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1.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.09.05.23295073

ABSTRACT

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 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 1,497 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.


Subject(s)
COVID-19
2.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.03.31.23288018

ABSTRACT

Abstract Background Bivalent BA.1 booster vaccines were offered to adults aged 50 years and older and clinically vulnerable individuals as part of the autumn COVID-19 booster vaccination programme 2022 in England. Methods A test-negative case-control study was used to estimate the duration of protection of the monovalent vaccines against hospitalisation as compared to those unvaccinated. In addition, the incremental VE of the bivalent BA.1 booster vaccines was estimated relative to those with waned immunity where the last dose was at least 6 months prior amongst those aged 50 years and older. Findings The protection conferred by the monovalent vaccines was well maintained long-term: absolute VE against hospitalisation amongst those aged 65 years and older who had received at least 3 doses plateaued from 6 months after the last dose at around 50%. Incremental VE (in addition to the protection from earlier vaccines) of the bivalent BA.1 boosters against hospitalisation peaked at 53.0% (95% C.I.; 47.9-57.5%) (equivalent to an absolute VE of approximately 75%) before waning to around 35.9% (95% C.I.; 31.4-40.1%) after 10 or more weeks. Interpretation This study provides evidence of the long-term duration of protection of the monovalent vaccines, suggesting individuals at lower risk of severe disease who did not receive a booster in autumn 2022 may not require regular re-vaccination. Furthermore, this study finds good evidence that the bivalent BA.1 booster vaccines are highly effective against hospitalisation amongst those aged 50 years and older with the sub-lineages of Omicron present in the autumn/winter of 2022 in England. Funding None.


Subject(s)
COVID-19
3.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.31.22279444

ABSTRACT

The Omicron sub-lineages BA.4 and BA.5 were first detected in England in April 2022. A case surge followed despite England having recently experienced waves with BA.1 and BA.2. This study used a whole population test-negative case-control study design to estimate the effectiveness of the vaccines currently in use as part of the UK COVID-19 vaccination programme against hospitalisation following infection with BA.4 and BA.5 as compared to BA.2 during a period of co-circulation. Incremental VE was estimated in those vaccinated with either a third or fourth dose as compared to individuals with waned immunity who had received their second dose at least 25 weeks prior. Vaccination status was included as an independent variable and effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls. During the study period, there were 32,845 eligible tests from hospitalised individuals. Of these, 25,862 were negative (controls), 3,432 were BA.2, 273 were BA.4, 947 were BA.5 and 2,331 were either BA.4 or BA.5 cases. There was no evidence of reduced VE against hospitalisation for BA.4 or BA.5 as compared to BA.2. The incremental VE was 56.8% (95% C.I.; 24.0-75.4%), 59.9% (95% C.I.; 45.6-70.5%) and 52.4% (95% C.I.; 43.2-60.1%) for BA.4, BA.5 and BA.2, respectively, at 2 to 14 weeks after a third or fourth dose. VE against hospitalisation with BA.4/5 or BA.2 was slightly higher for the mRNA-1273 booster than the BNT162b2 booster at all time-points investigated, but confidence intervals overlapped. These data provide reassuring evidence of the protection conferred by the current vaccines against severe disease with BA.4 and BA.5.


Subject(s)
COVID-19
4.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.19.22278987

ABSTRACT

Background Little is known about the protection following prior infection with different SARS-CoV-2 variants, COVID-19 vaccination, and a combination of the two (hybrid immunity) in adolescents. Methods We used national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England to estimate protection following previous infection and vaccination against symptomatic PCR-confirmed delta and omicron (BA.1 or BA.2) variants in 11-17-year-olds using a test-negative case-control design. Findings By 31 March 2022, 63.6% of 16-17-year-olds and 48.2% of 12-15-year-olds had received more than one COVID-19 mRNA vaccine dose. Between 08 August 2021 and 31 March 2022, 1,161,704 SARS-CoV-2 PCR-tests were successfully linked to COVID-19 vaccination status. In unvaccinated adolescents, prior infection with wildtype, alpha or delta provided greater protection against subsequent delta infection than subsequent omicron; prior omicron infection provided had the highest protection against omicron reinfection (59.3%; 95%CI: 46.7-69.0). In infection-naive adolescents, vaccination provided lower protection against symptomatic omicron infection than delta, peaking at 64.5% (95%CI; 63.6-65.4) 2-14 days after dose two and 62.9% (95%CI; 60.5-65.1) 2-14 weeks after dose three, with rapidly waning protection after each dose. Previously infected and vaccinated adolescents had the highest protection, irrespective of primary infecting SARS-CoV-2 strain. The highest protection against omicron was observed in vaccinated adolescents with prior omicron infection, reaching 96.4% (95%CI, 84.4-99.1) at 15-24 weeks post dose two. Interpretation All variants provide some protection against symptomatic reinfection and vaccination adds to protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provides the most robust protection.


