Exploring drugs and vaccines associated with altered risks and severity of COVID-19: a UK Biobank cohort study of all ATC level-4 drug categories

AbstractBackgroundCOVID-19 is a major public health concern, yet its risk factors are not well-understood and effective therapies are lacking. It remains unclear how different drugs may increase or decrease the risks of infection and severity of disease.MethodsWe studied associations of prior use of all level-4 ATC drug categories (including vaccines) with COVID-19 diagnosis and outcome, based on a prospective cohort of UK Biobank(UKBB). Drug history was based on general practitioner(GP) records. Effects of prescribed medications/vaccinations on the risk of infection, severity of disease and mortality were investigated separately. Hospitalized and fatal cases were categorized as ‘severe’ infection. We also considered different study designs and conducted analyses within infected patients, tested subjects and the whole population respectively, and for 5 different time-windows of prescriptions. Missing data were accounted for by multiple imputation and inverse probability weighting was employed to reduce testing bias. Multivariable logistic regression was conducted which controls for main confounders.ResultsWe placed a greater focus on protective associations here, as (residual) confounding by indication and comorbidities tends to bias towards harmful effects. Across all categories, statins showed the strongest and most consistent protective associations. Significant protective effects against severe infection were seen among infected subjects (OR for prescriptions within a 12-month window, same below: 0.50, 95% CI:0.42-0.60), tested subjects (OR=0.63, 0.54-0.73) or in the general population (OR=0.49, 0.42-0.57). A number of top-listed drugs with protective effects were also cardiovascular medications, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blocker and beta-blockers. Some other drugs showing protective associations included biguanides (metformin), estrogens, thyroid hormones and proton pump inhibitors, among others.Interestingly, we also observed protective associations by numerous vaccines. The most consistent association was observed for influenza vaccines, which showed reduced odds of infection (OR= 0.73 for vaccination in past year, CI 0.65-0.83) when compared cases to general population controls or test-negative controls (OR=0.60, 0.53-0.68). Protective associations were also observed when severe or fatal infection was considered as the outcome. Pneumococcal, tetanus, typhoid and combined bacterial and viral vaccines (ATC code J07CA) were also associated with lower odds of infection/severity.Further subgroup and interaction analyses revealed difference in protective effects in different clinical subgroups. For example, protective effects of flu and pneumococcal vaccines were weaker in obese individuals, while we observed stronger protective effects of statins in those with cardiometabolic disorders, such as diabetes, coronary artery disease, hypertension and obesity.ConclusionsA number of drugs, including many for cardiometabolic disorders, may be associated with lower odds of infection/severity of infection. Several existing vaccines, especially flu vaccines, may be beneficial against COVID-19 as well. However, causal relationship cannot be established due to risk of confounding. While further studies are required to validate the findings, this work provides a useful reference for future meta-analyses, clinical trials or experimental studies.

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Association of Renin--Angiotensin--Aldosterone System Blocker use with Covid-19 Hospitalization and All-cause Mortality in the UK Biobank

10.22541/au.163252572.25645081/v1 ◽

2021 ◽

Author(s):

Fatemeh Safizadeh ◽

Thi Ngoc Mai Nguyen ◽

Hermann Brenner ◽

Ben Schöttker

Keyword(s):

Angiotensin Receptor Blockers ◽

Multivariable Logistic Regression Analysis ◽

Protective Effects ◽

Uk Biobank ◽

Antihypertensive Medications ◽

Converting Enzyme Inhibitors ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Wide Range ◽

The Uk

Aim: The risk-benefit profile of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19) is still a matter of debate. With growing evidence on the protective effect of this group of commonly used antihypertensives in Covid-19, we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. Methods: We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. Results: The use of either beta-blockers (BBs), calcium-channel blockers (CCBs), or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR, 1.63; 95% CI, 1.40 to 1.90) and ARB use (adjusted OR, 1.50; 95% CI, 1.27 to 1.77). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (adjusted OR, 1.64; 95% CI, 1.23 to 2.19) but not when compared to ARB users (adjusted OR, 1.18; 95% CI, 0.87 to 1.59). However, no associations were observed when the same analysis was conducted among hospitalized Covid-19 patients only. Conclusion: Our results suggest protective effects of blocking of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality among patients with pharmaceutically treated hypertension, which should be addressed by randomized controlled trials. If confirmed, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

