Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission: a prospective cohort study in England

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated the effectiveness of Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford AstraZeneca adenovirus vector vaccine (ChAdOx1) vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: : Households were recruited based on adult purported index cases testing positive after reverse transcription-quantitative (RT-q)PCR testing of oral-nasal swabs. Purported index cases and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment and a subset of the PCR-positive swabs underwent genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Results: : Between 2 February 2021 and 10 September 2021, 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained, of whom 113 (41%) became PCR positive. Delta lineages had 1.53 times the risk (95% Credible Interval: 1.04 – 2.20) of transmission than Alpha;contacts older than 18 years old were 1.48 (1.20 – 1.91) and 1.02 (0.93 – 1.16) times more likely to acquire an Alpha or Delta infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 36% (-1%, 66%) and 49% (18%, 73%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 69% (9%, 95%) vs. 18% (-11%, 59%), respectively, for BNT162b2 and 24% (-41%, 72%) vs. 9% (-15%, 42%), respectively, for ChAdOx1. Conclusions: : BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting, although their protection against infection within this setting is low.

Protection against symptomatic infection with delta (B.1.617.2) and omicron (B.1.1.529) BA.1 and BA.2 SARS-CoV-2 variants after previous infection and vaccination in adolescents in England, August, 2021-March, 2022: a national, observational, test-negative, case-control study.

BACKGROUND: Little is known about protection against SARS-CoV-2 infection following previous infection with specific individual SARS-CoV-2 variants, COVID-19 vaccination, and a combination of previous infection and vaccination (hybrid immunity) in adolescents. We aimed to estimate protection against symptomatic PCR-confirmed infection with the delta (B.1.617.2) and omicron (B.1.1.529) variants in adolescents with previous infection, mRNA vaccination, and hybrid immunity. METHODS: We conducted an observational, test-negative, case-control study using national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England. Symptomatic adolescents aged 12-17 years who were unvaccinated or had received primary BNT162b2 immunisation at symptom onset and had a community SARS-CoV-2 PCR test were included. Vaccination and previous SARS-CoV-2 infection status in adolescents with PCR-confirmed COVID-19 (cases) were compared with vaccination and previous infection status in adolescents who had a negative SARS-CoV-2 PCR test (controls). Vaccination data were collected from the National Immunisation Management System, and were linked to PCR testing data. The primary outcome was protection against SARS-CoV-2 delta and omicron infection (defined as 1 - odds of vaccination or previous infection in cases divided by odds of vaccination or previous infection in controls). FINDINGS: Between Aug 9, 2021, and March 31, 2022, 1 161 704 SARS-CoV-2 PCR tests were linked to COVID-19 vaccination status, including 390 467 positive tests with the delta variant and 212 433 positive tests with the omicron variants BA.1 and BA.2. In unvaccinated adolescents, previous SARS-CoV-2 infection with wildtype, alpha (B.1.1.7), or delta strains provided greater protection against subsequent delta infection (>86·1%) than against subsequent omicron infection (<52·4%); previous delta or omicron infection provided similar protection against omicron reinfection (52·4% [95% CI 50·9-53·8] vs 59·3% [46·7-69·0]). In adolescents with no previous infection, vaccination provided lower protection against omicron infection than against delta infection, with omicron protection peaking at 64·5% (95% CI 63·6-65·4) at 2-14 weeks after dose two and 62·9% (60·5-65·1) at 2-14 weeks after dose three, with waning protection after each dose. Adolescents with hybrid immunity from previous infection and vaccination had the highest protection, irrespective of the SARS-CoV-2 strain in the primary infection. The highest protection against omicron infection was observed in adolescents with vaccination and previous omicron infection, reaching 96·4% (95% CI 84·4-99·1) at 15-24 weeks after vaccine dose two. INTERPRETATION: Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection. FUNDING: None.

Monitoring the COVID-19 immunisation programme through a national immunisation Management system - England's experience.

