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1.
Vaccine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1815247

ABSTRACT

Vaccine effectiveness is lower and wanes faster against infection and symptomatic disease caused by the omicron variant of SARS-CoV-2 than was observed with previous variants. Vaccine effectiveness against severe omicron disease, on average, is higher, but has shown variability, including rapid apparent waning, in some studies. Assessing vaccine effectiveness against omicron severe disease using hospital admission as a measure of severe disease has become more challenging because of omicron’s attenuated intrinsic severity and its high prevalence of infection. Many hospital admissions likely occur among people with incidental omicron infection or among those with infection-induced exacerbation of chronic medical conditions. To address this challenge, the World Health Organization held a virtual meeting on March 15, 2022, to review evidence from several studies that assessed Covid-19 vaccine effectiveness against severe omicron disease using several outcome definitions. Data was shown from studies in South Africa, the United States, the United Kingdom and Qatar. Several approaches were proposed that better characterize vaccine protection against severe Covid-19 disease caused by the omicron variant than using hospitalization of omicron-infected persons to define severe disease. Using more specific definitions for severe respiratory Covid-19 disease, such as indicators of respiratory distress (e.g. oxygen requirement, mechanical ventilation, and ICU admission), showed higher vaccine effectiveness than against hospital admission. Second, vaccine effectiveness against progression from omicron infection to hospitalization, or severe disease, also showed higher vaccine protection. These approaches might better characterize vaccine performance against severe Covid-19 disease caused by omicron, as well as future variants that evade humoral immunity, than using hospitalization with omicron infection as an indicator of severe disease.

2.
Research and Practice in Thrombosis and Haemostasis ; 6(3):e12698, 2022.
Article in English | Wiley | ID: covidwho-1797756

ABSTRACT

Background Several studies have found increased risks of thrombosis with thrombocytopenia syndrome (TTS) following the ChAdOx1 vaccination. However, case ascertainment is often incomplete in large electronic health record (EHR)-based studies. Objectives To assess for an association between clinically validated TTS and COVID-19 vaccination. Methods We used the self-controlled case series method to assess the risks of clinically validated acute TTS after a first COVID-19 vaccine dose (BNT162b2 or ChAdOx1) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case ascertainment was performed uninformed of vaccination status via a retrospective clinical review of hospital EHR systems, including active ascertainment of thrombocytopenia. Results One hundred seventy individuals were admitted to the hospital for a TTS event at the study sites between January 1 and March 31, 2021. A significant increased risk (relative incidence [RI], 5.67;95% confidence interval [CI], 1.02-31.38) of TTS 4 to 27 days after ChAdOx1 was observed in the youngest age group (18- to 39-year-olds). No other period had a significant increase, although for ChAdOx1 for all ages combined the RI was >1 in the 4- to 27- and 28- to 41-day periods (RI, 1.52;95% CI, 0.88-2.63;and (RI, 1.70;95% CI, 0.73-3.8, respectively). There was no significant increased risk of TTS after BNT162b2 in any period. Increased risks of TTS following a positive SARS-CoV-2 test occurred across all age groups and exposure periods. Conclusions We demonstrate an increased risk of TTS in the 4 to 27 days following COVID-19 vaccination, particularly for ChAdOx1. These risks were lower than following SARS-CoV-2 infection. An alternative vaccine may be preferable in younger age groups in whom the risk of postvaccine TTS is greatest.

3.
J Infect ; 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1788130

ABSTRACT

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.

4.
J Infect ; 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1778314

ABSTRACT

OBJECTIVES: To monitor changes in seroprevalence of SARS-CoV-2 antibodies in populations over time and between different demographic groups. METHODS: A subset of practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network provided serum samples, collected when volunteer patients had routine blood tests. We tested these samples for SARS-CoV-2 antibodies using Abbott (Chicago, USA), Roche (Basel, Switzerland) and/or Euroimmun (Luebeck, Germany) assays, and linked the results to the patients' primary care computerised medical records. We report seropositivity by region and age group, and additionally examined the effects of gender, ethnicity, deprivation, rurality, shielding recommendation and smoking status. RESULTS: We estimated seropositivity from patients aged 18-100 years old, which ranged from 4.1% (95% CI 3.1-5.3%) to 8.9% (95% CI 7.8-10.2%) across the different assays and time periods. We found higher Euroimmun seropositivity in younger age groups, people of Black and Asian ethnicity (compared to white), major conurbations, and non-smokers. We did not observe any significant effect by region, gender, deprivation, or shielding recommendation. CONCLUSIONS: Our results suggest that prior to the vaccination programme, most of the population remained unexposed to SARS-CoV-2.