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Effects and Mechanisms of Tea for the Prevention and Management of Diabetes Mellitus and Diabetic Complications: An Updated Review

Antioxidants ◽

10.3390/antiox8060170 ◽

2019 ◽

Vol 8 (6) ◽

pp. 170 ◽

Cited By ~ 32

Author(s):

Jin-Ming Meng ◽

Shi-Yu Cao ◽

Xin-Lin Wei ◽

Ren-You Gan ◽

Yuan-Feng Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Experimental Studies ◽

Epidemiological Studies ◽

Mechanisms Of Action ◽

Health Concern ◽

High Morbidity ◽

Protective Effects ◽

Public Health Concern ◽

Β Cells ◽

Patients With Diabetes

Diabetes mellitus has become a serious and growing public health concern. It has high morbidity and mortality because of its complications, such as diabetic nephropathy, diabetic cardiovascular complication, diabetic neuropathy, diabetic retinopathy, and diabetic hepatopathy. Epidemiological studies revealed that the consumption of tea was inversely associated with the risk of diabetes mellitus and its complications. Experimental studies demonstrated that tea had protective effects against diabetes mellitus and its complications via several possible mechanisms, including enhancing insulin action, ameliorating insulin resistance, activating insulin signaling pathway, protecting islet β-cells, scavenging free radicals, and decreasing inflammation. Moreover, clinical trials also confirmed that tea intervention is effective in patients with diabetes mellitus and its complications. Therefore, in order to highlight the importance of tea in the prevention and management of diabetes mellitus and its complications, this article summarizes and discusses the effects of tea against diabetes mellitus and its complications based on the findings from epidemiological, experimental, and clinical studies, with the special attention paid to the mechanisms of action.

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Exploring causal relationships between COVID-19 and cardiometabolic disorders: A bi-directional Mendelian randomization study

10.1101/2021.03.20.21254008 ◽

2021 ◽

Author(s):

Yong XIANG ◽

Carlos Kwan-Long CHAU ◽

Jinghong QIU ◽

Shitao RAO ◽

Hon-Cheong So

Keyword(s):

Risk Factors ◽

Kidney Disease ◽

General Population ◽

Genetic Correlation ◽

Mendelian Randomization ◽

Severe Disease ◽

Severe Infection ◽

Large Artery ◽

Causal Relationships ◽

Cardiometabolic Disorders

Background: More than 100 million cases of COVID-19 have been reported worldwide. A number of risk factors for infection or severe infection have been identified, however observational studies were subject to confounding bias. In addition, there is still limited knowledge about the complications or medical consequences of the disease. Methods: Here we performed bi-directional Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of around 30 cardiometabolic disorders (CMD) or traits. Genetic correlation (rg) was assessed by LD score regression(LDSC). The latest GWAS summary statistics from the COVID-19 Host Genetics Initiative was used, which comprised comparisons of general population controls with critically ill, hospitalized and any infected cases. Results: Overall we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of type 2 diabetes mellitus(T2DM), chronic kidney disease(CKD), ischemic stroke (especially large artery stroke[LAS]) and heart failure(HF) when compared to the general population. On the other hand, our findings suggested that liability to atrial fibrillation (AF), stroke (especially LAS), obesity, diabetes (T1DM and T2DM), low insulin sensitivity and impaired renal function (low eGFR and diabetic kidney disease) may be causal risk factors for COVID-19 or severe disease. In genetic correlation analysis, T2DM, CAD, obesity, fasting insulin, CKD, gout, stroke and urate showed positive rg with critical or hospitalized infection. All above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. Conclusions: In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 and severe disease and a number of CM disorders. Further replications and prospective studies are required to verify the findings.