BACKGROUND: In England routine vaccinations are recorded in either the patients General Practice record or in series of sub-national vaccine registers that are not interoperable. During the COVID-19 pandemic it was established that COVID vaccines would need to be delivered in multiple settings where current vaccine registers do not exist. We describe how a national vaccine register was created to collect data on COVID-19 vaccines. METHODS: The National Immunisation Management System (NIMS) was developed by a range of health and digital government agencies. Vaccinations delivered are entered on an application which is verified by individual National Health Service number in a centralised system. UKHSA receive a feed of this data to use for monitoring vaccine coverage, effectiveness, and safety. To validate the vaccination data, we compared vaccine records to self-reported vaccination dose, manufacturer, and vaccination date from the enhanced surveillance system from 11 February 2021 to 24 August 2021. RESULTS: With the Implementation of NIMS, we have been able to successfully record COVID-19 vaccinations delivered in multiple settings. Of 1,129 individuals, 97.8% were recorded in NIMS as unvaccinated compared to those who self-reported as unvaccinated. One hundred percent and 99.3% of individuals recorded in NIMS as having at least one dose and two doses of the COVID-19 vaccine were also self-reported as having at least one and two doses, respectively. Of the 100% reporting at least one dose, 98.3% self-reported the same vaccination date as NIMS. A total of 98.8% and 99.3% had the same manufacturer information for their first dose and second dose as that which was self-reported, respectively. DISCUSSION: Daily access to individual-level vaccine data from NIMS has allowed UKHSA to estimate vaccine coverage and provide some of the world's first vaccine effectiveness estimates rapidly and accurately.

Effectiveness of ChAdOx1-S COVID-19 booster vaccination against the Omicron and Delta variants in England.

Despite the availability of the ChAdOx1-S booster vaccine, little is known about the real-world effectiveness although clinical trials have demonstrated enhanced immunity following a ChAdOx1-S booster. In England 43,171 individuals received a ChAdOx1-S booster whilst 13,038,908 individuals received BNT162b2 in the same period. ChAdOx1-S booster recipients 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 clinically extremely vulnerable group (adjusted OR 1.84 (1.79-1.89)) or severely immunosuppressed (adjusted OR 2.05 (1.96-2.13)). The effectiveness of the ChAdOx1-S and BNT162b2 boosters is estimated here using a test-negative case-control study. Protection against symptomatic disease with the Omicron variant peaks at 66.1% (16.6 to 86.3%) and 68.5% (65.7 to 71.2%) for the ChAdOx1-S and BNT162b2 boosters in older adults. Protection against hospitalisation peaks at 82.3% (64.2 to 91.3%) and 90.9% (88.7 to 92.7%). For Delta, effectiveness against hospitalisation is 80.9% (15.6% to 95.7%) and 93.9% (92.8% to 94.9%) after ChAdOx1-S and BNT162b2 booster vaccination. This study supports the consideration of ChAdOx1-S booster vaccination for protection against severe COVID-19 in settings yet to offer boosters and suggests that individuals who received a ChAdOx1-S booster do not require re-vaccination ahead of others.

Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study.

The Omicron variant has been associated with reduced vaccine effectiveness (VE) against mild disease with rapid waning. Meanwhile Omicron has also been associated with milder disease. Protection against severe disease has been substantially higher than protection against infection with previous variants. We used a test-negative case-control design to estimate VE against hospitalisation with the Omicron and Delta variants using PCR testing linked to hospital records. We investigated the impact of increasing the specificity and severity of hospitalisation definitions on VE. Among 18-64-year-olds using cases admitted via emergency care, VE after a 3rd dose peaked at 82.4% and dropped to 53.6% by 15+ weeks after the 3rd dose; using all admissions for > = 2 days stay with a respiratory code in the primary diagnostic field VE ranged from 90.9% to 67.4%; further restricting to those on oxygen/ventilated/intensive care VE ranged from 97.1% to 75.9%. Among 65+ year olds the equivalent VE estimates were 92.4% to 76.9%; 91.3% to 85.3% and 95.8% to 86.8%. Here we show that with milder Omicron disease contamination of hospitalisations with incidental cases is likely to reduce VE estimates. VE estimates increase, and waning is reduced, when specific hospitalisation definitions are used.

