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1.
J Immunol Res ; 2023: 2345062, 2023.
Article in English | MEDLINE | ID: covidwho-20235988

ABSTRACT

Recent research has associated the interferon-induced transmembrane protein 3 gene (IFITM3) with the outcomes of coronavirus disease 2019 (COVID-19), although the findings are contradictory. This study aimed to determine the relationship between IFITM3 gene rs34481144 polymorphism and clinical parameters with COVID-19 mortality. The tetra-primer amplification refractory mutation system-polymerase chain reaction assay was used to analyze IFITM3 rs34481144 polymorphism in 1,149 deceased and 1,342 recovered patients. The clinical parameters were extracted from the patients' medical records. In this study, the frequency of IFITM3 rs34481144 CT genotypes (OR 1.47, 95% CI 1.23-1.76, P < 0.0001) in both sexes was significantly higher in deceased patients than in recovered patients. Moreover, IFITM3 rs34481144 TT genotypes (OR 3.38, 95% CI 1.05-10.87, P < 0.0001) in women were significantly associated with COVID-19 mortality. The multivariable logistic regression model results indicated that mean age (P < 0.001), alkaline phosphatase (P = 0.005), alanine aminotransferase (P < 0.001), low-density lipoprotein (P < 0.001), high-density lipoprotein (P < 0.001), fasting blood glucose (P = 0.010), creatinine (P < 0.001), uric acid (P < 0.001), C-reactive protein (P = 0.004), 25-hydroxyvitamin D (P < 0.001), erythrocyte sedimentation rate (P < 0.001), and real-time PCR Ct values (P < 0.001) were linked with increased COVID-19 death rates. In conclusion, IFITM3 rs34481144 gene polymorphism was linked to the mortality of COVID-19, with the rs34481144-T allele being especially important for mortality. Further studies are needed to confirm the results of this study.


Subject(s)
COVID-19 , Genetic Predisposition to Disease , Male , Humans , Female , Polymorphism, Single Nucleotide , Membrane Proteins/genetics , COVID-19/genetics , Genotype , Interferons/genetics , RNA-Binding Proteins/genetics
2.
PLoS One ; 18(5): e0285991, 2023.
Article in English | MEDLINE | ID: covidwho-20234386

ABSTRACT

As findings on the epidemiological and genetic risk factors for coronavirus disease-19 (COVID-19) continue to accrue, their joint power and significance for prospective clinical applications remains virtually unexplored. Severity of symptoms in individuals affected by COVID-19 spans a broad spectrum, reflective of heterogeneous host susceptibilities across the population. Here, we assessed the utility of epidemiological risk factors to predict disease severity prospectively, and interrogated genetic information (polygenic scores) to evaluate whether they can provide further insights into symptom heterogeneity. A standard model was trained to predict severe COVID-19 based on principal component analysis and logistic regression based on information from eight known medical risk factors for COVID-19 measured before 2018. In UK Biobank participants of European ancestry, the model achieved a relatively high performance (area under the receiver operating characteristic curve ~90%). Polygenic scores for COVID-19 computed from summary statistics of the Covid19 Host Genetics Initiative displayed significant associations with COVID-19 in the UK Biobank (p-values as low as 3.96e-9, all with R2 under 1%), but were unable to robustly improve predictive performance of the non-genetic factors. However, error analysis of the non-genetic models suggested that affected individuals misclassified by the medical risk factors (predicted low risk but actual high risk) display a small but consistent increase in polygenic scores. Overall, the results indicate that simple models based on health-related epidemiological factors measured years before COVID-19 onset can achieve high predictive power. Associations between COVID-19 and genetic factors were statistically robust, but currently they have limited predictive power for translational settings. Despite that, the outcomes also suggest that severely affected cases with a medical history profile of low risk might be partly explained by polygenic factors, prompting development of boosted COVID-19 polygenic models based on new data and tools to aid risk-prediction.


