Study on the correlation between DPP9 rs2109069 and IFNAR2 rs2236757 polymorphisms with COVID-19 mortality.

Understanding the complex mechanisms of the immune system in dealing with the COVID-19 infection, which is probably related to the polymorphism in cytokine and chemokine genes, can explain the pro-inflammatory condition of patients. Therefore, in this study, the relationship between the frequency of single nucleotide polymorphisms in the two pro-inflammatory genes dipeptidylpeptidase 9 (DPP9) and interferon alpha and beta receptor subunit 2 (IFNAR2) and the severity of COVID-19 was assessed. This study involved 954 COVID-19 patients, including 528 recovered and 426 deceased patients. To investigate the polymorphisms of IFNAR2 rs2236757 and DPP9 rs2109069, we used the polymerase chain reaction with the restriction fragment length polymorphism assay. The results showed that IFNAR2 rs2236757 A allele is related to the reduced severity of the disease, whereas the incidence of DPP9 rs2109069 A allele was higher among the deceased than recovered individuals. On the other hand, in people carrying the G allele in the DPP9 gene polymorphism and the allele A in the IFNR2 gene polymorphism, the improvement of the disease was significantly higher. In conclusion, the results showed that IFNAR2 rs2236757 A allele is related to the decrease in the severity of the disease, while the frequency of DPP9 rs2109069 A allele was higher in deceased people than in recovered people. This shows the important role of genes related to inflammatory responses as well as the role of genetic variants of these genes in the severity of COVID-19.

The importance of heteroresistance and efflux pumps in bedaquiline-resistant Mycobacterium tuberculosis isolates from Iran.

BACKGROUND: Tuberculosis (TB) continues to pose a threat to communities worldwide and remains a significant public health issue in several countries. We assessed the role of heteroresistance and efflux pumps in bedaquiline (BDQ)-resistant Mycobacterium tuberculosis isolates. METHODS: Nineteen clinical isolates were included in the study, of which fifteen isolates were classified as MDR or XDR, while four isolates were fully susceptible. To evaluate BDQ heteroresistance, the Microplate Alamar Blue Assay (MABA) method was employed. For screening mixed infections, MIRU-VNTR was performed on clinical isolates. Mutations in the atpE and Rv0678 genes were determined based on next-generation sequencing data. Additionally, real-time PCR was applied to assess the expression of efflux pump genes in the absence and presence of verapamil (VP). RESULTS: All 15 drug-resistant isolates displayed resistance to BDQ. Among the 19 total isolates, 21.05% (4/19) exhibited a heteroresistance pattern to BDQ. None of the isolates carried a mutation of the atpE and Rv0678 genes associated with BDQ resistance. Regarding the MIRU-VNTR analysis, most isolates (94.73%) showed the Beijing genotype. Fifteen (78.9%) isolates showed a significant reduction in BDQ MIC after VP treatment. The efflux pump genes of Rv0676c, Rv1258c, Rv1410c, Rv1634, Rv1819, Rv2459, Rv2846, and Rv3065 were overexpressed in the presence of BDQ. CONCLUSIONS: Our results clearly demonstrated the crucial role of heteroresistance and efflux pumps in BDQ resistance. Additionally, we established a direct link between the Rv0676c gene and BDQ resistance. The inclusion of VP significantly reduced the MIC of BDQ in both drug-susceptible and drug-resistant clinical isolates.

Tuberculosis and lung cancer: metabolic pathways play a key role.

Despite the fact that some cases of tuberculosis (TB) are undiagnosed and untreated, it remains a serious global public health issue. In the diagnosis, treatment, and control of latent and active TB, there may be a lack of effectiveness. An understanding of metabolic pathways can be fundamental to treat latent TB infection and active TB disease. Rather than targeting Mycobacterium tuberculosis, the control strategies aim to strengthen host responses to infection and reduce chronic inflammation by effectively enhancing host resistance to infection. The pathogenesis and progression of TB are linked to several metabolites and metabolic pathways, and they are potential targets for host-directed therapies. Additionally, metabolic pathways can contribute to the progression of lung cancer in patients with latent or active TB. A comprehensive metabolic pathway analysis is conducted to highlight lung cancer development in latent and active TB. The current study aimed to emphasize the association between metabolic pathways of tumor development in patients with latent and active TB. Health control programs around the world are compromised by TB and lung cancer due to their special epidemiological and clinical characteristics. Therefore, presenting the importance of lung cancer progression through metabolic pathways occurring upon TB infection can open new doors to improving control of TB infection and active TB disease while stressing that further evaluations are required to uncover this correlation.

