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1.
J Interferon Cytokine Res ; 41(11): 407-414, 2021 11.
Article in English | MEDLINE | ID: covidwho-1758604

ABSTRACT

Genetic polymorphisms at the IFNL4 loci are known to influence the clinical outcome of several different infectious diseases. Best described is the association between the IFNL4 genotype and hepatitis C virus clearance. However, an influence of the IFNL4 genotype on the adaptive immune system was suggested by several studies but never investigated in humans. In this cross-sectional study, we have genotyped 201 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive participants for 3 IFNL4 polymorphisms (rs368234815, rs12979860, and rs117648444) and stratified them according to the IFNλ4 activity. Based on this stratification, we investigated the association between the IFNL4 genotype and the antibody as well as the CD8+ T cell response in the acute phase of the SARS-CoV-2 infection. We observed no differences in the genotype distribution compared with a Danish reference cohort or the 1,000 Genome Project, and we were not able to link the IFNL4 genotype to changes in either the antibody or CD8+ T cell responses of these patients.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Interleukins/immunology , SARS-CoV-2/immunology , Adaptive Immunity/genetics , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , Cohort Studies , Cross-Sectional Studies , Female , Genotype , Humans , Interleukins/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Polymorphism, Single Nucleotide/immunology , SARS-CoV-2/genetics , Young Adult
2.
Virol J ; 18(1): 221, 2021 11 14.
Article in English | MEDLINE | ID: covidwho-1518281

ABSTRACT

BACKGROUND: The recent pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has elevated several clinical and scientific questions. These include how host genetic factors influence the pathogenesis and disease susceptibility. Therefore, the aim of this study was to evaluate the impact of interferon lambda 3 and 4 (IFNL3/4) gene polymorphisms and clinical parameters on the resistance and susceptibility to coronavirus disease 2019 (COVID-19) infection. METHODS: A total of 750 SARS-CoV-2 positive patients (375 survivors and 375 nonsurvivors) were included in this study. All single-nucleotide polymorphisms (SNPs) on IFNL3 (rs12979860, rs8099917, and rs12980275) and IFNL4 rs368234815 were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In this study, a higher viral load (low PCR Ct value) was shown in nonsurvivor patients. In survivor patients, the frequency of the favorable genotypes of IFNL3/4 SNPs (rs12979860 CC, rs12980275 AA, rs8099917 TT, and rs368234815 TT/TT) was significantly higher than in nonsurvivor patients. Multivariate logistic regression analysis has shown that a higher low-density lipoprotein (LDL), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and PCR Ct value, and lower 25-hydroxyvitamin D, and also IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 rs368234815 ∆G/∆G genotypes were associated with the severity of COVID-19 infection. CONCLUSIONS: The results of this study proved that the severity of COVID-19 infection was associated with clinical parameters and unfavorable genotypes of IFNL3/IFNL4 SNPs. Further studies in different parts of the world are needed to show the relationship between severity of COVID-19 infection and host genetic factors.


Subject(s)
COVID-19/diagnosis , Interferons/genetics , Interleukins/genetics , SARS-CoV-2/isolation & purification , Adult , Aged , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Disease Susceptibility , Female , Genotype , Humans , Iran/epidemiology , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , SARS-CoV-2/genetics , Severity of Illness Index
3.
Sci Rep ; 11(1): 21185, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1493214

ABSTRACT

Interferon lambda 4 (IFNλ4) has shown antiviral activity against RNA viruses, including some coronaviruses. Besides, genetic variants of IFNL4 can be predictive of the clearance of RNA viruses. However, little is known about the effect of these genetic variants on SARS-CoV-2 infection. In this study, we investigated whether there was a relationship of the rs12979860 polymorphism of IFNL4 with COVID-19. We found that the T allele of rs12979860 was overexpressed in COVID-19 patients with regard to the general population without this disease (36.16% vs. 26.40%, p = 6.4 × 10-4; OR 0.633 C vs T; 95% CI 0.487, 0.824), suggesting that this allele could be a risk factor for COVID-19. Accordingly, the CC genotype was significantly lower in COVID-19 patients compared to controls (37.85% vs. 55.51%, p = 8 × 10-5; OR 0.488; 95% CI 0.342, 0.698). These results were not affected by sex, age, and disease severity in patients with COVID-19. Our findings suggest that, like other infectious diseases caused by RNA viruses, genetic variants of IFNL4 can predispose to COVID-19. Confirmation of our results may contribute to better understanding the mechanisms of this disease.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Interleukins/genetics , Polymorphism, Single Nucleotide , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Pandemics , Risk Factors , Spain/epidemiology
4.
J Med Virol ; 93(10): 5853-5863, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1432418