Subject(s)
COVID-19 , Humans , Prospective Studies , COVID-19/epidemiology , COVID-19/genetics , Risk Factors , Logistic Models , Multifactorial Inheritance/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease
3.
Transl Psychiatry ; 13(1): 189, 2023 06 06.
Article in English | MEDLINE | ID: covidwho-20232070

ABSTRACT

Despite the high contagion and mortality rates that have accompanied the coronavirus disease-19 (COVID-19) pandemic, the clinical presentation of the syndrome varies greatly from one individual to another. Potential host factors that accompany greater risk from COVID-19 have been sought and schizophrenia (SCZ) patients seem to present more severe COVID-19 than control counterparts, with certain gene expression similarities between psychiatric and COVID-19 patients reported. We used summary statistics from the last SCZ, bipolar disorder (BD), and depression (DEP) meta-analyses available on the Psychiatric Genomics Consortium webpage to calculate polygenic risk scores (PRSs) for a target sample of 11,977 COVID-19 cases and 5943 subjects with unknown COVID-19 status. Linkage disequilibrium score (LDSC) regression analysis was performed when positive associations were obtained from the PRS analysis. The SCZ PRS was a significant predictor in the case/control, symptomatic/asymptomatic, and hospitalization/no hospitalization analyses in the total and female samples; and of symptomatic/asymptomatic status in men. No significant associations were found for the BD or DEP PRS or in the LDSC regression analysis. SNP-based genetic risk for SCZ, but not for BD or DEP, may be associated with higher risk of SARS-CoV-2 infection and COVID-19 severity, especially among women; however, predictive accuracy barely exceeded chance level. We believe that the inclusion of sexual loci and rare variations in the analysis of genomic overlap between SCZ and COVID-19 will help to elucidate the genetic commonalities between these conditions.


Subject(s)
Bipolar Disorder , COVID-19 , Schizophrenia , Male , Humans , Female , Schizophrenia/genetics , Schizophrenia/metabolism , Genetic Predisposition to Disease , COVID-19/genetics , SARS-CoV-2/genetics , Bipolar Disorder/metabolism , Multifactorial Inheritance , Genome-Wide Association Study
4.
Mol Biol Rep ; 50(7): 5871-5877, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-20245064

ABSTRACT

BACKGROUND: Mannose-binding lectin (MBL) is a member of innate immunity and acts with MASP (MBL-associated serine protease) to activate the lectin pathway of the complement system. MBL gene polymorphisms are associated with susceptibility to infectious diseases. This study investigated whether MBL2 genotype, serum MBL levels, and serum MASP-2 levels affect the course of SARS-CoV-2 infection. METHODS AND RESULTS: Pediatric patients diagnosed with COVID-19 by positive real-time polymerase chain reaction (PCR) were included in the study. Single nucleotide polymorphisms in the promoter and exon 1 in the MBL2 gene (rs11003125, rs7096206, rs1800450, rs1800451, rs5030737) were identified by a PCR and restriction fragment length polymorphisms analysis. Serum MBL and MASP-2 levels were measured by ELISA. COVID-19 patients were divided into asymptomatic and symptomatic. Variables were compared between these two groups. A total of 100 children were included in the study. The mean age of the patients was 130 ± 67.2 months. Of the patients, 68 (68%) were symptomatic, and 32 (32%) were asymptomatic. The polymorphisms in the - 221nt and - 550nt promoter regions did not differ between groups (p > 0.05). All codon 52 and codon 57 genotypes were determined as wild-type AA. AB genotypes were found 45.6% in symptomatic patients while 23.5% in asymptomatics. Moreover, BB genotype was detected 9.4% in symptomatic and 6.3% in asymptomatic patients (p < 0.001). B allele was more frequent in symptomatic patients (46.3%) compared to asymptomatic patients (10.9%). (p < 0.001). Serum MBL and MASP-2 levels did not differ statistically between the groups (p = 0.295, p = 0.073). CONCLUSION: These findings suggest that codon 54 polymorphism in the MBL2 gene exon-1 region can be associated with the symptomatic course of COVID-19.