Subject(s)
COVID-19
5.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.07.26.501570

ABSTRACT

The Omicron variant of SARS-CoV-2 is now globally dominant but despite high prevalence little is known regarding the immune response in children. We determined the antibody and cellular immune response following Omicron infection in children aged 6-14 years and related this to prior SARS-CoV-2 infection and vaccination status. Primary Omicron infection elicited a weak antibody response and only 53% of children developed detectable neutralising antibodies. In contrast, children with secondary Omicron infection following prior infection with a pre-Omicron variant developed 24-fold higher antibody titres and neutralisation of Omicron. Vaccination elicited the highest levels of antibody response and was also strongly immunogenic following prior natural infection with Omicron. Cellular responses against Omicron were robust and broadly equivalent in all study groups. These data reveal that primary Omicron infection elicits a weak humoral immune response in children and may presage a clinical profile of recurrent infection as seen with antecedent seasonal coronaviruses. Vaccination may represent the most effective approach to control infection whilst cellular immunity should offer strong clinical protection.


Subject(s)
COVID-19
6.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1646307.v1

ABSTRACT

Background: In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries and assess the risk of SARS-CoV-2 infection and incidence rates in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England. Methods This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak. Results 324 nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21–3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01–4.19%) or staff (3.44%; 95%CI, 3.10–3.82%). Among staff, incidence rates were lower if the index case was a child (26.28%; 95%CI, 23.54–29.21%%) compared to a staff member (32.98%; 95%CI, 31.19–34.82%), with the highest incidence rate when the index case was also a staff member (37.52%; 95%CI, 35.39–39.70%). Compared to November 2020, outbreak sizes and incidence rates were higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in


Subject(s)
COVID-19
7.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.04.29.22274483

ABSTRACT

BackgroundDespite the potential widespread global use of the ChAdOx1-S booster, to date there are no published data on the real-world effectiveness. VE studies have found one and two doses of the ChAdOx1-S vaccine to be highly effective, and clinical trial data have demonstrated enhanced immunity following a ChAdOx1-S booster. In England, some individuals received a ChAdOx1-S booster where vaccination with mRNA vaccines was clinically contraindicated. MethodsThe demographic characteristics of those who received a ChAdOx1-S booster were compared to those who received a BNT162b2 booster. A test-negative case control design was used to estimate vaccine effectiveness of the ChAdOx1-S booster against symptomatic disease and hospitalisation in England. FindingsThose who received a ChAdOx1-S booster were more likely to be female (adjusted odds ratio (OR) 1.67 (1.64-1.71)), in a clinical risk group (adjusted OR 1.58 (1.54-1.63)), in the CEV group (adjusted OR 1.84 (1.79-1.89)) or severely immunosuppressed (adjusted OR 2.05 (1.96-2.13)). Protection against symptomatic disease in those aged 65 years and older peaked at 66.1% (16.6 to 86.3%) and 68.5% (65.7 to 71.2%) amongst those who received the ChAdOx1-S and BNT162b2 booster vaccines, respectively. Protection waned to 44.5% (22.4 to 60.2%) and 54.1% (50.5 to 57.5%) after 5-9 weeks. Protection against hospitalisation following Omicron infection peaked at 82.3% (64.2 to 91.3%) after receiving a ChAdOx1-S booster, as compared to 90.9% (88.7 to 92.7%) for those who received a BNT162b2 booster. InterpretationDifferences in the population boosted with ChAdOx1-S in England renders direct comparison of vaccine effectiveness by manufacturer challenging. Nonetheless, this study supports the use of the ChAdOx1-S booster for protection against severe disease with COVID-19 in settings that have not yet offered booster doses and suggests that those who received ChAdOx1-S as a booster in England do not require re-vaccination ahead of others. FundingUKHSA


Subject(s)
COVID-19 , Protein S Deficiency
8.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.04.01.22273281

