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1.
J Glob Health ; 12: 05014, 2022 May 21.
Article in English | MEDLINE | ID: covidwho-1863240

ABSTRACT

Background: Long COVID is defined as symptoms and signs related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are present at least four weeks following acute infection. These symptoms and signs are poorly characterised but may be associated with significant morbidity. We sought to synthesise the evidence on their incidence to guide future research, policy and practice. Methods: We searched Medline and Embase for longitudinal cohort studies from January 2020 to July 2021 that investigated adults with long COVID at least four weeks after acute infection. Risk of bias was assessed using the Joanna Briggs Institute checklist for cohort studies. Random-effects meta-analyses were performed with subgroup analysis by follow-up time (4-12 vs more than 12 weeks). Results: 19 studies were included, 13 of which included patients hospitalised with COVID-19. The total sample size was 10 643 and the follow-up time ranged from 30 to 340 days. Risk of bias was assessed as high in one study, moderate in two studies and low in the remaining 16 studies. The most common symptoms and signs seen at any time point in long COVID were fatigue (37%; 95% confidence interval (CI) = 23-55), dyspnoea (21%; 95% CI = 14-30), olfactory dysfunction (17%; 95% CI = 9-29), myalgia (12%; 95% CI = 5-25), cough (11%; 95% CI = 6-20) and gustatory dysfunction (10%; 95% CI = 7-17). High heterogeneity was seen for all meta-analyses and the presence of some funnel plot asymmetry may indicate reporting bias. No effect of follow-up time was found for any symptom or sign included in the subgroup analysis. Conclusions: We have summarised evidence from longitudinal cohort studies on the most common symptoms and signs associated with long COVID. High heterogeneity seen in the meta-analysis means pooled incidence estimates should be interpreted with caution. This heterogeneity may be attributable to studies including patients from different health care settings and countries.


Subject(s)
COVID-19 , Adult , COVID-19/complications , Cohort Studies , Humans , Longitudinal Studies , SARS-CoV-2
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337871

ABSTRACT

Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted such a study in 9003 adults from the United Kingdom (UK) general population receiving SARS-COV-2 vaccines as part of the national vaccination programme. Data relating to incidence and type of reactive symptoms after vaccination were captured using online questionnaires, along with information on 56 potential determinants of symptom risk. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI 0.81–0.90), male vs. female sex (aOR 0.59, 95% CI 0.53–0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26–0.32 for BNT162b2;0.06, 0.01–0.26 for mRNA-1273). Higher risk of such symptoms was associated with a history of symptomatic SARS-CoV-2 infection prior to vaccination (2.23, 1.78–2.81) and presence vs. absence of self-rated anxiety or depression at cohort enrolment (1.24, 1.12–1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.

3.
EClinicalMedicine ; 49: 101462, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1850967

ABSTRACT

Background: Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups. Methods: We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted. Findings: Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively. Interpretation: Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely. Funding: This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.

4.
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.

5.
J R Soc Med ; : 1410768221095239, 2022 May 03.
Article in English | MEDLINE | ID: covidwho-1820012

ABSTRACT

OBJECTIVES: COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic. DESIGN: We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020-28 March 2021. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from NHS Scotland. MAIN OUTCOME MEASURES: We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018-2019. RESULTS: As restrictions were gradually lifted in Scotland after the first lockdown, hospital-based admissions increased approaching pre-pandemic levels. Subsequent tightening of restrictions in September 2020 were associated with a change in slope of relative weekly admissions rate: -1.98% (-2.38, -1.58) in accident and emergency attendance, -1.36% (-1.68, -1.04) in emergency admissions and -2.31% (-2.95, -1.66) in planned admissions. A similar pattern was seen across sex, socioeconomic status and most age groups, except children (0-14 years) where accident and emergency attendance, and emergency admissions were persistently low over the study period. CONCLUSIONS: We found substantial disruption to urgent and planned inpatient healthcare provision in hospitals across NHS Scotland. There is the need for urgent policy responses to address continuing unmet health needs and to ensure resilience in the context of future pandemics.