Subject(s)
COVID-19 , Magnoliopsida , Mannose-Binding Lectin , Humans , Child , Mannose-Binding Protein-Associated Serine Proteases/genetics , COVID-19/genetics , SARS-CoV-2 , Mannose-Binding Lectin/genetics , Genotype , Polymorphism, Single Nucleotide/genetics , Genetic Predisposition to Disease
5.
Ann Saudi Med ; 43(3): 125-142, 2023.
Article in English | MEDLINE | ID: covidwho-20243067

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations. OBJECTIVES: Determine associations of demographic, clinical, laboratory, and single nucleotide polymorphisms in the ACE2, TMPRSS2, TNF-α, and IFN-γ genes to the incidence of infection and mortality in COVID-19 patients. DESIGN: Prospective cohort study SETTINGS: Various cities in the Kurdistan Region of Iraq. PATIENTS AND METHODS: This prospective cohort study compared laboratory markers (D-dimer, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], C-reactive protein [CRP], lymphocyte and neutrophil counts) between COVID-19 patients and healthy controls. DNA was extracted from blood, and genotypes were done by Sanger sequencing. MAIN OUTCOME MEASURES: Single nucleotide polymorphisms of the ACE2, TMPRSS2, TNF-α, and IFN-γ genes and demographic characteristics and laboratory markers for predicting mortality in COVID-19. SAMPLE SIZE: 203 (153 COVID-19 patients, 50 health control subjects). RESULTS: Forty-eight (31.4%) of the COVID-19 patients died. Age over 40 and comorbidities were risk factors for mortality, but the strongest associations were with serum IFN-γ, the neutrophil-to-lymphocyte ratio (NLR), and serum TNF-α. The AA genotype and A allele of TMPRSS2 rs2070788 decreased while the GA genotype and A allele of TNF-α increased susceptibility to COVID-19. Patients with the GA genotype of TNF-α rs1800629 had shorter survival times (9.9 days) than those carrying the GG genotype (18.3 days) (P<.0001 by log-rank test). The GA genotype versus the GG genotype was associated with higher levels of serum TNF-α. The GA genotype increased mortality rates by up to 3.8 fold. The survival rate for COVID-19 patients carrying the IFN-γ rs2430561 TT genotype (58.5%) was lower than in patients with the TA and AA genotypes (80.3%). The TT genotype increased the risk of death (HR=3.664, P<.0001) and was linked to high serum IFN-γ production. Olfactory dysfunction was a predictor of survival among COVID-19 patients. CONCLUSIONS: Age older than 40, comorbidities, the NLR and particular genotypes for and the IFN-γ and TNF-α genes were risk factors for death. Larger studies in different populations must be conducted to validate the possible role of particular SNPs as genetic markers for disease severity and mortality in COVID-19 disease. LIMITATIONS: Small sample size. CONFLICT OF INTEREST: None.


Subject(s)
COVID-19 , Tumor Necrosis Factor-alpha , Humans , Tumor Necrosis Factor-alpha/genetics , Genetic Predisposition to Disease , Angiotensin-Converting Enzyme 2/genetics , Prospective Studies , COVID-19/genetics , Genotype , Polymorphism, Single Nucleotide , Interferon-gamma/genetics , Genetic Markers , Demography , Case-Control Studies
6.
Med Microbiol Immunol ; 212(3): 221-229, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-20235475

ABSTRACT

Pattern recognition receptors of the innate immune system, such as RIG-I and MDA5, are responsible for recognizing viruses and inducing interferon production. Genetic polymorphisms in the coding regions of RLR may be associated with the severity of COVID-19. Considering the contribution of the RLR signaling in immune-mediated reactions, this study investigated the association between three SNP in the coding region of IFIH1 and DDX58 genes with the susceptibility to COVID-19 in the Kermanshah population, Iran. 177 patients with severe and 182 with mild COVID-19 were admitted for this study. Genomic DNA was extracted from peripheral blood leukocytes of patients to determine the genotypes of two SNPs, rs1990760(C>T) and rs3747517(T>C) IFIH1 gene and rs10813831(G>A) DDX58 gene using PCR-RFLP method. Our results showed that the frequency of the AA genotype of rs10813831(G>A) was associated with susceptibility to COVID-19 compared to the GG genotype (p = 0.017, OR = 2.593, 95% CI 1.173-5.736). We also observed a statistically significant difference in the recessive model for SNPs rs10813831 variant (AA versus GG + GA, p = 0.003, OR = 2.901, 95% CI 1.405-6.103). Furthermore, No significant association was found between rs1990760 (C>T) and rs3747517(T>C) of IFIH1 gene polymorphisms with COVID-19. Our findings suggest that DDX58 rs10813831(A>G) polymorphism may be associated with COVID-19 severity in the Kermanshah population, Iran.


