People living with human immunodeficiency virus (HIV) infection typically have hypovitaminosis D, which is linked to a large number of pathologies, including immune disorders and infectious diseases. Vitamin D (VitD) is a key regulator of host defense against infections by activating genes and pathways that enhance innate and adaptive immunity. VitD mediates its biological effects by binding to the Vitamin D receptor (VDR), and activating and regulating multiple cellular pathways. Single nucleotide polymorphisms in genes from those pathways have been associated with protection from HIV-1 infection. High levels of VitD and VDR expression are also associated with natural resistance to HIV-1 infection. Conversely, VitD deficiency is linked to more inflammation and immune activation, low peripheral blood CD4+ T-cells, faster progression of HIV disease, and shorter survival time in HIV-infected patients. VitD supplementation and restoration to normal values in HIV-infected patients may improve immunologic recovery during combination antiretroviral therapy, reduce levels of inflammation and immune activation, and increase immunity against pathogens. Additionally, VitD may protect against the development of immune reconstitution inflammatory syndrome events, pulmonary tuberculosis, and mortality among HIV-infected patients. In summary, this review suggests that VitD deficiency may contribute to the pathogenesis of HIV infection. Also, VitD supplementation seems to reverse some alterations of the immune system, supporting the use of VitD supplementation as prophylaxis, especially in individuals with more severe VitD deficiency.

MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to ...

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10⁻⁸) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10⁻²² and P = 8.1 × 10⁻¹², respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10⁻⁸). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10⁻⁸) and ARHGAP33 (P = 1.3 × 10⁻⁸), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10⁻⁸). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Since 2009, several studies have identified single-nucleotide polymorphisms (SNPs) near the gene encoding for interleukin (IL)-28 (IL28B) that are strongly associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Because this large amount of data includes some inconsistencies, we consider assessment of the global estimate for each SNP to be essential.

There is growing evidence that vitamin D is related to chronic hepatitis C (CHC) pathogenicity. We analyzed the relationship of vitamin D status with advanced liver fibrosis (ALF) in CHC treatment-naïve patients and sustained virologic response (SVR) in CHC patients on pegylated interferon alpha plus ribavirin (pegIFNα/ribavirin) therapy. We performed a meta-analysis of all eligible studies published to date (April, 2014) in PubMed, SCOPUS, LILACS, and the Cochrane Library, assessing plasma/serum vitamin D levels related to ALF and/or SVR. Pooled odds ratios (ORs) were estimated by either fixed or random effects models. Fourteen studies were selected from the literature search, seven for ALF (1,083 patients) and 11 for SVR (2,672 patients). For liver fibrosis, low vitamin D status was related to a diagnosis of ALF, with the cutoffs of 10 ng/mL (OR = 2.37, 95% confidence interval [CI] = 1.20, 4.72) and 30 ng/mL (OR = 2.22, 95% CI = 1.24, 3.97) being significant, and a near-significance for 20 ng/mL (OR = 1.44, 95% CI = 0.99, 2.12). Regarding SVR, a significant heterogeneity among studies was found ( P < 0.001), and we only found a significant association with SVR for a vitamin D cutoff of 20 ng/mL (OR = 0.53, 95% CI = 0.31, 0.91). When meta-analysis was performed excluding the outliers, significant pooled ORs were found for all patients (10 ng/mL [OR = 0.48, 95% CI = 0.34, 0.67] and 20 ng/mL [OR = 0.58, 95% CI = 0.45, 0.76]) and GT1/4 patients (10 ng/mL [OR = 0.53, 95% CI = 0.34, 0.81] and 20 ng/mL [OR = 0.54, 95% CI = 0.39, 0.74]). Conclusion : Low vitamin D status in CHC patients is associated with a higher likelihood of having ALF and lower odds of achieving SVR following pegIFNα/ribavirin therapy. (Hepatology 2014;60:1541–1550)

Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways (“cytokine-cytokine receptor interaction”, “viral protein interaction with cytokine and cytokine receptor”, “chemokine signaling pathway”, and “hepatitis C”). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.