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1.
Lancet Respir Med ; 2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1621137

ABSTRACT

BACKGROUND: There is considerable uncertainty over whether adults with asthma should be offered booster vaccines against SARS-CoV-2 and, if so, who should be prioritised for booster vaccination. We were asked by the UK's Joint Commission on Vaccination and Immunisation to undertake an urgent analysis to identify which adults with asthma were at an increased risk of serious COVID-19 outcomes to inform deliberations on booster COVID-19 vaccines. METHODS: This national incident cohort study was done in all adults in Scotland aged 18 years and older 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 and the composite outcome of intensive care unit (ICU) admission or death from COVID-19 among adults with asthma. A Cox proportional hazard model was used to derive adjusted hazard ratios (HRs) and 95% CIs for the association between asthma and COVID-19 hospital admission and ICU admission or death, stratified by markers of history of an asthma attack defined by either oral corticosteroid prescription (prednisolone, prednisone, and dexamethasone) in the 2 years before March 1, 2020, or hospitalisation for asthma before March 1, 2020. Analyses were adjusted for age, sex, socioeconomic status, comorbidity, previous hospitalisation, and vaccine status. FINDINGS: Between March 1, 2020, and July 27, 2021, 561 279 (12·7%) of 4 421 663 adults in Scotland had clinician-diagnosed-and-recorded-asthma. Among adults with asthma, 39 253 (7·0%) had confirmed SARS-CoV-2 infections, of whom 4828 (12·3%) were admitted to hospital for COVID-19 (among them, an estimated 600 [12·4%] might have been due to nosocomial infections). Adults with asthma were found to be at an increased risk of COVID-19 hospital admission (adjusted HR 1·27, 95% CI 1·23-1·32) compared with those without asthma. When using oral corticosteroid prescribing in the preceding 2 years as a marker for history of an asthma attack, the adjusted HR was 1·54 (95% CI 1·46-1·61) for those with three or more prescribed courses of oral corticosteroids, 1·37 (1·26-1·48) for those with two prescribed courses, 1·30 (1·23-1·37) for those with one prescribed course, and 1·15 (1·11-1·21) for those without any courses, compared with those aged 18 years or older without asthma. Adults with asthma were found to be at an increased risk of COVID-19 ICU admission or death compared with those without asthma (adjusted HR 1·13, 95 % CI 1·05-1·22). The adjusted HR was 1·44 (95% CI 1·31-1·58) for those with three or more prescribed courses of oral corticosteroids, 1·27 (1·09-1·48) for those with two prescribed courses, 1·04 (0·93-1·16) for those with one prescribed course, and 1·06 (0·97-1·17) for those without any course, compared with adults without asthma. INTERPRETATION: Adults with asthma who have required two or more courses of oral corticosteroids in the previous 2 years or a hospital admission for asthma before March 1, 2020, are at increased risk of both COVID-19 hospitalisation and ICU admission or death. Patients with a recent asthma attack should be considered a priority group for booster COVID-19 vaccines. FUNDING: UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and Scottish Government.

2.
Anal Chem ; 94(2): 714-722, 2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1596741

ABSTRACT

Considering the large-scale outbreak of the coronavirus, it is essential to develop a versatile sensing system for different coronaviruses diagnostics, such as COVID-19, severe acute respiratory syndrome-related coronavirus (SARS-CoV), and bat SARS-like coronavirus (Bat-SL-CoVZC45). In this work, a tetrahedron-based constitutional dynamic network was built as the sensing platform for coronavirus detection. Four different DNA probes were used to construct the tetrahedron structure. DNAzyme and the fluorophore modified substrate strand were used to generate different fluorescence signals, which can be used to distinguish different coronaviruses. The coronavirus biosensor shows a high sensitivity for COVID-19, Bat-SL-CoVZC45, and SARS-CoV detection, with detection limits of 2.5, 3.1, and 2.9 fM, respectively. Also, the platform is robust, and the possible interference from clinical samples was negligible. Using different coronaviruses as inputs, we have fabricated several concatenated logic gates, such as "AND-OR", "INHIBIT-AND", "AND-AND-AND", and "AND-INHIBIT". Importantly, our logic system can also be used to identify SARS-CoV-2 Delta and Lambda variants in the logic operations. Due to the unique advantages of high sensitivity and selectivity, multiple logic biocomputing capabilities, and multireadout mode, this flexible sensing system provides a versatile sensing strategy for intelligent diagnostics of different coronaviruses with low false-negative rates.