Subject(s)
COVID-19 , DEAD-box RNA Helicases , Humans , Interferon-Induced Helicase, IFIH1/genetics , DEAD-box RNA Helicases/genetics , Genetic Predisposition to Disease , COVID-19/genetics , Genotype , Polymorphism, Single Nucleotide , DEAD Box Protein 58/genetics , Receptors, Immunologic/genetics
7.
Viruses ; 15(5)2023 05 19.
Article in English | MEDLINE | ID: covidwho-20242059

ABSTRACT

Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects.


Subject(s)
COVID-19 , Interleukin-6 , Humans , Interleukin-6/genetics , Cross-Sectional Studies , Receptors, Interleukin-6/genetics , COVID-19/genetics , Genotype , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease , Cytokine Receptor gp130/genetics
8.
Nature ; 617(7962): 764-768, 2023 May.
Article in English | MEDLINE | ID: covidwho-2325395

ABSTRACT

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).


Subject(s)
COVID-19 , Critical Illness , Genetic Predisposition to Disease , Genetic Variation , Genome-Wide Association Study , Humans , COVID-19/genetics , Genetic Predisposition to Disease/genetics , Genotype , Phenotype , Genetic Variation/genetics , Whole Genome Sequencing , Transcriptome , Monocytes/metabolism , rab GTP-Binding Proteins/genetics , Genotyping Techniques
9.
Int Immunopharmacol ; 119: 110217, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2324989

ABSTRACT

As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.


Subject(s)
COVID-19 , Chemokine CCL2 , Polymorphism, Single Nucleotide , Humans , Case-Control Studies , Chemokine CCL2/genetics , COVID-19/genetics , Genetic Predisposition to Disease , Genotype , Iran/epidemiology , SARS-CoV-2
10.
Math Biosci Eng ; 20(6): 10659-10674, 2023 Apr 13.
Article in English | MEDLINE | ID: covidwho-2324457

ABSTRACT

To comprehend the etiology and pathogenesis of many illnesses, it is essential to identify disease-associated microRNAs (miRNAs). However, there are a number of challenges with current computational approaches, such as the lack of "negative samples", that is, confirmed irrelevant miRNA-disease pairs, and the poor performance in terms of predicting miRNAs related with "isolated diseases", i.e. illnesses with no known associated miRNAs, which presents the need for novel computational methods. In this study, for the purpose of predicting the connection between disease and miRNA, an inductive matrix completion model was designed, referred to as IMC-MDA. In the model of IMC-MDA, for each miRNA-disease pair, the predicted marks are calculated by combining the known miRNA-disease connection with the integrated disease similarities and miRNA similarities. Based on LOOCV, IMC-MDA had an AUC of 0.8034, which shows better performance than previous methods. Furthermore, experiments have validated the prediction of disease-related miRNAs for three major human diseases: colon cancer, kidney cancer, and lung cancer.


Subject(s)
Colonic Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , Genetic Predisposition to Disease , Algorithms , Computational Biology/methods , Colonic Neoplasms/genetics
12.
Nature ; 617(7961): 555-563, 2023 May.
Article in English | MEDLINE | ID: covidwho-2323608

ABSTRACT

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.


