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1.
Spatial and Spatio-temporal Epidemiology ; : 100523, 2022.
Article in English | ScienceDirect | ID: covidwho-1882529

ABSTRACT

Better understanding the risk factors that exacerbate Covid-19 symptoms and lead to worse health outcomes is vitally important in the public health fight against the virus. One such risk factor that is currently under investigation is air pollution concentrations, with some studies finding statistically significant effects while other studies have found no consistent associations. The aim of this paper is to add to this global evidence base on the potential association between air pollution concentrations and Covid-19 hospitalisations and deaths, by presenting the first study on this topic at the small-area scale in Scotland, United Kingdom. Our study is one of the most comprehensive to date in terms of its temporal coverage, as it includes all hospitalisations and deaths in Scotland between 1st March 2020 and 31st July 2021. We quantify the effects of air pollution on Covid-19 outcomes using a small-area spatial ecological study design, with inference using Bayesian hierarchical models that allow for the residual spatial correlation present in the data. A key advantage of our study is its extensive sensitivity analyses, which examines the robustness of the results to our modelling assumptions. We find clear evidence that PM2.5 concentrations are associated with hospital admissions, with a 1 μgm−3 increase in concentrations being associated with between a 7.4% and a 9.3% increase in hospitalisations. In addition, we find some evidence that PM2.5 concentrations are associated with deaths, with a 1 μgm−3 increase in concentrations being associated with between a 2.9% and a 10.3% increase in deaths.

2.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-334531

ABSTRACT

Background: Two doses of COVID-19 vaccine offer greater protection than one dose. There are known disparities in COVID-19 outcomes and vaccine uptake. However, it is not known whether non-uptake of the second dose in people who have already received their first dose is predicted by differences in demographic characteristics and disease risk. Methods: We conducted a retrospective cohort study using computerised medical record data from the nationally representative Oxford-Royal College of General Practitioners primary care sentinel cohort (N=7,952,861). Among adults who received at least one dose of Oxford-AstraZeneca ChAdOx1, mRNA Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccines, we used univariable and multivariable logistic regressions to estimate the odds ratios (ORs) and adjusted ORs (aORs), and their 95% confidence intervals (95% CI), of second dose uptake. Findings: In adults vaccinated with one dose (n=2,802,314), younger age, ethnic minorities, rurality (aOR=0.93 (95% CI 0.91-0.94)), East of England and the South West, current (0.59 (0.58-0.60)) and ex-smokers (0.93 (0.91-0.94)), severe mental illness (0.58 (0.56-0.60)) among other comorbidities, COVID-19 (0.57 (0.55-0.58)) or adverse events after their first dose, were associated with lower second dose uptake. Male sex (1.02 (1.00-1.03)), increasing socioeconomic status, asthma (1.04 (1.02-1.07)), and first dose mRNA vaccine (1.28 (1.27-1.30)) were associated with higher likelihood of second dose uptake. Interpretation: Several demographic and risk groups at higher risk of adverse COVID-19 outcomes are less likely to receive second COVID-19 vaccination. Initiatives to increase vaccine uptake targeting people in sociodemographic groups and with comorbidities where interventions might have the greatest impact are needed.

3.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-333394

ABSTRACT

Background: Brazil and Scotland have used mRNA boosters in their respective populations since September, 2021 with Omicron’s emergence accelerating their booster programme. Despite this, both countries have reported substantial recent increases in COVID-19 cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear. Methods: Using a test-negative design, we analysed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus a mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes (hospitalisation or death) during the period of Omicron dominance in Brazil and Scotland. We also stratified analyses by age and primary series vaccine type. Findings: At 2-4 weeks after the mRNA booster, VE of ChAdOx1 or BNT162b2 vaccines plus a mRNA booster against symptomatic SARS-CoV-2 infection was 42.3% (95% confidence interval [CI] 41.6-42.9) in Brazil and 53.4% (95%CI 51.4-55.3) in Scotland, waning to 5.4% (95%CI 3.2-7.5) in Brazil and 29.2% (95%CI 25.0-33.1) in Scotland at ≥13 weeks. VE against severe outcomes in Brazil was 89.8% (95%CI 88.9-90.6) at 2-4 weeks post-booster, decreasing to 80.2% (95%CI 78.0-82.2) at ≥13 weeks (p for trend <0.0001). During the same period in Scotland, VE went from 81.8% (95%CI 69.1-89.3) to 75.8% (95%CI 55.0-87.0) (p for trend = 0.127). In Brazil, individuals aged ≥65 years showed evidence of waning with VE dropping from 83.1% (95%CI 80.3-85.4) at 2-4 weeks after booster to 76.9% (95%CI 74.0-79.5) at ≥13 weeks. Interpretation: mRNA boosters after a primary vaccination schedule with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron, but substantial and more sustained protection against severe COVID-19 outcomes for at least 13 weeks.

