ABSTRACT
Background SARS-CoV-2 vaccines stimulate production of antibodies targeting the spike protein (anti-S). The level of antibodies following vaccination and trajectories of waning may differ between vaccines influencing the level of protection, how soon protection is reduced and, consequently the optimum timing of booster doses. Methods We measured SARS-CoV-2 anti-S titre in the context of seronegativity for SARS-CoV-2 anti-Nucleocapsid (anti-N), in samples collected between 1st July and 24th October 2021 in a subset of adults in the Virus Watch community cohort. We compared anti-S levels after BNT162b2 (BioNTech/Pfizer) or ChAdOx1 (AstraZeneca/Oxford) vaccination using time since second dose of vaccination, age, sex and clinical vulnerability to investigate antibody waning. To investigate the use of anti-S levels as a correlate of protection against SARS-CoV-2 infection, we undertook a survival analysis (Kaplan-Meier and Cox) with individuals entering 21 days after their second dose of vaccine, or first antibody test after 1st July (whichever was latest) and exiting with the outcome of SARS-Cov-2 infection or at the end of follow up 24th October 2021. We also undertook a negative test design case-control analysis of infections occurring after the second vaccine dose (breakthrough infections) to determine whether the type of vaccine affected the risk of becoming infected. Results 24049 samples from 8858 individuals (5549 who received a second dose of ChAdOx1 and 3205 BNT162b2) who remained anti-N negative were included in the analysis of anti-S waning over time. Three weeks after the second dose of vaccine BNT162b2 mean anti-S levels were 9039 (95%CI: 7946-10905) U/ml and ChadOx1 were 1025 (95%CI: 917-1146) U/ml. For both vaccines, waning anti-S levels followed a log linear decline from three weeks after the second dose of vaccination. At 20 weeks after the second dose of vaccine, the mean anti-S levels were 1521 (95%CI: 1432-1616) U/ml for BNT162b2 and 342 (95%CI: 322-365) U/ml for ChadOx1. We identified 197 breakthrough infections and found a reduced risk of infection post second dose of vaccine for individuals with anti-S levels greater than or equal to 500 U/ml compared to those with levels under 500 U/ml (HR 0.62; 95%CIs:0.44-0.87; p=0.007). Time to reach an anti-S threshold of 500 U/ml was estimated at 96 days for ChAdOx1 and 257 days for BNT162b2. We found an increased risk of a breakthrough infection for those who received the ChAdOx1 compared to those who received BNT162b2 (OR: 1.43, 95% CIs:1.18-1.73, p<0.001). Discussion Anti-S levels are substantially higher following the second dose of BNT162b2 compared to ChAdOx1. There is a log linear waning in levels for both vaccines following the second dose. Anti-S levels are an important correlate of protection as demonstrated by those with anti-S levels < 500U/ml following vaccination being at significantly greater risk of subsequent infection. Since anti-S levels are substantially lower in ChAdOx1 than in BNT162b2 and both decline at similar rates we would expect waning immunity to occur earlier in ChAdOx1 compared to BNT162b2. Our results showing an increased risk of breakthrough infections for those who were vaccinated with ChAdOx1 compared to BNT162b2 are in line with this hypothesis. Consistent with our data, national analyses of vaccine effectiveness also suggest that waning of immunity for infection and, to a lesser extent for severe disease, is seen earlier in ChAdOx1 than in BNT162b2. Our data demonstrate the importance of booster doses to maintain protection in the elderly and clinically vulnerable and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.
Subject(s)
COVID-19ABSTRACT
Background: Household overcrowding is associated with increased risk of infectious diseases across cultures and countries. Limited data exist in England and Wales linking household overcrowding and risk of COVID-19. We used data collected from the Virus Watch cohort to examine the association between overcrowded households and infection to pandemic coronavirus SARS-CoV-2. Methods: The Virus Watch study is a household community cohort of acute respiratory infections in England & Wales that began recruitment in June 2020. We calculated the persons per room for each household and classified accommodation as overcrowded when the number of roomswas fewer than the number of people. We considered two primary outcomes - PCR-confirmed positive SARS-CoV-2 antigen tests and laboratory confirmed SARS-CoV-2 antibodies (Roche Elecsys anti-N total immunoglobulin assay). We used mixed effects logistic regression models that accounted for household structure to estimate the association between household overcrowding and SARS-CoV-2 infection. Results: The proportion of participants with a positive SARS-CoV-2 PCR result was highest in the overcrowded group (6.6%; 73/1,102) and lowest in the under-occupied group (2.9%; 682/23,219). In a mixed effects logistic regression model that included age, sex, ethnicity, household income and geographical region as fixed effects, and a household-level random effect, we found strong evidence of an increased odds of having a positive PCR SARS-CoV-2 antigen result (Odds Ratio 3.67; 95% CI: 1.91, 7.06; p-value < 0.001) and increased odds of having a positive SARS-CoV-2 antigen result in individuals living in overcrowded houses (2.99; 95% CI: 1.14, 7.81; p-value =0.03) compared to people living in under-occupied houses. Discussion: Public health interventions to prevent and stop the spread of SARS-CoV-2 should consider the much greater risk of infection for people living in overcrowded households and pay greater attention to reducing household transmission. There is an urgent need to better recognise housing as a leading determinant of health in the context of a pandemic and beyond.