Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334173

ABSTRACT

BACKGROUND Covid-19 vaccination has been associated with an increased risk of venous thromboembolism (VTE). However, it is unknown whether genetic predisposition to VTE is associated with an increased risk of thrombosis following vaccination. METHODS Using data from the UK Biobank, which contains in-depth genotyping data and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants identified from a previous large genome-wide association study. We prospectively assessed associations between PRS and incident VTE after first and the second-dose vaccination separately. We conducted sensitivity analyses stratified by vaccine type (adenovirus- and mRNA-based) and using two historical unvaccinated cohorts. We estimated hazard ratios (HR) for PRS-VTE associations using Cox models. RESULTS Of 359,310 individuals receiving one dose of a Covid-19 vaccine, 160,327 (44.6%) were males, and the mean age at the vaccination date was 69.05 (standard deviation [SD] 8.04) years. After 28- and 90-days follow-up, 88 and 299 individuals developed VTE respectively, equivalent to an incidence rate of 0.88 (95% confidence interval [CI] 0.70 to 1.08) and 0.92 (95% CI 0.82 to 1.04) per 100,000 person-days. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (95% CI 1.15 to 1.73) in 28 days and 1.36 (95% CI 1.22 to 1.52) in 90 days). Similar associations were found after stratification by vaccine type, in the two-dose cohort and across the historical unvaccinated cohorts. CONCLUSIONS The genetic determinants of post-Covid-19-vaccination VTE are similar to those seen in historical data. This suggests that, at the population level, post-vaccine VTE has similar aetiology to conventional VTE. Additionally, the observed PRS-VTE associations were equivalent for adenovirus- and mRNA-based vaccines.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331084

ABSTRACT

Background: Substantial evidence suggests that severe Covid-19 leads to an increased risk of Venous Thromboembolism (VTE). We aimed to quantify the risk of VTE associated with ambulatory Covid-19, study the potential protective role of vaccination, and establish key clinical and genetic determinants of post-Covid VTE. Methods We analyzed a cohort of ambulatory Covid-19 patients from UK Biobank, and compared their 30-day VTE risk with propensity-score-matched non-infected participants. We fitted multivariable models to study the associations between age, sex, ethnicity, socio-economic status, obesity, vaccination status and inherited thrombophilia with post-Covid VTE. Results Overall, VTE risk was nearly 20-fold higher in Covid-19 vs matched non-infected participants (hazard ratio [HR] 19.49, 95% confidence interval [CI] 11.50 to 33.05). However, the risk was substantially attenuated amongst the vaccinated (HR: 2.79, 95% CI 0.82 to 9.54). Older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 2.00 (1.61 to 2.47) per 10 years, 1.66 (1.28 to 2.15), and 1.85 (1.29 to 2.64), respectively. Further, inherited thrombophilia led to an HR 2.05, 95% CI 1.15 to 3.66. Conclusions Ambulatory Covid-19 was associated with a striking 20-fold increase in incident VTE, but no elevated risk after breakthrough infection in the fully vaccinated. Older age, male sex, and obesity were clinical determinants of Covid-19-related VTE. Additionally, inherited thrombophilia doubled risk further, comparable to the effect of 10-year ageing. These findings reinforce the need for vaccination, and call for targeted strategies to prevent VTE during outpatient care of Covid-19

3.
J Am Heart Assoc ; 10(22): e022433, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1511553

ABSTRACT

Background The relationship between COVID-19 and ischemic stroke is poorly understood due to potential unmeasured confounding and reverse causation. We aimed to leverage genetic data to triangulate reported associations. Methods and Results Analyses primarily focused on critical COVID-19, defined as hospitalization with COVID-19 requiring respiratory support or resulting in death. Cross-trait linkage disequilibrium score regression was used to estimate genetic correlations of critical COVID-19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both COVID-19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C-reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical COVID-19 was associated with increased risk of any cardiovascular outcome for which genetic correlation was identified. There was evidence of genetic correlation between critical COVID-19 and ischemic stroke (rg=0.29, false discovery rate [FDR]=0.012), body mass index (rg=0.21, FDR=0.00002), and C-reactive protein (rg=0.20, FDR=0.00035), but no other trait investigated. In Mendelian randomization, liability to critical COVID-19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical COVID-19 liability 1.03, 95% CI 1.00-1.06, P-value=0.03). Similar estimates were obtained for ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking, and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical COVID-19. Conclusions These data support that liability to critical COVID-19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe COVID-19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.