4.
Lancet Infect Dis ; 2022 Apr 22.
Article in English | MEDLINE | ID: covidwho-1799641

ABSTRACT

BACKGROUND: Since its emergence in November, 2021, in southern Africa, the SARS-CoV-2 omicron variant of concern (VOC) has rapidly spread across the world. We aimed to investigate the severity of omicron and the extent to which booster vaccines are effective in preventing symptomatic infection. METHODS: In this study, using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, we did a cohort analysis with a nested test-negative design incident case-control study covering the period Nov 1-Dec 19, 2021, to provide initial estimates of omicron severity and the effectiveness of vaccine boosters against symptomatic disease relative to 25 weeks or more after the second vaccine dose. Primary care data derived from 940 general practices across Scotland were linked to laboratory data and hospital admission data. We compared outcomes between infection with the delta VOC (defined as S-gene positive) and the omicron VOC (defined as S-gene negative). We assessed effectiveness against symptomatic SARS-CoV-2 infection, with infection confirmed through a positive RT-PCR. FINDINGS: By Dec 19, 2021, there were 23 840 S-gene-negative cases in Scotland, which were predominantly among those aged 20-39 years (11 732 [49·2%]). The proportion of S-gene-negative cases that were possible reinfections was more than ten times that of S-gene-positive cases (7·6% vs 0·7%; p<0·0001). There were 15 hospital admissions in S-gene-negative individuals, giving an adjusted observed-to-expected admissions ratio of 0·32 (95% CI 0·19-0·52). The booster vaccine dose was associated with a 57% (54-60) reduction in the risk of symptomatic S-gene-negative infection relative to individuals who tested positive 25 weeks or more after the second vaccine dose. INTERPRETATION: These early national data suggest that omicron is associated with a two-thirds reduction in the risk of COVID-19 hospitalisation compared with delta. Although offering the greatest protection against delta, the booster dose of vaccination offers substantial additional protection against the risk of symptomatic COVID-19 for omicron compared with 25 weeks or more after the second vaccine dose. FUNDING: Health Data Research UK, National Core Studies, Public Health Scotland, Scottish Government, UK Research and Innovation, and University of Edinburgh.

