scholarly journals Genetic screening for TLR7 variants in young and previously healthy men with severe COVID-19: a case series

2021 ◽  
Author(s):  
Xavier Solanich ◽  
Gardenia Vargas-Parra ◽  
Caspar I. van der Made ◽  
Annet Simons ◽  
Janneke Schuurs-Hoeijmakers ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Variants ◽  
Genetic Screening ◽  
Severe Disease ◽  
Case Series ◽  
Young Male ◽  
Therapeutic Interventions ◽  
Young Brother ◽  
Loss Of Function ◽  
Coding Region

Advanced age, male sex and chronic comorbidities are associated with severe COVID-19. However, these general risk factors cannot explain why critical illness occurs in young and apparently healthy individuals. In the past months, several publications have identified susceptibility loci and genes using comprehensive GWAS studies or genome, exome or candidate genes analysis. A recent study reported rare, loss-of-function TLR7 variants in otherwise healthy young brother pairs from two families with severe COVID-19. We aimed to prospectively study the prevalence of rare X-chromosomal TLR7 genetic variants in our cohort of young male patients with severe COVID-19. We recruited 13 patients ≤50 years who had no risk factors known to be associated with severe disease. We studied the entire TLR7 coding region and identified two missense variants (p.Asn215Ser, c.644A>G and p.Trp933Arg, c.2797T>C) in two out of 13 cases (15.4%). These variants were not previously reported in population control databases (gnomAD) and were predicted to be damaging by all in silico predictors. The male index patients were between 25 and 30 years old and had no apparent comorbidities. The TLR7 p.Asn215Ser co-segregated in 2 first-degree relatives severely affected by COVID-19, in a younger previously healthy the variant was found in hemizygous state , and in an older than 60 was in heterozygous state. No family members were available for testing the segregation of the p.Trp933Arg variant. These results further support that susceptibility to severe COVID-19 could be determined by inherited rare genetic variants in TLR7. Understanding the causes and mechanisms of life-threatening COVID-19 is crucial and could lead to novel preventive and therapeutic options. This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but it also enables for pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions.

scholarly journals Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Xavier Solanich ◽  
Gardenia Vargas-Parra ◽  
Caspar I. van der Made ◽  
Annet Simons ◽  
Janneke Schuurs-Hoeijmakers ◽  
...  
Keyword(s):  
Genetic Screening ◽  
Rare Variants ◽  
Population Control ◽  
Treatment Options ◽  
Young Men ◽  
Therapeutic Interventions ◽  
Type I ◽  
Loss Of Function ◽  
Coding Region ◽  
Peripheral Mononuclear Blood

IntroductionLoss-of-function TLR7 variants have been recently reported in a small number of males to underlie strong predisposition to severe COVID-19. We aimed to determine the presence of these rare variants in young men with severe COVID-19.MethodsWe prospectively studied males between 18 and 50 years-old without predisposing comorbidities that required at least high-flow nasal oxygen to treat COVID-19. The coding region of TLR7 was sequenced to assess the presence of potentially deleterious variants.ResultsTLR7 missense variants were identified in two out of 14 patients (14.3%). Overall, the median age was 38 (IQR 30-45) years. Both variants were not previously reported in population control databases and were predicted to be damaging by in silico predictors. In a 30-year-old patient a maternally inherited variant [c.644A>G; p.(Asn215Ser)] was identified, co-segregating in his 27-year-old brother who also contracted severe COVID-19. A second variant [c.2797T>C; p.(Trp933Arg)] was found in a 28-year-old patient, co-segregating in his 24-year-old brother who developed mild COVID-19. Functional testing of this variant revealed decreased type I and II interferon responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect.ConclusionsThis study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions.

scholarly journals Predisposition Factors Analysis for Fournier’s Gangrene Defects Closure Complication

2021 ◽  
Vol 5 (1) ◽  
pp. 13
Author(s):  
Bayu Fasi Bermani ◽  
Sitti Rizaliyana ◽  
Ira Handriani
Keyword(s):  
Risk Factors ◽  
Mortality Rate ◽  
Medical Records ◽  
Early Recognition ◽  
Severe Disease ◽  
Case Series ◽  
Fournier’S Gangrene ◽  
Defect Closure ◽  
Fournier's Gangrene ◽  
Fournier Gangrene

