Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Dieter C
PROVIDER: S-EPMC9258831 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The COVID-19 pandemic has spawned global health crisis of unprecedented magnitude, claiming millions of lives and pushing healthcare systems in many countries to the brink. Among several factors that contribute to an increased risk of COVID-19 and progression to exacerbated manifestations, host genetic landscape is increasingly being recognized as a critical determinant of susceptibility/resistance to infection and a prognosticator of clinical outcomes in infected individuals. Recently, several case-control association studies investigated the influence of human gene variants on COVID-19 susceptibility and severity to identify the culpable mutations. However, a comprehensive synthesis of the recent advances in COVID-19 host genetics research was lacking, and the inconsistent findings of the association studies required reliable evaluation of the strength of association with greater statistical power. In this study, we embarked on a systematic search of all possible reports of genetic association with COVID-19 till April 07, 2022, and performed meta-analyses of all the genetic polymorphisms that were examined in at least three studies. After identifying a total of 84 studies that investigated the association of 130 polymorphisms in 61 genes, we performed meta-analyses of all the eligible studies. Seven genetic polymorphisms involving 15,550 cases and 444,007 controls were explored for association with COVID-19 susceptibility, of which, ACE1 I/D rs4646994/rs1799752, APOE rs429358, CCR5 rs333, and IFITM3 rs12252 showed increased risk of infection. Meta-analyses of 11 gene variants involving 6702 patients with severe COVID-19 and 8640 infected individuals with non-severe manifestations revealed statistically significant association of ACE2 rs2285666, ACE2 rs2106809, ACE2 rs2074192, AGTR1 rs5186, and TNFA rs1800629 with COVID-19 severity. Overall, our study presents a synthesis of evidence on all the genetic determinants implicated in COVID-19 to date, and provides evidence of correlation between the above polymorphisms with COVID-19 susceptibility and severity.
| S-EPMC9384365 | biostudies-literature
Project description:BackgroundRecent evidence has linked the interferon-induced transmembrane protein 3 gene (IFITM3) to coronavirus disease 2019 (COVID-19) outcomes, but the results are inconsistent. The purpose of this meta-analysis was to evaluate the association of IFITM3 gene polymorphisms with COVID-19 susceptibility and severity.MethodA systematic search was performed with PubMed, Web of Science, Cochrane Library, and Embase from the date of inception to 20 December 2021. The results were analyzed with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). The robustness was performed using the method of sequential removal for each trial.ResultsFour studies involving 1989 subjects were included, from which 1114 patients were positive for COVID-19. For IFITM3 rs12252, the pooled OR showed that there was a significant association between the genotype frequencies and infection with COVID-19 in any of the gene models, i.e., the allelic model (OR = 1.91, 95% CI, 1.36-2.68), the dominant model (OR = 1.80, 95% CI, 1.27-2.56), the recessive model (OR = 5.67, 95% CI, 1.01-31.77), the heterozygous model (OR = 1.65, 95% CI, 1.16-2.36) and the homozygous model (OR = 5.88, 95% CI, 1.05-32.98). The results stratified by severity showed that there was a significant correlation only between the allelic (OR = 0.69, 95% CI, 0.49-0.97) and recessive (OR = 0.43, 95% CI, 0.20-0.93) models. Our results did not support the associations between the IFITM3 rs34481144 gene polymorphism and COVID-19 susceptibility or severity in any of the gene models.ConclusionsThe findings indicated that IFITM3 rs12252 gene polymorphisms were associated with COVID-19 susceptibility and that the rs12252-C variant was particularly critical for severity. Genetic factors should be considered in future vaccine development.
| S-EPMC9022375 | biostudies-literature
Project description:BackgroundCOVID-19 is associated with several risk factors such as distinct ethnicities (genetic ancestry), races, sexes, age, pre-existing comorbidities, smoking, and genetics. The authors aim to evaluate the correlation between variability in the host genetics and the severity and susceptibility towards COVID-19 in this study.MethodsFollowing the PRISMA guidelines, we retrieved all the relevant articles published until September 15, 2021, from two online databases: PubMed and Scopus.FindingsHigh-risk HLA haplotypes, higher expression of ACE polymorphisms, and several genes of cellular proteases such as TMPRSS2, FURIN, TLL-1 increase the risk of susceptibility and severity of COVID-19. In addition, upregulation of several genes encoding for both innate and acquired immune systems proteins, mainly CCR5, IFNs, TLR, DPPs, and TNF, positively correlate with COVID-19 severity. However, reduced expression or polymorphisms in genes affecting TLR and IFNλ increase COVID-19 severity.ConclusionHigher expression, polymorphisms, mutations, and deletions of several genes are linked with the susceptibility, severity, and clinical outcomes of COVID-19. Early treatment and vaccination of individuals with genetic predisposition could help minimize the severity and mortality associated with COVID-19.