The death rate of COVID-19 infection in different SARS-CoV-2 variants was related to C-reactive protein gene polymorphisms.

The serum level of C-reactive protein (CRP) is a significant independent risk factor for Coronavirus disease 2019 (COVID-19). A link was found between serum CRP and genetic diversity within the CRP gene in earlier research. This study examined whether CRP rs1205 and rs1800947 polymorphisms were associated with COVID-19 mortality among various severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) variants. We genotyped CRP rs1205 and rs1800947 polymorphisms in 2023 deceased and 2307 recovered patients using the polymerase chain reaction-restriction fragment length polymorphism method. There was a significant difference between the recovered and the deceased patients in terms of the minor allele frequency of CRP rs1205 T and rs1800947 G. In all three variants, COVID-19 mortality rates were associated with CRP rs1800947 GG genotype. Furthermore, CRP rs1205 CC and rs1800947 GG genotypes showed higher CRP levels. It was found that the G-T haplotype was prevalent in all SARS-CoV-2 variants. The C-C and C-T haplotypes were statistically significant in Delta and Omicron BA.5 variants, respectively. In conclusion, polymorphisms within the CRP gene may relate to serum CRP levels and mortality among COVID-19 patients. In order to verify the utility of CRP polymorphism correlation in predicting COVID-19 mortality, a replication of these results is needed.

The Effect of Akkermansia muciniphila and Its Outer Membrane Vesicles on MicroRNAs Expression of Inflammatory and Anti-inflammatory Pathways in Human Dendritic Cells.

Probiotics play a crucial role in immunomodulation by regulating dendritic cell (DC) maturation and inducing tolerogenic DCs. Akkermansia muciniphila affects inflammatory response by elevating inhibitory cytokines. We aimed to evaluate whether Akkermansia muciniphila and its outer membrane vesicles (OMVs) affect microRNA-155, microRNA-146a, microRNA-34a, and let-7i expression of inflammatory and anti-inflammatory pathways. Peripheral blood mononuclear cells (PBMCs) were isolated from the healthy volunteers. To produce DCs, monocytes were cultivated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were allocated into six subgroups: DC + Lipopolysaccharide (LPS), DC + dexamethasone, DC + A. muciniphila (MOI 100, 50), DC + OMVs (50 µg/ml), and DC + PBS. The surface expression of human leukocyte antigen-antigen D related (HLA-DR), CD86, CD80, CD83, CD11c, and CD14 was examined using flow cytometry, and the expression of microRNAs was assessed using qRT-PCR, and the levels of IL-12 and IL-10 were measured using ELISA. A. muciniphila (MOIs 50, 100) could significantly decrease IL-12 levels relative to the LPS group. The IL-10 levels were decreased in the DC + LPS group than the DC + dexamethasone group. Treatment with A. muciniphila (MOI 100) and OMVs could elevate the concentrations of IL-10. DC treatment with LPS led to a significant increment in the expression of microRNA-155, microRNA-34a, and microRNA-146a. The expression of these microRNAs was reversed by A. muciniphilia and its OMVs treatment. Let-7i increased in treatment groups compared to the DC + LPS group. A. muciniphilia (MOI 50) had a substantial effect on the expression of HLA-DR, CD80, and CD83 on DCs. Therefore, DCs treatment with A. muciniphila led to induce tolerogenic DCs and the production of anti-inflammatory IL-10.

Expression of TRIM56 gene in SARS-CoV-2 variants and its relationship with progression of COVID-19.