ABSTRACT

Background The omicron (B.1.1.529) variant has been associated with reduced vaccine effectiveness (VE) against infection and mild disease with rapid waning, even after a third dose, nevertheless omicron has also been associated with milder disease than previous variants. With previous variants protection against severe disease has been substantially higher than protection against infection. Methods We used a test-negative case-control design to estimate VE against hospitalisation with the omicron and delta variants using community and in hospital testing linked to hospital records. As a milder disease, there may be an increasing proportion of hospitalised individuals with Omicron as an incidental finding. We therefore investigated the impact of using more specific and more severe hospitalisation indicators on VE. Results Among 18 to 64 year olds using all Covid-19 cases admitted via emergency care VE after a booster peaked at 82.4% and dropped to 53.6% by 15+ weeks after the booster; using all admissions for >= 2 days stay with a respiratory code in the primary diagnostic field VE ranged from 90.9% down to 67.4%; further restricting to those on oxygen/ventilated/on intensive care VE ranged from 97.1% down to 75.9%. Among 65+ year olds the equivalent VE estimates were 92.4% down to 76.9%; 91.3% down to 85.3% and 95.8% down to 86.8%. Conclusions With generally milder disease seen with Omicron, in particular in younger adults, contamination of hospitalisations with incidental cases is likely to reduce VE estimates against hospitalisation. VE estimates improve and waning and waning is more limited when definitions of hospitalisation that are more specific to severe respiratory disease are used.


Subject(s)
COVID-19 , Respiratory Tract Diseases
9.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.03.22.22272691

ABSTRACT

The BA.1 sub-lineage of the Omicron (B.1.1.529) variant, first detected in the UK in mid-November 2021, rapidly became the dominant strain partly due to reduced vaccine effectiveness. An increase in a second Omicron sub-lineage BA.2 was observed in early January 2022. In this study we use a test-negative case control study design to estimate vaccine effectiveness against symptomatic disease with BA.1 and BA.2 after one or two doses of BNT162b2, ChAdOx1-S or mRNA-1273, and after booster doses of BNT162b2 or mRNA-1273 during a period of co-circulation. Overall, there was no evidence that vaccine effectiveness against symptomatic disease is reduced following infection with the BA.2 sub-lineage as compared to BA.1. Furthermore, similar rates of waning were observed after the second and booster dose for each sub-lineage. These data provide reassuring evidence of the effectiveness of the vaccines currently in use against symptomatic disease caused by BA.2.


Subject(s)
COVID-19
10.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.14.21267615

ABSTRACT

Abstract Background A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. Methods We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. Results Between 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. Conclusions Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.


Subject(s)
COVID-19
11.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1108654.v1

ABSTRACT

We present a comprehensive analysis of antibody and cellular responses in children aged 12-16 years who received COVID-19 vaccination with ChAdOx1 (n=6) or mRNA vaccine (mRNA-1273 or BNT162b2, n=9) using a 12-week extended-interval schedule. mRNA vaccination of seropositive children induces high antibody levels, with one dose, but a second dose is required in infection-naïve children. Following a second ChAdOx1 dose, antibody titres were higher than natural infection, but lower than mRNA vaccination. Vaccination induced live virus neutralising antibodies against Alpha, Beta and Delta variants, however, a second dose is required in infection-naïve children. We found higher T-cell responses following mRNA vaccination than ChAdOx1. Phenotyping of responses showed predominantly early effector-memory CD4 T cell populations, with a type-1 cytotoxic cytokine signature, with IL-10. These data demonstrate mRNA vaccination induces a co-ordinated superior antibody and robust cellular responses in children. Seronegative children require a prime-boost regime for optimal protection.


Subject(s)
COVID-19
12.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.11.15.21266341

ABSTRACT

Background In September 2021, the UK Government introduced a booster programme targeting individuals over 50 and those in a clinical risk group. Individuals were offered either a full dose of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine or a half dose of the mRNA-1273 (Spikevax, Moderna) vaccine, irrespective of the vaccine received as the primary course Methods We used a test-negative case-control design to estimate the Vaccine Effectiveness (VE) of the booster dose BNT162b2 (Comirnaty, Pfizer-BioNTech) in those aged over 50 against symptomatic disease in post booster time intervals compared to individuals at least 140 days post a second dose with no booster dose recorded. In a secondary analysis, we also compared to unvaccinated individuals and to the 2 to 6 day period after a booster dose was received. Analyses were stratified by which primary doses had been received and any mixed primary courses were excluded. Results The relative VE estimate in the 14 days after the BNT162b2 (Comirnaty, Pfizer-BioNTech) booster dose, compared to individuals that received a two-dose primary course, was 87.4 (95% confidence interval 84.9-89.4) in those individuals who received two doses ChAdOx1-S (Vaxzevria, AstraZeneca) as a primary course and 84.4 (95% confidence interval 82.8-85.8) in those individuals who received two doses of BNT162b2 (Comirnaty, Pfizer-BioNTech) as a primary course. Using the 2-6 day period post the booster dose as the baseline gave similar results. The absolute VE from 14 days after the booster, using the unvaccinated baseline, was 93.1(95% confidence interval 91.7-94.3) in those with ChAdOx1-S (Vaxzevria, AstraZeneca) as their primary course and 94.0 (93.4-94.6) for BNT162b2 (Comirnaty, Pfizer-BioNTech) as their primary course. Conclusions Our study provides real world evidence of significant increased protection from the booster vaccine dose against symptomatic disease in those aged over 50 year of age irrespective of which primary course was received.


