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Coronavirus disease 2019 (COVID-19) is a fatal pandemic viral disease caused by the severe acute respiratory syndrome corona virus type-2 (SARS-CoV-2). The aim of this study is to observe the associations of IL-6, SARS-COV-2 viral load (RNAemia), IL- 6 gene polymorphism and lymphocytes and monocytes in peripheral blood with disease severity in COVID-19 patients. This study was carried out from March 2021 to January 2022. RT-PCR positive 84 COVID-19 patients and 28 healthy subjects were enrolled. Blood was collected to detect SARS-COV-2 viral RNA (RNAemia) by rRT-PCR, serum IL-6 level by chemiluminescence method, SNPs of IL-6 by SSP-PCR, immunophenotyping of lymphocytes and monocyte by flow cytometry. Serum IL-6 level (pg/ml) was considerably high among critical patients (102.02 +/- 149.7) compared to severe (67.20 +/- 129.5) and moderate patients (47.04 +/- 106.5) and healthy controls (3.5 +/- 1.8). Serum SARS-CoV-2 nucleic acid positive cases detected mostly in critical patients (39.28%) and was correlated with extremely high IL-6 level and high mortality (R =.912, P < 0.001). Correlation between IL-6 and monocyte was statistically significant with disease severity (severe group, p < 0.001, and 0.867*** and critical group p < 0.001 and 0.887***). In healthy controls, moderate, severe and critically ill COVID-19 patients, IL-6 174G/C (rs 1800795) GG genotype was 82.14%, 89.20%, 67.85% and 53.57% respectively. CC and GC genotype had strong association with severity of COVID-19 when compared with GG genotype. Significant statistical difference found in genotypes between critical and moderate groups (p < 0.001, OR-10.316, CI-3.22-23.86), where CC genotype was associated with COVID-19 severity and mortality. The absolute count of T cell, B cell, NK cell, CD4+ T cells and CD8+ T cells were significantly decreased in critical group compared to healthy, moderate and severe group (P < 0.001). Exhaustion marker CD94/NKG2A was increased on NK cells and CD8+ cytotoxic T cell among critical and severe group. Absolute count of monocyte was significantly increased in critical group (P < 0.001). Serum IL-6, IL-6 174 G/C gene and SARS-CoV-2 RNAaemia can be used in clinical practice for risk assessment;T cell subsets and monocyte as biomarkers for monitoring COVID-19 severity. Monoclonal antibody targeting IL-6 receptor and NKG2A for therapeutics may prevent disease progression and decrease morbidity and mortality.Copyright © 2023 Elsevier Inc.
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Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.
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Background/Objectives: COVID-19 still represents a lifethreatening disease in individuals with a specific genetic background. We successfully applied a new Machine Learning method on WES data to extract a set of coding variants relevant for COVID- 19 severity. We aim to identify personalized add-on therapy. Method(s): A subset of identified variants, "actionable" by repurposed drugs, were functionally tested by in vitro and in vivo experiments. Result(s): Males with either rare loss of function variants in the TLR7 gene or L412F polymorphism in the TLR3 gene benefit from IFN-gamma, which is specifically defective in activated PBMCs, restoring innate immunity. Females heterozygous for rare variants in the ADAMTS13 gene and males with D603N homozygous polymorphism in the SELP gene benefit from Caplacizumab, which reduces vWF aggregation and thrombus formation. Males with either the low-frequency gain of function variant T201M in CYP19A1 gene or with poly-Q repeats >=23 in the AR gene benefit from Letrozole, an aromatase inhibitor, which restores normal testosterone levels, reducing inflammation and which rescues male golden hamsters from severe COVID-19. Conclusion(s): By adding these commonly used drugs to standard of care of selected patients, the rate of intubation is expected to decrease consistently, especially in patients with high penetrance rare genetic markers, mitigating the effect of the pandemic with a significant impact on the healthcare system.
