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2.
Cells ; 10(11)2021 11 16.
Article in English | MEDLINE | ID: covidwho-1523883

ABSTRACT

While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-specific antibodies, as well as the expression of factors involved in the anti-viral immune response were analyzed. Moreover, we set up an in vitro coinfection assay to study the mechanisms correlated to the coinfection process. Our results did not show any increased risk of severe COVID-19 in HIV-positive young individuals. In those subjects who contracted SARS-CoV-2 infection, an increase in IL-10 expression and production was observed. Furthermore, in the in vitro coinfection assay, we revealed a reduction in SARS-CoV-2 replication associated to an upregulation of IL-10. We speculate that IL-10 could play a crucial role in the course of SARS-CoV-2 infection in HIV-positive individuals. These results might help defining clinical management of HIV/SARS-CoV-2 co-infected young individuals, or putative indications for vaccination schedules in this population.


Subject(s)
COVID-19/immunology , Coinfection/immunology , HIV Infections/immunology , Adolescent , Adult , COVID-19/virology , Child , Child, Preschool , Coinfection/virology , HIV Infections/virology , Humans , Infant , Inflammation , Interleukin-10/blood , Interleukin-10/genetics , Male , RNA, Messenger/blood , SARS-CoV-2/immunology , Young Adult
3.
Int Immunopharmacol ; 101(Pt A): 108264, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1487769

ABSTRACT

Topoisomerase (TOP) inhibitors were commonly used as chemotherapeutic agents in the treatment of cancers. In our present study, we found that etoposide (ETO), a topoisomerase 2 (TOP2) inhibitor, upregulated the production of Interleukin 10 (IL-10) in lipopolysaccharide (LPS)-stimulated macrophages. Besides, other TOP2 inhibitors including doxorubicin hydrochloride (DOX) and teniposide (TEN) were also able to augment IL-10 production. Meanwhile, the expression levels of pro-inflammatory factors, for example IL-6 and TNF-α, were also decreased accordingly by the treatment of the TOP2 inhibitors. Of note, ETO facilitated IL-10 secretion, which might be regulated by transcription factor Maf via PI3K/AKT pathway, as pharmaceutic blockage of kinase PI3K or AKT attenuated ETO-induced Maf and IL-10 expression. Further, in LPS-induced mice sepsis model, the enhanced generation of IL-10 was observed in ETO-treated mice, whereas pro-inflammatory cytokines were decreased, which significantly reduced the mortality of mice from LPS-induced lethal cytokine storm. Taken together, these results indicated that ETO may exhibit an anti-inflammatory role by upregulating the alteration of transcription factor Maf and promoting subsequential IL-10 secretion via PI3K/Akt pathway in LPS-induced macrophages. Therefore, ETO may serve as a potential anti-inflammatory agent and employed to severe pro-inflammatory diseases including COVID-19.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Etoposide/pharmacology , Interleukin-10/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-maf/genetics , Topoisomerase II Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Cell Line , Disease Models, Animal , Down-Regulation/drug effects , Etoposide/therapeutic use , Female , Interleukin-10/genetics , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/toxicity , Macrophages/drug effects , Mice , Mice, Inbred C57BL , Proto-Oncogene Proteins c-maf/metabolism , Shock, Septic/chemically induced , Shock, Septic/drug therapy , Topoisomerase II Inhibitors/therapeutic use , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation/drug effects
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.
Viral Immunol ; 34(8): 567-572, 2021 10.
Article in English | MEDLINE | ID: covidwho-1266103

ABSTRACT

Interleukin-10 (IL-10) gene polymorphisms have been associated with severity and outcomes in patients with respiratory and nonrespiratory viral infections. The aim of this study was to assess whether rs1800871 and rs1800872 polymorphisms of IL-10 gene are associated with the clinical outcomes of COVID-19 in a Mexican population. Study subjects were 193 COVID-19 patients. The genotyping was carried out with real-time PCR and serum IL-10 levels were measured with enzyme-linked immunosorbent assay. Logistic regression analysis was used for analysis association with clinical outcomes. There was no evidence of an association between alleles, genotypes, or haplotypes frequencies between patient groups according to severity and outcomes. The rs1800871 and rs1800872 polymorphisms might not be genetic risk factors for severity and mortality for COVID-19 in Mexican mestizos patients from northwest Mexico.


Subject(s)
COVID-19/genetics , Interleukin-10/genetics , Polymorphism, Genetic , Adult , Aged , Alleles , COVID-19/immunology , COVID-19/therapy , Female , Genotype , Haplotypes , Humans , Interleukin-10/metabolism , Male , Mexico , Middle Aged , SARS-CoV-2
7.
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.
J Int Med Res ; 49(3): 3000605211002695, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1145418