Aim: The present study aimed to determine a correlation between differential TRIM56 expression levels and severe infections of COVID-19 between the Alpha, Delta and Omicron BA.5 variants. Materials & methods: This study was performed on 330 COVID-19 patients, including 142 with severe and 188 with mild infections, as well as 160 healthy controls. The levels of TRIM56 gene expression were determined using a qPCR. Results: TRIM56 gene showed significantly lower mRNA expression in the severe and mild groups compared with healthy individuals. Our finding indicated the high and low reduction of TRIM56 mRNA expression in Delta and Omicron BA.5 variant, respectively. Conclusion: Further research is needed to characterize the impact of TRIM proteins on the severity of COVID-19.

Scientists looked at a protein called TRIM that helps fight viruses to see if a specific TRIM protein, TRIM56, was linked to how poorly people became with COVID-19. The study looked at the blood samples of 330 patients and found that COVID-19 patients had less TRIM56 than healthy people, especially those who were particularly ill.

A potent subset of Mycobacterium tuberculosis glycoproteins as relevant candidates for vaccine and therapeutic target.

Tuberculosis (TB) remains one of the most afflictive bacterial infections globally. In high burden TB countries, surveillance, diagnosis and treatment of drug resistant TB (RR and X/MDRTB) display a crucial public health challenge. Therefore, we need new TB vaccines; diagnostic and therapeutic strategies to briskly prevent disease promotion; reduce drug-resistant TB and protect everyone from disease. The study identified various potent membrane and cell wall M. tuberculosis glycolipoproteins that are relevant for diagnostics, drug and vaccine discovery. A M. tuberculosis Proskauer and Beck broth culture was extracted for total proteins by ammonium sulfate method. After ConA-Affinity Chromatography reputed glycoproteins were collected followed by 2DE gel electrophoresis and LC Mass spectrometry. A total of 293 glycoproteins were identified using GlycoPP and IEDB database. Probable conserved trans-membrane protein (Rv0954), LpqN (Rv0583), PPE68 (Rv3873), Phosphate-binding protein (Rv0932c), PPE61 (Rv3532) and LprA (Rv1270c), had the highest glycosylation percentage value with 13.86%, 11.84%, 11.68%, 11.1%, 10.59% and10.2%, respectively. Our study discloses several dominant glycoproteins that play roles in M. tuberculosis survival, and immunogenicity. These include glycoproteins involved in antigenicity, transport and biosynthesis of M. tuberculosis cell envelope, pathogen-host interaction and drug efflux pumps, which are considered as a feasible drug targets or TB new vaccine candidates.

Evaluation of miR-let-7f, miR-125a, and miR-125b expression levels in sputum and serum samples of Iranians and Afghans with pulmonary tuberculosis.

Background and Objectives: The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microRNAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b). Materials and Methods: A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs. Results: Iranian (P<0.0001) and Afghan (P<0.0001) serum samples and Afghan (P<0.0001) sputum samples overexpressed miR-125a, whereas Iranian sputum samples showed downregulation (P=0.0039). In both Iranian (P<0.0001; P=0.0007) and Afghan (P<0.0001; P<0.0001) serum and sputum samples, miR-125b was overexpressed. Furthermore, miR-let-7f down-regulation was observed in serum and sputum samples (P<0.0001), whereas Iranian sputum samples had no statistically significant differences (P=0.348). Conclusion: Overexpression of miR-125a and miR-125b has been detected in Iranian and Afghan samples. In both races, miR-let-7f downregulation has been confirmed. Identification of miRNA profiles under different conditions opens the door to evaluating potential new biomarkers for diagnosis, disease monitoring, and therapeutic markers in TB infection.