6.
Journal of Global Health ; 12, 2022.
Article in English | EuropePMC | ID: covidwho-1801608

ABSTRACT

Background The COVID-19 pandemic has caused disruptions to the functioning of societies and their health systems. Prior to the pandemic, health systems in low- and middle-income countries (LMIC) were particularly stretched and vulnerable. The International Society of Global Health (ISoGH) sought to systematically identify priorities for health research that would have the potential to reduce the impact of the COVID-19 pandemic in LMICs. Methods The Child Health and Nutrition Research Initiative (CHNRI) method was used to identify COVID-19-related research priorities. All ISoGH members were invited to participate. Seventy-nine experts in clinical, translational, and population research contributed 192 research questions for consideration. Fifty-two experts then scored those questions based on five pre-defined criteria that were selected for this exercise: 1) feasibility and answerability;2) potential for burden reduction;3) potential for a paradigm shift;4) potential for translation and implementation;and 5) impact on equity. Results Among the top 10 research priorities, research questions related to vaccination were prominent: health care system access barriers to equitable uptake of COVID-19 vaccination (ranked 1st), determinants of vaccine hesitancy (4th), development and evaluation of effective interventions to decrease vaccine hesitancy (5th), and vaccination impacts on vulnerable population/s (6th). Health care delivery questions also ranked highly, including: effective strategies to manage COVID-19 globally and in LMICs (2nd) and integrating health care for COVID-19 with other essential health services in LMICs (3rd). Additionally, the assessment of COVID-19 patients’ needs in rural areas of LMICs was ranked 7th, and studying the leading socioeconomic determinants and consequences of the COVID-19 pandemic in LMICs using multi-faceted approaches was ranked 8th. The remaining questions in the top 10 were: clarifying paediatric case-fatality rates (CFR) in LMICs and identifying effective strategies for community engagement against COVID-19 in different LMIC contexts. Interpretation Health policy and systems research to inform COVID-19 vaccine uptake and equitable access to care are urgently needed, especially for rural, vulnerable, and/or marginalised populations. This research should occur in parallel with studies that will identify approaches to minimise vaccine hesitancy and effectively integrate care for COVID-19 with other essential health services in LMICs. ISoGH calls on the funders of health research in LMICs to consider the urgency and priority of this research during the COVID-19 pandemic and support studies that could make a positive difference for the populations of LMICs.

7.
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.

8.
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.

9.
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).

10.
J Glob Health ; 12: 04023, 2022.
Article in English | MEDLINE | ID: covidwho-1776559

ABSTRACT

Background: Asthma was one of the top causes of hospitalization and unscheduled medical attendances due to acute exacerbations and its complications. In Malaysia, all pilgrims must undergo a mandatory health examination and certified fit to perform pilgrimage. We studied the current organisational and clinical routines of Hajj health examination in Malaysia with a focus on the delivery of care for pilgrims with asthma. Methods: We conducted non-participant observation to obtain ethnographic understanding of Hajj health examination activities for 2019. Observations were guided by a checklist and recorded as notes that were analysed thematically. The study was conducted at 11 public (from each region in Malaysia, namely, North, South, East, West of Peninsular Malaysia, and Sabah and Sarawak of East Malaysia) and two private primary care clinics. Results: We observed considerable variation in the implementation and practice of Hajj health examinations among the 11 public clinics but no marked variation among the private clinics. The short time span of between three to four months was inadequate for disease control measures and had put pressure on health care providers. They mostly viewed the Hajj health examination as merely a certification of fitness to perform the pilgrimage, though respiratory health assessment was often inadequate. The opportunity to optimise the health of pilgrims with asthma by providing the appropriate medications, asthma action plan and asthma education including the preventive measures was disregarded. The preliminary health screening, which aimed to optimise pilgrims' health before the actual Hajj health examination was not appreciated by either pilgrims or health care providers. Conclusions: There is great potential to reform the current system of Hajj health certification in order to optimise its potential benefits for pilgrims with asthma. A systematic approach to restructuring the delivery of Hajj health examination could address the time constraints, clinical competency of primary health care providers and resources limitations.


Subject(s)
Asthma , Travel , Asthma/diagnosis , Humans , Islam , Malaysia
11.
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
12.
Thorax ; 2022 Mar 30.
Article in English | MEDLINE | ID: covidwho-1769954

ABSTRACT

BACKGROUND: We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19. METHODS: We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included. RESULTS: Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12-17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic. DISCUSSION: People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma.

13.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330891

ABSTRACT

BACKGROUND: Vitamin D metabolites support innate immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Randomized controlled trials of vitamin D to prevent coronavirus disease 2019 (Covid-19) have not yet reported. METHODS: We randomly assigned 6200 U.K. adults to receive an offer of a postal finger-prick 25-hydroxyvitamin D (25[OH]D) test with provision of a 6-month supply of higher-dose vitamin D (3200 IU/d, n=1550) or lower-dose vitamin D (800 IU/d, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). The primary outcome was the proportion of participants experiencing at least one swab test- or doctor-confirmed acute respiratory infection (ARI) of any cause at six months. Secondary outcomes included incidence of swab test-confirmed Covid-19. RESULTS: Of 3100 participants offered testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D <75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no-offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no-offer 1.09, 95% CI 0.82-1.46;lower-dose vs. no-offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no-offer groups developed Covid-19 (OR for higher-dose vs. no-offer 1.13, 0.78-1.63;lower-dose vs. no-offer 1.39, 0.98-1.97). CONCLUSIONS: Among adults with a high baseline prevalence of vitamin D insufficiency, implementation of a test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or Covid-19.