Subject(s)
COVID-19
13.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.10.22.21264701

ABSTRACT

Background This study measured the long-term health-related quality of life of non-hospitalised COVID-19 cases with PCR-confirmed SARS-CoV-2(+) infection using the recommended instrument in England (the EQ-5D). Methods Prospective cohort study of SARS-CoV-2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARS-CoV-2(-) controls. Main outcomes were loss of quality-adjusted life days (QALDs); physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. Results Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on non-prescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 15.9 (95%-CI: 12.1, 19.7) QALDs, while those reporting symptoms at month 6 lost 34.1 (29.0, 39.2) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 21% of the total COVID-19-related disease burden in England. Conclusions One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms. summary Losses of health-related quality of life in non-hospitalised COVID-19 cases increase by age and for cases with symptoms after 6 months. At a population level, at least 21% of the total COVID-19-related disease burden in England is attributable to morbidity.


Subject(s)
COVID-19 , Dyspnea
14.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.09.14.21263578

ABSTRACT

In England, the National Immunisation Management System (NIMS) has been used to deliver COVID-19 vaccinations across England, monitor vaccine coverage, and assess vaccine effectiveness and safety. The NIMS was developed by a joint collaboration between a range of health and digital government agencies. Vaccinations delivered at large vaccination sites, pharmacies, hospitals and in primary care are entered on a point of care application which is verified using the unique NHS number in a centralised system containing information for everyone resident and registered with a GP in England. Vaccination details and additional data from hospital and GP records (such as priority groups) are sent to NHS Digital for data linkage. The NIMS constantly receives updated details from NHS Digital for all individuals and these data are provided to Public Health England (PHE) in a secure environment. PHE primarily use the NIMS for vaccine coverage, vaccine effectiveness and safety. Daily access to individual-level vaccine data has allowed PHE to rapidly and accurately estimate vaccine coverage and provide some of the worlds first vaccine effectiveness estimates. Other countries evaluating the roll-out and effect of COVID-19 vaccine programmes should consider a vaccine register or immunisation information system similar to the NIMS.


Subject(s)
COVID-19
15.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.09.15.21263583

ABSTRACT

BackgroundCOVID-19 vaccines have been used for 9 months in the UK. Real world data have demonstrated the vaccines to be highly effective against COVID-19, severe disease and death. Here, we estimate vaccine effectiveness over time since the second dose of Comirnaty, Vaxzevria and Spikevax in England. MethodsWe used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease, hospitalisation and mortality by age, comorbidity status and over time after the second dose to investigate waning separately for Alpha and Delta variants. ResultsVaccine effectiveness against symptomatic disease peaked in the early weeks after the second dose and then fell to 47.3 (95% CI 45 to 49.6) and 69.7 (95% CI 68.7 to 70.5) by 20+ weeks against the Delta variant for Vaxzevria and Comirnaty, respectively. Waning of vaccine effectiveness was greater for 65+ year-olds compared to 40-64 year-olds. Vaccine effectiveness fell less against hospitalisations to 77.0 (70.3 to 82.3) and 92.7 (90.3 to 94.6) beyond 20 weeks post-vaccination and 78.7 (95% CI 52.7 to 90.4) and 90.4 (95% CI 85.1 to 93.8) against death for Vaxzevria and Comirnaty, respectively. Greater waning was observed among 65+ year-olds in a clinically extremely vulnerable group and 40-64-year olds with underlying medical conditions compared to healthy adults. ConclusionsWe observed limited waning in vaccine effectiveness against hospitalisation and death more than 20 weeks post-vaccination with Vaxzevria or Comirnaty. Waning was greater in older adults and those in a clinical risk group, suggesting that these individuals should be prioritised for booster doses.