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SUMMARY. Different genetic and immunological factors can affect the severity of Coronavirus disease 19. Angiotensin-converting enzyme 2 is a human receptor for Severe Acute Respiratory Syndrome Coro-navirus-2, and the successful interaction between the spike protein of the novel virus and Angiotensin-converting enzyme 2 is responsible for the initial and complete infection. The study aimed to evaluate the correlation between Single Nucleotide Polymorphisms of Angiotensin converting-enzyme 2, with disease severity of Coronavirus disease 19 in AL-Najaf province. The allele Specific-polymerase Chain reaction method was used for investigating Single Nucleotide polymorphisms of Angiotensin converting-enzyme 2 rs4646116 A/G in different states of Coronavirus disease 19 (COVID-19). The wild genotypes (GG) for ACE2 rs4646116 gene recorded a highly significant association p = 0.0009, and a high ratio in the control group (90%) in comparison with moderate cases of COVID-19 (60%). While the heterozygote genotype (GA) of the same gene showed a significant (p-value = 0.0144) and high ratio in moderate cases (30%) in comparison with the control group (10%). Conclusion(s): the wild genotype (GG) for Angiotensin convert-ing-enzyme 2 rs4646116 gene may be associated with more protection from infection with COVID-19. While the polymorphism heterozygote genotype (GA) for the same gene may be associated with more susceptibility to infection with COVID-19.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.
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The incidence of new coronavirus infection (COVID-19) varies significantly between countries and continents. Until now, there has been no clear explanation for this observation. Epidemiological studies have demonstrated a large difference in infection and mortality rates between men and women. This may be due to the gender difference in the polymorphism of genes linked to the X chromosome, which play an important role in the immune response. In addition, there is a different degree of severity of the disease: from an asymptomatic course and mild symptoms to a life-threatening condition requiring hospitalization in the intensive care unit and artificial lung ventilation. Several factors are associated with the severity of COVID-19, such as elderly age, multiple comorbid diseases, smoking, hypercholesterolemia, etc. However, we observe that severe disease is also observed in patients who do not have the above risk factors. In recent months, severe forms of COVID-19 have been reported in children, including early infancy. In this connection, it is relevant, in our opinion, to focus the problem on genetic factors, such as the carriage of single-nucleotide polymorphisms, which can affect susceptibility to infection and variability in the severity of the disease.Copyright © 2022 Sorbtsionnye i Khromatograficheskie Protsessy. All rights reserved.
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While RNA folding was originally seen as a simple problem to solve, it has been shown that the promiscuous interactions of the nucleobases result in structural polymorphism, with several competing structures generally observed for non-coding RNA. This inherent complexity limits our understanding of these molecules from experiments alone, and computational methods are commonly used to study RNA. Here, we discuss three advanced sampling schemes, namely Hamiltonian-replica exchange molecular dynamics (MD), ratchet-and-pawl MD and discrete path sampling, as well as the HiRE-RNA coarse-graining scheme, and highlight how these approaches are complementary with reference to recent case studies. While all computational methods have their shortcomings, the plurality of simulation methods leads to a better understanding of experimental findings and can inform and guide experimental work on RNA polymorphism.Copyright ©
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Objectives: Toll-like receptors (TLRs) are an important family of receptors that recognize infectious agents and play an important role in the innate immune system. TLRs are a potential candidate to control infection in the early stages of the disease and to produce vaccines against SARS-CoV-2. In addition, studies have suggested that TLR polymorphisms are also associated with antiviral responses against SARS-CoV-2. Therefore, we aimed to investigate the relationship of TLR7 and TLR8 polymorphisms with COVID-19 disease prognosis. Materials-Methods: A total of 120 COVID-19 patients, including 40 outpatients, 40 patients with mild and moderate clinical status, hospitalized and severe pneumonia, and 40 patients followed in the intensive care unit (ICU), were included in the study. The classification of disease severity was made according to WHO criteria. TLR7 (rs179009), TLR8 -129 C/G (rs3764879) and TLR8 Met1Val (rs3764880) polymorphisms were genotyped using the PCR-RFLP method. Result(s): Since TLR7 and TLR8 are located on the X chromosome, men and women were analyzed separately. There was no significant difference between the groups in terms of 3 polymorphisms in males. On the other hand, in women, individuals carrying AG genotype and G allele for TLR8 Met1Val polymorphism were found at a higher rate in patients hospitalized in ICU than in patients followed in the service (p <0.05). In terms of the other two polymorphisms, no significant difference was found between the groups in women. Conclusion(s): We suggest that the AG genotype and G allele of TLR8 Met1Val polymorphism can be considered as an important risk factor that increases the severity of the disease in women.