Relationship Between Human FCγRIIA rs1801274 G Allele and Risk of Death Among Different SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and spread very quickly across the world. Different responses to infections have been related to fragment crystallizable gamma-receptor II alpha (FcγRIIA) polymorphisms. The purpose of this investigation was to determine if FCγRIIA rs1801274 polymorphism was related to COVID-19 mortality among different variants of SARS-CoV-2. The FCγRIIA rs1801274 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism technique in 1,734 recovered and 1,450 deceased patients. Deceased patients had significantly higher minor allele frequency of the FCγRIIA rs1801274 G allele than in the recovered cases. The COVID-19 mortality was associated with FCγRIIA rs1801274 GG and AG genotypes in the Delta variant and with FCγRIIA rs1801274 GG genotypes in the Alpha and Omicron BA.5 variants. The reverse transcription-quantitative polymerase chain reaction Ct values revealed statistically significant differences between individuals with a G allele and those with an A allele. In conclusion, among the several SARS-CoV-2 variants, there may be a correlation between the mortality rate of COVID-19 and the G allele of FCγRIIA rs1801274. To confirm our findings, thorough research is still required.

The impact of Akkermansia muciniphila and its extracellular vesicles in the regulation of serotonergic gene expression in a small intestine of mice.

OBJECTIVES: A better understanding of host-microbe interactions as a cross-talk between the gastrointestinal (GI) tract and the gut microbiota can help treat and prevent GI disorders by improving the maintenance of GI homeostasis. The gut microbiota can affect signaling molecules, such as serotonin, which regulates endocrine systems through the GI tract. Moreover, studying the effects of gut microbiota in the small intestine on the human GI tract health is pivotal. METHODS: Male C57BL/6J mice (n = 30, 10 mice per group) were orally gavaged with 200 µL of PBS (control group); mice in group II were orally gavaged with 109 colony-forming units (CFU)/200 µL of viable A. muciniphila, suspended in PBS (A. muciniphila group); and mice in group III were orally gavaged with 10 µg of protein/200 µL of EVs (A. muciniphila-EV group) once daily for four weeks. The gene expression of serotonin system-related genes (Slc6a4, Tph1, Mao, Htr3, Htr4, and Htr7) was examined by quantitative real-time PCR (qPCR) method. RESULTS: Based on the results, A. muciniphila significantly affected the mRNA expression of genes related to the serotonin system (Tph1, Mao, Htr3B, and Htr7) in the duodenum and (Htr3B, Htr4 and Htr7) in the ileum of mice (P < 0.05). Moreover, A. muciniphila-derived EVs affected the expression of major genes related to the serotonin system (Tph1, slc6a4a, Mao, Htr3B, Htr4, and Htr7) in the duodenum and ileum of mice (P < 0.05). CONCLUSIONS: The present findings may pave the way for further investigation of the effects of strain-specific probiotics on the serotonergic system, which is currently in its infancy.

Tuberculosis prevention, diagnosis, and treatment financial profile during 2006-2021: PART A.

BACKGROUND: Tuberculosis (TB) is a communicable disease that is a major cause of death and one of the leading causes of death worldwide. Currently, there is no analyzed data to examine the financial profile of TB by country, continent, and year; this article analyzed TB prevention, diagnosis, and treatment financial profile during the last two decades. METHODS: Original research, reviews, and governmental databases are analyzed to present the financial profile of TB. RESULTS: Analyzed data showed Europe (23137.133), Asia (20137.073), and Africa (15237.973) had the most allocated funds (US $ million), and Oceania (236.702), and America (4745.043) had the lowest allocated fund (US $ million) during 2006-2021. Additionally, the allocation of funds (domestic funds, global funds, and grants [excluding global funds]) in different countries and proper planning for TB eradication has caused that in the last two decades, the slope of the confirmed cases and deaths graph line is negative. CONCLUSION: The number of confirmed cases and deaths reported globally is decreasing. The trend lines showed that the assigned funds are increasing, indicating that the TB eradication plan can be apprehended soon.

Introduction and effect of natural selection analysis at common mutations of SARS-CoV-2 spike gene in Iran.