Subject(s)
COVID-19 , Death
16.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3922678

ABSTRACT

Background: We investigated the effect of both doses of either BNT162b2 or ChAdOx-1 vaccine among residents of Long-term care facilities (LTCFs) in England. This cohort is at particularly high risk for severe outcomes related to COVID-19 and is regularly tested regardless of symptoms.Methods: This observational study uses testing, immunisation and mortality data from 8 December 2020 to 25 June 2021 in LTCF residents aged 65 years and above. Cox proportional hazards models were used to derive adjusted hazard ratios (aHR) for the risk of infection and death within 28 days of positive test result, adjusted for sex, age-group, previous infection, deprivation, and incidence rate in the local authority area. The impact of interval between first and second dose was also explored. Findings: Of 219733 LTCF residents, 41828 (19%) had a positive test and 10719 (4.9%) died within 28 days of a positive test during the study period. Relative to unvaccinated individuals, aHR for infection were lowest at 0.43 (95% CI 0.35-0.52) 36-49 days after first dose and 0.27 (0.20-0.38) at 29-60 days following second dose . Against death, aHR was lowest at 0.25 (0.20-0.31) 28-56 days after first dose and 0.13 (0-05-0.32) in the 1-14 days after second dose. As expected, some waning of protection against infection was observed after seven weeks from first dose which persisted to 2-4 weeks following second dose. Interpretation: Vaccination with one dose of BNT162b2 and ChAdOx-1 provides moderate protection against infection and death in residents in LTCFs. Protection is strong after two doses.Funding: None to declare.Declaration of Interest: None to declare. Ethical Approval: Vaccine effectiveness studies are undertaken by Public Health England as part of ongoing surveillance activities and did not require ethical approval.


Subject(s)
COVID-19
17.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.08.27.21262422

ABSTRACT

ObjectiveTo determine characteristics associated with COVID-19 vaccine coverage among individuals aged 50 years and above in England since the beginning of the programme. DesignObservational cross-sectional study assessed by logistic regression and mean prevalence margins. SettingCOVID-19 vaccinations delivered in England from 08 December 2020 - 17 May 2021. Participants30,624,257/ 61,967,781 (49.4%) and 17,360,045/ 61,967,781 (28.1%) individuals in England were recorded as vaccinated in the National Immunisation Management System with a first dose and a second dose of a COVID-19 vaccine, respectively. InterventionsVaccination status with COVID-19 vaccinations. Main Outcome MeasuresProportion, adjusted odds ratios and mean prevalence margins for individuals not vaccinated with dose 1 among those aged 50-69 years old and dose 1 and 2 among those aged 70 years old and above. ResultsAmong individuals aged 50 years and above, Black/African/Caribbean ethnic group was the least likely of all ethnic groups to be vaccinated with dose 1 of the COVID-19 vaccine. However, among those aged 70 years and above, the odds of not having dose 2 was 5.53 (95% CI 5.42 to 5.63) and 5.36 (90% CI 5.29 to 5.43) greater among Pakistani and Black/African/Caribbean compared to White British ethnicity, respectively. The odds of not receiving dose 2 was 1.18 (95% CI 1.16 to 1.20) higher among individuals who lived in a care home compared to those who did not. This was the opposite to that observed for dose 1, where the odds of not being vaccinated was significantly higher among those not living in a care home (0.89 (95% CI 0.87 to 0.91)). ConclusionsWe found that there are characteristics associated with low COVID-19 vaccine coverage. Inequalities, such as ethnicity are a major contributor to suboptimal coverage and tailored interventions are required to improve coverage and protect the population from SARS-CoV-2. Article summaryO_ST_ABSStrengths and Limitations of this studyC_ST_ABSO_LIThis is the is the first study assessing characteristics associated with COVID-19 vaccine coverage for all individuals aged 50 years and above in England. C_LIO_LIThis study uses data from the National Immunisation Management System (NIMS) which is based on all individuals in England with a registered NHS number. C_LIO_LIThis centralised national system captures individual level data for both vaccination status and demographic characteristics and allows for linkage to other datasets such as health care worker and care home resident status. C_LIO_LIThis study does not include those without an NHS number and, therefore, it is possible we have underestimated the number of vaccines delivered and odds of not being vaccinated for characteristics such as ethnic groups where we have seen the greatest impact. C_LIO_LIResidual errors in data entry on the point of care apps at the vaccination sites may have also occurred, though these errors are not likely to be widespread. C_LI


Subject(s)
COVID-19
18.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3895741

ABSTRACT

Background: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. Methods: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. Results: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. Interpretation: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.


