Novel coronavirus disease 2019 (COVID‐19) poses a global threat, due to its fluctuating frequency and lethality. Published data revealed associations of COVID‐19 susceptibility and severity with host genetic polymorphisms in renin‐angiotensin‐aldosterone system (RAAS)‐related genes including angiotensin‐converting enzyme (ACE)1, ACE2, and transmembrane protease (TMPRSS)2. However, the findings remain inconclusive. Accordingly, we aimed to clarify associations of genetic variants in those genes with COVID‐19 susceptibility and severity using a systematic review with meta‐analysis. From inception through 1 July 2021, a literature search was performed using PubMed, Scopus, Web of Science, and Cochrane Library databases. Allelic distributions for each polymorphism were calculated as pooled odds ratios (OR) with 95% confidence intervals (CI) to assess the strength of association. A total of 3333 COVID‐19 patients and 5547 controls from 11 eligible studies were included. From a systematic review, ACE1 rs1799752, ACE1 rs4646994, ACE2 rs2285666, and TMPRSS2 rs12329760 were identified as common polymorphisms of RAAS‐related genes. Meta‐analysis showed a significant association between TMPRSS2 rs12329760 C‐allele and an increased risk of developing severe COVID‐19 (OR = 1.32, 95% CI: 1.01, 1.73). Likewise, additional meta‐analyses uncovered that both ACE1 rs4646994 DD‐genotype and ACE2 rs2285666 GG‐genotype carriers had a significantly increased risk of developing severe COVID‐19 (OR = 2.06, 95% CI: 1.45, 2.93; OR = 2.14, 95% CI: 1.26, 3.66; respectively). Genetic polymorphisms of ACE1 rs4646994 DD‐genotype, ACE2 rs2285666 GG‐genotype, and TMPRSS2 rs12329760 CC‐genotype and C‐allele may serve as predictive models of COVID‐19 severity.

Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID‐19 severity: A systematic review with meta‐analysis

ACE I/D polymorphism in Czech first-wave SARS-CoV-2-positive survivors.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.27076

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

/pdf/ace-and-ace2-gene-variants-are-associated-with-severe-2kznm5y5.pdf

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin-angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)-angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.

The Renin-Angiotensin System: A Key Role in SARS-CoV-2-Induced COVID-19.

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

Coronavirus disease‐2019 (COVID‐19) is pro‐inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin‐6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID‐19 patients. The differential expression of IL6 cytokine in COVID‐19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (–597G > A and –174G > C) with the severity of COVID‐19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID‐19. Genotyping of two selected SNPs, rs1800795 (–174G > C) and rs1800797 (–597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). In our study, individuals with GC genotypes of IL6 (–174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID‐19 severity with rs1800797 (–597G > A) polymorphism. The COVID‐19 severity was significantly higher in individuals having ‘C’ allele of IL6 (–174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (–174G > C) and rs1800797 (–597G > A) showed that individuals having AC* haplotype significantly association with COVID‐19 severity (p = .034). Our results suggest that ‘C’ allele of rs1800795 (–174G > C) polymorphism of IL6 may be the risk allele for severity of COVID‐19 in North Indian population.

Genetic polymorphisms of IL6 gene –174G > C and –597G > A are associated with the risk of COVID‐19 severity

Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.

/pdf/genetic-variants-and-drug-efficacy-in-tuberculosis-a-step-inxz9qm9.pdf

Genetic Variants and Drug Efficacy in Tuberculosis: A Step toward Personalized Therapy

Simple Summary Humane Society International (HSI) facilitates dog sterilisation programmes internationally, which includes population surveys of street dogs to gain basic demographic information and to set a baseline for future monitoring operations. HSI has developed a web and mobile application suite called ‘HSIApps’ with custom tailored workflows to improve the efficiency (lower programmatic cost) and improve the welfare of dogs in care throughout the sterilisation process. The Android-based mobile app is simple and easy to use for teams in the field. The web app has data dashboards, record views, and reports for monitoring and evaluation purposes. The use of such digital applications can improve dog population management programme implementation, ensure positive outcomes for dogs postoperatively, and facilitate programmatic monitoring and evaluation. We describe here the use of this application and insights gained through its use in HSI’s street dog monitoring, evaluation, and impact assessment (MEIA) programmes in India. Abstract Street dogs survive on food handouts provided by individuals, or the wider community yet typically receive limited to no veterinary care. They can also carry a variety of zoonotic diseases such as rabies, posing a significant risk to human and dog population health. Dog sterilisation is one of the most humane and effective methods available to control street dog populations. Dog sterilisation programmes, particularly those operating at a large-scale, often face a variety of challenges including limited resources, staffing, and less-than-ideal facilities. Recordkeeping is often a challenge as well, which can complicate the return of a sterilised dog to their location of capture. Street dogs are territorial, and the return of a dog to an incorrect location is fraught with various welfare issues, as well as an increased risk of postoperative complications, including death. Humane Society International developed a mobile phone-based application called ‘HSIApps’ drawing on years of field experience and data collection in street dog location recording, as well as clinical and postoperative treatment. HSIApps facilitates the return of dogs back to their exact captured location, which ensures dog welfare, and generates reports of a variety of useful data variables to maximise the efficacy and reliability of sterilisation programmes.

/pdf/technology-for-improving-street-dog-welfare-and-capturing-ukuzx8fe.pdf

Shrikant Verma

Papers

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.

Genetic polymorphisms of IL6 gene –174G > C and –597G > A are associated with the risk of COVID‐19 severity

Genetic Variants and Drug Efficacy in Tuberculosis: A Step toward Personalized Therapy

Technology for Improving Street Dog Welfare and Capturing Data in Digital Format during Street Dog Sterilisation Programmes