| S-EPMC9195407 | biostudies-literature
Project description:IntroductionWhile COVID-19 pandemic continues to spread worldwide, researchers have linked patterns of traits to poor disease outcomes. Risk factors for COVID-19 include asthma, elderly age, being pregnant, having any underlying diseases such as cardiovascular disease, diabetes, obesity, and experiencing lifelong systemic racism. Recently, connections to certain genes have also been found, although the susceptibility has not yet been established. We aimed to investigate the available evidence for the genetic susceptibility to COVID-19.MethodsThis study was a systematic review of current evidence to investigate the genetic susceptibility of COVID-19. By systematic search and utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct, we retrieved all the related papers and reports published in English from December 2019 to September 2020.ResultsAccording to the findings, COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. Previous studies have shown that people with ACE2 polymorphism who have type 2 transmembrane serine proteases (TMPRSS2) are at high risk of SARS-CoV-2 infection. Also, two studies have shown that males are more likely to become infected with SARS-CoV-2 than females. Besides, research has also shown that patients possessing HLA-B*15:03 genotype may become immune to the infection.ConclusionCombing through the genome, several genes related to immune system's response were related to the severity and susceptibility to the COVID-19. In conclusion, a correlation was found between the ACE2 levels and the susceptibility to SARS-CoV-2 infection.
| S-EPMC8135169 | biostudies-literature
Project description:We aimed to identify prevalence and association of comorbid chronic kidney disease (CKD), acute kidney injury (AKI) and utilization prevalence of continuous renal replacement therapy (CRRT) in COVID-19-hospitalized patients as a function of severity status. With the ongoing struggle across the globe to combat COVID-19 disease, published literature has described the role of kidney disease in COVID-19 patients based on single/multicenter experiences across the globe. We extracted data from observational studies describing comorbid CKD, AKI and CRRT and outcomes and severity of COVID-19-hospitalized patients from December 1, 2019-August 20, 2020 following PRISMA guidelines. Severity of COVID-19 includes intensive care unit admission, oxygen saturation < 90%, invasive mechanical ventilation utilization, in-hospital admission and mortality. Meta-analysis was performed using a random-effects model to calculate pooled estimates, and forest plots were created. In total, 29 studies with 15,017 confirmed COVID-19 patients were included. The overall prevalence of AKI was 11.6% [(430/3693)], comorbid CKD 9.7% [(1342/13,728)] and CRRT 2.58% [(102/3946)] in our meta-analysis. We also found higher odds of comorbid CKD (pooled OR: 1.70; 95%CI: 1.21-2.40; p = 0.002), AKI (8.28; 4.42-15.52; p < 0.00001) and utilization of CRRT (16.90; 9.00-31.74; p < 0.00001) in patients with severe COVID-19 disease. Conclusion Our meta-analysis suggests that comorbid CKD, AKI and utilization of CRRT were significantly associated with COVID-19 disease severity. Clinicians should focus on early triaging of COVID-19 patients with comorbid CKD and at risk for AKI to prevent complication and mortality.
| S-EPMC8063780 | biostudies-literature
Project description:Plasmatic presepsin (PSP) is a novel biomarker reported to be useful for sepsis diagnosis and prognosis. During the pandemic, only few studies highlighted a possible correlation between PSP and COVID-19 severity, but results remain inconsistent. The present study aims to establish the correlation between PSP and COVID-19 severity. English-language papers assessing a correlation between COVID-19 and PSP from MEDLINE, PubMed, Google Scholar, Cochrane Library, MeSH, LitCovid NLM, EMBASE, CINAHL Plus and the World Health Organization (WHO) website, published from January 2020 were considered with no publication date limitations. Two independent reviewers performed data abstraction and quality assessment, and one reviewer resolved inconsistencies. The protocol was registered on PROSPERO (CRD42022325971).Fifteen articles met our eligibility criteria. The aggregate study population included 1373 COVID-19 patients who had undergone a PSP assessment. The random-effect meta-analysis was performed in 7 out of 15 selected studies, considering only those reporting the mean PSP levels in low- and high-severity cases (n = 707).The results showed that the pooled mean difference of PSP levels between high- and low-severity COVID-19 patients was 441.70 pg/ml (95%CI: 150.40-732.99 pg/ml).Our data show that presepsin is a promising biomarker that can express COVID-19 severity.
| S-EPMC9666937 | biostudies-literature
Project description:The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing.
| S-EPMC8512556 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is a recently described infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since late 2019, COVID-19 has rapidly spread in virtually all countries, imposing the adoption of significant lockdown and social distancing measures. The activation of the coagulation cascade is a common feature of disseminated intravascular coagulation and adverse clinical outcomes in COVID-19 patients. In this study, we conducted a meta-analysis aiming to investigate differences in serum D-dimer concentrations in patients with and without severe COVID-19 disease. An electronic search in Medline (PubMed), Scopus and Web of Science was performed with no language restrictions, and 13 articles were reporting on 1,807 patients (585, 32.4% with severe disease) were finally identified and included in the meta-analysis. The pooled results of all studies revealed that the D-dimer concentrations were significantly higher in patients with more severe COVID-19 (SMD: 0.91 mg/L; 95% CI, 0.75 to 1.07 mg/L, p < 0.0001). The heterogeneity was moderate (I 2 = 46.5%; p = 0.033). Sensitivity analysis showed that the effect size was not modified when any single study was in turn removed (effect size range, 0.87 mg/L to 0.93 mg/L). The Begg's (p = 0.76) and Egger's tests (p = 0.38) showed no publication bias. In conclusion, our systematic review and meta-analysis showed that serum D-dimer concentrations in patients with severe COVID-19 are significantly higher when compared to those with non-severe forms.
| S-EPMC7438945 | biostudies-literature
Project description:In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity.
| S-EPMC7823574 | biostudies-literature
Project description:BackgroundMany nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival.ObjectiveThe aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19.MethodsWe synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020.ResultsAcross the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials.ConclusionsCurrently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.
| S-EPMC8194602 | biostudies-literature