The epidemic of coronavirus disease 2019 (COVID-19) was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-Cov-2 is composed of two subunits, S1 and S2. This study aimed to describe SARS-CoV-2 haplotypes in Iranians based on the S gene, which plays a key role in the receptor recognition and cell membrane fusion proses. 95 positive saliva samples for SARS-CoV-2 were amplified and sequenced for the S gene. The sequences were classified into 35 haplotypes, which 11 haplotypes were new (H1, H2, H3, H4, H6, H7, H11, H13, H15, H16, H25) and have not been reported so far. Amino acid substitutions were found at 40 positions that 23 were located at S1 subunit and 16 were at S2 subunit and one was at cleavage loop (P681H/R), thus polymorphisms at S1 subunit were found to be higher than S2. The neutrality index (NI) analyses showed a negative departure from the neutral substitution patterns (NI > 1) for S1 and S2 subunit in the studied sequences. The co-occurrence of B-cell epitopes and mutation sites were found in seven positions with more probably to be exposed the immune system pressure. In conclusion, the results provide the significant data to design an effective vaccine based on this protein.

The impact of ACE2 polymorphisms (rs1978124, rs2285666, and rs2074192) and ACE1 rs1799752 in the mortality rate of COVID-19 in different SARS-CoV-2 variants.

BACKGROUND: Clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes could be influenced by genetic polymorphisms in angiotensin I-converting enzyme (ACE1) and ACE2. This study aims to examine three polymorphisms (rs1978124, rs2285666, and rs2074192) on the ACE2 gene and ACE1 rs1799752 (I/D) in patients who have coronavirus disease 2019 (COVID-19) with various SARS-CoV-2 variants. METHODS: Based on polymerase chain reaction-based genotyping, four polymorphisms in the ACE1 and ACE2 genes have been identified in 2023 deceased patients and 2307 recovered patients. RESULTS: The ACE2 rs2074192 TT genotype was associated with the COVID-19 mortality in all three variants, whereas the CT genotype was associated with the Omicron BA.5 and Delta variants. ACE2 rs1978124 TC genotypes were related to COVID-19 mortality in the Omicron BA.5 and Alpha variants, but TT genotypes were related to COVID-19 mortality in the Delta variant. It was found that ACE2 rs2285666 CC genotypes were associated with COVID-19 mortality in Delta and Alpha variants, and CT genotypes in Delta variants. There was an association between ACE1 rs1799752 DD and ID genotypes in the Delta variant and COVID-19 mortality, whereas there was no association in the Alpha or Omicron BA.5 variants. In all variants of SARS-CoV-2, CDCT and TDCT haplotypes were more common. In Omicron BA.5 and Delta, CDCC and TDCC haplotypes were linked with COVID-19 mortality. In addition to COVID-19 mortality, the CICT, TICT, and TICC were significantly correlated. CONCLUSION: The ACE1/ACE2 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To confirm these results, however, more research needs to be conducted.

Relationship between CDX2 rs11568820 and EcoRV rs4516035 polymorphisms on the vitamin D receptor gene with susceptibility to different SARS-CoV-2 variants.

Several studies have revealed that vitamin D deficiency is linked to an increased risk of developing coronavirus disease 19 (COVID-19). In individuals with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, vitamin D receptor activation is required to decrease acute respiratory distress syndrome. The purpose of this study was to examine the genotypic distribution and allelic frequencies of CDX2 rs11568820 and EcoRV rs4516035 polymorphisms in COVID-19 patients with various SARS-CoV-2 variants. For genotyping of CDX2 rs11568820 and EcoRV rs4516035 polymorphisms, we used the polymerase chain reaction-restriction fragment length polymorphism technique in 1734 and 1450 recovered and deceased patients, respectively. The results indicated the rate of COVID-19 mortality was associated with CDX2 rs11568820 AA and GA genotypes in the Delta variant and with CDX2 rs11568820 AA in the Omicron BA.5 variant, while no association was shown in the Alpha variant. Therefore, the rate of COVID-19 mortality was associated with EcoRV rs4516035 TC and CC genotypes in the Delta variant, while no association was shown in the Alpha and Omicron BA.5 variants. According to our analysis, the T-G haplotype was more common in all SARS-CoV-2 variants. The C-A haplotype was associated with COVID-19 mortality in the Delta and Omicron BA.5 variants, and the T-A haplotype was related to the Alpha variant. In conclusion, the genotype frequencies of the CDX2 rs11568820 and EcoRV rs4516035 polymorphisms between SARS-CoV-2 variants were significantly different between the deceased patients and recovered patients. However, more studies should be done to confirm the results.