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The most significant single nucleotide human leukocyte antigen genes polymorphisms and innate immunity genes associated with varying degrees of acute respiratory infection severity are considered-COVID-19 caused by the SARS-CoV-2 coronavirus. As data accumulated, it became clear that the SARS-CoV-2 virus exhibits significant regional, ethnic, and individual specificity. This is due to the population groups' genetic characteristics. This is necessary to reliably know the human genotype relationship with the COVID-19 course severity (asymptomatic, mild, moderate, severe, and extremely severe up to fatal outcomes) for more successful therapy and vaccination. At the same time, it was also known that the innate immunity system is on the first line of defense against the pathogenic penetration into the body, and the human leukocyte antigen system encodes molecules of the same name on the surface of cells that present various antigens, including viral infection pathogens, and determine the severity of the course of many diseases;therefore, these systems' genes. This approach makes it possible to assess the likelihood of a severe and extremely severe disease course in healthy and infected people, which in turn contributes to the correct therapy strategy, pharmacotherapy, and vaccination, as well as to create new antiviral therapeutic and preventive medicines. The genetically determined immune response heterogeneity to SARS-CoV-2 infection requires further study, since there is no unambiguous opinion about the leading mechanism that determines disease severity.
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Background/Purpose: Pediatric Acute Lymphoblastic Leukemia (ALL) affects ~4000 young Americans each year. Steroids are essential to curative ALL treatment yet have significant neuropsychiatric side effects that decrease quality of life for patients and families. However, incidence and predisposing risk factors are not well understood. This review aims to describe the current literature on neuropsychiatric side effects of steroids in Pediatric ALL. Method(s): A precise search in PubMed and Embase was cultivated using controlled vocabulary terms (MeSH, Emtree) and keywords for the following concepts: pediatrics, steroids, side effects, cancer, and neurobehavioral manifestations. Keywords and controlled vocabulary for each subject were arranged logically and combined with other concepts by Boolean Logic, using the Boolean operator AND, resulting in 642 precise results exploring neurobehavioral side effects of steroids in children with cancer. Results (2010 to date of search) were imported into Covidence systematic review software, and reviewed by SB and AM. Result(s): Twenty-three articles met inclusion criteria. There is marked variability in research methodology and no standard measurement of neuropsychiatric symptoms. Commonly reported symptoms include mood swings, irritability, depression, anxiety, aggression, insomnia, mania, and psychosis with prevalence between 5% and 75%. Heterogeneous research methodology and descriptions of psychiatric symptoms make it difficult to determine risk factors, though dexamethasone, family psychiatric history, and younger age are consistently associated with greater risk of behavioral dysregulation. Genetic predisposition (Bcl1 polymorphism, SNPs in GR gene) may increase susceptibility to developing depression during treatment. Data suggest variable efficacy of antipsychotics, benzodiazepines, hydrocortisone, and potassium-chloride. Conclusions and Implications: Existing data about neuropsychiatric side effects of steroids in pediatric ALL is extremely heterogeneous, creating challenges for standardized assessment and treatment. The burden of these symptoms necessitates further research to identify and treat vulnerable patients. Standard measurement of these symptoms could be a first step in eventually alleviating this source of distress.