Subject(s)
Adenovirus Infections, Human , Dependovirus , Hepatitis , Child , Humans , Acute Disease/epidemiology , Adenovirus Infections, Human/epidemiology , Adenovirus Infections, Human/genetics , Adenovirus Infections, Human/virology , Alleles , Case-Control Studies , CD4-Positive T-Lymphocytes/immunology , Coinfection/epidemiology , Coinfection/virology , Dependovirus/isolation & purification , Genetic Predisposition to Disease , Helper Viruses/isolation & purification , Hepatitis/epidemiology , Hepatitis/genetics , Hepatitis/virology , Hepatocytes/virology , HLA-DRB1 Chains/genetics , HLA-DRB1 Chains/immunology , Liver/virology
13.
J Epidemiol Glob Health ; 13(2): 279-291, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2320923

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was varied in disease symptoms. We aim to explore the effect of host genetic factors and comorbidities on severe COVID-19 risk. METHODS: A total of 20,320 COVID-19 patients in the UK Biobank cohort were included. Genome-wide association analysis (GWAS) was used to identify host genetic factors in the progression of COVID-19 and a polygenic risk score (PRS) consisted of 86 SNPs was constructed to summarize genetic susceptibility. Colocalization analysis and Logistic regression model were used to assess the association of host genetic factors and comorbidities with COVID-19 severity. All cases were randomly split into training and validation set (1:1). Four algorithms were used to develop predictive models and predict COVID-19 severity. Demographic characteristics, comorbidities and PRS were included in the model to predict the risk of severe COVID-19. The area under the receiver operating characteristic curve (AUROC) was applied to assess the models' performance. RESULTS: We detected an association with rs73064425 at locus 3p21.31 reached the genome-wide level in GWAS (odds ratio: 1.55, 95% confidence interval: 1.36-1.78). Colocalization analysis found that two genes (SLC6A20 and LZTFL1) may affect the progression of COVID-19. In the predictive model, logistic regression models were selected due to simplicity and high performance. Predictive model consisting of demographic characteristics, comorbidities and genetic factors could precisely predict the patient's progression (AUROC = 82.1%, 95% CI 80.6-83.7%). Nearly 20% of severe COVID-19 events could be attributed to genetic risk. CONCLUSION: In this study, we identified two 3p21.31 genes as genetic susceptibility loci in patients with severe COVID-19. The predictive model includes demographic characteristics, comorbidities and genetic factors is useful to identify individuals who are predisposed to develop subsequent critical conditions among COVID-19 patients.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/genetics , SARS-CoV-2 , Genetic Predisposition to Disease , Genome-Wide Association Study , Comorbidity , Membrane Transport Proteins
14.
J Affect Disord ; 335: 233-238, 2023 08 15.
Article in English | MEDLINE | ID: covidwho-2319459

ABSTRACT

BACKGROUND: Epidemiological studies have reported associations between subjective well-being (SWB), depression, and suicide with COVID-19 illness, but the causality has not been established. We performed a two-sample Mendelian randomization (MR) analysis to investigate the causal link between SWB, depression, suicide and COVID-19 susceptibility and severity. METHODS: Summary statistics for SWB (298,420 cases), depression (113,769 cases) and suicide (52,208 cases) were obtained from three large-scale GWAS. Data on the associations between the Single Nucleotide Polymorphisms (SNPs) and COVID-19 (159,840 cases), hospitalized COVID-19 (44,986 cases), and severe COVID-19 (18,152 cases) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by the Inverse Variance Weighted, MR Egger and Weighted Median methods. Sensitivity tests were used to evaluate the validity of the causal relationship. RESULTS: Our results showed that genetically predicted SWB (OR = 0.98, 95 % CI: 0.86-1.10, P = 0.69), depression (OR = 0.76, 95 % CI: 0.54-1.06, P = 0.11), and suicide (OR = 0.99, 95 % CI: 0.96-1.02, P = 0.56) were not causally related to COVID-19 susceptibility. Similarly, we did not find a potential causal relationship between SWB, depression, suicide and COVID-19 severity. CONCLUSIONS: This indicated that positive or negative emotions would not make COVID-19 better or worse, and strategies that attempted to use positive emotions to improve COVID-19 symptoms may be useless. Improving knowledge about the SARS-CoV-2 and timely medical intervention to reduce panic during a pandemic is one of the effective measures to deal with the current decrease in well-being and increase in depression and suicide rates.