14.
Int J Popul Data Sci ; 5(4): 1697, 2020.
Article in English | MEDLINE | ID: covidwho-1754159

ABSTRACT

Introduction: COVID-19 risk prediction algorithms can be used to identify at-risk individuals from short-term serious adverse COVID-19 outcomes such as hospitalisation and death. It is important to validate these algorithms in different and diverse populations to help guide risk management decisions and target vaccination and treatment programs to the most vulnerable individuals in society. Objectives: To validate externally the QCOVID risk prediction algorithm that predicts mortality outcomes from COVID-19 in the adult population of Wales, UK. Methods: We conducted a retrospective cohort study using routinely collected individual-level data held in the Secure Anonymised Information Linkage (SAIL) Databank. The cohort included individuals aged between 19 and 100 years, living in Wales on 24th January 2020, registered with a SAIL-providing general practice, and followed-up to death or study end (28th July 2020). Demographic, primary and secondary healthcare, and dispensing data were used to derive all the predictor variables used to develop the published QCOVID algorithm. Mortality data were used to define time to confirmed or suspected COVID-19 death. Performance metrics, including R2 values (explained variation), Brier scores, and measures of discrimination and calibration were calculated for two periods (24th January-30th April 2020 and 1st May-28th July 2020) to assess algorithm performance. Results: 1,956,760 individuals were included. 1,192 (0.06%) and 610 (0.03%) COVID-19 deaths occurred in the first and second time periods, respectively. The algorithms fitted the Welsh data and population well, explaining 68.8% (95% CI: 66.9-70.4) of the variation in time to death, Harrell's C statistic: 0.929 (95% CI: 0.921-0.937) and D statistic: 3.036 (95% CI: 2.913-3.159) for males in the first period. Similar results were found for females and in the second time period for both sexes. Conclusions: The QCOVID algorithm developed in England can be used for public health risk management for the adult Welsh population.


Subject(s)
COVID-19 , Adult , Aged , Aged, 80 and over , Algorithms , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Wales/epidemiology , Young Adult
15.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330349

ABSTRACT

Background Little is known about the relative influence of demographic, behavioural, and vaccine-related factors on risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations. Methods We undertook a prospective population-based study in UK adults (≥16 years) vaccinated against SARS-CoV-2, including data from Jan 12, 2021, to Feb 21, 2022. We modelled risk of post-vaccination SARS-CoV-2 infection separately for participants who had completed a primary course of vaccination (two-dose or, in the immunosuppressed, three-dose course of either ChAdOx1 nCoV-19 [ChAdOx1] or BNT1262b2) and for those who had additionally received a booster dose (BNT1262b2 or mRNA-1273). Cox regression models were used to explore associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and breakthrough infection, defined as a self-reported positive result on a lateral flow or reverse transcription PCR (RT-PCR) test for SARS-CoV-2. Models were further adjusted for weekly SARS-CoV-2 incidence at the local (lower tier local authority) level. Findings 14,713 participants were included in the post-primary analysis and 10,665 in the post-booster analysis, with a median follow-up of 203 days (IQR 195–216) in the post-primary cohort and 85 days (66–103) in the post-booster cohort. 1051 (7.1%) participants in the post-primary cohort and 1009 (9.4%) participants in the post-booster cohort reported a breakthrough SARS-CoV-2 infection. A primary course of ChAdOx1 ( vs BNT182b2) was associated with higher risk of infection, both in the post-primary cohort (adjusted hazard ratio 1.63, 95% CI 1.41–1.88) and in the post-booster cohort after boosting with mRNA-1273 (1.29 [1.03–1.61] vs BNT162b2 primary plus BNT162b2 booster). A lower risk of breakthrough infection was associated with older age (post-primary: 0.96 [0.96–0.97] per year;post-booster: 0.97 [0.96–0.98]), whereas a higher risk of breakthrough infection was associated with lower levels of education (post-primary: 1.66 [1.35–2.06] for primary or secondary vs postgraduate;post-booster: 1.36 [1.08–1.71]) and at least three weekly visits to indoor public places (post-primary: 1.38 [1.15–1.66] vs none;post-booster: 1.33 [1.10–1.60]). Conclusions Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough SARS-CoV-2 infection following a primary schedule and a booster dose. Research in context Evidence before this study We searched PubMed, medRxiv, and Google Scholar for papers published up to Feb 18, 2022, using the search terms (breakthrough OR post-vaccin*) AND (SARS-CoV-2 OR COVID) AND (disease OR infection) AND (determinant OR “risk factor” OR associat*), with no language restrictions. Existing studies on risk factors for breakthrough SARS-CoV-2 infection among vaccinated individuals have found associations with age, comorbidities, vaccine type, and previous infection;however, findings have been inconsistent across studies. Most studies have been limited to specific subgroups or have focused on severe outcomes, and very few have considered breakthrough infections after a booster dose or have adjusted for behaviours affecting exposure to other people. Added value of this study This study is among the first to provide a detailed analysis of a wide range of risk factors for breakthrough SARS-CoV-2 infection, both after the primary course of vaccination and after a booster dose. Our large study size and detailed data have allowed us to investigate associations with various sociodemographic, clinical, pharmacological, and nutritional factors. Monthly follow-up data have additionally given us the opportunity to consider the effects of behaviours that may have changed across the pandemic, while adjusting for local SARS-CoV-2 incidence. Implications of all the available evidence Our findings add to growing evidence that risk factors for SARS-CoV-2 infecti n after primary or booster vaccinations can differ to those in unvaccinated populations, with effects attenuated for previously observed risk factors such as body-mass index and Asian ethnicity. The clear difference we observed between the efficacies of ChAdOx1 and BNT162b2 as the primary course of vaccination appears to have been reduced by the use of BNT162b2 boosters, but not by mNRA-1273 boosters. As more countries introduce booster vaccinations, future population-based studies with longer follow-up will be needed to investigate our findings further.

