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1.
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.

2.
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.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329658

ABSTRACT

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

4.
Lancet ; 399(10332): 1303-1312, 2022 04 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
5.
N Engl J Med ; 386(16): 1532-1546, 2022 04 21.
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.).


Subject(s)
COVID-19 Vaccines , COVID-19 , /therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Case-Control Studies , Dihydrotachysterol , Humans , Immunization, Secondary/adverse effects , SARS-CoV-2/drug effects , SARS-CoV-2/genetics
6.
Nat Commun ; 13(1): 1012, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1709629

ABSTRACT

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16-20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.


Subject(s)
COVID-19/prevention & control , Communicable Diseases, Imported/prevention & control , Quarantine/legislation & jurisprudence , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/transmission , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/transmission , Contact Tracing , England/epidemiology , Genome, Viral/genetics , Genomics , Health Impact Assessment , Humans , SARS-CoV-2/classification , Travel/legislation & jurisprudence , Travel-Related Illness
7.
Clin Infect Dis ; 74(7): 1208-1219, 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1704072

ABSTRACT

BACKGROUND: Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. METHODS: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. RESULTS: In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} < .01-.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [95% CI .02-.38]) and 85% (0.15 [95% CI .08-.26]), respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [95% CI .21-.52]) and any PCR-positive result by 64% (0.36 [95% CI .26-.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7. CONCLUSIONS: Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cohort Studies , Health Personnel , Humans , Immunoglobulins , Incidence , Longitudinal Studies , Vaccination
8.
N Engl J Med ; 386(13): 1207-1220, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1692473

ABSTRACT

BACKGROUND: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. METHODS: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. RESULTS: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. CONCLUSIONS: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).


Subject(s)
Adaptive Immunity , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Adaptive Immunity/immunology , Asymptomatic Diseases , COVID-19/diagnosis , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Health Personnel , Humans , Prospective Studies , United Kingdom , Vaccination/methods
9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308994

ABSTRACT

Background: The emergence of VOC202012/01 in England, known as B.1.1.7 or informally as the ‘UK variant’, has coincided with rapid increases in the number of PCR-confirmed positive cases in areas where the variant has been concentrated. Methods: To assess whether infection with SARS-CoV-2 variant VOC202012/01 is associated with more severe clinical outcomes compared to wild-type infection, genomically sequenced and confirmed variant and wild-type cases were linked to routine healthcare and surveillance datasets. Two statistical analyses were conducted to compare the risk of hospital admission and death within 28 days of test between variant and wild-type cases: a case-control study and an adjusted Cox proportional hazards model. Differences in severity of disease were assessed by comparing hospital admission and mortality, including length of hospitalisation and time to death.Results: Of 63,609 genomically sequenced COVID-19 cases tested in England between October and December 2020 6,038 were variant cases. In the matched cohort analysis 2,821 variant cases were matched to 2,821 to wild-type cases. In the time to event analysis we observed a 34% increased risk in hospitalisation associated with the variant compared to wild-type cases, however, no significant difference in the risk of mortality was observed. Conclusion: We found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increase infection severity associated with this variant. Follow-up studies are needed to assess potential longer-term differences in the clinical outcomes of people infected with the VOC-202012/01 variant.

10.
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.

11.
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

12.
N Engl J Med ; 386(4): 340-350, 2022 01 27.
Article in English | MEDLINE | ID: covidwho-1621313

ABSTRACT

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.


Subject(s)
COVID-19/prevention & control , Adolescent , Adult , Age Factors , Aged , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Female , Hospitalization/statistics & numerical data , Humans , Immunization, Secondary , Immunogenicity, Vaccine , Male , Middle Aged , Patient Acuity , Risk Factors , SARS-CoV-2 , Time Factors , United Kingdom/epidemiology
13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296519

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.

14.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296241

ABSTRACT

The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterisation. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of sub-epidemics that peaked in the early autumn of 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. Alpha grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed Alpha and eliminated nearly all other lineages in early 2021. However, a series of variants (mostly containing the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. Accounting for sustained introductions, however, indicates that their transmissibility is unlikely to have exceeded that of Alpha. Finally, B.1.617.2/Delta was repeatedly introduced to England and grew rapidly in the early summer of 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on June 26.

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293307

ABSTRACT

Background: Understanding the duration and effectiveness of infection and vaccine-acquired SARS-CoV-2 immunity is essential to inform pandemic policy interventions, including the timing of vaccine-boosters. We investigated this in our large prospective cohort of UK healthcare workers undergoing routine asymptomatic PCR testing. Methods We assessed vaccine effectiveness (VE) (up to 10-months after first dose) and infection-acquired immunity by comparing time to PCR-confirmed infection in vaccinated and unvaccinated individuals using a Cox regression-model, adjusted by prior SARS-CoV-2 infection status, vaccine-manufacturer/dosing-interval, demographics and workplace exposures. Results Of 35,768 participants, 27% (n=9,488) had a prior SARS-CoV-2 infection. Vaccine coverage was high: 97% had two-doses (79% BNT162b2 long-interval, 8% BNT162b2 short-interval, 8% ChAdOx1). There were 2,747 primary infections and 210 reinfections between 07/12/2020 and 21/09/2021. Adjusted VE (aVE) decreased from 81% (95% CI 68%-89%) 14-73 days after dose-2 to 46% (95% CI 22%-63%) >6-months;with no significant difference for short-interval BNT162b2 but significantly lower aVE (50% (95% CI 18%-70%) 14-73 days after dose-2 from ChAdOx1. Protection from infection-acquired immunity showed evidence of waning in unvaccinated follow-up but remained consistently over 90% in those who received two doses of vaccine, even in those infected over 15-months ago. Conclusion Two doses of BNT162b2 vaccination induce high short-term protection to SARS-CoV-2 infection, which wanes significantly after six months. Infection-acquired immunity boosted with vaccination remains high over a year after infection. Boosters will be essential to maintain protection in vaccinees who have not had primary infection to reduce infection and transmission in this population. Trial registration number ISRCTN11041050