Subject(s)
COVID-19 , Suicide , Humans , COVID-19/genetics , Genetic Predisposition to Disease/genetics , SARS-CoV-2 , Depression/epidemiology , Depression/genetics , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Genome-Wide Association Study
15.
Rev Alerg Mex ; 67(4): 401-407, 2020.
Article in Spanish | MEDLINE | ID: covidwho-2291048

ABSTRACT

BACKGROUND: Inborn errors of immunity manifest with a greater susceptibility to infections, autoimmunity, autoinflammatory diseases, allergies, or malignancies. One of these is the mendelian susceptibility to mycobacterial disease. The most frequent etiology is the complete autosomal recessive deficiency of the ß1 subunit of the interleukin 12 receptor. CASE REPORT: A female patient who, by the age of six months, started with a nodular lesion in the right shoulder and ipsilateral axillary adenitis after the bacillus Calmette-Guérin vaccine was applied. Later, she developed a cutaneous fistula in the anterior thorax, the inframammary region, and chronic recidivant suppurative lymphadenitis. A disseminated infection caused by Mycobacterium bovis was diagnosed, therefore, individualized pharmacological treatment was required due to failure with the primary treatment. The patient was diagnosed with deficiency in the ß1 subunit of the interleukin 12 receptor at age six. During her last hospitalization, she presented fever, cough, and tachypnea, and SARS-CoV-2 was detected by quantitative polymerase chain reaction. The patient has had a favorable evolution. CONCLUSION: In patients with disseminated infections caused by bacillus Calmette-Guérin vaccination or by environmental mycobacteria, there should be suspicion of an inborn error of immunity and the patient should be referred to a third level hospital for an early immunological assessment.


Antecedentes: Los errores innatos de la inmunidad se manifiestan con una mayor susceptibilidad a infecciones, autoinmunidad, enfermedades autoinflamatorias, alergia o malignidad. Uno de estos es la susceptibilidad mendeliana a infecciones micobacterianas. La etiología más frecuente es la deficiencia completa autosómica recesiva de la subunidad ß1 del receptor de interleucina 12. Caso clínico: Paciente que comenzó a los seis meses de edad con una lesión nodular en hombro derecho y adenitis axilar ipsolateral posterior a la vacuna con bacilo de Calmette-Guérin. Posteriormente desarrolló una fistula cutánea en tórax anterior, región inframamaria y linfadenitis supurativa crónica recidivante. Se diagnosticó infección diseminada por Mycobacterium bovis, por lo que requirió tratamiento farmacológico individualizado debido al fracaso con el tratamiento primario. La paciente fue diagnosticada con deficiencia de la subunidad ß1 del receptor de interleucina 12 a los seis años. Durante su última hospitalización presentó fiebre, tos y taquipnea, detectándose SARS-CoV-2 por reacción en cadena de la polimerasa cuantitativa. La paciente evolucionó favorablemente. Conclusión: En los pacientes con infecciones diseminadas por la vacuna con bacilo de Calmette-Guérin o micobacterias ambientales, debe sospecharse un error innato de la inmunidad y derivarlos a tercer nivel de atención para la evaluación inmunológica temprana.


Subject(s)
BCG Vaccine/adverse effects , COVID-19/complications , Interleukin-12 Subunit p40/deficiency , Mycobacterium bovis/pathogenicity , SARS-CoV-2 , Tuberculosis/etiology , Candidiasis, Oral/complications , Child , Coinfection , Cutaneous Fistula/etiology , Female , Genetic Predisposition to Disease , Humans , Immunocompromised Host , Interleukin-12 Subunit p40/genetics , Tuberculosis, Lymph Node/etiology , Vasculitis, Leukocytoclastic, Cutaneous/complications
16.
Genes (Basel) ; 14(4)2023 04 14.
Article in English | MEDLINE | ID: covidwho-2295858