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Attention Deficit Hyperactivity Disorder (ADHD) is characterized by oppositional, defiant, disobedient, disruptive and also aggressive behavior. Many genes are involved in its onset, particularly dopaminergic pathway genes. Moreover, genetic predisposition to aggression appears affected by the polymorphic genetic variants of the serotoninergic system, among which, functional polymorphisms in monoamine oxidase A (MAOA). The risk of contracting coronavirus infection may arouse in some people severe emotional distress characterized by symptoms of fatigue, guilt, and aggression. A survey on the psychological impact of COVID-19 pandemic in Italian families of children with neurodevelopmental disorders such as ADHD showed how children have been particularly affected by the emergency. The aim of this study was to determine whether polymorphisms at the MAOA gene are associated with increased or reduced susceptibility to develop ADHD. Therefore, the variants rs6323, rs587777457 and rs1137070 of the MAOA gene were evaluated by SBT in 35 children (mean age 10.257 range 6-16) with ADHD and 27 healthy individuals. Our analysis allowed us to identify the G/G genotype of the variant rs6323 (Arg297Arg) was significantly associated with an increased risk of ADHD (p = 0.015). Allele G indicates higher levels of the enzyme, while the T allele indicates lower levels of enzyme production. When compared in patients, the G allele was associated with higher anger (p-value = 0.01) and might cause aggressive behavior in males. Our study shows that defining a genetic profile of ADHD can provide important information on the etiopathogenesis of the disease and help identify the best therapeutic option for patients with this disorder.
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Low plasma levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] and the vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been associated with the body's susceptibility to infectious diseases, including COVID-19. In this pilot retrospective study, representatives of the Kazakh population (central Kazakhstan) were divided into groups based on the test for IgM and IgG for coronavirus infection. We compared the 25(OH)D plasma levels and concluded that the COVID-19-positive group values (25.17 ng/mL ± 16.65) were statistically lower (p = 0.0114) compared to the COVID-19-negative ones (35.58 ng/mL ± 20.67). There was no association between age, gender and 25(OH)D concentration within the groups (p > 0.05). The genotyping of rs2228570 was performed using a TaqMan Real-Time PCR assay. Allele C predominated among the COVID-19-negative participants and significantly reduced the likelihood of coronavirus infection (p < 0.0001; OR = 0.0804; 95% CI 0.02357-0.2798). There were no statistically significant differences in the frequencies of the A, G and T alleles in the studied groups (p > 0.05). The GG genotype of rs2228570 was associated with a 4.131-fold increased likelihood of COVID-19 infection (p = 0.0288; χ2 = 5.364; OR = 4.131; 95% CI 1.223-13.71). Comprehensive studies are required to determine whether low 25(OH)D plasma concentrations and genetic background represent a risk factor for COVID-19 infection.
Subject(s)
COVID-19 , Genetic Predisposition to Disease , Humans , Ethnicity , Polymorphism, Single Nucleotide , Pilot Projects , Retrospective Studies , Receptors, Calcitriol/genetics , COVID-19/genetics , Vitamin D , Genotype , Calcifediol , Case-Control StudiesABSTRACT
The clinical picture of COVID-19 ranges from asymptomatic to mild, moderate or severe disease sometimes leading to death. Differences in the interaction between SARS-CoV-2 Spike (S) protein and angiotensin converting enzyme 2 (ACE2) protein may lead to differences in disease severity. We studied whether ACE2 polymorphisms are associated with disease severity and outcome. We recruited 114 patients between July 2020 - March 2022 confirmed positive by RTPCR for COVID-19 with different degrees of severity (21 mild, 29 moderate, 34 severe, 30 death) and 30 controls (10 non-vaccinated+ 20 vaccinated) who were RT-PCR negative inspite of high-risk contact. Next-gen sequencing was done on MiSeq (Illumina) using amplicon-based targeted sequencing approach using a custom-designed panel to sequence all the exons of ACE2 gene. SPSS ver.26 was used for analysis. The following ACE2 variants were identified on the Local Run Manager (LRM) software from Illumina: (i) rs2285666 (c.439+4G>A) splice region variant, in controls (60%) and Patients (45.8%), (ii) rs4646140 (c.802+24G>A) intronic variant in 4/114 patients and 1/30 controls, (iii) rs41303171 ( c.2158A>G) missense variant in 2/114 patients, (iv) rs536749578 (c.2114+9T>C) intron variant, (v) rs763994205 (c.868A>C) missense variant and (vi) rs7595907 (c.656G>A) missense variant in 1/114 patient each only. rs2285666 was observed in equal frequency ( 60%) in vaccinated and non-vaccinated controls. rs2285666 was observed amongst different severity groups: Mild (80.95%), Moderate (37.93%), Severe (44.11%), and Death (56.67%) revealing association with disease severity, probably having a protective effect. However, these results need to be confirmed on larger sample sizes.