5.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-332238

ABSTRACT

Background: Little is known about vaccine effectiveness (VE) over time among adolescents, especially against the SARS-CoV-2 B.1.1.529 (Omicron) variant. This study assessed the associations between time since two-dose vaccination with BNT162b2 and the occurrence of symptomatic SARS-CoV-2 infection and severe COVID-19 among adolescents in Brazil and Scotland. Methods: We conducted test-negative design in adolescents aged 12-17 years with COVID-19 related symptoms in Brazil from September 8, 2021, to March 8, 2022, and Scotland from August 6, 2021, to March 1, 2022. We linked records of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) and antigen tests to national vaccination and clinical records. We estimated the adjusted odds ratio and VE with 95% CI, using logistic regression, across fortnightly periods, against symptomatic COVID-19 for both countries and against severe COVID-19 (hospitalisation or death) for Brazil. Findings: Among adolescents, we analysed 447,882 tests in Brazil and 375,385 tests in Scotland. VE against symptomatic COVID-19 varied by the predominant circulating SARS-CoV-2 variant. It was substantially lower for symptomatic infection during the Omicron dominant period (62.8% in Brazil and 78.3 in Scotland at peak) than in the Delta predominant period (85.8% in Brazil and 90.7 in Scotland). VE started to decline 27 days after the second dose, reaching 13.9% in Brazil and 31.3% in Scotland at ≥98 days during the Omicron period. In Brazil, protection against severe disease remained over 80% at 98 days after receiving the second dose. Interpretation: We found waning vaccine protection of BNT162b2 against symptomatic COVID-19 infection among adolescents in both Brazil and Scotland. However, protection against severe outcomes in infected remained high at ≥ 98 days after the second dose in the Omicron period. Consideration about booster doses for adolescents needs to be given. Funding: Medical Research Council, Scottish Government, Health Data Research UK BREATHE Hub, Fiocruz, Fazer o Bem Faz Bem Programme;CNPQ, Wellcome Trust. Declaration of Interest: MB-N reports grants from the Fazer o bem faz bem program from JBS S.A.. VdAO, VB, MLB, JC and MB-N are employees of Fiocruz, a federal public institution, which manufactures Vaxzevria in Brazil, through a full technology transfer agreement with AstraZeneca. Fiocruz allocates all its manufactured products to the Ministry of Health for public health use. SVK was Co-Chair of the Scottish Government's Expert Reference Group on Ethnicity and COVID-19 and a member of the UK Government's Scientific Advisory Group on Emergencies (SAGE) subgroup on Ethnicity. IR is a member of the Scientific Advisory Committee of the Government of the Republic of Croatia and co-Editor-in-Chief of the Journal of Global Health.CRS declares funding from the Medical Research Council, the National Institute for Health Research, the Chief Scientist Office and the New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study Ethical Approval: This study analysed de-identified data and was approved by the National Ethics committee (CONEP) (CAAE registration no. 50199321.9.0000.0040).

6.
J Glob Health ; 12: 05008, 2022.
Article in English | MEDLINE | ID: covidwho-1771702

ABSTRACT

Background: The emergence of the B.1.617.2 Delta variant of concern was associated with increasing numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and COVID-19 hospital admissions. We aim to study national population level SARS-CoV-2 infections and COVID-19 associated hospitalisations by vaccination status to provide insight into the association of vaccination on temporal trends during the time in which the SARS-CoV-2 Delta variant became dominant in Scotland. Methods: We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE II) platform, covering the period when Delta was pervasive (May 01 to October 23, 2021). We performed a cohort analysis of every vaccine-eligible individual aged 20 or over from across Scotland. We determined the vaccination coverage, SARS-CoV-2 incidence rate and COVID-19 associated hospitalisations incidence rate. We then stratified those rates by age group, vaccination status (defined as "unvaccinated", "partially vaccinated" (1 dose), or "fully vaccinated" (2 doses)), vaccine type (BNT162b2 or ChAdOx1 nCoV-19), and coexisting conditions known to be associated with severe COVID-19 outcomes. Results: During the follow-up of 4 183 022 individuals, there were 407 405 SARS-CoV-2 positive cases with 10 441 (2.6%) associated with a hospital admission. Those vaccinated with two doses (defined as fully vaccinated in the current study) of either vaccine had lower incidence rates of SARS-CoV-2 infections and much lower incidence rates of COVID-19 associated hospitalisations than those unvaccinated in the Delta era in Scotland. Younger age groups were substantially more likely to get infected. In contrast, older age groups were much more likely to be hospitalised. The incidence rates stratified by coexisting conditions were broadly comparable with the overall age group patterns. Conclusions: This study suggests that national population level vaccination was associated with a reduction in SARS-CoV-2 infections and COVID-19 associated hospitalisation in Scotland throughout the Delta era.


