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1.
Euro Surveill ; 27(15)2022 04.
Article in English | MEDLINE | ID: covidwho-1869325

ABSTRACT

BackgroundHouseholds appear to be the highest risk setting for COVID-19 transmission. Large household transmission studies in the early stages of the pandemic in Asia reported secondary attack rates ranging from 5 to 30%.AimWe aimed to investigate the transmission dynamics of COVID-19 in household and community settings in the UK.MethodsA prospective case-ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. We estimated household secondary attack rates (SAR), serial intervals and individual and household basic reproduction numbers. The incubation period was estimated using known point source exposures that resulted in secondary cases.ResultsWe included 233 households with two or more people with 472 contacts. The overall household SAR was 37% (95% CI: 31-43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. SAR were lower in larger households and highest when the primary case was younger than 18 years. We estimated a mean incubation period of around 4.5 days.ConclusionsRates of COVID-19 household transmission were high in the UK for ages above and under 18 years, emphasising the need for preventative measures in this setting. This study highlights the importance of the FFX protocol in providing early insights on transmission dynamics.


Subject(s)
COVID-19 , Adolescent , Family Characteristics , Humans , Pandemics , SARS-CoV-2 , United Kingdom/epidemiology
2.
Euro Surveill ; 27(20)2022 05.
Article in English | MEDLINE | ID: covidwho-1862539

ABSTRACT

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , England/epidemiology , Hospitalization , Hospitals , Humans , SARS-CoV-2/genetics
3.
Clin Infect Dis ; 2022 Mar 05.
Article in English | MEDLINE | ID: covidwho-1852990

ABSTRACT

BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of COVID-19 cases using quality-adjusted life days (QALDs) and the recommended EQ-5D instrument in England. METHODS: Prospective cohort study of non-hospitalised, PCR-confirmed SARSCoV2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARSCoV2() controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. RESULTS: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on non-prescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95%-CI: 9.7, 17.7) QALDs, while those reporting symptoms at month 6 lost 32.9 (24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in England. CONCLUSIONS: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337001

ABSTRACT

Objective In September 2020, records of 15,861 SARS-CoV-2 cases failed to upload from the Second Generation Laboratory Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, resulting in a delay in the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on health outcomes: transmission events, hospitalisations, and mortality. Previously, a modelling study had suggested a substantial impact. Design Observational study Setting England. Population Individuals testing positive for SARS-CoV-2 and their reported contacts. Main outcome measures Secondary attack rates (SARs), hospitalisations, and deaths amongst primary and secondary contacts were calculated, compared to all other concurrent, unaffected cases. SGSS records affected by the event were matched to CTAS records and successive contacts and cases were identified. Results The initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared to the control group (3 days). This was associated with lower completion of contact tracing of primary cases in the delay group: 80% (95%CI: 79-81%) in the delay group and 83% (95%CI: 83-84%) in the control group. There was some evidence to suggest an increase in transmission to non-household contacts amongst those affected by the delay. The SAR for non-household contacts was higher amongst secondary contacts in the delay group than the control group (delay group: 7.9%, 95%CI:6.4% to 9.2%;control group: 5.9%, 95%CI: 5.3% to 6.6%). There was no evidence of a difference between the delay and control groups in the odds of hospitalisation (crude odds ratio: 1.1 (95%CI: 0.9 to 1.2) or death (crude odds ratio: 0.7 (0.1 to 4.0)) amongst secondary contacts. Conclusions The delay in contact tracing had a limited impact on population health outcomes. Strengths and limitations of the study Shows empirical data on the health impact of an event leading to a delay in contact tracing so can test hypotheses generated by models of the potential impact of a delay in contact tracing Estimates the extent of further transmission and odds of increased mortality or hospitalisation in up to the third generation of cases affected by the event The event acts as a natural experiment to describe the possible impact of contact tracing, comparing a group affected by chance by delayed contact tracing to a control group who experienced no delay Contact tracing was not completed for all individuals, so the study might not capture all affected contacts or transmissions

5.
Epidemiol Infect ; 150: e99, 2022 05 12.
Article in English | MEDLINE | ID: covidwho-1839478

ABSTRACT

We investigated risk factors associated with COVID-19 by conducting a retrospective, frequency-matched case-control study, with three sampling periods (August-October 2020). We compared cases completing routine contact tracing to asymptomatic population controls. Multivariable analyses estimated adjusted odds ratios (aORs) for non-household community settings. Meta-analyses using random effects provided pooled odds ratios (pORs). Working in healthcare (pOR 2.87; aORs 2.72, 2.81, 3.08, for study periods 1-3 respectively), social care (pOR 4.15; aORs 2.46, 5.06, 5.41, for study periods 1-3 respectively) or hospitality (pOR 2.36; aORs 2.01, 2.54, 2.63, for study periods 1-3 respectively) were associated with increased odds of being a COVID-19 case. Additionally, working in bars, pubs and restaurants, warehouse settings, construction, educational settings were significantly associated. While definitively determining where transmission occurs is impossible, we provide evidence that in certain sectors, the impact of mitigation measures may only be partial and reinforcement of measures should be considered in these settings.