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A large number of studies show conflicting results and point to multiple factors that may influence the course of COVID-19 in patients with asthma: severity asthma, phenotypes, genetic characteristics, underlying asthma therapy, and comorbidities. The aim of the study was to determine the course of Covid-19 in patients with asthma depending on the Gln27Glu polymorphism of the ADRB2 gene in the Ukrainian population. Material(s) and Method(s): 553 patients with asthma were preliminarily examined and the distribution of ADRB2 genotypes was determined. Among these patients, 116 patients aged 18 to 70 suffered from mild, moderate and severe Covid-19. The diagnosis of asthma was established based on the GINA recommendations. The severity of Covid-19 is set according on the World Health Organization. Results of the study. Depending on the severity of Covid-19, patients with asthma were divided into 3 groups. Group I included 66 patients with a mild severity of Covid-19, group II - 33 patients with a moderate severity, and group III - 23 patients with a severe. After statistical processing of the data, the following frequencies of ADRB2 genotypes were obtained: in group I Gln27Gln-genotype - 93.9%, Gln27Glu-genotype - 6.1%, Glu27Glu-genotype - 0;in group II - 6.1%, 66.7%, 27.2%, respectively;and in group III - 5.9%, 11.8%, 82.3%, respectively. The obtained results indicate that the Gln27Gln- genotype was significantly more common in asthma patients with mild severity Covid-19, while the Glu27Glu-genotype was significantly more common in patients with severe Covid-19 (chi2 121.5;p < 0.001). Conclusion(s): A more severe course of Covid-19 in asthma patients is associated with the ADRB2 Glu27Glugenotype.
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Significant risks to human health are posed by the 2019 coronavirus illness (COVID-19). SARS coronavirus type 2 receptor, also known as the major enzyme in the renin-angiotensin system (RAS), angiotensin-converting enzyme 2 (ACE-2), connects COVID-19 and RAS. This study was conducted with the intention of determining whether or not RAS gene polymorphisms and ACE-2 (G8790A) play a part in the process of predicting susceptibility to infection with COVID-19. In this study 127 participants, 67 of whom were deemed by a physician to be in a severe state of illness, and 60 of whom were categorized as "healthy controls".The genetic study included an extraction of genomic DNA from blood samples of each covid 19 patients and healthy controls, then amplification the site of SNP (rs2285666) Within the ACE2 gene by using specific primers, sequencing PCR products, and genotyping to detect the role of the ACE-2 gene (rs2285666) in the incidence of COVID-19. ACE-2 (rs2285666) is statistically associated to COVID-19. The COVID-19 group had 65.67 %of individuals with the wild-type homozygous genotype (GG) and 20% in the control group, while the control group had 63.33% of individuals with the mutant genotype (AA). Consequently, the wild-type homozygous (GG) and allele (G) may be considered a risk factor (etiological fraction E. F) for COVID-19 in Iraqi patients, whereas the mutant homozygous (AA) and allele (A) may be considered a protective factor (preventive fraction). The findings of the present study reveal that carriers of the GG genotype of ACE2 (rs2285666) are substantially more susceptible to COVID-19.Copyright © 2023 Allami et al.