ABSTRACT

Recently, we have observed two significant pandemics caused by communicable (COVID-19) and non-communicable factors (obesity). Obesity is related to a specific genetic background and characterized by immunogenetic features, such as low-grade systemic inflammation. The specific genetic variants include the presence of polymorphism of the Peroxisome Proliferator-Activated Receptors gene (PPAR-γ2; Pro12Ala, rs1801282, and C1431T, rs3856806 polymorphisms), ß-adrenergic receptor gene (3ß-AR; Trp64Arg, rs4994), and Family With Sequence Similarity 13 Member A gene (FAM13A; rs1903003, rs7671167, rs2869967). This study aimed to analyze the genetic background, body fat distribution, and hypertension risk in obese metabolically healthy postmenopausal women (n = 229, including 105 lean and 124 obese subjects). Each patient underwent anthropometric and genetic evaluations. The study has shown that the highest value of BMI was associated with visceral fat distribution. The analysis of particular genotypes has revealed no differences between lean and obese women except for FAM13A rs1903003 (CC), which was more prevalent in lean patients. The co-existence of the PPAR-γ2 C1431C variant with other FAM13A gene polymorphisms [rs1903003(TT) or rs7671167(TT), or rs2869967(CC)] was related to higher BMI values and visceral fat distribution (WHR > 0.85). The co-association of FAM13A rs1903003 (CC) and 3ß-AR Trp64Arg was associated with higher values of systolic (SBP) and diastolic blood pressure (DBP). We conclude that the co-existence of FAM13A variants with C1413C polymorphism of the PPAR-γ2 gene is responsible for body fat amount and distribution.


Subject(s)
COVID-19 , PPAR gamma , Humans , Female , PPAR gamma/genetics , Postmenopause/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Obesity/genetics , GTPase-Activating Proteins/genetics
17.
Egypt J Immunol ; 30(2): 119-130, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2295618

ABSTRACT

Severe COVID-19 disease was linked to a severe proinflammatory response and cytokine storm interleukin 17 (IL-17) is one of these cytokines, was associated with severe acute lung injury and multiorgan dysfunction. Single nucleotide polymorphisms (SNPs) in genes coding IL-17 can affect level of IL-17 hence its role in diseases. Also, SNPs in IL-23 R which control IL-23 is the main activator of IL-17 production. This study aimed to determine whether the IL-17A (G/A-rs2275913), IL-23R (A/G rs11209026) SNPs and serum levels of IL-17 were related to the risk of severe COVID-19. This case-control study included 120 confirmed COVID-19 patients, divided into two categories according to the severity of the disease and 74 normal subjects as controls. COVID-19 patients were SARS-CoV-2 positive by a reverse transcription-polymerase chain reaction and subjected to full clinical examinations, routine laboratory tests, and radiographic evaluations. The IL-17 levels were assessed using ELISA method, and genotyping of IL-17A (197 A/G; rs2275913) and IL-23R rs11209026 (A/G) was performed by the TaqMan Genotyping Assay. There were no differences in the distribution of IL-17A or IL-23R genotypes between COVID-19 groups and the control group (p=0.93 and p=0.84, respectively). Severe COVID-19 patients had significantly higher IL-17 serum levels than non-severe COVID-19 (p=0.0001). The GG genotypes of IL-17A were significantly higher in severe COVID-19 patients (p=0.004). Multivariate logistic regression analysis revealed that AG, GG genotypes of IL-17 and IL-17A were independent predictors of COVID-19 disease severity (p < 0.0001, p=0.06 and p=0.04, respectively). ROC curve analysis for IL-17, as predictor of severe COVID-19 disease revealed a sensitivity of 87.9% and specificity of 66.1% at a cutoff point of 114 pg/ml with AUC = 0.799. In conclusion, these findings indicated that IL-17 may be considered a marker of severe COVID-19. IL-17A SNPs may have a role in COVID-19 severity. IL-23R SNPs had no role in COVID-19.