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) infection may rely on a potential genetic background for the variations in the inflammatory response. We aimed to investigate the possible correlation between polymorphisms in the IL-6 gene at rs1800796/rs1800795, in IL-6R at rs2228145, in IL-10 at rs1800896 and rs1800871, in IL-17 at rs2275913 and rs763780 loci, and COVID-19 prevalence and mortality rates among populations of 23 countries. METHODS: We searched the literature for polymorphisms in China, Japan, India, Spain, Mexico, Sweden, Turkey, Brazil, Russia, Poland, Italy, South Africa, Netherlands, Greece, Germany, UK, Iran, Finland, Czechia, Tunisia, Norway, Egypt, Croatia. We recorded the prevalence and mortality rates (per million) caused by the Coronavirus infection recorded on 7th September 2020 and 6th December 2020. RESULTS: There was a significant positive correlation between the frequency of AG genotype of rs1800896 and prevalence recorded on 6th December 2020 (r: 0.53, r2 : 0.28, p < .05). There was a significant negative correlation between the mortality rates recorded on 7th September, and the AG genotype of rs2275913 (r: -0.51, r2 : 0.26, p < .05). There was a significant positive correlation between the prevalence recorded on 6th December, and TT genotype at rs763780 (r: 0.65, r2 :0.42, p < .05) while a negative correlation between prevalence and TC genotype at rs763780 (r: -0.66, r2 : 0.43, p < .05). Also, a significant negative correlation was found between mortality rates recorded on 6th December 2020 and CC genotype at rs763780 (r: -0.56, r2 : 0.31, p < .05). CONCLUSION: The variations in prevalence of COVID-19 and its mortality rates among countries may be explained by the polymorphisms at rs1800896 in IL-10, rs2275913 in IL-17A, and rs763780 loci in the IL-17F gene.


Subject(s)
COVID-19/epidemiology , COVID-19/genetics , Interleukins/genetics , COVID-19/mortality , Genetic Association Studies , Genotype , Humans , Interleukin-10/genetics , Interleukin-17/genetics , Interleukin-6/genetics , Polymorphism, Single Nucleotide , Prevalence , Receptors, Interleukin-6/genetics , SARS-CoV-2
6.
Molecules ; 25(12)2020 Jun 26.
Article in English | MEDLINE | ID: covidwho-1389454

ABSTRACT

Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Data Mining/methods , HIV Infections/epidemiology , HIV Infections/metabolism , Host-Pathogen Interactions/immunology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Anti-Inflammatory Agents/therapeutic use , Antigens, Differentiation/genetics , Antigens, Differentiation/immunology , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Complement System Proteins/genetics , Complement System Proteins/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Databases, Genetic , Gene Expression Regulation , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/drug effects , HIV-1/immunology , HIV-1/pathogenicity , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Inflammation , Interferons/genetics , Interferons/immunology , Interleukins/genetics , Interleukins/immunology , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Repressor Proteins/genetics , Repressor Proteins/immunology , SARS-CoV-2 , Signal Transduction , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/immunology
7.
Mol Cells ; 44(6): 384-391, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1259762

ABSTRACT

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Host-Pathogen Interactions/immunology , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/immunology , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Dexamethasone/therapeutic use , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate/drug effects , Inflammation , Interferon Type I/genetics , Interferon Type I/immunology , Interleukins/genetics , Interleukins/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Signal Transduction , Survival Analysis
8.
J Med Virol ; 93(10): 5853-5863, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1252013

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) infection may rely on a potential genetic background for the variations in the inflammatory response. We aimed to investigate the possible correlation between polymorphisms in the IL-6 gene at rs1800796/rs1800795, in IL-6R at rs2228145, in IL-10 at rs1800896 and rs1800871, in IL-17 at rs2275913 and rs763780 loci, and COVID-19 prevalence and mortality rates among populations of 23 countries. METHODS: We searched the literature for polymorphisms in China, Japan, India, Spain, Mexico, Sweden, Turkey, Brazil, Russia, Poland, Italy, South Africa, Netherlands, Greece, Germany, UK, Iran, Finland, Czechia, Tunisia, Norway, Egypt, Croatia. We recorded the prevalence and mortality rates (per million) caused by the Coronavirus infection recorded on 7th September 2020 and 6th December 2020. RESULTS: There was a significant positive correlation between the frequency of AG genotype of rs1800896 and prevalence recorded on 6th December 2020 (r: 0.53, r2 : 0.28, p < .05). There was a significant negative correlation between the mortality rates recorded on 7th September, and the AG genotype of rs2275913 (r: -0.51, r2 : 0.26, p < .05). There was a significant positive correlation between the prevalence recorded on 6th December, and TT genotype at rs763780 (r: 0.65, r2 :0.42, p < .05) while a negative correlation between prevalence and TC genotype at rs763780 (r: -0.66, r2 : 0.43, p < .05). Also, a significant negative correlation was found between mortality rates recorded on 6th December 2020 and CC genotype at rs763780 (r: -0.56, r2 : 0.31, p < .05). CONCLUSION: The variations in prevalence of COVID-19 and its mortality rates among countries may be explained by the polymorphisms at rs1800896 in IL-10, rs2275913 in IL-17A, and rs763780 loci in the IL-17F gene.


