We report that in a cohort of 45,965 adults, who were receiving either the ChAdOx1 or the BNT162b2 SARS-CoV-2 vaccines, in those who had no prior infection with SARS-CoV-2, seroconversion rates and quantitative antibody levels after a single dose were lower in older individuals, especially in those aged >60 years. Two vaccine doses achieved high responses across all ages. Antibody levels increased more slowly and to lower levels with a single dose of ChAdOx1 compared with a single dose of BNT162b2, but waned following a single dose of BNT162b2 in older individuals. In descriptive latent class models, we identified four responder subgroups, including a ‘low responder’ group that more commonly consisted of people aged >75 years, males and individuals with long-term health conditions. Given our findings, we propose that available vaccines should be prioritized for those not previously infected and that second doses should be prioritized for individuals aged >60 years. Further data are needed to better understand the extent to which quantitative antibody responses are associated with vaccine-mediated protection.

Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as ‘non-responders’ not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies.

Following primary SARS-CoV-2 vaccination, whether boosters or breakthrough infections provide greater protection against SARS-CoV-2 infection is incompletely understood. Here we investigated SARS-CoV-2 antibody correlates of protection against new Omicron BA.4/5 (re-)infections and anti-spike IgG antibody trajectories after a third/booster vaccination or breakthrough infection following second vaccination in 154,149 adults ≥18 y from the United Kingdom general population. Higher antibody levels were associated with increased protection against Omicron BA.4/5 infection and breakthrough infections were associated with higher levels of protection at any given antibody level than boosters. Breakthrough infections generated similar antibody levels to boosters, and the subsequent antibody declines were slightly slower than after boosters. Together our findings show breakthrough infection provides longer-lasting protection against further infections than booster vaccinations. Our findings, considered alongside the risks of severe infection and long-term consequences of infection, have important implications for vaccine policy.

ObjectivesAn initial report of findings from 1.14 million SARS CoV-2 serology tests in National Health Service (NHS) staff to compare NHS staff seroconversion with community seroconversion rates at a regional level.DesignA national cross-sectional survey.SettingA SARS-CoV-2 antibody testing programme offered across all NHS Trusts.Participants1.14 million NHS staff.InterventionSARS-CoV-2 antibody testing.Primary and secondary outcome measuresSARS-CoV-2 antibody testing was used to estimate the seroprevalence of SARS-CoV-2 in NHS staff by region, compared with community seroprevalence as determined by the COVID-19 Infection Survey (Office for National Statistics). We also explored seroprevalence trends by regional COVID-19 activity, using regional death rates as a proxy for COVID-19 ‘activity’.Results1 146 310 tests were undertaken on NHS staff between 26 May and 31 August 2020. 186 897 NHS tests were positive giving a seroconversion rate of 16.3% (95% CI 16.2% to 16.4%), in contrast to the national community seroconversion rate of 5.9% (95% CI 5.3% to 6.6%). There was significant geographical regional variation, which mirrored the trends seen in community prevalence rates. NHS staff were infected at a higher rate than the general population (OR 3.1, 95% CI 2.8 to 3.5). NHS seroconversion by regional death rate suggested a trend towards higher seroconversion rates in the areas with higher COVID-19 ‘activity’.ConclusionsThis is the first cross-sectional survey assessing the risk of COVID-19 disease in healthcare workers at a national level. It is the largest study of its kind. It suggests that NHS staff have a significantly higher rate of COVID-19 seroconversion compared with the general population in England, with regional variation across the country which matches the background population prevalence trends. There was also a trend towards higher seroconversion rates in areas which had experienced high COVID-19 clinical activity. This work has global significance in terms of the value of such a testing programme and contributing to the understanding of healthcare worker seroconversion at a national level.

The physiological effects of vaccination against SARS-CoV-2 (COVID-19) are well documented, yet the behavioural effects not well known. Risk compensation suggests that gains in personal safety, as a result of vaccination, are offset by increases in risky behaviour, such as socialising, commuting and working outside the home. This is potentially important because transmission of SARS-CoV-2 is driven by contacts, which could be amplified by vaccine-related risk compensation. Here, we show that behaviours were overall unrelated to personal vaccination, but—adjusting for variation in mitigation policies—were responsive to the level of vaccination in the wider population: individuals in the UK were risk compensating when rates of vaccination were rising. This effect was observed across four nations of the UK, each of which varied policies autonomously.