Subject(s)
COVID-19 , Viral Vaccines , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Hospitalization , Humans , Incidence , SARS-CoV-2 , Vaccination , Young Adult
7.
Br J Psychiatry ; 221(1): 417-424, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1731562

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has disproportionately affected people with mental health conditions. AIMS: We investigated the association between receiving psychotropic drugs, as an indicator of mental health conditions, and COVID-19 vaccine uptake. METHOD: We conducted a cross-sectional analysis of a prospective cohort of the Northern Ireland adult population using national linked primary care registration, vaccination, secondary care and pharmacy dispensing data. Univariable and multivariable logistic regression analyses investigated the association between anxiolytic, antidepressant, antipsychotic, and hypnotic use and COVID-19 vaccination status, accounting for age, gender, deprivation and comorbidities. Receiving any COVID-19 vaccine was the primary outcome. RESULTS: There were 1 433 814 individuals, of whom 1 166 917 received a COVID-19 vaccination. Psychotropic medications were dispensed to 267 049 people. In univariable analysis, people who received any psychotropic medication had greater odds of receiving COVID-19 vaccination: odds ratio (OR) = 1.42 (95% CI 1.41-1.44). However, after adjustment, psychotropic medication use was associated with reduced odds of vaccination (ORadj = 0.90, 95% CI 0.89-0.91). People who received anxiolytics (ORadj = 0.63, 95% CI 0.61-0.65), antipsychotics (ORadj = 0.75, 95% CI 0.73-0.78) and hypnotics (ORadj = 0.90, 95% CI 0.87-0.93) had reduced odds of being vaccinated. Antidepressant use was not associated with vaccination (ORadj = 1.02, 95% CI 1.00-1.03). CONCLUSIONS: We found significantly lower odds of vaccination in people who were receiving treatment with anxiolytic and antipsychotic medications. There is an urgent need for evidence-based, tailored vaccine support for people with mental health conditions.


Subject(s)
Anti-Anxiety Agents , Antipsychotic Agents , COVID-19 , Adult , Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Cross-Sectional Studies , Humans , Hypnotics and Sedatives/therapeutic use , Prospective Studies , Psychotropic Drugs/therapeutic use , Vaccination
8.
PLoS Med ; 19(2): e1003927, 2022 02.
Article in English | MEDLINE | ID: covidwho-1705011

ABSTRACT

BACKGROUND: Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales. METHODS AND FINDINGS: We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates. CONCLUSIONS: In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.


Subject(s)
COVID-19/prevention & control , SARS-CoV-2/pathogenicity , Sinus Thrombosis, Intracranial/etiology , Adult , Aged , COVID-19 Vaccines/adverse effects , Case-Control Studies , Cohort Studies , Humans , Male , Middle Aged , United Kingdom , Vaccination/statistics & numerical data , Wales
9.
Lancet Respir Med ; 10(6): 566-572, 2022 06.
Article in English | MEDLINE | ID: covidwho-1703650