Subject(s)
COVID-19
19.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3895187

ABSTRACT

Background : Little is known about the views of adolescents returning to secondary school during the current COVID-19 pandemic. Methods: In September 2020, Public Health England (PHE) recruited staff and students in secondary schools to provide nasal swabs, oral fluid and blood samples for SARS-CoV-2 infection and antibody testing. Students aged 11-18 years in five London schools completed a short questionnaire about their perception of the pandemic, returning to school, risk to themselves and to others and infection control measures, and participating in school testing. Results: A questionnaire was completed by 64% (297/462) participants. Students were generally not anxious at all (19.7%; 58/294) or not really anxious (40.0%, 114/295) about returning to school, although 5.4% (n=16/295) were extremely nervous. Most students were very worried about transmitting the virus to their family (60.2%; 177/294) rather than other students (22.0%; 65/296) or school staff (19.3%; 57/296), or catching the infection themselves (12.5%; 37/296). Students better maintained physical distancing in the presence of school staff (84.6%; 247/292) and in public places (79.5%; 233/293) but not when with other students (46.8%; 137/293) or friends (40.8%; 120/294). A greater proportion of younger students (school years 7-9) reported not being anxious at all than 16-18 year olds (47/174 [27.0%] vs 3/63 [4.8%]; p=0.001). They were also less likely to adhere to physical distancing and wearing face masks. Most students reported positive experiences with testing in schools, with 92.3% (262/284) agreeing to have another blood test in future visits.Conclusions: Younger students were less concerned about catching and transmitting SARS-CoV-2 and were less likely to adhere to protective measures. Greater awareness of the potential risks of COVID-19 transmission between secondary school students potentially leading to increased risk of infection in their teachers and their household members may increase adherence to infection control measures within and outside schools.


Subject(s)
COVID-19
20.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.07.14.21260496

ABSTRACT

Background In England, the rapid spread of the SARS-Cov-2 Alpha (B.1.1.7) variant from November 2020 led to national lockdown, including school closures in January 2021. We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021. Methods Public Health England initiated SARS-CoV-2 surveillance in 18 secondary schools across six regions in September 2020. Participants provided nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term and at the start of the spring term (March 2021). Findings In March 2021, 1895 participants (1100 students, 795 staff) were tested; 5.6% (61/1094) students and 4.4% (35/792) staff had laboratory-confirmed SARS-CoV-2 infection between December 2020 and March 2021. Nucleoprotein antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike protein antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021 (median 15.9 weeks), 14.8% (97/656; 95% CI: 12.2-17.7) students and 10.0% (59/590; 95% CI: 7.7-12.7) staff seroconverted. Weekly seroconversion rates were similar from September to December 2020 (8.0/1000) and from December 2020 to March 2021 (7.9/1000; students: 9.3/1,000; staff: 6.3/1,000). Interpretation By March 2021, a third of secondary school students and staff had serological evidence of prior infection based on N-antibody seropositivity, and an additional third of staff had evidence of vaccine-induced immunity based on S-antibody seropositivity. Further studies are needed to assess the impact of the Delta variant. Research in Context Evidence Before this study The Alpha variant is 30-70% more transmissible than previously circulating SARS-CoV-2 strains in adults and children. One outbreak investigation in childcare settings estimated similar secondary attack rates with the Alpha variant in children and adults. There are limited data on the impact of the Alpha variant in educational settings. In England, cases in primary and secondary school aged children increased rapidly from late November 2020 and peaked at the end of December 2020, leading to national lockdown including school closures. Added Value of This Study Seroconversion rates in staff and students during December 2020 to March 2021, when the Alpha variant was the primary circulating strain in England, were similar to the period between September 2020 and December 2020 when schools were fully open for in-person teaching. By March 2021, a third of students overall and more than half the students in some regions were seropositive for SARS-CoV-2 antibodies. Among staff, too, around a third had evidence of prior infection on serological testing and a further third had vaccine-induced immunity. Implications of all the Available Evidence SARS-CoV-2 antibody seroprevalence was high among secondary school students in March 2021 and is likely to be higher following the emergence of an even more transmissible Delta variant in May 2021. Education staff are increasingly being protected by the national COVID-19 immunisation programme. These findings have important implications for countries that are considering vaccination of children to control the pandemic


Subject(s)
COVID-19
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