Effectiveness of BNT162b2 and ChAdOx-1 vaccines in residents of long-term care facilities in England using a time-varying proportional hazards model.

INTRODUCTION: residents of long-term care facilities (LTCFs) are at high risk of adverse outcomes from SARS-CoV-2. We aimed to estimate the vaccine effectiveness (VE) of one and two doses of BNT162b2 and ChAdOx-1 against SARS CoV-2 infection and COVID-19-related death in residents of LTCFs. METHODS: this observational study used testing, vaccination and mortality data for LTCF residents aged ≥ 65 years who were regularly tested regardless of symptoms from 8 December 2020 to 30 September 2021 in England. Adjusted VE, calculated as one minus adjusted hazard ratio, was estimated using time-varying Cox proportional hazards models for infection and death within 28 days of positive test result. Vaccine status was defined by receipt of one or two doses of vaccine and assessed over a range of intervals. RESULTS: of 197,885 LTCF residents, 47,087 (23.8%) had a positive test and 11,329 (5.8%) died within 28 days of a positive test during the study period. Relative to unvaccinated individuals, VE for infection was highest for ChAdOx-1 at 61% (40-74%) at 1-4 weeks and for BNT162b2 at 69% (52-80%) at 11-15 weeks following the second dose. Against death, VE was highest for ChAdOx-1 at 83% (58-94%) at 1-4 weeks and for BNT162b2 at 91% (75-97%) at 11-15 weeks following second dose. CONCLUSIONS: compared with unvaccinated residents, vaccination with one dose of BNT162b2 or ChAdOx-1 provided moderate protection against infection and death in residents of LTCFs. Protection against death improved after two doses. However, some waning of protection over time was noted.

Effectiveness of COVID-19 booster vaccines against COVID-19-related symptoms, hospitalization and death in England.

Booster vaccination with messenger RNA (mRNA) vaccines has been offered to adults in England starting on 14 September 2021. We used a test-negative case-control design to estimate the relative effectiveness of a booster dose of BNT162b2 (Pfizer-BioNTech) compared to only a two-dose primary course (at least 175 days after the second dose) or unvaccinated individuals from 13 September 2021 to 5 December 2021, when Delta variant was dominant in circulation. Outcomes were symptomatic coronavirus disease 2019 (COVID-19) and hospitalization. The relative effectiveness against symptomatic disease 14-34 days after a BNT162b2 or mRNA-1273 (Moderna) booster after a ChAdOx1-S (AstraZeneca) and BNT162b2 as a primary course ranged from around 85% to 95%. Absolute vaccine effectiveness ranged from 94% to 97% and was similar in all age groups. Limited waning was seen 10 or more weeks after the booster. Against hospitalization or death, absolute effectiveness of a BNT162b2 booster ranged from around 97% to 99% in all age groups irrespective of the primary course, with no evidence of waning up to 10 weeks. This study provides real-world evidence of substantially increased protection from the booster vaccine dose against mild and severe disease irrespective of the primary course.

Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant.

BACKGROUND: A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. RESULTS: Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. CONCLUSIONS: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).

Effects of COVID-19 Pandemic Response on Service Provision for Sexually Transmitted Infections, HIV, and Viral Hepatitis, England.

Since the coronavirus disease pandemic response began in March 2020, tests, vaccinations, diagnoses, and treatment initiations for sexual health, HIV, and viral hepatitis in England have declined. The shift towards online and outreach services happened rapidly during 2020 and highlights the need to evaluate the effects of these strategies on health inequalities.

Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. RESULTS: Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. CONCLUSIONS: We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.