COVID-19 prevalence and mortality is associated with the allele frequency of CCR5-Δ32
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PROVIDER: S-EPMC8275944 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Project description:coronavirus disease 2019 (COVID-19) causes severe illness including cytokine storms, but mortality among countries differs largely. In the present study, we investigated the association between human leukocyte antigen (HLA) class I, which plays a major role in susceptibility to viral infections, and the mortality of COVID-19. data of allele frequencies of HLA-A, -B and -C and COVID-19 mortality were obtained for 74 countries from the Allele Frequency Net Database and worldometer.info. Association between allele frequency of each HLA and mortality was assessed by linear regression followed by multivariable regression. Subsequently, association of HLA-C*05 to its receptor KIR2DS4fl, expressed on natural killer (NK) cells, and differential mortality to historic pandemics were analyzed. HLA-A*01, -B*07, -B*08, -B*44 and -C*05 were significantly associated with the risk of deaths (adjusted p = 0.040, 0.00081, 0.047, 0.0022, 0.00032, respectively), but only HLA-C*05 remained statistically significant (p = 0.000027) after multivariable regression. A 1% increase in the allele frequency of HLA-C*05 was associated with an increase of 44 deaths/million. Countries with different mortality could be categorized by the distribution of HLA-C*05 and its receptor KIR2DS4fl, which in combination cause NK cell-induced hyperactive immune response. Countries with similar ethnic and/or geographic background responded in a similar pattern to each pandemic. we demonstrated that allele frequency of HLA-C*05 and the distribution pattern with its receptor KIR2DS4fl strongly correlated with COVID-19 mortality. Host genetic variance of innate immunity may contribute to the difference in mortality among various countries and further investigation using patient samples is warranted.
| S-EPMC7699862 | biostudies-literature
Project description:In this study we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived.
2022-06-16 | GSE178399 | GEO
Project description: Not available
| S-EPMC7347491 | biostudies-literature
Project description:BackgroundA naturally occurring loss-of-function mutation in the gene for C-C chemokine receptor type 5 (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether this mutation also prevented the development of depressive symptoms up to 2 years after a stroke.MethodsParticipants were survivors of a first-ever mild to moderate ischemic stroke or transient ischemic attack from the TABASCO prospective study who underwent a 3 T MRI at baseline and were examined by a multiprofessional team 6, 12 and 24 months after the event, including an evaluation of depressive symptoms using the Geriatric Depression Scale.ResultsCCR5-Δ32 status and a baseline depression evaluation were available for 435 patients. Compared with noncarriers, CCR5-Δ32 carriers (16.1%) had fewer depressive symptoms at admission (p = 0.035) and at 6 months (p < 0.001), 12 months (p < 0.001) and 24 months (p = 0.006) after the index event. This association remained significant at 6 and 12 months after adjustment for age, sex, education, antidepressant use, ethnicity and the presence of cortical infarcts. These findings were more robust in women. Compared to baseline, depressive symptoms in CCR5-Δ32 noncarriers tended to remain stable or grow worse over time, but in CCR5-Δ32 carriers, symptoms tended to improve.LimitationsA limitation of this study was the exclusion of patients who had a severe stroke or who had pre-stroke depression.ConclusionCarriers of the CCR5-Δ32 allele had a lower tendency to develop depressive symptoms post-stroke, and this phenomenon was more prominent in women. These findings could have clinical implications; they suggest a mechanism-based treatment target for post-stroke depression. Drugs mimicking this loss-of-function mutation exist and could serve as a novel antidepressant therapy.
| S-EPMC8519488 | biostudies-literature
Project description:Purpose: To investigate molecular mechanisms of SARS-CoV-2-induced mucin expression and synthesis and test candidate countermeasures. Methods: Bulk RNA-seq was performed on well-differentiated human bronchial epithelial (HBE) cell culture lysates with/without SARS-CoV-2 inoculation. Results: SARS-CoV-2-infected HBE cultures exhibited peak titers 3 days post inoculation, whereas induction of MUC5B/MUC5AC peaked 7-14 days post inoculation. Conclusions: SARS-CoV-2-infection to HBE culture causes mucus goblet cell metaplasia and increased expression of MUC5B-dominated mucin overproduction.