Subject(s)
Brain Ischemia , COVID-19 , Ischemic Stroke , Body Mass Index , Brain Ischemia/epidemiology , Brain Ischemia/genetics , Brain Ischemia/virology , C-Reactive Protein , COVID-19/epidemiology , Genome-Wide Association Study , Humans , Inflammation , Ischemic Stroke/epidemiology , Ischemic Stroke/genetics , Ischemic Stroke/virology , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Risk Factors , Smoking
5.
Br J Clin Pharmacol ; 88(4): 1935-1941, 2022 02.
Article in English | MEDLINE | ID: covidwho-1483821

ABSTRACT

The ChAdOx1 nCoV-19 vaccine has been associated with increased risk of thrombosis. Understanding of the management of these rare events is evolving, and currently recommended treatments include human normal immunoglobulin and nonheparin anticoagulation such as direct oral anticoagulants. Our report describes three consecutive patients presenting to a London teaching hospital with vaccine-induced thrombotic thrombocytopenia (VITT), also referred to as vaccine-induced prothrombotic immune thrombocytopenia. The patients ranged in age from 40 to 54 years and two had no known previous medical comorbidities. Two patients had cerebral venous sinus thrombosis and one had a deep vein thrombosis. Two were treated with anticoagulation, one with oral rivaroxaban and the other with an intravenous argotraban infusion that was later converted to oral apixaban. One patient received three doses of human normal immunoglobulin and 5 days of therapeutic plasma exchange. This case series may be used to improve understanding of the clinical course and management of VITT.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Adult , COVID-19 Vaccines/adverse effects , Hospitals, Teaching , Humans , London , Middle Aged , Thrombocytopenia/chemically induced , Thrombosis/chemically induced , Vaccines/adverse effects
7.
COVID ; 1(1):20-38, 2021.
Article in English | MDPI | ID: covidwho-1288817

ABSTRACT

This review explores and positions the value of serology testing to support current immunization policies and the broader policy response to the coronavirus disease 2019 (COVID-19) crisis in Europe. We applied an exploratory approach to analysing existing evidence, international recommendations, and national policies using desk research from secondary sources, document analysis, and expert information. Regional and country-level resources from five focus countries were included: France, Germany, Italy, Spain, and the United Kingdom. Seven experts in the fields of COVID-19 immunization, serology testing, seroepidemiology, and vaccine safety and effectiveness studies contributed to the review and convened in two online panel sessions. The paper includes an overview of (1) the impact of the pandemic to date, (2) testing strategies, (3) COVID-19 vaccination policies, (4) lessons on using serology testing to support immunization, (5) current policies and recommendations on the use of a serology testing strategy, and (6) implementation barriers and challenges. Finally, this paper also provides a set of knowledge-based recommendations to advance the effective and timely inclusion of serology testing and resolve impeding knowledge gaps. The recommendations herein are intended to support timely decision-making, raise awareness, guide advocacy initiatives, and inspire future studies.

9.
BMJ : British Medical Journal (Online) ; 373, 2021.
Article in English | ProQuest Central | ID: covidwho-1210312

ABSTRACT

Guidance must be faster, bolder, and problem based

10.
R Soc Open Sci ; 7(11): 200958, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1005759

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 × 10-4) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.

14.
BMJ ; 371: m4288, 2020 11 11.
Article in English | MEDLINE | ID: covidwho-970809
SELECTION OF CITATIONS
SEARCH DETAIL