Interferon-Induced Transmembrane Protein 3 rs34481144 C/T Genotype and Clinical Parameters Related to Progression of COVID-19.

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.

Molecular epidemiology of nontuberculous mycobacteria isolated from tuberculosis-suspected patients.

It is a growing problem around the world to deal with nontuberculous mycobacteria infection (NTM), but its clinical significance is still largely unknown. This study aims to investigate the epidemiology of NTM infections from various clinical samples and determine their clinical significance. From December 2020 to December 2021, 6125 clinical samples were collected. In addition to phenotypic detection, genotypic detection through multilocus sequence typing (hsp65, rpoB, and 16S rDNA genes) and sequencing was also conducted. Records of patients were consulted for clinical information, such as symptoms and radiological findings. Of the 6,125 patients, 351 (5.7%) were positive for acid-fast bacteria (AFB). Out of 351 AFB, 289 (82.3%) and 62 (17.7%) subjects were identified as M. tuberculosis complex (MTC) and NTM strains, respectively. Isolates of Mycobacterium simiae and M. fortuitum were the most frequent, followed by isolates of M. kansasii and M. marinum. We also isolated M. chelonae, M. canariasense, and M. jacuzzii, which are rarely reported. Symptoms (P = 0.048), radiographic findings (P = 0.013), and gender (P = 0.039) were associated with NTM isolates. M. Fortuitum, M. simiae, and M. kansasii presented with bronchiectasis, infiltration, and cavitary lesions most frequently, while cough was the most common symptom. In conclusion, Mycobacterium simiae and M. fortuitum were presented in seventeen and twelve NTM isolates from the collected samples. There is evidence that NTM infections in endemic settings may contribute to the dissemination of various diseases and the control of tuberculosis. In spite of this, further research is needed to evaluate the clinical significance of NTM isolates.

Role of FokI rs2228570 and Tru9I rs757343 Polymorphisms in the Mortality of Patients Infected with Different Variants of SARS-CoV-2.

BACKGROUND AND AIM: Low vitamin D levels are associated with the severity of coronavirus disease 19 (COVID-19). Vitamin D receptor gene polymorphisms, such as Tru9I rs757343 and FokI rs2228570, have been suggested to be potential risk factors for severe COVID-19 outcomes. This study investigated how Tru9I rs757343 and FokI rs2228570 polymorphisms influenced the mortality rate of COVID-19 in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: The polymerase chain reaction-restriction fragment length polymorphism assay was used to genotype Tru9I rs757343 and FokI rs2228570 genotypes in 1,734 recovered and 1,450 deceased patients. RESULTS: Our results demonstrated that the high mortality rate was correlated with FokI rs2228570 TT genotype in all three variants but was much higher in the Omicron BA.5 variant than in the Alpha and Delta variants. Furthermore, in patients infected with the Delta variant, FokI rs2228570 CT genotype was more highly correlated with the mortality rate compared to other variants. Thus, a high mortality rate was correlated with the Tru9I rs757343 AA genotype in the Omicron BA.5 variant, whereas this relationship was not observed in the other two variants. The T-A haplotype was related to COVID-19 mortality in all three variants, but its effect was more pronounced in the Alpha variant. Moreover, the T-G haplotype was significantly associated with all three variants. CONCLUSION: Our findings showed that the effects of Tru9I rs757343 and FokI rs2228570 polymorphisms were related to SARS-CoV-2 variants. However, further studies are still required to validate our findings.

Association of ApaI rs7975232 and BsmI rs1544410 in clinical outcomes of COVID-19 patients according to different SARS-CoV-2 variants.