ABSTRACT

Over the past several decades, studies have demonstrated the existence of bi-directional relationships between periodontal disease and systemic conditions. Periodontitis is a polymicrobial and multifactorial disease involving both host and environmental factors. Tissue destruction is primarily associated with hyperresponsiveness of the host resulting in release of inflammatory mediators. Pro-inflammatory cytokines play a major role in bacterial stimulation and tissue destruction. In addition, these cytokines are thought to underlie the associations between periodontitis and systemic conditions. Current research suggests that increased release of cytokines from host cells, referred to as the cytokine storm, is associated with disease progression in patients with coronavirus disease 2019 (COVID-19). An intersection between periodontitis and pulmonary disease is biologically plausible. Hence, we reviewed the evidence linking COVID-19, cytokines, and periodontal disease. Plaque control is essential to prevent exchange of bacteria between the mouth and the lungs, reducing the risk of lung disease. Understanding these associations may help identify individuals at high risk and deliver appropriate care at early stages.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Dental Plaque/immunology , Host-Pathogen Interactions/immunology , Periodontitis/immunology , SARS-CoV-2/pathogenicity , Stress, Psychological/immunology , COVID-19/complications , COVID-19/genetics , COVID-19/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/virology , Dental Plaque/complications , Dental Plaque/genetics , Dental Plaque/virology , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-10/genetics , Interleukin-10/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Lung/immunology , Lung/pathology , Lung/virology , Pathogen-Associated Molecular Pattern Molecules/immunology , Pathogen-Associated Molecular Pattern Molecules/metabolism , Periodontitis/complications , Periodontitis/genetics , Periodontitis/virology , SARS-CoV-2/immunology , Signal Transduction , Stress, Psychological/complications , Stress, Psychological/genetics , Stress, Psychological/virology , Tooth/immunology , Tooth/pathology , Tooth/virology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
10.
PLoS One ; 16(3): e0248730, 2021.
Article in English | MEDLINE | ID: covidwho-1136301

ABSTRACT

COVID-19 (coronavirus disease 2019) patients exhibiting gastrointestinal symptoms are reported to have worse prognosis. Ace2 (angiotensin-converting enzyme 2), the gene encoding the host protein to which SARS-CoV-2 spike proteins bind, is expressed in the gut and therefore may be a target for preventing or reducing severity of COVID-19. Here we test the hypothesis that Ace2 expression in the gastrointestinal and respiratory tracts is modulated by the microbiome. We used quantitative PCR to profile Ace2 expression in germ-free mice, conventional raised specific pathogen-free mice, and gnotobiotic mice colonized with different microbiota. Intestinal Ace2 expression levels were significantly higher in germ-free mice compared to conventional mice. A similar trend was observed in the respiratory tract. Intriguingly, microbiota depletion via antibiotics partially recapitulated the germ-free phenotype, suggesting potential for microbiome-mediated regulation of Ace2 expression. Variability in intestinal Ace2 expression was observed in gnotobiotic mice colonized with different microbiota, partially attributable to differences in microbiome-encoded proteases and peptidases. Together, these data suggest that the microbiome may be one modifiable factor determining COVID-19 infection risk and disease severity.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Colon/enzymology , Gastrointestinal Microbiome , Intestine, Small/enzymology , Lung/enzymology , Adenomatous Polyposis Coli Protein/deficiency , Adenomatous Polyposis Coli Protein/genetics , Angiotensin-Converting Enzyme 2/genetics , Animals , Female , Gene Expression , Interleukin-10/deficiency , Interleukin-10/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout
11.
Hum Immunol ; 82(4): 247-254, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1039364

ABSTRACT

Immunorelevant genes are among the most probable modulators of coronavirus disease 2019 (COVID-19) progression and prognosis. However, in the few months of the pandemic, data generated on host genetics has been scarce. The present study retrieved data sets of HLA-B alleles, KIR genes and functional single nucleotide polymorphisms (SNPs) in cytokines related to COVID-19 cytokine storm from two publicly available databases: Allele Frequency Net Database and Ensembl, and correlated these frequency data with Case Fatality Rate (CFR) and Daily Death Rates (DDR) across countries. Correlations of eight HLA-B alleles and polymorphisms in three cytokine genes (IL6, IL10, and IL12B) were observed and were mainly associated with DDR. Additionally, HLA-B correlations suggest that differences in allele affinities to SARS-CoV-2 peptides are also associated with DDR. These results may provide rationale for future host genetic marker surveys on COVID-19.


Subject(s)
COVID-19/pathology , Cytokines/genetics , HLA-B Antigens/genetics , Receptors, KIR/genetics , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/mortality , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Gene Frequency/genetics , Genetic Markers/genetics , Humans , Interleukin-10/genetics , Interleukin-12 Subunit p40/genetics , Interleukin-6/genetics , Polymorphism, Single Nucleotide/genetics
12.
JCI Insight ; 6(1)2021 01 11.
Article in English | MEDLINE | ID: covidwho-1027164

ABSTRACT

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Biomarkers , COVID-19/genetics , COVID-19/therapy , Calgranulin B/genetics , Calgranulin B/immunology , Case-Control Studies , Chemokine CCL2/genetics , Chemokine CCL2/immunology , Chemokine CXCL9/genetics , Chemokine CXCL9/immunology , Enzyme Inhibitors/therapeutic use , Female , Ferritins/genetics , Ferritins/immunology , Gene Expression Profiling , Humans , Hydroxychloroquine/therapeutic use , Immunologic Factors/therapeutic use , Interferon Type I/genetics , Interferon Type I/immunology , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-1 Receptor-Like 1 Protein/immunology , Interleukin-10/genetics , Interleukin-10/immunology , Interleukin-15/genetics , Interleukin-15/immunology , Interleukin-2/genetics , Interleukin-2/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Lactoferrin/genetics , Lactoferrin/immunology , Lipocalin-2/genetics , Lipocalin-2/immunology , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/immunology , Middle Aged , Multivariate Analysis , NF-kappa B/genetics , NF-kappa B/immunology
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