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Exploring Drugs and Vaccines Associated with Altered Risks and Severity of COVID-19: A UK Biobank Cohort Study of All ATC Level-4 Drug Categories Reveals Repositioning Opportunities

Pharmaceutics ◽

10.3390/pharmaceutics13091514 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1514

Author(s):

Yong Xiang ◽

Kenneth Chi-Yin Wong ◽

Hon-Cheong So

Keyword(s):

Enzyme Inhibitors ◽

Drug Repositioning ◽

Beta Blockers ◽

Angiotensin Receptor Blockers ◽

Angiotensin Converting Enzyme Inhibitors ◽

Protective Effects ◽

Uk Biobank ◽

Converting Enzyme Inhibitors ◽

Reductase Inhibitors ◽

Cardiovascular Medications

Effective therapies for COVID-19 are still lacking, and drug repositioning is a promising approach to address this problem. Here, we adopted a medical informatics approach to repositioning. We leveraged a large prospective cohort, the UK-Biobank (UKBB, N ~ 397,000), and studied associations of prior use of all level-4 ATC drug categories (N = 819, including vaccines) with COVID-19 diagnosis and severity. Effects of drugs on the risk of infection, disease severity, and mortality were investigated separately. Logistic regression was conducted, controlling for main confounders. We observed strong and highly consistent protective associations with statins. Many top-listed protective drugs were also cardiovascular medications, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium channel blocker (CCB), and beta-blockers. Some other drugs showing protective associations included biguanides (metformin), estrogens, thyroid hormones, proton pump inhibitors, and testosterone-5-alpha reductase inhibitors, among others. We also observed protective associations by influenza, pneumococcal, and several other vaccines. Subgroup and interaction analyses were also conducted, which revealed differences in protective effects in various subgroups. For example, protective effects of flu/pneumococcal vaccines were weaker in obese individuals, while protection by statins was stronger in cardiovascular patients. To conclude, our analysis revealed many drug repositioning candidates, for example several cardiovascular medications. Further studies are required for validation.

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Food Bioactive Compounds and Emerging Techniques for Their Extraction: Polyphenols as a Case Study

Foods ◽

10.3390/foods10010037 ◽

2020 ◽

Vol 10 (1) ◽

pp. 37 ◽

Cited By ~ 1

Author(s):

José S. Câmara ◽

Bianca R. Albuquerque ◽

Joselin Aguiar ◽

Rúbia C. G. Corrêa ◽

João L. Gonçalves ◽

...

Keyword(s):

Bioactive Compounds ◽

Chemical Structure ◽

Experimental Studies ◽

Analytical Techniques ◽

Convincing Evidence ◽

Protective Effects ◽

Extraction Techniques ◽

Biological Impact ◽

Preventive Effects

Experimental studies have provided convincing evidence that food bioactive compounds (FBCs) have a positive biological impact on human health, exerting protective effects against non-communicable diseases (NCD) including cancer and cardiovascular (CVDs), metabolic, and neurodegenerative disorders (NDDs). These benefits have been associated with the presence of secondary metabolites, namely polyphenols, glucosinolates, carotenoids, terpenoids, alkaloids, saponins, vitamins, and fibres, among others, derived from their antioxidant, antiatherogenic, anti-inflammatory, antimicrobial, antithrombotic, cardioprotective, and vasodilator properties. Polyphenols as one of the most abundant classes of bioactive compounds present in plant-based foods emerge as a promising approach for the development of efficacious preventive agents against NCDs with reduced side effects. The aim of this review is to present comprehensive and deep insights into the potential of polyphenols, from their chemical structure classification and biosynthesis to preventive effects on NCDs, namely cancer, CVDs, and NDDS. The challenge of polyphenols bioavailability and bioaccessibility will be explored in addition to useful industrial and environmental applications. Advanced and emerging extraction techniques will be highlighted and the high-resolution analytical techniques used for FBCs characterization, identification, and quantification will be considered.