A growing body of research has shown how important vitamin D is in the prognosis of coronavirus disease 19 (COVID-19). The vitamin D receptor is necessary for vitamin D to perform its effects, and its polymorphisms can help in this regard. Therefore, we aimed to evaluate whether the association of ApaI rs7975232 and BsmI rs1544410 polymorphisms in different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were influential in the outcomes of COVID-19. The polymerase chain reaction-restriction fragment length polymorphism method was utilized to determine the different genotypes of ApaI rs7975232 and BsmI rs1544410 in 1734 and 1450 patients who had recovered and deceased, respectively. Our finding revealed that the ApaI rs7975232 AA genotype in the Delta and Omicron BA.5 and the CA genotype in the Delta and Alpha variants were associated with higher mortality rate. Also, the BsmI rs1544410 GG genotype in the Delta and Omicron BA.5 and the GA genotype in the Delta and Alpha variants were related to a higher mortality rate. The A-G haplotype was linked with COVID-19 mortality in both the Alpha and Delta variants. The A-A haplotype for the Omicron BA.5 variants was statistically significant. In conclusion, our research revealed a connection between SARS-CoV-2 variants and the impacts of ApaI rs7975232 and BsmI rs1544410 polymorphisms. However, more research is still needed to substantiate our findings.

Association between interleukin-10 gene polymorphisms (rs1800871, rs1800872, and rs1800896) and severity of infection in different SARS-CoV-2 variants.

BACKGROUND: Polymorphisms in the interleukin-10 (IL10) gene have been linked to the severity of the patients infected with the viral infections. This study aimed to assess if the IL10 gene polymorphisms rs1800871, rs1800872, and rs1800896 were linked to coronavirus disease 19 (COVID-19) mortality in different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the Iranian population. METHODS: For genotyping IL10 rs1800871, rs1800872, and rs1800896, this study used the polymerase chain reaction-restriction fragment length polymorphism method in 1,734 recovered and 1,450 deceased patients. RESULTS: The obtained finding indicated IL10 rs1800871 CC genotype in the Alpha variant and CT genotype in the Delta variant had a relationship with COVID-19 mortality; however, there was no association between rs1800871 polymorphism and the Omicron BA.5 variant. The COVID-19 mortality rate was associated with IL10 rs1800872 TT genotype in the Alpha and Omicron BA.5 variants and GT in the Alpha and Delta variants. The COVID-19 mortality rate was associated with IL10 rs1800896 GG and AG genotypes in the Delta and Omicron BA.5; nevertheless, there was no association between rs1800896 polymorphism with the Alpha variant. According to the obtained data, the GTA haplotype was the most common of haplotype in different SARS-CoV-2 variants. The TCG haplotype was related to COVID-19 mortality in the Alpha, Delta and Omicron BA.5 variants. CONCLUSION: The IL10 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To verify the obtained results, further studies should be conducted on various ethnic groups.

Impact of TRIM5α and TRIM22 Genes Expression on the Clinical Course of Coronavirus Disease 2019.

OBJECTIVE: The innate immune response in humans involves a wide variety of factors, including the tripartite motif-containing 5α (TRIM5α) and 22 (TRIM22) as a cluster of genes on chromosome 11 that have exhibited antiviral activity in several viral infections. We analyzed the correlation of the expression of TRIM5α and TRIM22 with the severity of Coronavirus Disease 2019 (COVID-19) in blood samples of 330 patients, divided into two groups of severe and mild disease, versus the healthy individuals who never had contact with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS: The transcription level of TRIM5α and TRIM22 was determined by quantitative real-time polymerase chain reaction (qPCR). The laboratory values were collected from the patients' records. RESULTS: The expression of both genes was significantly lower in the severe group containing the hospitalized patients than in both the mild group and the control group. However, in the mild group, TRIM22 expression was significantly higher (p <0.0001) than in the control group while TRIM5α expression was not significantly different between these two groups. We found a relationship between the cycle threshold (Ct) value of patients and the expression of the aforementioned genes. CONCLUSION: The results of our study indicated that lower Ct values or higher RNA viral load might be associated with the downregulation of TRIM5α and TRIM22 and the severity of COVID-19. Additional studies are needed to confirm the results of this study.