Subject(s)
COVID-19 , COVID-19/epidemiology , Case-Control Studies , Humans , Retrospective Studies , SARS-CoV-2 , Workplace
6.
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.

7.
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
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;
Preprint in English | EuropePMC | ID: ppcovidwho-327707

ABSTRACT

Background: The SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources. Methods Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. Logistic regression was used to control for factors associated with transmission. Findings Analysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16). Interpretation Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

10.
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

11.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326102

ABSTRACT

The introduction of vaccination has changed the landscape for COVID-19 infection, vastly altering the presentation of symptoms and reducing morbidity of infection. We estimate monthly trends and the impact of vaccination upon hospitalised mortality, controlling for baseline demographics and hospital load. We apply competing risks methods to comprehensive public health surveillance data on patients hospitalised with COVID-19 in England. Among a total of 259,727 individuals hospitalised with COVID-19, 51,948 (20.0%) experienced mortality in hospital, with the remainder being discharged or remaining in hospital by end of September 2021. Hospitalised fatality risk ranged from a high of 40.3% (95% confidence interval 39.4, 41.3%) among those admitted in March 2020 to a low of 8.1% (7.2, 9.0%) in June 2021. Older patients and those with multiple co-morbidities were more likely to die in hospital (46.5% for those aged 85 and over vs. 0.5% for those aged 15-24, and 6.3% for those with no comorbidity at baseline vs. 43.0% for those with a Charleson comorbidity index of 5 or above) or else experienced longer stays prior to discharge (median stays of between 5.1-10.4 days for those aged 85+ vs. 0.9-2.4 days for those aged 15-24). The hazard ratio for mortality following hospital admission was 0.72 (0.67, 0.77) among those admitted with a first vaccine dose, and 0.58 (0.54, 0.62) with a second vaccine dose, compared to a reference category of unvaccinated. The prognosis for patients hospitalised with COVID-19 in England has varied substantially throughout the pandemic and is confounded with age, sex, deprivation, baseline comorbidity and hospital load at admission. After controlling for other factors, outcomes for single and double vaccinated patients were significantly improved compared to unvaccinated patients.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321615

ABSTRACT

Background: The SARS-CoV-2 Delta variant is highly transmissible and spreading globally but a detailed understanding of community transmission risks in highly vaccinated populations is lacking.Methods: Between September 2020 and August 2021, we recruited 510 community contacts of 422 UK COVID-19 cases to a cohort study. A total of 7194 upper respiratory tract (URT) samples were tested from sequential daily sampling of participants for up to 20 days. We analysed transmission risk by vaccination status for 139 contacts exposed to the Delta variant. We compared viral load (VL) trajectories from fully-vaccinated cases of Delta infection (n=19) with unvaccinated Delta (n=10), Alpha (n=39) and pre-Alpha (n=49) infections.Findings: The household secondary attack rate for fully-vaccinated contacts exposed to Delta was 19.7% (95%CI:11.6-31.3%), compared with 35.7% (95%CI:16.4-61.2%) in the unvaccinated. One third of infections in Delta-exposed contacts arose from fully-vaccinated index cases and one half of infected contacts were also fully-vaccinated. Seven transmission events between fully vaccinated index-contact pairs occurred. Genomic analysis confirmed transmission pathways between fully-vaccinated individuals within three households. Peak VL was similar in vaccinated and unvaccinated individuals with Delta variant infection but vaccinated Delta cases saw significantly faster VL decline than unvaccinated Alpha or Delta cases. Within infected individuals, faster VL growth was correlated with higher peak VL and slower decline.Interpretation: Although vaccination reduces the risk of Delta infection and causes some changes to viral kinetics, fully-vaccinated individuals with breakthrough infections have peak URT VL similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts.Funding: National Institute for Health Research (Award:NIHR200927)Declaration of Interest: The authors declare no relevant conflicts.Ethical Approval: The study was approved by the Health Research Authority (Research Ethics Committee reference: 20/NW/0231).