5.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-332455

ABSTRACT

Background: Many high-income countries have deployed third “booster” doses of COVID-19 vaccines to populations and some countries have started offering fourth doses. Methods: The COV-BOOST trial is a multicentre, randomised, controlled, phase II trial of seven COVID-19 vaccines as third dose boosters. The current study invited participants who received BNT162b2 (BNT) as third dose in COV-BOOST to be randomised to receive a fourth dose of BNT or mRNA1273 (50 µg, half-m1273). The COV-BOOST trial is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. Results: Between 11 and 25 January 2022, 166 participants in the original BNT arm were randomised and received a fourth dose vaccine. The median age was 70.1 (interquartile range: 51.6-77.5) years with 51.8 % (n=86) female participants. The median interval between third and fourth dose was 208.5 (interquartile range: 203.25-214.75) days.Pain and fatigue were the most common local and systemic solicited adverse events for BNT and half-m1273. None of three serious adverse events reported after a fourth dose were related to study vaccine.The fold rises in anti-spike IgG pre- and post-fourth dose were 12.19 (95%CI: 10.37-14.32) and 15.90 (95%CI: 12.92-19.58) in BNT and half-m1273 arms respectively, with fold changes compared to the post third dose-peak of 1.59 (95%CI: 1.41-1.78) and 2.19 (95%CI: 1.90-2.52). T cell responses also boosted. Conclusions: Fourth dose COVID-19 mRNA booster vaccines are well-tolerated and boost cellular and humoral immunity up to, and beyond peak levels achieved following third dose boosters (ISRCTN: 73765130).

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331526

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.

7.
Lancet ; 399(10328): 924-944, 2022 03 05.
Article in English | MEDLINE | ID: covidwho-1768606

ABSTRACT

BACKGROUND: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. METHODS: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1-6 months after full vaccination. FINDINGS: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer-BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9-29·8) among people of all ages and 20·7 percentage points (10·2-36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4-41·6) in people of all ages and 32·0 percentage points (11·0-69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1-15·4) in people of all ages and 9·5 percentage points (5·7-14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. INTERPRETATION: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20-30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. FUNDING: Coalition for Epidemic Preparedness Innovations.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Immunization Schedule , Immunization, Secondary , /therapeutic use , Humans , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Time Factors
8.
J Infect Dis ; 2022 Feb 20.
Article in English | MEDLINE | ID: covidwho-1758754

ABSTRACT

To investigate if the AY.4.2 sub-lineage of the SARS-CoV-2 Delta variant is associated with hospitalisation and mortality risks that differ from non-AY.4.2 Delta risks, we performed a retrospective cohort study of sequencing-confirmed COVID-19 cases in England based on linkage of routine healthcare datasets. Using stratified Cox regression, we estimated adjusted hazard ratios (aHR) of hospital admission (aHR=0.85, 95% CI 0.77-0.94), hospital admission or emergency care attendance (aHR=0.87, 95% CI 0.81-0.94) and COVID-19 mortality (aHR=0.85, 95% CI 0.71-1.03). The results indicate that the risks of hospitalisation and mortality is similar or lower for AY.4.2 compared to cases with other Delta sub-lineages.

10.
Elife ; 112022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1742929

ABSTRACT

The distribution of the generation time (the interval between individuals becoming infected and transmitting the virus) characterises changes in the transmission risk during SARS-CoV-2 infections. Inferring the generation time distribution is essential to plan and assess public health measures. We previously developed a mechanistic approach for estimating the generation time, which provided an improved fit to data from the early months of the COVID-19 pandemic (December 2019-March 2020) compared to existing models (Hart et al., 2021). However, few estimates of the generation time exist based on data from later in the pandemic. Here, using data from a household study conducted from March to November 2020 in the UK, we provide updated estimates of the generation time. We considered both a commonly used approach in which the transmission risk is assumed to be independent of when symptoms develop, and our mechanistic model in which transmission and symptoms are linked explicitly. Assuming independent transmission and symptoms, we estimated a mean generation time (4.2 days, 95% credible interval 3.3-5.3 days) similar to previous estimates from other countries, but with a higher standard deviation (4.9 days, 3.0-8.3 days). Using our mechanistic approach, we estimated a longer mean generation time (5.9 days, 5.2-7.0 days) and a similar standard deviation (4.8 days, 4.0-6.3 days). As well as estimating the generation time using data from the entire study period, we also considered whether the generation time varied temporally. Both models suggest a shorter mean generation time in September-November 2020 compared to earlier months. Since the SARS-CoV-2 generation time appears to be changing, further data collection and analysis is necessary to continue to monitor ongoing transmission and inform future public health policy decisions.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Humans , Pandemics , Public Health , United Kingdom/epidemiology
11.
Nat Med ; 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1740457

ABSTRACT

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.