Background: Fournier’s gangrene is a rare and rapidly progressive, necrotizing fasciitis affecting the external genitalia and perineum. Based on the case series that have been reported, the incidence rate of this case is 88% with mortality rate of 20%-40%. The study aims to share our policy in managing Fournier’s gangrene and identifying risk factors that can affect the outcome of defect closure.Method: The medical records of 10 patients with Fournier’s gangrene who presented at the Dr. Soetomo Hospital Surabaya from January 2017 to December 2018 were reviewed retrospectively. We analyzed characteristics of the patients, risk factors, methods of defect closure, and case outcome. There are 10 Fournier’s gangrene patients at Dr. Soetomo Academic General Hospital from January 2017 to December 2018. We analyzed the patient’s medical records retrospectively on the patient’s characteristics, risk factors, method of closing Fournier’s gangrene defects, and the final outcome of the case.Results: There were ten men enrolled in the study, and the mean age was 49.3 ± 11.51 years. All patients received broad-spectrum antibiotic therapy, and extensive surgical excision. This study found that diabetes mellitus and uncontrolled patient blood sugar levels, statistically there is no effect on failure of defect closure in Fournier gangrene patients, but clinically, the relative risk value shows that blood glucose levels have a risk factor of 6 times. increasing the incidence of failure to close the Fournier gangrene defect.Conclusions: Fournier’s gangrene is still considered a severe disease with fairly high mortality rate. Early recognition of predisposition factors associated with invasive and aggressive treatment options is very important in efforts to to reduce morbidity.

scholarly journals Epidemiological Risk Factors Associated with Death and Severe Disease in Patients Suffering From COVID-19: A Comprehensive Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Kunchok Dorjee ◽  
Hyunju Kim
Keyword(s):  
Risk Factors ◽  
Heart Disease ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Severe Disease ◽  
Case Series ◽  
Adverse Outcomes ◽  
Smoking History ◽  
Increased Risk ◽  
The Us

AbstractIntroductionProgression of COVID-19 to severe disease and death is insufficiently understood.ObjectiveSummarize the prevalence adverse outcomes, risk factors, and association of risk factors with adverse outcomes in COVID-19 patients.MethodsWe searched Medline, Embase and Web of Science for case-series and observational studies of hospitalized COVID-19 patients through May 22, 2020. Data were analyzed by fixed-effects meta-analysis, using Shore’s adjusted confidence intervals to address heterogeneity.ResultsForty-four studies comprising 20594 hospitalized patients met inclusion criteria; 12591 from the US-Europe and 7885 from China. Pooled prevalence of death [%(95% CI)] was 18% (15-22%). Of those that died, 76% were aged≥ 60 years, 68% were males, and 63%, 38%, and 29% had hypertension, diabetes and heart disease, respectively. The case fatality risk [%(95% CI)] were 62% (48-78) for heart disease, 51% (36-71) for COPD, and 42% (34-50) for age≥ 60 years and 49% (33-71) for chronic kidney disease (CKD). Summary relative risk (sRR) of death were higher for age≥ 60 years [sRR=3.8; 95% CI: 2.9-4.8; n=12 studies], males [1.3; 1.2-1.5; 17], smoking history [1.9; 1.1-3.3; n=6], COPD [2.0; 1.6-2.4; n=9], hypertension [1.8; 1.7-2.0; n=14], diabetes [1.5; 1.4-1.7; n=16], heart disease [2.0; 1.7-2.4; 16] and CKD [2.0; 1.3-3.1; 8]. The overall prevalence of hypertension (55%), diabetes (31%) and heart disease (16%) among COVODI-19 patients in the US were substantially higher than the general US population.ConclusionsPublic health screening for COVID-19 can be prioritized based on risk-groups. A higher prevalence of cardiovascular risk factors in COVID-19 patients can suggest increased risk of SARS-CoV-2 acquisition in the population.

scholarly journals Genetic Screening of Cerebral Venous Thrombosis Susceptible Women, an Effective Step in Identifying Women at Risk for Obstetric CVT

2021 ◽  
Author(s):  
Khalil Khashei Varnamkhasti
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
High Risk ◽  
Venous Thrombosis ◽  
Genetic Variants ◽  
Genetic Screening ◽  
Cerebral Venous Thrombosis ◽  
Genetic Basis ◽  
Clinical Presentation

Introduction: Predisposition to cerebral venous thrombosis (CVT) also has a genetic basis and inherited thrombophilias constitute 22.4 % of the CVT cases. CVT with a varied clinical presentation and pathogenesis is one of the important causes of stroke which is not very common. Inherited thrombophilias with concomitant acquired risk factors like pregnancy may increase the risk of CVT manifold. Identification of a number of genetic variants increasing susceptibility to CVT and related traits opened up opportunity, to screening of women at high risk of developing obstetric CVT.  