ABSTRACT

BACKGROUND: Reports have suggested that the efficacy of vaccines against COVID-19 might have fallen since the delta (B.1.617.2) SARS-CoV-2 variant replaced the alpha (B.1.1.7) variant as the predominant variant. We aimed to investigate, for the two main classes of vaccine, whether efficacy against severe COVID-19 has decreased since delta became the predominant variant and whether the efficacy of two doses of vaccine against severe COVID-19 wanes with time since second dose. METHODS: In the REACT-SCOT case-control study, vaccine efficacy was estimated using a matched case-control design that includes all diagnosed cases of COVID-19 in Scotland up to Sept 8, 2021. For every incident case of COVID-19 in the Scottish population, ten controls matched for age rounded to the nearest year, sex, and primary care practice, and alive on the day of presentation of the case that they were matched to were selected using the Community Health Index database. To minimise ascertainment bias we prespecified the primary outcome measure to assess vaccine efficacy as severe COVID-19, defined as diagnosed patients with entry to critical care within 21 days of first positive test, death within 28 days of first positive test, or any death for which COVID-19 was coded as underlying cause. Although the data extracted for this study included cases presenting up to Sept 22, 2021, the analyses reported here are restricted to cases and controls presenting from Dec 1, 2020, to Sept 8, 2021, ensuring follow-up for at least 14 days after presentation date to allow classification of hospitalisation and (for most cases) severity based on entry to critical care or fatal outcome. FINDINGS: During the study period, a total of 5645 severe cases of COVID-19 were recorded; these were matched to 50 096 controls. Of the severe cases, 4495 (80%) were not vaccinated, and of the controls, 36 879 (74%) were not vaccinated. Of the severe cases of COVID-19 who had been vaccinated, 389 had received an mRNA vaccine and 759 had received the ChAdOx1 vaccine. The efficacy of vaccination against severe COVID-19 decreased in May, 2021, coinciding with the replacement of the alpha SARS-CoV-2 variant by the delta variant in Scotland, but this decrease was reversed over the following month. In the most recent time window centred on July 29, 2021, the efficacy of two doses was 91% (95% CI 87-94) for the ChAdOx1 vaccine and 92% (88-95) for mRNA (Pfizer or Moderna) vaccines. The efficacy of the ChAdOx1 vaccine against severe COVID-19 declined with time since second dose to 69% (95% CI 52-80) at 20 weeks from second dose. The efficacy of mRNA vaccines declined in the first ten weeks from second dose but more slowly thereafter to 93% (88-96) at 20 weeks from second dose. INTERPRETATION: Our results are reassuring with respect to concerns that vaccine efficacy against severe COVID-19 might have fallen since the delta variant became predominant, or that efficacy of mRNA vaccines wanes within the first 5-6 months after second dose. However, the efficacy of the ChAdOx1 vaccine against severe COVID-19 wanes substantially by 20 weeks from second dose. Efficacy of mRNA vaccines after 20 weeks and against newer variants remains to be established. Our findings support the case for additional protective measures for those at risk of severe disease, including, but not limited to, booster doses, at times when transmission rates are high or expected to rise. FUNDING: None.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Case-Control Studies , Humans , SARS-CoV-2/genetics , Scotland/epidemiology , Vaccines, Synthetic
11.
BMJ Open ; 12(2): e050062, 2022 02 14.
Article in English | MEDLINE | ID: covidwho-1691320

ABSTRACT

INTRODUCTION: The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK. METHODS AND ANALYSIS: We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations. ETHICS AND DISSEMINATION: We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.


Subject(s)
COVID-19 Vaccines , COVID-19 , Case-Control Studies , Humans , Observational Studies as Topic , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Scotland/epidemiology , State Medicine
12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323923

ABSTRACT

Faced with the 2020 SARS-CoV2 epidemic, public health officials have been seeking models that could be used to predict not only the number of new cases but also the levels of hospitalisation, critical care and deaths. In this paper we present a stochastic compartmental model capable of real-time monitoring and forecasting of the pandemic incorporating multiple streams of real-world data, reported cases, testing intensity, deaths, hospitalisations and critical care occupancy. Model parameters are estimated via a Bayesian particle filtering technique. The model successfully tracks the key variables (reported cases, critical care and deaths) throughout the two waves (March-June and September-November 2020) of the COVID-19 outbreak in Scotland. The model hospitalisation predictions in Summer 2020 are consistently lower than the recorded data, but consistent with the change to the reporting criteria by the Health Protection Scotland on 15th September. Most parameter estimates were constant over the two waves, but the infection rate and consequently the reproductive number decrease in the later stages of the first wave and increase again from July 2020. The death rates are initially high but decrease over Summer 2020 before rising again in November. The model can also be used to provide short-term predictions. We show that the 2-week predictability is very good for the period from March to June 2020, even at early stages of the pandemic. The model has been slower to pick up the increase in the case numbers in September 2020 but forecasting improves again in the later stages of the epidemic.