12.
Lancet ; 399(10332): 1303-1312, 2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1740323

ABSTRACT

BACKGROUND: The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort. METHODS: Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases). FINDINGS: The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54-0·58); for hospital admission and death, HR estimates were 0·41 (0·39-0·43) and 0·31 (0·26-0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85-1·42) in those younger than 10 years, decreasing to 0·25 (0·21-0·30) in 60-69-year-olds, and then increasing to 0·47 (0·40-0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32-0·68]) and unvaccinated (0·18 [0·06-0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88-1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48-0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28-0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8-11 weeks post-booster vs unvaccinated: 0·22 [0·20-0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2. INTERPRETATION: The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections. FUNDING: Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Cohort Studies , England/epidemiology , Hospitalization , Humans , Vaccines, Synthetic
13.
N Engl J Med ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1730372

ABSTRACT

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.).

14.
BMJ Open ; 12(3): e055278, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1723800

ABSTRACT

OBJECTIVE: To determine characteristics associated with COVID-19 vaccine coverage among individuals aged 50 years and above in England since the beginning of the programme. DESIGN: Observational cross-sectional study assessed by logistic regression and mean prevalence margins. SETTING: COVID-19 vaccinations delivered in England from 8 December 2020 to 17 May 2021. PARTICIPANTS: 30 624 257/61 967 781 (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. INTERVENTIONS: Vaccination status with COVID-19 vaccinations. MAIN OUTCOME MEASURES: Proportion, adjusted ORs and mean prevalence margins for individuals not vaccinated with dose 1 among those aged 50-69 years and dose 1 and 2 among those aged 70 years and above. RESULTS: Of 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, of 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 (95% CI 5.29 to 5.43) greater among Pakistani and black/African/Caribbean compared with 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 with those who did not. This was the opposite to that observed for dose 1, where the odds of being unvaccinated was significantly higher among those not living in a care home (0.89 (95% CI 0.87 to 0.91)). CONCLUSIONS: We 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.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , England/epidemiology , Humans , Middle Aged , SARS-CoV-2 , Vaccination
15.
Microbiol Spectr ; 10(1): e0228921, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702730

ABSTRACT

In March 2020, the Rare and Imported Pathogens Laboratory at the UK Health Security Agency (UKHSA) (formerly Public Health England [PHE]) Porton Down, was tasked by the Department of Health and Social Care with setting up a national surveillance laboratory facility to study SARS-CoV-2 antibody responses and population-level sero-surveillance in response to the growing SARS-CoV-2 outbreak. In the following 12 months, the laboratory tested more than 160,000 samples, facilitating a wide range of research and informing UKHSA, DHSC, and UK government policy. Here we describe the implementation and use of the Euroimmun anti-SARS-CoV-2 IgG assay and provide an extended evaluation of its performance. We present a markedly improved overall sensitivity of 91.39% (≥14 days 92.74%, ≥21 days 93.59%) compared to our small-scale early study, and a specificity of 98.56%. In addition, we detail extended characteristics of the Euroimmun assay: intra- and interassay precision, correlation to neutralization, and assay linearity. IMPORTANCE Serology assays have been useful in determining those with previous SARS-CoV-2 infection in a wide range of research and serosurveillance projects. However, assays vary in their sensitivity at detecting SARS-CoV-2 antibodies. Here, we detail an extended evaluation and characterization of the Euroimmun anti-SARS-CoV-2 IgG assay, one that has been widely used within the United Kingdom on over 160,000 samples to date.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/blood , Immunoglobulin G/blood , SARS-CoV-2/immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Humans , Public Health , Reagent Kits, Diagnostic , SARS-CoV-2/genetics , Sensitivity and Specificity , United Kingdom/epidemiology
17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311891

