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BackgroundSARS-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. MethodsWe 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. Results24049 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). DiscussionAnti-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.
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BackgroundDiagnostic testing forms a major part of the UKs response to the current COVID-19 pandemic with tests offered to people with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. MethodsIn this analysis of the Bug Watch prospective community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests and four second wave scenarios and then compared to current national capacity. ResultsThe baseline incidence of cough or fever in the UK is expected to rise rapidly from 154,554 (95%CI 103,083 - 231,725) cases per day in August 2020 to 250,708 (95%CI 181,095 - 347,080) in September, peaking at 444,660 (95%CI 353,084 - 559,988) in December. If 80% of baseline cough or fever cases request tests, average daily UK testing demand would exceed current capacity for five consecutive months (October 2020 to February 2021), with a peak demand of 147,240 (95%CI 73,978 - 239,502) tests per day above capacity in December 2020. ConclusionsOur results show that current national COVID-19 testing capacity is likely to be exceeded by demand due to baseline cough and fever alone. This study highlights that the UKs response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is immediately scaled up to meet this high predicted demand.
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BackgroundThere is an ongoing pandemic of the viral respiratory disease COVID-19. People experiencing homelessness are vulnerable to infection and severe disease. Health and housing authorities in England have developed a residential intervention that aims to isolate those vulnerable to severe disease (COVID-PROTECT) and care for people with symptoms (COVID-CARE). MethodsWe used a discrete-time Markov chain model to forecast COVID-19 infections among people experiencing homelessness, given strong containment measures in the general population and some transmission among 35,817 people living in 1,065 hostels, and 11,748 people sleeping rough (the do nothing scenario). We then estimated demand for beds if those eligible are offered COVID-PROTECT and COVID-CARE. We estimated the reduction in the number of COVID-19 cases, deaths, and hospital admissions that could be achieved by these interventions. We also conducted sensitivity and scenario analyses to identify programme success factors. ResultsIn a do nothing scenario, we estimate that 34% of the homeless population could get COVID-19 between March and August 2020, with 364 deaths, 4,074 hospital admissions and 572 critical care admissions. In our base intervention scenario, demand for COVID-PROTECT peaks at 9,934 beds, and demand for COVID-CARE peaks at 1,366 beds. The intervention could reduce transmission by removing symptomatic individuals from the community, and preventing vulnerable individuals from being infected. This could lead to a reduction of 164 deaths, 2,624 hospital admissions, and 248 critical care admissions over this period. Sensitivity analyses showed that the number of deaths is sensitive to transmission of COVID-19 in COVID-PROTECT. If COVID-PROTECT capacity is limited, scenario analyses show the benefit of prioritising people who are vulnerable to severe disease. ConclusionSupportive accommodation can mitigate the impact of the COVID-19 pandemic on the homeless population of England, and reduce the burden on acute hospitals.