Subject(s)
COVID-19 , Interleukin-17 , Humans , Interleukin-17/genetics , Genetic Predisposition to Disease , Case-Control Studies , COVID-19/genetics , SARS-CoV-2 , Genotype , Polymorphism, Single Nucleotide , Interleukin-23/genetics
18.
J Psychiatr Res ; 162: 79-87, 2023 06.
Article in English | MEDLINE | ID: covidwho-2295339

ABSTRACT

BACKGROUND: Currently, there is increasing evidence from clinic, epidemiology, as well as neuroimaging, demonstrating neuropsychiatric abnormalities in COVID-19, however, whether there were associations between brain changes caused by COVID-19 and genetic susceptibility of psychiatric disorders was still unknown. METHODS: In this study, we performed a meta-analysis to investigate these associations by combing single-cell RNA sequencing datasets of brain tissues of COVID-19 and genome-wide association study summary statistics of psychiatric disorders. RESULTS: The analysis demonstrated that among ten psychiatric disorders, gene expression perturbations implicated by COVID-19 in excitatory neurons of choroid plexus were significantly associated with schizophrenia. CONCLUSIONS: Our analysis might provide insights for the underlying mechanism of the psychiatric consequence of COVID-19.


Subject(s)
COVID-19 , Mental Disorders , Humans , Genome-Wide Association Study/methods , Mental Disorders/genetics , Genetic Predisposition to Disease/genetics , Brain/diagnostic imaging , Brain/metabolism , Gene Expression , Polymorphism, Single Nucleotide
19.
Viruses ; 15(4)2023 03 30.
Article in English | MEDLINE | ID: covidwho-2293804

ABSTRACT

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development.


Subject(s)
COVID-19 , Thrombophilia , Humans , Post-Acute COVID-19 Syndrome , Gene Frequency , Genetic Markers , Cross-Sectional Studies , COVID-19/genetics , Genotype , Genetic Predisposition to Disease , Thrombophilia/genetics , Polymorphism, Single Nucleotide , Case-Control Studies
20.
Int J Immunogenet ; 50(3): 117-126, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2292823

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the mortality rate of the disease has been relatively under control as of 2022, more than 15 million confirmed COVID-19 cases have been detected in Turkey to date, causing more than 100,000 deaths. The clinical manifestation of the disease varies widely, ranging from asymptomatic to acute respiratory distress syndrome causing death. The immune response mechanisms have an important impact on the fine adjustment between healing and enhanced tissue damage. This study aims to investigate the relationship between the variants of the interleukin 1 receptor antagonist (IL1RN), interleukin 17A (IL17A), and interleukin 17F (IL17F) genes and COVID-19 severity. The study population comprised 202 confirmed COVID-19 cases divided into three groups according to severity. The IL1RN variable number of a tandem repeat (VNTR) polymorphism was genotyped by polymerase chain reaction (PCR), and IL17A rs2275913, IL17F rs763780 and rs2397084 polymorphisms were genotyped by the PCR-based restriction fragment length polymorphism method. Statistical analysis revealed a significant association between IL17A rs2275913 variant and COVID-19 severity. The AA genotype and the A allele of IL17A rs2275913 were found significant in the severe group. Additionally, we found a significant relationship between haplotype frequency distributions and severity of COVID-19 for the IL17F rs763780/rs2397084 (p = 0.044) and a combination of IL17F rs763780/rs2397084/ IL17A rs2275913 (p = 0.04). The CG and CGA haplotype frequencies were significantly higher in the severe group. IL17A rs2275913, IL17F rs763780 and rs2397084 variants appear to have important effects on the immune response in COVID-19. In conclusion, variants of IL17A rs2275913, IL17F rs763780 and rs2397084 may be the predictive markers for the clinical course and potential immunomodulatory treatment options in COVID-19, a disease that has placed a significant burden on our country.


Subject(s)
COVID-19 , Interleukin-17 , Humans , Interleukin-17/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , COVID-19/genetics , SARS-CoV-2 , Genotype , Disease Progression , Case-Control Studies
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