ABSTRACT

Background: BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK. We determined the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in our healthcare worker (HCW) cohort study of staff undergoing regular asymptomatic testing.Methods: The SIREN study is a prospective cohort study among staff working in publicly funded hospitals. Baseline risk factors, vaccination status (from 8/12/2020-5/2/2021), and symptoms are recorded at 2 weekly intervals and all SARS-CoV-2 polymerase chain reaction (PCR) and antibody test results documented. A mixed effect proportional hazards frailty model using a Poisson distribution was used to calculate hazard ratios to compare time to infection in unvaccinated and vaccinated participants to estimate the impact of the BNT162b2 vaccine on all (asymptomatic and symptomatic) infection.Findings: Vaccine coverage was 89% on 5/2/2021. Significantly lower coverage was associated with prior infection (aOR 0.59 95% confidence interval [CI] 0.54-0.64), female (aOR 0.72, 95% CI 0.63-0.82), aged under 35 years, being from minority ethnic groups (especially Black, aOR 0.26, 95% CI 0.21-0.32), porters/security guards (aOR 0.61, 95% CI 0.42-0.90),or midwife (aOR 0.74, 95% CI 0.57-0.97), and living in more deprived neighbourhoods (IMD 1 (most) vs. 5 (least) (aOR 0.75, 95% CI 0.65-0.87). A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort.Conclusion: Our study demonstrates that the BNT162b2 vaccine effectively prevents both symptomatic and asymptomatic infection in working age adults;this cohort was vaccinated when the dominant variant in circulation was B1.1.7 and demonstrates effectiveness against this variant.Trial Registration: IRAS ID 284460, REC reference 20/SC/0230 Berkshire Research Ethics Committee, Health Research Authority and Health and Care Research Wales approval granted 22 May 2020. Trial registered with ISRCTN, Trial ID: ISRCTN11041050. https://www.isrctn.com/ISRCTN11041050Funding: The study is funded by the United Kingdom’s Department of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments. Funding is also provided by the National Institute for Health Research (NIHR) as an Urgent Public Health Priority Study (UPHP). SH, VH are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (PHE) (NIHR200915). AC is supported by NIHR HealthProtection Research Unit in Behavioural Science and Evaluation at University of Bristol in partnership with Public Health England. MR, NA, AC are supported by NIHR HealthProtection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England.Conflict of Interest: The Immunisation and Countermeasures Division has provided vaccine manufacturers(including Pfizer) with post-marketing surveillance reports on pneumococcal andmeningococcal infection which the companies are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports.Ethical Approval: The study was approved by the Berkshire Research Ethics Committee, Health Research Authority (IRAS ID 284460, REC reference 20/SC/0230) on 22 May 2020;the vaccine amendment was approved on 12/1/2021.

18.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305510

ABSTRACT

Background: Streptococcus pneumoniae coinfection with seasonal and pandemic influenza results in synergistic lethality, but there are limited data on pneumococcal coinfection with SARS-CoV-2 during the current COVID-19 pandemic.Methods: Public Health England conducts invasive pneumococcal disease (IPD) and COVID-19 surveillance in England. IPD trends from 2000/01 to 2019/20 were analysed and cases between 01 February and 30 June 2020 were linked with laboratory-confirmed SARS-CoV-2 infections.Findings: IPD incidence in 2019/20 (7.6/100,000;3,964 cases) was 30% (IRR 0.70, 95%CI, 0.18-2.67) lower compared to 2018/19 (10.9/100,000, 3,964 cases) with large reductions observed across all age-groups during March-June 2020. The serotypes responsible for IPD during 2019/20 were similar to previous years. There were 160,886 SARS-CoV-2 infections and 1,159 IPD cases between February and June 2020, including 40 IPD/SARS-CoV-2 coinfections (0.025% [95%CI, 0.018-0.034] of SARS-CoV-2 infections;3.5% [95%CI, 2.5-4.8] of IPD cases), 21 with COVID-19 diagnosed 3-28 days after IPD and 27 who developed COVID-19 >28 days after IPD. Case fatality was 63.2% (25/40) in the coinfection group compared to 47.6% (10/21) in those who developed COVID-19 3-14 days after IPD, and 33.3% (9/27) in patients who developed IPD and COVID-19 more than 28 days apart (p<0.001).Interpretation: The COVID-19 pandemic and the consequent lockdown was associated with large declines in IPD across all age groups. IPD/SARS-CoV-2 confections were rare but associated with high case-fatality, mainly in older adults. The rarity, age distribution and serotype distribution of IPD/SARS-CoV-2 coinfections does not support wider extension of pneumococcal vaccination during the COVID-19 pandemicFunding: PHEDeclaration of Interests: SNL performs contract research for vaccine manufacturers (including GSK, Pfizer, and Sanofi Pasteur) on behalf of St George’s University of London and Public Health England but receives no personal remuneration. The Immunisation and Countermeasures Division at PHE has provided pharmaceutical companies with post-marketing surveillance reports on vaccine-preventable infections, which the companies are required to submit to the UK Licensing Authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. All other authors declare no competing interests.Ethics Approval Statement: PHE has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information for national surveillance of communicable diseases. This includes PHE’s responsibility to monitor the safety and effectiveness of vaccines, and as such, individual patient consent is not required.