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323239

ABSTRACT

Background: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines have demonstrated high efficacy against infection in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. There is an urgent need to study the ‘real-world’ effects of these vaccines. The aim of our study was to estimate the effectiveness of the first dose of these COVID-19 vaccines in preventing hospital admissions.Methods: We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database comprising of linked vaccination, primary care, Real-Time Polymerase Chain Reaction (RT-PCR) testing, hospitalisation and mortality records for 5.4 million people in Scotland (covering ~99% of population). A time-dependent Cox model and Poisson regression models were fitted to estimate effectiveness against COVID-19 related hospitalisation (defined as 1- Adjusted Hazard Ratio) following the first dose of vaccine.Findings: The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95% confidence interval [CI] 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95% CI 73 to 99). Results of combined vaccine effect for prevention of COVID-19 related hospitalisation were comparable when restricting the analysis to those aged ≥80 years (81%;95% CI 65 to 90 at 28-34 days post-vaccination).Interpretation: A single dose of the BNT162b2 mRNA and ChAdOx1 vaccines resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland.Funding: UK Research and Innovation (Medical Research Council);Research and Innovation Industrial Strategy Challenge Fund;Health Data Research UK.Conflict of Interest: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. All other authors report no conflicts of interest.Ethical Approval: Approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201) and Public Benefit and Privacy Panel for Health and Social Care (reference number: 1920-0279).

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321605

ABSTRACT

Background: The QCovid algorithm is a risk prediction tool for COVID-19 hospitalisation and mortality that can be used to stratify patients by risk into vulnerability groups . We carried out an external validation of the QCovid algorithm in Scotland.Methods: We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription polymerase chain reaction (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisation and deaths in our dataset for two time periods: 1 March, 2020 to 30 April, 2020, and 1 May, 2020 to 30 June, 2020.Findings: Our dataset comprised 5,384,819 individuals, representing 99% of the estimated population (5,463,300) resident in Scotland in 2020. The algorithm showed excellent calibration in both time periods with close correspondence between observed and predicted risks. Harrell ’s C for deaths in males and females in the first period was 0.946 (95% CI: 0.941 - 0.951) and 0.925 (95% CI: 0.919 - 0.931) respectively. Harrell’s C for hospitalisations in males and females in the first period was 0.809 (95% CI: 0.801 - 0.817) and 0.816 (95% CI: 0.808 - 0.823) respectively.Interpretation: The QCovid algorithm shows high levels of external validity in predicting the risk of COVID- 19 hospitalisation and death in the population of Scotland.Funding: Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, funded through the UK Research and Innovation Industrial Strategy Challenge Fund Health Data Research UK.Declaration of Interests: Dr. Hippisley-Cox reports grants from MRC, grants from Wellcome Trrust, grants from NIHR, during the conduct of the study;other from ClinRisk Ltd, outside the submitted work. Dr. Sheikh reports grants from NIHR, grants from MRC, grants from HRR UK, during the conduct of the study. All other authors report no conflict of interest.Ethics Approval Statement: Ethical permission for this study was granted from South East Scotland Research Ethics Committee 02 [12/SS/0201]. The Public Benefit and Privacy Panel Committee of Public Health Scotland, approved the linkage and analysis of the de-identified datasets for this project [1920-0279].

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316787

ABSTRACT

Background: Although COVID-19 vaccines have been shown to have high efficacy in the general population, it has not been established whether this applies to vulnerable groups. The objective of this study was to estimate the efficacy of vaccination in reducing the risk of severe COVID-19 among those designated as clinically extremely vulnerable in Scotland. Methods: : In a matched case-control design (REACT-SCOT), all 111295 cases of COVID-19 in Scotland diagnosed from 1 December 2020 to 16 March 2021 were matched for age, sex and primary care practice to 1093449 controls from the general population. This was linked to national data on vaccinations and those designated as clinically extremely vulnerable and thus eligible for shielding support. Severe COVID-19 was defined as cases with entry to critical care or fatal outcome. Rate ratios associated with vaccination within risk groups were estimated by conditional logistic regression. Results: : The rate ratio for severe COVID-19 associated with vaccination at least 14 days before was 0.29 (95% CI 0.22 to 0.37) in those eligible for shielding, compared with 0.29 (95% CI 0.25 to 0.34) in those ineligible for shielding. The rate ratio for hospitalized or fatal COVID-19 was 0.39 (95% CI 0.33 to 0.46) in those eligible and 0.37 (95% CI 0.33 to 0.41) in those not eligible for shielding. Examined by specific shielding conditions, the rate ratio for hospitalized or fatal COVID-19 ranged from 0.33 (95% CI 0.21 to 0.51) in those with specific cancers to 0.74 (95% CI 0.36 to 1.51) in solid organ transplant recipients, and 0.53 (95% CI 0.33 to 0.84) in others on immunosuppressants (excluding solid organ transplant recipients). Conclusions: : These results are reassuring with respect to efficacy in clinically vulnerable individuals including immunocompromised individuals, but studies in larger populations are needed to estimate efficacy in solid organ transplant recipients.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310544