Evaluation of the PC-1 K121Q and G2906C variants as independent risk factors for ischaemic stroke

2011 ◽  
Vol 31 (03) ◽  
pp. 196-200 ◽  
Author(s):  
M. Rieger ◽  
G. Endler ◽  
M. Funk ◽  
W. Lalouschek ◽  
W. Lang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischaemic Stroke ◽  
Vascular Disease ◽  
Genetic Variants ◽  
Coding Region ◽  
Atherosclerotic Vascular Disease ◽  
Total Study Population ◽  
Insulin Receptor Tyrosine Kinase ◽  
Genotype Frequencies ◽  
Increased Risk

SummaryOverexpression of plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor tyrosine kinase activity and thus favours insulin resistance and atherosclerotic vascular disease. Recent findings indicate that the minor variant K121Q in the PC-1 gene confers an increased risk for early myocardial infarction independent of other established risk factors. We hypothesized that genetic variants in PC-1 may also influence the risk for cerebrovascular disease.Therefore, we assessed the association of the PC-1 K121Q variant in the coding region and a polymorphism (G2906C) in the 3’ untranslated region of the PC-1 gene with the risk of stroke.We analyzed 1014 patients with a history of ischaemic stroke from the Vienna stroke registry and 1001 control individuals without vascular disease.Genotype frequencies of both genetic variants were similar in patients and controls in the total study population. By multivariate analysis, no interactions were observed between the PC-1 genotype and established vascular risk factors. However, the PC-1 2906C allele was significantly more frequent in patients who suffered from stroke before the age of 40 years. In these patients the risk for ischaemic stroke was increased fourfold.

scholarly journals Common genetic variants identify therapeutic targets for COVID-19 and individuals at high risk of severe disease

2020 ◽  
Author(s):  
Julie E. Horowitz ◽  
Jack A. Kosmicki ◽  
Amy Damask ◽  
Deepika Sharma ◽  
Genevieve H. L. Roberts ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Genetic Variants ◽  
Severe Disease ◽  
Therapeutic Targets ◽  
Common Genetic Variants ◽  
Increased Risk ◽  
Genetic Burden

The need to identify and effectively treat COVID-19 cases at highest risk for severe disease is critical. We identified seven common genetic variants (three novel) that modulate COVID-19 susceptibility and severity, implicating IFNAR2, CCHCR1, TCF19, SLC6A20 and the hyaluronan pathway as potential therapeutic targets. A high genetic burden was strongly associated with increased risk of hospitalization and severe disease among COVID-19 cases, especially among individuals with few known risk factors.

Pediatric Visual Snow Syndrome (VSS): A Case Series

2019 ◽  
pp. 249-254
Author(s):  
Kenneth J. Ciuffreda ◽  
MH Esther Han ◽  
Barry Tannen
Keyword(s):  
Visual Field ◽  
Case Series ◽  
Therapeutic Interventions ◽  
Visual Condition ◽  
Visual Phenomena ◽  
Entire Visual Field ◽  
The Individual ◽  
Vision Therapy ◽  
Abnormal Visual

Visual snow syndrome (VSS) is a relatively rare, unusual, and disturbing abnormal visual condition. The individual perceives “visual snow” (VS) throughout the entire visual field, as well as other abnormal visual phenomena (e.g., photopsia). Only relatively recently has treatment been proposed (e.g., chromatic filters) in adults with VSS, but rarely in the pediatric VSS population (i.e., medications). In this paper, we present three well-documented cases of VSS in children, including their successful neuro-optometric therapeutic interventions (i.e., chromatic filters and saccadic-based vision therapy)

Cardiovascular Risk in Perimenopausal Women

2019 ◽  
Vol 17 (6) ◽  
pp. 591-594 ◽  
Author(s):  
John C. Stevenson ◽  
Sophia Tsiligiannis ◽  
Nick Panay
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Ovarian Function ◽  
Density Lipoprotein ◽  
Premenopausal Women ◽  
Therapeutic Interventions ◽  
Additional Risk Factor ◽  
Chd Risk ◽  
Perimenopausal Women ◽  
Chd Risk Factors

Cardiovascular disease, and particularly coronary heart disease (CHD), has a low incidence in premenopausal women. Loss of ovarian hormones during the perimenopause and menopause leads to a sharp increase in incidence. Although most CHD risk factors are common to both men and women, the menopause is a unique additional risk factor for women. Sex steroids have profound effects on many CHD risk factors. Their loss leads to adverse changes in lipids and lipoproteins, with increases being seen in low density lipoprotein (LDL) cholesterol and triglycerides, and decreases in high density lipoprotein (HDL) cholesterol. There is a reduction in insulin secretion and elimination, but increases in insulin resistance eventually result in increasing circulating insulin levels. There are changes in body fat distribution with accumulation in central and visceral fat which links to the other adverse metabolic changes. There is an increase in the incidence of hypertension and of type 2 diabetes mellitus, both major risk factors for CHD. Oestrogens have potent effects on blood vessels and their loss leads to dysfunction of the vascular endothelium. All of these changes result from loss of ovarian function contributing to the increased development of CHD. Risk factor assessment in perimenopausal women is recommended, thereby permitting the timely introduction of lifestyle, hormonal and therapeutic interventions to modify or reverse these adverse changes.

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