19.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-326260

ABSTRACT

Background: The Omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection compared with Delta (B.1.617.2). We sought to better characterise Omicron severity relative to Delta by assessing the relative risk of hospital attendance, hospital admission or death in a large national cohort. Methods: Individual-level data on laboratory-confirmed COVID-19 cases resident in England between 22 November 2021 and 9 January 2022 were linked to routine datasets on vaccination status, hospitalisation and mortality. The relative risk of attendance at hospital within 14 days, or death within 28 days following confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, region and vaccination status and further adjusted for sex, index of multiple deprivation decile, evidence of a prior infection and year of age within each age band. A secondary analysis estimated variant- and vaccine-specific vaccine effectiveness and the intrinsic relative severity of Omicron infection compared with Delta;i.e. the relative risk in unvaccinated cases. Findings: We found that the adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with Omicron compared with Delta was 0.56 (95%CI: 0.54-0.58);for hospital admission and death the estimates were 0.41 (95%CI: 0.39-0.43) and 0.31 (95%CI: 0.26-0.37), respectively. Omicron vs Delta HR estimates varied with age for all endpoints examined: the adjusted HR for hospital admission was 1.07 (95%CI: 0.83-1.38) in <10 year-olds, falling to 0.25 (95%CI: 0.21-0.30) in 60-69 year-olds, and rising to 0.48 (95%CI: 0.40-0.57) in ≥80 year-olds. For both variants, past infection gave some protection against death both in vaccinated (HR: 0.45 [95%CI: 0.30-0.68]) and unvaccinated (0.14 [95%CI: 0.04-0.45]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR: 0.99 [95%CI: 0.9-1.08]), whilst for unvaccinated cases moderate protection remained (HR: 0.53 [95%CI: 0.46-0.61]). Estimation of variant-specific vaccine effectiveness gave lower Omicron vs Delta HR estimates for hospital admission (0.29 [95%CI: 0.28-0.31]) in unvaccinated cases than estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in Omicron cases (HR for hospital admission 8-11 weeks post booster, compared with unvaccinated: 0.22 [95%CI: 0.19-0.24]), with the protection afforded after a booster not being significantly affected by the vaccine used for doses 1 and 2. Interpretation: The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for Omicron compared with Delta cases, with higher reductions for more severe endpoints and significant variation with age. The (low) risk of hospital admission in children <10 years of age did not differ significantly by variant, while 60-69 year-olds had an approximately 75% reduced risk of hospital admission with Omicron compared with Delta. Underlying the observed HRs is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. A documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvac

20.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323456

ABSTRACT

Background: In England, the reopening of universities in September 2020 coincided with a rapid increase in SARS-CoV-2 infection rates in university aged young adults. This study aimed to estimate SARS-CoV-2 antibody prevalence in students attending universities that had experienced a COVID-19 outbreak after reopening for the autumn term in September 2020.Methods: A cross-sectional serosurvey was conducted during 02-11 December 2020 in students aged ≤ 25 years across five universities in England. Blood samples for SARS-CoV-2 antibody testing were obtained using a self-sampling kit and analysed using the Abbott SARS-CoV-2 N antibody and/or an in-house receptor binding domain (RBD) assay. Findings: SARS-CoV-2 seroprevalence in 2,905 university students was 17.8% (95%CI, 16.5-19.3), ranging between 7.6%-29.7% across the five universities. Seropositivity was associated with being younger likely to represent first year undergraduates (aOR 3.2, 95% CI 2.0-4.9), living in halls of residence (aOR 2.1, 95% CI 1.7-2.7) and sharing a kitchen with an increasing number of students (shared with 4-7 individuals, aOR 1.43, 95%CI 1.12-1.82;shared with 8 or more individuals, aOR 1.53, 95% CI 1.04-2.24). Seropositivity was 49% in students living in halls of residence that reported high SARS-CoV-2 infection rates (>8%) during the autumn term.Interpretation: Despite large numbers of cases and outbreaks in universities, less than one in five students (17.8%) overall had SARS-CoV-2 antibodies at the end of the autumn term in England. In university halls of residence affected by a COVID-19 outbreak, however, nearly half the resident students became infected and developed SARS-CoV-2 antibodies.

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