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Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Cancer Cell International ◽

10.1186/s12935-021-01906-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Marjan Talebi ◽

Mohsen Talebi ◽

Tahereh Farkhondeh ◽

Jesus Simal-Gandara ◽

Dalia M. Kopustinskiene ◽

...

Keyword(s):

Blood Cells ◽

Molecular Mechanisms ◽

Web Of Science ◽

Experimental Studies ◽

Protective Effects ◽

Pharmacological Activities ◽

Current Review ◽

Mesh Terms ◽

Online Databases ◽

Anti Cancer

AbstractChrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

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Retrospective Seroepidemiology study of dengue virus infection in Taiwan

BMC Infectious Diseases ◽

10.1186/s12879-021-05809-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying-Hsuan Lee ◽

Yu-Chia Hsieh ◽

Chih-Jung Chen ◽

Tzou-Yien Lin ◽

Yhu-Chering Huang

Keyword(s):

General Population ◽

Virus Infection ◽

Dengue Virus ◽

Dengue Fever ◽

Health Concern ◽

Age Group ◽

Dengue Virus Infection ◽

Recent Infection ◽

Seropositive Rate ◽

Significant Difference

Abstract Background Dengue virus infection has been an important and serious public health concern in Taiwan, where local outbreaks of dengue fever occurred almost every year. To our knowledge, no nationwide investigation has been carried out to determine the actual extent of infection in the general population. Methods A total of 1308 random serum samples were collected from the general population in Taiwan in 2010. The antibody-captured enzyme-linked immunosorbent assays were used to detect DENV-specific IgM and IgG. Demographics data were used for risk analysis. Results The weighted overall seroprevalence was 1.96% for anti-DENV IgM, and 3.4% for anti-DENV IgG, respectively. A significant rise of DENV IgG seropositive rate had been noted since late adulthood stage, from 1.1% at the age group of 50–59 years to 7.6% at the age group of 60–69 years. For people aged over 70 years, the seropositive rate reached 19%. Age, nationality, and regions of residency were associated with the IgG seropositivity. There was no statistically significant difference in seroprevalence of anti-Dengue IgM, indicating recent infection, among univariate predictors we proposed, including gender, age, residency, nationality, and household size. Conclusions Our results indicated that the majority of population in Taiwan born after 1940 is naive to dengue virus and the prevalence of IgG antibody against dengue virus rises with age. Nationality, and regions of residency are associated with the exposure of population to infection by dengue viruses. Further studies are needed to realize the current situation of seroprevalence of dengue fever in Taiwan.

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Associations between Nature Exposure and Health: A Review of the Evidence

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094790 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4790

Author(s):

Marcia P. Jimenez ◽

Nicole V. DeVille ◽

Elise G. Elliott ◽

Jessica E. Schiff ◽

Grete E. Wilt ◽

...

Keyword(s):

Mental Health ◽

Physical Activity ◽

Cognitive Function ◽

Observational Studies ◽

Green Space ◽

Current Knowledge ◽

Experimental Studies ◽

Empirical Literature ◽

Protective Effects ◽

Long Term Effects

There is extensive empirical literature on the association between exposure to nature and health. In this narrative review, we discuss the strength of evidence from recent (i.e., the last decade) experimental and observational studies on nature exposure and health, highlighting research on children and youth where possible. We found evidence for associations between nature exposure and improved cognitive function, brain activity, blood pressure, mental health, physical activity, and sleep. Results from experimental studies provide evidence of protective effects of exposure to natural environments on mental health outcomes and cognitive function. Cross-sectional observational studies provide evidence of positive associations between nature exposure and increased levels of physical activity and decreased risk of cardiovascular disease, and longitudinal observational studies are beginning to assess long-term effects of nature exposure on depression, anxiety, cognitive function, and chronic disease. Limitations of current knowledge include inconsistent measures of exposure to nature, the impacts of the type and quality of green space, and health effects of duration and frequency of exposure. Future directions include incorporation of more rigorous study designs, investigation of the underlying mechanisms of the association between green space and health, advancement of exposure assessment, and evaluation of sensitive periods in the early life-course.