Subject(s)
COVID-19/epidemiology , COVID-19/genetics , Interleukins/genetics , COVID-19/mortality , Genetic Association Studies , Genotype , Humans , Interleukin-10/genetics , Interleukin-17/genetics , Interleukin-6/genetics , Polymorphism, Single Nucleotide , Prevalence , Receptors, Interleukin-6/genetics , SARS-CoV-2
9.
Molecules ; 25(11)2020 Jun 11.
Article in English | MEDLINE | ID: covidwho-981163

ABSTRACT

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1ß, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiß as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus OC43, Human/drug effects , Flavonoids/pharmacology , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Animals , Antiviral Agents/chemistry , Betacoronavirus/chemistry , Betacoronavirus/growth & development , Binding Sites , COVID-19 , Chloroquine/chemistry , Chloroquine/pharmacology , Coronavirus Infections/genetics , Coronavirus OC43, Human/chemistry , Coronavirus OC43, Human/growth & development , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Flavonoids/chemistry , Humans , Interleukins/antagonists & inhibitors , Interleukins/chemistry , Interleukins/genetics , Interleukins/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/virology , Lung/drug effects , Lung/pathology , Lung/virology , Mice , Molecular Docking Simulation , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phytotherapy/methods , Pneumonia, Viral/genetics , Primary Cell Culture , Protein Binding , Protein Interaction Domains and Motifs , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/chemistry , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Thermodynamics , Virus Internalization/drug effects
10.
Vaccine ; 38(48): 7581-7584, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-845859

ABSTRACT

Today, Coronavirus Disease 2019 (COVID-19) is a global public health emergency and vaccination measures to counter its diffusion are deemed necessary. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the disease, unleashes a T-helper 2 immune response in those patients requiring intensive care. Here, we illustrate the immunological mechanism to train the immune system towards a more effective and less symptomatic T-helper 1 immune response, to be exploited against SARS-CoV-2.


Subject(s)
BCG Vaccine/administration & dosage , Bacterial Vaccines/administration & dosage , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunity, Innate/drug effects , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Propionibacteriaceae/immunology , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Corynebacterium , Humans , Immunization Schedule , Immunogenicity, Vaccine , Interleukins/genetics , Interleukins/immunology , Patient Safety , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/virology , Th1-Th2 Balance/drug effects , Th2 Cells/drug effects , Th2 Cells/immunology , Th2 Cells/virology , Vaccination , Viral Vaccines/administration & dosage , Viral Vaccines/biosynthesis
11.
Adv Biol Regul ; 77: 100737, 2020 08.
Article in English | MEDLINE | ID: covidwho-597242

ABSTRACT

Natural killer (NK) cells are pivotal effectors of the innate immunity protecting an individual from microbes. They are the first line of defense against invading viruses, given their substantial ability to directly target infected cells without the need for specific antigen presentation. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify and modulate antiviral adaptive immune responses. In this review, we will examine the role of NK cells in SARS-COV2 infections causing the ongoing COVID19 pandemic, keeping in mind the controversial role of NK cells specifically in viral respiratory infections and in inflammatory-driven lung damage. We discuss lessons learnt from previous coronavirus outbreaks in humans (caused by SARS-CoV-1 and MERS-COV).


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Host-Pathogen Interactions/immunology , Killer Cells, Natural/immunology , Pandemics , Pneumonia, Viral/epidemiology , Respiratory Insufficiency/epidemiology , Acute Disease , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Gene Expression Regulation , Immunity, Innate , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukins/genetics , Interleukins/immunology , Killer Cells, Natural/pathology , Killer Cells, Natural/virology , Lung/immunology , Lung/pathology , Lung/virology , Lymphocyte Activation , Lysosomal-Associated Membrane Protein 1/genetics , Lysosomal-Associated Membrane Protein 1/immunology , NK Cell Lectin-Like Receptor Subfamily C/genetics , NK Cell Lectin-Like Receptor Subfamily C/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/immunology , SARS-CoV-2 , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
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