2022-08-03 | GSE210223 | GEO
Project description:Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.
| S-EPMC4271057 | biostudies-literature
Project description:Stroke and small vessel disease cause gait disturbances and falls. The naturally occurring loss-of-function mutation in the C-C chemokine receptor 5 gene (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether it also influences gait and balance measures up to 2 years after stroke. Participants were 575 survivors of first-ever, mild-moderate ischaemic stroke or transient ischaemic attack from the TABASCO prospective study, who underwent a 3 T magnetic resonance imaging at baseline and were examined by a multi-professional team 6, 12 and 24 months after the event, using neurological, neuropsychological and mobility examinations. Gait rhythm and the timing of the gait cycle were measured by force-sensitive insoles. CCR5-Δ32 status and gait measures were available for 335 patients. CCR5-Δ32 carriers (16.4%) had higher gait speed and decreased (better) stride and swing time variability 6 and 12 months after the index event compared to non-carriers (p < 0.01 for all). The association remained significant after adjustment for age, gender, education, ethnicity and stroke severity. Significant associations were found between gait measurements and CCR5-Δ32 loss-of-function mutation amongst stroke survivors. This is the first study showing that genetic predisposition may predict long-term gait function after ischaemic stroke.
| S-EPMC10107159 | biostudies-literature
Project description:Background/aimAdult outpatients with symptomatic COVID-19 treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. Fluvoxamine strongly binds to the sigma-1 receptor (S1R) that regulates inflammation by inhibiting the production of cytokines, believed to be responsible for severe COVID-19. We evaluated the S1R locus on chr 9p13.3 in subjects tested positive for SARS-CoV-2. We focused on SNP rs17775810 that has been previously identified by examining loss-of-function mutations in the S1R gene associated with distal hereditary motor neuropathy.Patients and methodsWe utilized UK Biobank (UKB) data. Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai.ResultsThe effect of rs17775810 genotype on survival was significant (p=0.036, 2 tailed Fisher exact test). The minor allele homozygotes (TT) had the lowest death rate (0%), whereas the non-TT genotypes (i.e. CT and CC) had the highest death rate (16.2%).ConclusionThe rs17775810 analysis corroborates the favorable effect of fluvoxamine on COVID-19 survival.
| S-EPMC8045077 | biostudies-literature
Project description:ObjectivesThe main aim of this study was to find the prevalence of mortality among hospitalized COVID-19 infected patients and associated risk factors for death.MethodsThree electronic databases including PubMed, Science Direct and Google Scholar were searched to identify relevant cohort studies of COVID-19 disease from January 1, 2020, to August 11, 2020. A random-effects model was used to calculate pooled prevalence rate (PR), risk ratio (RR) and 95% confidence interval (CI) for both effect measures. Cochrane chi-square test statistic Q, [Formula: see text], and [Formula: see text] tests were used to measure the presence of heterogeneity. Publication bias and sensitivity of the included studies were also tested.ResultsIn this meta-analysis, a total of 58 studies with 122,191 patients were analyzed. The pooled prevalence rate of mortality among the hospitalized COVID-19 patients was 18.88%, 95% CI (16.46-21.30), p < 0.001. Highest mortality was found in Europe [PR 26.85%, 95% CI (19.41-34.29), p < 0.001] followed by North America [PR 21.47%, 95% CI (16.27-26.68), p < 0.001] and Asia [PR 14.83%, 95% CI (12.46- 17.21), p < 0.001]. An significant association were found between mortality among COVID-19 infected patients and older age (> 65 years vs. < 65 years) [RR 3.59, 95% CI (1.87-6.90), p < 0.001], gender (male vs. female) [RR 1.63, 95% CI (1.43-1.87), p < 0.001], ICU admitted patients [RR 3.72, 95% CI (2.70-5.13), p < 0.001], obesity [RR 2.18, 95% CI (1.10-4.34), p < 0.05], hypertension [RR 2.08,95% CI (1.79-2.43) p < 0.001], diabetes [RR 1.87, 95% CI (1.23-2.84), p < 0.001], cardiovascular disease [RR 2.51, 95% CI (1.20-5.26), p < 0.05], and cancer [RR 2.31, 95% CI (1.80-2.97), p < 0.001]. In addition, significant association for high risk of mortality were also found for cerebrovascular disease, COPD, coronary heart disease, chronic renal disease, chronic liver disease, chronic lung disease and chronic kidney disease.ConclusionThis meta-analysis revealed that the mortality rate among COVID-19 patients was highest in the European region and older age, gender, ICU patients, patients with comorbidity had a high risk for case fatality. Those findings would help the health care providers to reduce the mortality rate and combat this pandemic to save lives using limited resources.
| S-EPMC7486583 | biostudies-literature
Project description: Not available
| S-EPMC7912355 | biostudies-literature