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318164

ABSTRACT

Objective: To evaluate the relationship between coronavirus disease 2019 (COVID-19) diagnosis with SARS-CoV-2 variant B.1.1.7 (also known as Variant of Concern 202012/01) and the risk of hospitalisation compared to diagnosis with wildtype SARS-CoV-2 variants. Design: Retrospective cohort, analysed using stratified Cox regression. Setting: Community-based SARS-CoV-2 testing in England, individually linked with hospitalisation data. Participants: 839,278 laboratory-confirmed COVID-19 patients, of whom 36,233 had been hospitalised within 14 days, tested between 23rd November 2020 and 31st January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF). SGTF is a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test. Main outcome measures: Hospitalisation between 1 and 14 days after the first positive SARS-CoV-2 test. Results: 27,710 of 592,409 SGTF patients (4.7%) and 8,523 of 246,869 non-SGTF patients (3.5%) had been hospitalised within 1-14 days. The stratum-adjusted hazard ratio (HR) of hospitalisation was 1.52 (95% confidence interval [CI] 1.47 to 1.57) for COVID-19 patients infected with SGTF variants, compared to those infected with non-SGTF variants. The effect was modified by age (P<0.001), with HRs of 0.93-1.21 for SGTF compared to non-SGTF patients below age 20 years, 1.29 in those aged 20-29, and 1.45-1.65 in age groups 30 years or older. Conclusions: The results suggest that the risk of hospitalisation is higher for individuals infected with the B.1.1.7 variant compared to wildtype SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults above the age of 30.

14.
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.

15.
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.

16.
Clin Infect Dis ; 74(3): 407-415, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684538

ABSTRACT

BACKGROUND: How severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect clinical sensitivity is unknown. METHODS: We combined SARS-CoV-2 testing and contact tracing data from England between 1 September 2020 and 28 February 2021. We used multivariable logistic regression to investigate relationships between polymerase chain reaction (PCR)-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using 1 of 4 LFDs. RESULTS: In total, 231 498/2 474 066 (9%) contacts of 1 064 004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower cycle threshold [Ct] values), for example, 11.7% (95% confidence interval [CI] 11.5-12.0%) at Ct = 15 and 4.5% (95% CI 4.4-4.6%) at Ct = 30. B.1.1.7 infection increased PCR-positive results by ~50%, (eg, 1.55-fold, 95% CI 1.49-1.61, at Ct = 20). PCR-positive results were most common in household contacts (at Ct = 20.1, 8.7% [95% CI 8.6-8.9%]), followed by household visitors (7.1% [95% CI 6.8-7.3%]), contacts at events/activities (5.2% [95% CI 4.9-5.4%]), work/education (4.6% [95% CI 4.4-4.8%]), and least common after outdoor contact (2.9% [95% CI 2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5% (95% CI 89.4-89.6%) and 83.0% (95% CI 82.8-83.1%) of cases with PCR-positive contacts, respectively. CONCLUSIONS: SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ~50%. The best performing LFDs detect most infectious cases.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Child , Family Characteristics , Humans , Viral Load
17.
Lancet Infect Dis ; 22(1): 35-42, 2022 01.
Article in English | MEDLINE | ID: covidwho-1598838

ABSTRACT

BACKGROUND: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. METHODS: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. FINDINGS: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17-43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32-3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08-1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47-8·05] and for hospital admission or emergency care attendance 1·58 [0·69-3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29-4·16] and 1·43 [1·04-1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. INTERPRETATION: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. FUNDING: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.


Subject(s)
COVID-19/virology , Emergency Medical Services/statistics & numerical data , Hospitalization/statistics & numerical data , SARS-CoV-2/pathogenicity , Severity of Illness Index , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Child , Child, Preschool , Cohort Studies , England/epidemiology , Female , Humans , Male , Middle Aged , Proportional Hazards Models , SARS-CoV-2/classification , Young Adult
18.
Lancet Infect Dis ; 22(2): 183-195, 2022 02.
Article in English | MEDLINE | ID: covidwho-1598157