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These proceedings contains 30 articles that covered various topics related to immunology and related fields. The conference papers presented focused on investigating the role of genetics, microbiome, and immunological pathways in disease pathogenesis and treatment. Studies presented at the conference explored the genetic factors associated with obesity in Brazilian children, the role of flavonoids in reprogramming microglia towards a neuroprotective inflammatory profile, the gut microbiome in asthmatic individuals, and the involvement of the MTOR gene and its variants in the severity of COVID-19. Other studies evaluated the immunodiagnostic potential of a protein exclusive to Corynebacterium pseudotuberculosis, genetic markers associated with alcohol dependence and asthma, and the effects of nicotine on glial cells in Parkinson's disease. The conference also presented research on the molecular mechanisms associated with the anti-glioma and immunomodulatory effects of flavonoids, the influence of Trypanosoma cruzi co-infection on the immune response and clinical outcome of patients with cutaneous leishmaniasis, and the association of metalloproteinase gene variants with periodontitis. Furthermore, the papers presented discussed the production of Zika virus singular peptide for the development of serological immunassays, and the role of genetic polymorphisms in the IL1B and IL6 genes in periodontitis. Lastly, the conference included research on the immunological response of broiler chickens fed with diet supplemented with zinc, and the modulatory effects of Agatis flavone on the glial response in an ex vivo model of brain trauma.
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Introduction: Accumulating evidence recommends that infectious diseases including coronavirus disease 2019 (COVID-19) are often associated with oxidative stress and inflammation. Paraoxonase 1 (PON1, OMIM: 168,820), a member of the paraoxonase gene family, has antioxidant properties. Enzyme activity of paraoxonase depends on a variety of influencing factors such as polymorphisms of PON1, ethnicity, gender, age, and a number of environmental variables. The PON1 has two common functional polymorphisms, namely, Q192R (rs662) and L55M (rs854560). The R192 and M55 alleles are associated with increase and decrease in enzyme activity, respectively. Objective(s): The present study was conducted to investigate the possible association of rs662 and rs854560 polymorphisms with morbidity and mortality of COVID-19. Method(s): Data for the prevalence, mortality, and amount of accomplished diagnostic test (per 106 people) on 25 November 2020 from 48 countries were included in the present study. The Human Development Index (HDI) was used as a potential confounding variable. Result(s): The frequency of M55 was positively correlated with the prevalence (partial r = 0.487, df = 36, p = 0.002) and mortality of COVID-19 (partial r = 0.551, df = 36, p < 0.001), after adjustments for HDI and amount of the accomplished diagnostic test as possible confounders. Conclusion(s): This means that countries with higher M55 frequency have higher prevalence and mortality of COVID-19.Copyright © The Author(s) 2022.
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Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18-95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5;p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60;p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.
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BACKGROUND: Seemingly, the Matrix metalloproteinases (MMPs) play a role in the etiopathogenesis of coronavirus disease 2019 (COVID-19). Here in this study, we determined the association of MMP9 rs3918242, MMP3 rs3025058, and MMP2 rs243865 polymorphisms with the risk of COVID-19, especially in those with neurological syndrome (NS). METHODS: We enrolled 500 patients with COVID-19 and 500 healthy individuals. To genotype the target SNPs, the Real-time allelic discrimination technique was used. To determine serum levels of MMPs, Enzyme-linked immunosorbent assay (ELISA) was exerted. RESULTS: The MMP9 gene rs3918242 and MMP3 gene rs3025058 SNP were significantly associated with increased COVID-19 risk and susceptibility to COVID-19 with NS. The serum level of MMP-9 and MMP-3 was significantly higher in COVID-19 cases compared with the healthy controls. Serum MMP-9 and MMP-3 levels were also higher in COVID-19 subjects with NS in comparison to the healthy controls. The polymorphisms in MMP genes were not associated with serum level of MMPs. CONCLUSION: MMP9 and MMP3 gene polymorphisms increases the susceptibility to COVID-19 as well as COVID-19 with neurologic syndrome, but they probably have no role in the regulation of serum MMP-9 and MMP-3 levels.