SARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort

Abstract

A range of studies globally demonstrate that the effectiveness of SARS-CoV-2 vaccines wane over time, but the total effect of anti-S antibody levels on risk of SARS-CoV-2 infection and whether this varies by vaccine type is not well understood. Here we show that anti-S levels peak three to four weeks following the second dose of vaccine and the geometric mean of the samples is nine fold higher for BNT162b2 than ChAdOx1. Increasing anti-S levels are associated with a reduced risk of SARS-CoV-2 infection (Hazard Ratio 0.85; 95%CIs: 0.79-0.92). We do not find evidence that this antibody relationship with risk of infection varies by second dose vaccine type (BNT162b2 vs. ChAdOx1). In keeping with our anti-S antibody data, we find that people vaccinated with ChAdOx1 had 1.64 times the odds (95% confidence interval 1.45-1.85) of a breakthrough infection compared to BNT162b2. We anticipate our findings to be useful in the estimation of the protective effect of anti-S levels on risk of infection due to Delta. Our findings provide evidence about the relationship between antibody levels and protection for different vaccines and will support decisions on optimising the timing of booster vaccinations and identifying individuals who should be prioritised for booster vaccination, including those who are older, clinically extremely vulnerable, or received ChAdOx1 as their primary course. Our finding that risk of infection by anti-S level does not interact with vaccine type, but that individuals vaccinated with ChAdOx1 were at higher risk of infection, provides additional support for the use of using anti-S levels for estimating vaccine efficacy.

Cohort profile: Virus Watch: Understanding community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviour

“…Work investigating anti-spike SARS-CoV-2 antibody levels among Virus Watch participants who had received COVID-19 vaccines provided key insights into antibody waning and protection against breakthrough infections (8)(9)(10)(11). In one analysis following the vaccine rollout in the UK, we measured antibody levels in almost 9000 study participants who had received two doses of ChAdOx-S1 or BNT162b2 vaccine at 3 weeks after the second dose and 20 weeks after the second dose (9).…”

Determinants of protection against SARS-CoV-2 Omicron BA.1 and Delta infections in fully vaccinated outpatients

“…Higher titres of anti-spike and anti-RBD IgG in uninfected controls compared to breakthrough cases have proved to decrease the risk of symptomatic COVID-19 mainly with Alpha (1, 4) and Delta variants (5, 7, 22). In the present study, we observed a decrease in the risk of infection as anti-RBD IgG levels increased after adjusting for immunisation regimen in the Delta period.…”

“…The median [IQR] fold reduction in neutralisation titres against the Delta isolate compared to the 19A isolate was two [1.3-2.6] for the Delta and two [1. [1][2] for the Omicron period samples, positive and negative patients combined; for the Omicron BA.1 isolate there was a median twelve-fold reduction (IQR [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]) compared to the 19A for the Delta period samples and a median eight-fold reduction (IQR [5.3-12]) for Omicron period samples (Suppl. Fig.…”

High Anti-CoV2S Antibody Levels at Hospitalization Are Associated with Improved Survival in Patients with COVID-19 Vaccine Breakthrough Infection

“…In the literature, cases of breakthrough infections have been described. They are defined as SARS-CoV-2 infection with a positive PCR test in people who are considered fully vaccinated according to the vaccine-specific schemes at the time, i.e., the single vaccination for Janssen Ad26.COV2.S and the double vaccination for the other vaccines at least 14 days previously [ 7 ]. Several studies showed that the anti-CoV2S antibody level has a positive correlation with protection against SARS-CoV-2 infection [ 8 , 9 , 10 ].…”

“…Aldridge et al showed, that an anti-CoV2S level ≥ 500 U/mL has a reduced risk of breakthrough infections after the second vaccination dose [ 7 ]. However, it is not clearly described in the literature which antibody level protects against severe infection or death in fully vaccinated people with subsequent SARS-CoV-2 infection with the Delta variant and whether high levels of antibodies following vaccination are predictive of an improved outcome.…”