect of acute S antibody levels on the duration of positivity, the cycle threshold values, the self-reported symptom severity and the number of symptoms reported. RESULTS: A total of 1497 PCR positive individuals were included. A total of 369 (24.7%) individuals were unvaccinated, 359 (24.0%) participants were infected with Alpha, 762 (50.9%) with Delta and 376 (25.2%) with Omicron. The median age of participants was 49 years old (IQR 39-57). Convalescent anti-N antibody levels were lower in vaccinated individuals and convalescent anti-S antibody levels were higher in vaccinated individuals and increased with the number of doses received. Acute anti-S antibody level increased with the number of doses received. Higher acute anti-S antibody levels were associated with a shorter duration of positivity (overall and for the Delta variant). Higher acute anti-S antibody levels were also associated with higher Ct values (overall and for the Alpha and Delta variants). There was no association between the acute anti-S antibody level and self-reported symptom severity. Individuals with higher acute anti-S antibody level were less likely to report six or more symptoms (overall and for Delta variant). CONCLUSION: Understanding the characteristics of the antibody response, its dynamics over time and the immunity it confers is important to inform future vaccination strategies and policies. Our findings suggest that vaccination is associated with high acute anti-S antibody level but reduced convalescent anti-N antibody level. High anti-S antibody level is associated with reduced duration of infection, reduced infectiousness and may also be associated with reduced symptoms severity and number of symptoms.