ABSTRACT

BACKGROUND: The SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated individuals with mild delta variant infection in the community. METHODS: Between Sept 13, 2020, and Sept 15, 2021, 602 community contacts (identified via the UK contract-tracing system) of 471 UK COVID-19 index cases were recruited to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts cohort study and contributed 8145 upper respiratory tract samples from daily sampling for up to 20 days. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. We analysed transmission risk by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant-infected index cases. We compared viral load trajectories from fully vaccinated individuals with delta infection (n=29) with unvaccinated individuals with delta (n=16), alpha (B.1.1.7; n=39), and pre-alpha (n=49) infections. Primary outcomes for the epidemiological analysis were to assess the secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases' vaccination status. Primary outcomes for the viral load kinetics analysis were to detect differences in the peak viral load, viral growth rate, and viral decline rate between participants according to SARS-CoV-2 variant and vaccination status. FINDINGS: The SAR in household contacts exposed to the delta variant was 25% (95% CI 18-33) for fully vaccinated individuals compared with 38% (24-53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (median 101 days [IQR 74-120]) than for uninfected individuals (64 days [32-97], p=0·001). SAR among household contacts exposed to fully vaccinated index cases was similar to household contacts exposed to unvaccinated index cases (25% [95% CI 15-35] for vaccinated vs 23% [15-31] for unvaccinated). 12 (39%) of 31 infections in fully vaccinated household contacts arose from fully vaccinated epidemiologically linked index cases, further confirmed by genomic and virological analysis in three index case-contact pairs. Although peak viral load did not differ by vaccination status or variant type, it increased modestly with age (difference of 0·39 [95% credible interval -0·03 to 0·79] in peak log10 viral load per mL between those aged 10 years and 50 years). Fully vaccinated individuals with delta variant infection had a faster (posterior probability >0·84) mean rate of viral load decline (0·95 log10 copies per mL per day) than did unvaccinated individuals with pre-alpha (0·69), alpha (0·82), or delta (0·79) variant infections. Within individuals, faster viral load growth was correlated with higher peak viral load (correlation 0·42 [95% credible interval 0·13 to 0·65]) and slower decline (-0·44 [-0·67 to -0·18]). INTERPRETATION: Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host-virus interactions early in infection may shape the entire viral trajectory. FUNDING: National Institute for Health Research.


Subject(s)
COVID-19/transmission , COVID-19/virology , SARS-CoV-2/physiology , Viral Load/physiology , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Cohort Studies , England/epidemiology , Female , Humans , Kinetics , Longitudinal Studies , Male , Middle Aged , Prospective Studies , United Kingdom/epidemiology , Vaccination , Vaccination Coverage
19.
Lancet Reg Health Eur ; 12: 100252, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1568914

ABSTRACT

BACKGROUND: The SARS-CoV-2 Delta variant (B.1.617.2), first detected in India, has rapidly become the dominant variant in England. Early reports suggest this variant has an increased growth rate suggesting increased transmissibility. This study indirectly assessed differences in transmissibility between the emergent Delta variant compared to the previously dominant Alpha variant (B.1.1.7). METHODS: A matched case-control study was conducted to estimate the odds of household transmission (≥ 2 cases within 14 days) for Delta variant index cases compared with Alpha cases. Cases were derived from national surveillance data (March to June 2021). One-to-two matching was undertaken on geographical location of residence, time period of testing and property type, and a multivariable conditional logistic regression model was used for analysis. FINDINGS: In total 5,976 genomically sequenced index cases in household clusters were matched to 11,952 sporadic index cases (single case within a household). 43.3% (n=2,586) of cases in household clusters were confirmed Delta variant compared to 40.4% (n= 4,824) of sporadic cases. The odds ratio of household transmission was 1.70 among Delta variant cases (95% CI 1.48-1.95, p <0.001) compared to Alpha cases after adjusting for age, sex, ethnicity, index of multiple deprivation (IMD), number of household contacts and vaccination status of index case. INTERPRETATION: We found evidence of increased household transmission of SARS-CoV-2 Delta variant, potentially explaining its success at displacing Alpha variant as the dominant strain in England. With the Delta variant now having been detected in many countries worldwide, the understanding of the transmissibility of this variant is important for informing infection prevention and control policies internationally.

20.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295897

ABSTRACT

Assessing the impact of an intervention using time-series observational data on multiple units and outcomes is a frequent problem in many fields of scientific research. In this paper, we present a novel method to estimate intervention effects in such a setting by generalising existing approaches based on the factor analysis model and developing a Bayesian algorithm for inference. Our method is one of the few that can simultaneously: deal with outcomes of mixed type (continuous, binomial, count);increase efficiency in the estimates of the causal effects by jointly modelling multiple outcomes affected by the intervention;easily provide uncertainty quantification for all causal estimands of interest. We use the proposed approach to evaluate the impact that local tracing partnerships (LTP) had on the effectiveness of England's Test and Trace (TT) programme for COVID-19. Our analyses suggest that, overall, LTPs had a small positive impact on TT. However, there is considerable heterogeneity in the estimates of the causal effects over units and time.

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