ABSTRACT

Background: Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature, to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods: Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results: 1,238 papers were identified post-deduplication. 33 met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions: The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality;age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. This review was registered on PROSPERO as CRD42020177714.

17.
Nat Med ; 28(4): 838-843, 2022 04.
Article in English | MEDLINE | ID: covidwho-1684094

ABSTRACT

There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14-30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3-55.7) against confirmed infection and 82.1% (95% CI: 81.4-82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1-36.2) against infection and 72.5% (95% CI: 70.9-74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0-94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1-98.1) 14-30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2
18.
Lancet Respir Med ; 10(2): 191-198, 2022 02.
Article in English | MEDLINE | ID: covidwho-1641759

ABSTRACT

BACKGROUND: There is an urgent need to inform policy deliberations about whether children with asthma should be vaccinated against SARS-CoV-2 and, if so, which subset of children with asthma should be prioritised. We were asked by the UK's Joint Commission on Vaccination and Immunisation to undertake an urgent analysis to identify which children with asthma were at increased risk of serious COVID-19 outcomes. METHODS: This national incident cohort study was done in all children in Scotland aged 5-17 years who were included in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). We used data from EAVE II to investigate the risk of COVID-19 hospitalisation among children with markers of uncontrolled asthma defined by either previous asthma hospital admission or oral corticosteroid prescription in the previous 2 years. A Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% CIs for the association between asthma and COVID-19 hospital admission, stratified by markers of asthma control (previous asthma hospital admission and number of previous prescriptions for oral corticosteroids within 2 years of the study start date). Analyses were adjusted for age, sex, socioeconomic status, comorbidity, and previous hospital admission. FINDINGS: Between March 1, 2020, and July 27, 2021, 752 867 children were included in the EAVE II dataset, 63 463 (8·4%) of whom had clinician-diagnosed-and-recorded asthma. Of these, 4339 (6·8%) had RT-PCR confirmed SARS-CoV-2 infection. In those with confirmed infection, 67 (1·5%) were admitted to hospital with COVID-19. Among the 689 404 children without asthma, 40 231 (5·8%) had confirmed SARS-CoV-2 infections, of whom 382 (0·9%) were admitted to hospital with COVID-19. The rate of COVID-19 hospital admission was higher in children with poorly controlled asthma than in those with well controlled asthma or without asthma. When using previous hospital admission for asthma as the marker of uncontrolled asthma, the adjusted HR was 6·40 (95% CI 3·27-12·53) for those with poorly controlled asthma and 1·36 (1·02-1·80) for those with well controlled asthma, compared with those with no asthma. When using oral corticosteroid prescriptions as the marker of uncontrolled asthma, the adjusted HR was 3·38 (1·84-6·21) for those with three or more prescribed courses of corticosteroids, 3·53 (1·87-6·67) for those with two prescribed courses of corticosteroids, 1·52 (0·90-2·57) for those with one prescribed course of corticosteroids, and 1·34 (0·98-1·82) for those with no prescribed course, compared with those with no asthma. INTERPRETATION: School-aged children with asthma with previous recent hospital admission or two or more courses of oral corticosteroids are at markedly increased risk of COVID-19 hospital admission and should be considered a priority for vaccinations. This would translate into 9124 children across Scotland and an estimated 109 448 children across the UK. FUNDING: UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and Scottish Government.


Subject(s)
Asthma , COVID-19 , Adolescent , Asthma/complications , Asthma/drug therapy , Asthma/epidemiology , Child , Child, Preschool , Cohort Studies , Hospitalization , Hospitals , Humans , SARS-CoV-2 , Scotland/epidemiology
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