16.
Lancet Microbe ; 3(1): e21-e31, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1510521

ABSTRACT

BACKGROUND: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer-BioNTech) mRNA vaccine. METHODS: We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3-4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. FINDINGS: Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232-285). At 28 days (IQR 27-33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150-461] vs 55 [IQR 24-132] spot-forming units [SFUs] per 106 PBMCs; p<0·0001). With cryopreserved PBMCs, the T-cell response in previously infected individuals (n=52) after one vaccine dose was equivalent to that of infection-naive individuals (n=19) after receiving two vaccine doses (median 152 [IQR 119-275] vs 162 [104-258] SFUs/106 PBMCs; p=1·00). Anti-spike IgG antibody responses following a single dose in 142 previously infected health-care workers (median 270 373 [IQR 203 461-535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099-55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221-242 467] AU/mL; p<0·0001). INTERPRETATION: A single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern. Future studies should determine the additional benefit of a second dose on the magnitude and durability of immune responses in individuals vaccinated following infection, alongside evaluation of the impact of extending the interval between vaccine doses. FUNDING: UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , Leukocytes, Mononuclear , Prospective Studies , T-Lymphocytes , United Kingdom/epidemiology , Vaccines, Synthetic
17.
Nature ; 600(7889): 506-511, 2021 12.
Article in English | MEDLINE | ID: covidwho-1467111

ABSTRACT

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Genome, Viral/genetics , Genomics , SARS-CoV-2/genetics , Amino Acid Substitution , COVID-19/transmission , England/epidemiology , Epidemiological Monitoring , Humans , Molecular Epidemiology , Mutation , Quarantine/statistics & numerical data , SARS-CoV-2/classification , Spatio-Temporal Analysis , Spike Glycoprotein, Coronavirus/genetics
18.
Lancet Microbe ; 3(2): e151-e158, 2022 02.
Article in English | MEDLINE | ID: covidwho-1440435

ABSTRACT

We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities.


Subject(s)
COVID-19 , COVID-19/epidemiology , Disease Outbreaks , Genomics , Humans , Long-Term Care , SARS-CoV-2/genetics
19.
Microb Genom ; 7(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1349846

ABSTRACT

The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we undertook whole genome sequencing of the SARS-CoV-2 genomes present in positive clinical samples from the Norfolk region. These samples were collected by four major hospitals, multiple minor hospitals, care facilities and community organizations within Norfolk and surrounding areas. We combined clinical metadata with the sequencing data from regional SARS-CoV-2 genomes to understand the origins, genetic variation, transmission and expansion (spread) of the virus within the region and provide context nationally. Data were fed back into the national effort for pandemic management, whilst simultaneously being used to assist local outbreak analyses. Overall, 1565 positive samples (172 per 100 000 population) from 1376 cases were evaluated; for 140 cases between two and six samples were available providing longitudinal data. This represented 42.6 % of all positive samples identified by hospital testing in the region and encompassed those with clinical need, and health and care workers and their families. In total, 1035 cases had genome sequences of sufficient quality to provide phylogenetic lineages. These genomes belonged to 26 distinct global lineages, indicating that there were multiple separate introductions into the region. Furthermore, 100 genetically distinct UK lineages were detected demonstrating local evolution, at a rate of ~2 SNPs per month, and multiple co-occurring lineages as the pandemic progressed. Our analysis: identified a discrete sublineage associated with six care facilities; found no evidence of reinfection in longitudinal samples; ruled out a nosocomial outbreak; identified 16 lineages in key workers which were not in patients, indicating infection control measures were effective; and found the D614G spike protein mutation which is linked to increased transmissibility dominates the samples and rapidly confirmed relatedness of cases in an outbreak at a food processing facility. The large-scale genome sequencing of SARS-CoV-2-positive samples has provided valuable additional data for public health epidemiology in the Norfolk region, and will continue to help identify and untangle hidden transmission chains as the pandemic evolves.


Subject(s)
COVID-19/pathology , Genome, Viral , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/virology , Cluster Analysis , Disease Outbreaks , Genetic Linkage , Humans , Longitudinal Studies , Pandemics , Phylogeny , Polymorphism, Single Nucleotide , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , United Kingdom/epidemiology , Whole Genome Sequencing
20.
EClinicalMedicine ; 39: 101064, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1330784

ABSTRACT

BACKGROUND: Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. METHODS: We examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021. FINDINGS: Across data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May. INTERPRETATION: The outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control efforts. FUNDING: National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy, Academy of Medical Sciences Bill,Melinda Gates Foundation, Imperial College Healthcare NHS Trust, The Novo Nordisk Foundation, MRC Centre for Global Infectious Disease Analysis, Community Jameel, Cancer Research UK, Imperial College COVID-19 Research Fund, Medical Research Council, Wellcome Sanger Institute.

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