3.
Lancet ; 399(10319): 25-35, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1586218

ABSTRACT

BACKGROUND: Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon). METHODS: In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs. FINDINGS: 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks. INTERPRETATION: We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19. FUNDING: UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

5.
Lancet Respir Med ; 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1550164

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.

6.
Preprint in English | EuropePMC | ID: ppcovidwho-292399

ABSTRACT

We describe SARS-CoV-2 infection and COVID-19 vaccine uptake in Scotland in a prospective cohort of all pregnant women in Scotland drawn from national databases. As of mid-October 2021, the Covid-19 in pregnancy in Scotland (COPS) cohort included linked data on a total of 139,136 pregnancies in 126,749 women. Up to September 30, 2021, a total of 22,779 COVID-19 vaccinations had been administered to 16,229 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of reproductive age (23.7% of women giving birth in September 2021 were fully vaccinated compared to 74.9 % in women 18-44 years). Of the 4,274 cases of COVID-19 in pregnancy (confirmed by SARS-CoV-2 viral reverse transcriptase polymerase chain reaction) between December 2020 (the month the COVID-19 vaccination programme started in Scotland) and September 2021 inclusive, 629 women (14.7%) were admitted to hospital and 89 (2.1%) were admitted to critical care. Of the COVID-19 cases occurring in pregnant women, 81.7% (3,491/4,274;95% CI 80.5-82.8) were in unvaccinated women. Of the COVID-19 associated hospital admissions, 93.0% (585/629;95% CI 90.7-94.8) were in women who were unvaccinated at the time of COVID-19 diagnosis. Of the COVID-19 associated critical care admissions 98.9% (88/89;95% CI 93.9-100) were in women who were unvaccinated at the time of COVID-19 diagnosis. The extended perinatal mortality rate for women who gave birth within 28 days of COVID-19 diagnosis was 15.9 per 1000 births (95% CI 7.8 to 31.0;background rate in 2020 6.3 per 1,000 total births [95% CI 5.7-7.1];background rate 2019 5.7 per 1,000 total births [95% CI 5.0-6.4]). All baby deaths occurred after pregnancies in women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies.

7.
Nat Med ; 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1483142

ABSTRACT

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.

8.
Lancet ; 397(10285): 1646-1657, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1201750

ABSTRACT

BACKGROUND: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19. METHODS: We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19-EAVE II-database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1-adjusted rate ratio) following the first dose of vaccine. FINDINGS: Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85-94) for reduced COVID-19 hospital admission at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75-94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72-89 at 28-34 days post-vaccination). INTERPRETATION: Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding. FUNDING: UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Hospitalization/statistics & numerical data , Mass Vaccination , Pandemics/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Scotland/epidemiology , Social Class , Young Adult
9.
Chem Commun (Camb) ; 57(9): 1125-1128, 2021 Feb 02.
Article in English | MEDLINE | ID: covidwho-1012695

ABSTRACT

Two fragments of the COVID-19 genome (specific and homologous) were used as two inputs to construct an AND logic gate for COVID-19 detection based on exonuclease III and DNAzyme. The detection sensitivity of the assay can reach fM levels. Satisfactory recovery values were obtained in real sample analysis.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , DNA, Viral/analysis , SARS-CoV-2/genetics , Saliva/virology , DNA, Catalytic , DNA, Viral/blood , DNA, Viral/urine , Exodeoxyribonucleases , Genome, Viral , Humans , Logic
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