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Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we looked at how persistent inflammation affects peripheral body temperature and sympathovagal balance in individuals with long COVID. Increased temperature and reduced heart rate variability were directly related to the increase in inflammatory cytokines and reduction in anti-inflammatory cytokines. We identified a possible "molecular signature" for long COVID, characterised by a Th17 inflammatory profile with a reduced anti-inflammatory response, resulting in alterations in homeostatic functions and sympathovagal balance. A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies. [ABSTRACT FROM AUTHOR]

The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract The Major Histocompatibility Complex (MHC) harbors key genes of the immune response that are likely useful as biomarkers for infectious diseases. However, little is known about their microRNAs and what role they play in infections. The present study aimed to describe the miRNA genes in the MHC (MHC-miRNA), their variability and associations with infectious diseases. Additionally, MHC-miRNA host and target genes were also evaluated in associations with infectious diseases. Surveys in several databases and literature reviews identified 48 MHC-miRNA genes, with high SNP and CNV variability able to disrupt MHC-miRNA expression and putatively under selective pressure. Eight MHC-miRNAs were found inside or close regions of classical MHC rearrangements (RCCX and DRB genome organization). The proportion of MHC-miRNAs associated with infections (23%) was higher than the proportion found for the 1917 hsa-miRNA (4%). Additionally, 35 MHC-miRNAs (57%) have at least one of their target genes associated with infectious diseases, while all nine MHC-miRNA whose host genes were associated with infections have also their target genes associated with infections, being host and target genes of five MHC-miRNAs reported to be associated with the same diseases. This finding may reflect a concerted miRNA-mediated immune response mechanism triggered by infection. [ABSTRACT FROM AUTHOR]

• A molecular PCR technique for the detection of the antimicrobial peptide cecropin a and defensin genes was described in Anopheles darlingi and was applied to perform a phylogenetic study. • The phylogenetic trees showed unique and monophyletic clades among different species of anopheline mosquitoes for both cecropin A and defensin. • In both genes, Anopheles darlingi presented a significant genetic distance in relation to anopheline species from the African continent. Cecropins and defensins are the main classes of antimicrobial peptides in the mosquito innate immune system, acting against bacteria, fungi and protozoa. There is a knowledge gap concerning these peptide genes in anopheline mosquitoes from the Brazilian Amazon. Thus, this work aimed to describe molecular techniques for detecting the genes encoding the antimicrobial peptides cecropin A (CecA) and defensin in Anopheles darlingi mosquitoes and to perform molecular phylogeny of the sequenced genes using the maximum likelihood method and Bayesian inference with other species from different geographic areas. Our results show, for the first time, a molecular biology method for detecting CecA and defensin in Anopheles darlingi that allows for the use of these molecular markers for phylogenetic analysis in anopheline species, separating the species into single and monophyletic clades. [ABSTRACT FROM AUTHOR]

C-type lectin DC-SIGN receptor, encoded by CD209, plays a key role in the infection of dendritic cells by dengue virus (DENV). Because the -336A/G SNP (rs4804803) polymorphism in the promoter of CD209 modulates DC-SIGN expression, we investigated the putative association of this polymorphism with DENV infection and its pathogenesis. A control sample of 72 individuals, rigorously selected through a clinical investigation for absence of past dengue fever (DF) was compared to a sample of 168 patients (156 classical DF; 12 dengue hemorrhagic fever), all residents from Pará, Brazil. However, the prevalence of symptoms showed a trend higher in the AA genotype (Wilcoxon test; Z=2.02; p=0.04). Hence, our findings indicate that the G allele downregulates the spectrum of symptoms during the early acute phase of DENV infection, putatively decreasing the viremia, as suggested in the literature. [ABSTRACT FROM AUTHOR]

Abstract: In vitro-produced embryos store high lipid content in cytoplasmic lipid droplets (LD), and reduction or removal of LD has been demonstrated to improve freeze-thaw viability. The Perilipin Adipophilin Tail-interacting Protein of 47 kD (PAT) family of proteins is involved in the formation and regulation of LD in many cell types, but their presence has not been addressed either in cattle oocytes or preimplantation embryos. Therefore, this study aimed to detect the expression of PAT family transcripts (Perilipin-2 [PLIN2] and Perilipin-3 [PLIN3]) in immature and in vitro-matured (IVM) oocytes, and in in vitro-produced embryos at the stages of two to four cells, eight to 16 cells, morulae (MO), and blastocyst (BL). The expression of PLIN3 was downregulated in response to IVM, and PLIN2 was comparatively more expressed than PLIN3 in IVM oocytes (P < 0.001). During the early stages of embryo development, PLIN2 expression reached its peak at the MO stage (P < 0.001) and decreased again at the BL stage. In contrast, PLIN3 was expressed in low levels during the earliest stages of development, slightly upregulated at the MO stage (P < 0.05), and greatly increased its expression at the BL stage (15-fold; P < 0.001). PLIN3 was comparatively more expressed than PLIN2 during embryo culture in most stages analyzed (P < 0.05), except in eight- to 16-cell embryos. These results indicate that PLIN2 might be involved in the maintenance of lipid stocks necessary to support embryo development after fertilization of IVM oocytes. Also, we hypothesize that PLIN3 is the main PAT protein responsible for stabilization of LD formed in consequence of the acute lipid load seen during embryo development. We confirmed the presence of both PLIN2 and PLIN3 proteins in BL at Day 7 using immunocytochemistry: these PAT proteins colocalized with LD stained with BODIPY. PLIN3 seemed to be more ubiquitously spread out in the cytoplasm than PLIN2, consistent with the pattern seen in adipocytes. These findings suggest that both elderly (bigger) and newly formed (smaller) LD, positive for PLIN2 and PLIN3 respectively, coexist in blastocysts. To our knowledge this is the first report showing that transcripts of the PAT family are present in cattle oocytes and embryos. [Copyright &y& Elsevier]

Objectives: This investigation was performed to examine genetic variation at the β-globin locus in a sample of 30 healthy individuals from native populations in South America. The patterns of haplotypic variation were compared with those of previous studies including samples for various worldwide populations in an attempt to make inferences about the occupation of the Americas from a deeper temporal perspective than is typically available with haploid markers. Methods: A 2.67-kb segment containing the β-globin gene and its flanking regions was examined for genetic variation in a sample of 60 chromosomes from native populations in South America. The fragment was PCR-amplified and directly sequenced. To determine linkage relationships in compound heterozygotes, we used the amplification refractory mutation system. In addition, we assessed genetic variability and differentiation among populations, and we performed tests of selective neutrality. These analyses were performed for Brazilian Amerindian group and other worldwide populations previously studied. Results: Eleven polymorphic sites were found in the studied fragment, which distinguished eight different haplotypes, three recombinants haplotypes (present as single copies) and five previously described haplotypes, including some of those most highly differentiated. Genetic variation found in the pooled sample is substantial. Conclusions: Although only five known haplotypes are observed in Amazonia, some of these are highly divergent, resulting in patterns of molecular polymorphism equal to or higher than those from other world regions. Am. J. Hum. Biol. 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]