16.
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
17.
Curr Opin Pulm Med ; 28(3): 180-191, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1701670

ABSTRACT

PURPOSE OF REVIEW: We reviewed three leading strategies of vaccine development against coronavirus disease 2019 (COVID- 19): mRNA vaccines, adenoviral vector vaccines and recombinant nanoparticles. We also considered the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their impact on the effectiveness of the most widely implemented vaccines. RECENT FINDINGS: General properties, efficacy, safety and global uptake of Pfizer/BioNTech's Comirnaty (BNT162b2), Moderna's Spikevax (mRNA-1273), Oxford/AstraZeneca's ChAdOx1 nCoV-19, J&J/Janssen's Ad26.COV2.S and Novavax's NVX-CoV2373 vaccines at the end of the year 2021 were presented. We summarized the information on the effectiveness against COVID-19 infection, severe disease and death. We then focused on important missense mutations in the five variants of concern (VoC): Alpha, Beta, Gamma, Delta and Omicron. We explored the evidence for the effectiveness of the vaccines against those five VoC. SUMMARY: It is difficult to predict the further development of the COVID-19 pandemic. The development of vaccines of an increasingly broad spectrum against coronaviruses, more easily deliverable and conferring more durable immune protection is likely. However, the very large number of infections may lead to new mutations with unpredictable impacts. Interventions that would control COVID-19 more effectively and enable a safer coexistence with the SARS-CoV-2 virus and its emerging variants are still needed in early 2022.


Subject(s)
COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Pandemics , SARS-CoV-2/genetics
18.
Pathogens ; 11(2)2022 Feb 19.
Article in English | MEDLINE | ID: covidwho-1705975

ABSTRACT

Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed and Embase for papers reporting at least one-year follow-up results of COVID-19 survivors published by 6 November 2021. Random-effects meta-analyses were conducted to estimate pooled prevalence of specific post-COVID symptoms. Eighteen papers that reported one-year follow-up data from 8591 COVID-19 survivors were included. Fatigue/weakness (28%, 95% CI: 18-39), dyspnoea (18%, 95% CI: 13-24), arthromyalgia (26%, 95% CI: 8-44), depression (23%, 95% CI: 12-34), anxiety (22%, 95% CI: 15-29), memory loss (19%, 95% CI: 7-31), concentration difficulties (18%, 95% CI: 2-35), and insomnia (12%, 95% CI: 7-17) were the most prevalent symptoms at one-year follow-up. Existing evidence suggested that female patients and those with more severe initial illness were more likely to suffer from the sequelae after one year. This study demonstrated that a sizeable proportion of COVID-19 survivors still experience residual symptoms involving various body systems one year later. There is an urgent need for elucidating the pathophysiologic mechanisms and developing and testing targeted interventions for long-COVID patients.

19.
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
20.
PLoS Med ; 19(2): e1003916, 2022 02.
Article in English | MEDLINE | ID: covidwho-1703635

ABSTRACT

BACKGROUND: In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates. METHODS AND FINDINGS: We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK "lockdown". Data were obtained for Scotland from the Public Health Scotland "COVID19 wider impacts on the health care system" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of "6-in-1" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake. CONCLUSIONS: In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , Routinely Collected Health Data , SARS-CoV-2/drug effects , Child , Child, Preschool , Communicable Disease Control/methods , Female , Humans , Immunization Programs/statistics & numerical data , Infant , Male , SARS-CoV-2/pathogenicity , Vaccination/statistics & numerical data
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