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Right-to-left shunt is common in chronic migraine

Cephalalgia ◽

10.1111/j.1468-2982.2009.02002.x ◽

2009 ◽

Vol 30 (5) ◽

pp. 535-542 ◽

Cited By ~ 11

Author(s):

SJ Nahas ◽

WB Young ◽

R Terry ◽

A Kim ◽

T Van Dell ◽

...

Keyword(s):

General Population ◽

Chronic Migraine ◽

Tertiary Care ◽

Episodic Migraine ◽

Diagnostic Interview ◽

Neurological Symptoms ◽

Valsalva Manoeuvre ◽

Clinical Implications ◽

Severity Of Disease ◽

Headache Clinic

Our aim was to determine the prevalence of right-to-left shunt (RtLS) in patients with chronic migraine (CM), and to correlate the presence and grade of RtLS with aura and neurological symptoms, and duration and severity of disease. The prevalence of RtLS in migraine without aura is similar to that of the general population (between 20 and 35%). In migraine with aura, the prevalence is much higher (approximately 50%). The prevalence in CM, with or without aura, is unknown. Consecutive patients between the ages of 18 and 60 years with CM attending a tertiary care specialty headache clinic over an 8-week period were eligible. There were 131 patients in the study. A structured diagnostic interview was performed. Bubble transcranial Doppler with Valsalva manoeuvre determined RtLS presence and grade. Sixty-six percent (86/131) of patients had RtLS, a statistically significantly greater rate than those reported in the general population and in migraine with or without aura ( P < 0.001). There was no difference in RtLS rate or grade between those with and those without aura. Specific headache features and the presence of neurological symptoms were similar between those with and those without RtLS. Compared with both the general population and the episodic migraine population (with and without aura), patients with CM, with or without aura, are more likely to have RtLS. The clinical implications of our findings need to be determined.

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Estrogen Receptor and Vascular Aging

Frontiers in Aging ◽

10.3389/fragi.2021.727380 ◽

2021 ◽

Vol 2 ◽

Author(s):

Morgane Davezac ◽

Melissa Buscato ◽

Rana Zahreddine ◽

Patrick Lacolley ◽

Daniel Henrion ◽

...

Keyword(s):

Estrogen Receptor ◽

Cardiovascular Diseases ◽

Experimental Studies ◽

Hormonal Treatment ◽

Protective Effects ◽

Age Related ◽

Nuclear Receptor Family ◽

The Impact ◽

Receptor Family

Cardiovascular diseases remain an age-related pathology in both men and women. These pathologies are 3-fold more frequent in men than in women before menopause, although this difference progressively decreases after menopause. The vasculoprotective role of estrogens are well established before menopause, but the consequences of their abrupt decline on the cardiovascular risk at menopause remain debated. In this review, we will attempt to summarize the main clinical and experimental studies reporting the protective effects of estrogens against cardiovascular diseases, with a particular focus on atherosclerosis, and the impact of aging and estrogen deprivation on their endothelial actions. The arterial actions of estrogens, but also part of that of androgens through their aromatization into estrogens, are mediated by the estrogen receptor (ER)α and ERβ. ERs belong to the nuclear receptor family and act by transcriptional regulation in the nucleus, but also exert non-genomic/extranuclear actions. Beside the decline of estrogens at menopause, abnormalities in the expression and/or function of ERs in the tissues, and particularly in arteries, could contribute to the failure of classic estrogens to protect arteries during aging. Finally, we will discuss how recent insights in the mechanisms of action of ERα could contribute to optimize the hormonal treatment of the menopause.

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