OBJECTIVE:This study aimed to analyze the possible association between rs2814778, rs12075 ( ACKR1 gene), and rs4073 ( CXCL8 gene) single nucleotide variants and COVID-19 severity. METHODS:This cross-sectional study included 319 COVID-19 diagnosed patients at two hospitals in Paraná, Brazil between 2020 and 2021. Among them, 171 cases were classified as severe or critical and 148 were classified as non-severe. Genotyping was performed using polymerase chain reaction. RESULTS:We found an association between the rs2814778 variant of the ACKR1 gene and COVID-19 severity. The C allele in both the T/C and C/C genotypes was identified as a risk factor for severe COVID-19, independent of sex, age, smoking status, cardiovascular disease, diabetes, or obesity. No evidence of an association was observed for the other variants. CONCLUSION:The presence of the C allele in the rs2814778 variant indicated an increased risk of severe or critical COVID-19 in the southern Brazilian population across all possible genotypes and genetic inheritance models.

Bancos de leite humano enfrentam desafios relacionados ao armazenamento e distribuição do leite humano. Este estudo avaliou a estabilidade de ácidos graxos e das interleucinas IL-5 e IL-6 utilizando cromatografia gasosa, ensaio multiplex e análise multivariada em amostras de leite humano cru (CRU), pasteurizado (PAST) e liofilizado (LIO) armazenados por até 180 dias (D). As amostras foram armazenadas em condições especificamente recomendadas, sendo CRU e PAST mantidas a -18 °C, e LIO armazenadas à temperatura ambiente (LIO25) ou sob refrigeração (LIO5). Os resultados mostraram dois grupos distintos na composição de ácidos graxos, associando D0-D30 e D60-D180. CRU e PAST apresentaram perfis semelhantes nos períodos iniciais e maiores alterações entre D60 e D180, relacionadas a reações lipolíticas decorrentes da maior suscetibilidade à atividade da lipase no estado líquido congelado, enquanto as amostras LIO diferiram devido ao estado em pó. LIO5 destacou-se ainda com melhor preservação de ácidos graxos poli-insaturados (AGPIs) e saturados (AGSs), evidenciando que seu processamento e armazenamento minimiza reações oxidativas e hidrolíticas. IL-5 e IL-6 mostraram sensibilidade aos tratamentos, com expressão ativa apenas na CRU. A análise de componentes principais confirmou a transição dos perfis bioativos ao longo do armazenamento, associada ao equilíbrio entre biomarcadores inflamatórios. Conclui-se que a avaliação da qualidade do leite humano em condições reais é essencial para estimar a estabilidade dos compostos bioativos e garantir a qualidade nutricional e imunológica do alimento ofertado, considerando as necessidades do neonato para uma distribuição mais adequada.

A novel HLA-B allele was identified in a Brazilian volunteer bone marrow donor.

Two HLA class I alleles were confirmed and the sequences extended in our laboratory.

This study investigates the HLA allele diversity in Brazil, a reflection of the country's unique history of population admixture. The international comparison of findings emphasises the importance of incorporating underrepresented populations into global HLA databases. We present a comprehensive analysis of HLA alleles within the Brazilian population, utilising high-resolution sequencing data from 298,000 unrelated haematopoietic stem cell volunteer donors registered with the Brazilian Bone Marrow Donor Registry (REDOME). Our research encompasses donors from all regions of Brazil, identifying HLA alleles that are catalogued as common, intermediate or well-documented (CIWD Version 3.0). We evaluated the alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1. At a two-field resolution, we identified 1969 alleles: 418 were classified as common, 358 as intermediate and 1193 as non-CIWD in Brazil. Notably, we report HLA alleles that, while not classified as common or intermediate in the CIWD 3.0 catalogue, are prevalent within the Brazilian population. A detailed list of alleles from the registry, presented at a two-field resolution and supplemented with grouped ARD levels, including three- or four-field resolution when available, serves as an essential reference for HLA typing frequencies specific to the Brazilian population.

The aim of this study was to investigate the influence of HLA-A, -B and -C polymorphisms on the clinical course of SARS-CoV-2 infection and on the progression of COVID-19 in a population from southeastern Brazil. This study included 478 unvaccinated individuals. Of these, 369 were hospitalised with critical/severe (n = 309) or moderate/mild (n = 60) symptoms, and 109 were asymptomatic. The control group consisted of 150 volunteer bone marrow donors, recruited in the pre-pandemic period. The HLA-B*15 allele group (adjusted p value < 0.001) was associated with a protective factor against symptomatic infection. Investigating the effects of the distribution of HLA alleles on susceptibility and resistance to SARS-CoV-2 may provide a better understanding of the clinical course of infection in different geographical regions.

Human milk is recognized as the ideal food for newborns, especially premature and low birth weight infants, due to its nutritional composition and the presence of essential immunological and bioactive components. Colostrum, produced in the first days of lactation, stands out for its high concentration of proteins, immunoglobulins, cytokines, growth factors, and antimicrobial compounds, playing a fundamental role in the maturation of the immune system and protection against infections. However, the availability of human milk can be limited by maternal or logistical factors, and traditional preservation methods, such as pasteurization and freezing, can partially compromise its bioactivity. In this context, the present study evaluated the viability of lyophilizing human colostrum as a strategy to optimize its preservation and distribution in human milk banks. Colostrum samples were subjected to lyophilization under controlled conditions, and the yield and moisture content of the final product were evaluated. Freeze-dried human colostrum showed an average yield of 14.12%, with a moisture content of 4.72%, a value compatible with the standards established by current legislation. These results demonstrate efficiency in water removal, favoring greater product stability and reducing the risks of oxidative, enzymatic, and microbiological degradation. It is concluded that the freeze-drying of human colostrum is a promising strategy for preserving its nutritional and functional characteristics, as well as facilitating storage, transport, and distribution, especially in regions with limited infrastructure, expanding safe access to human milk.

The novel HLA-A*03:01:133 allele differs from A*03:01:01:01 by a change of C ➔ T in exon 4.

Five HLA-DRB1 alleles were confirmed and the sequences extended in our laboratory.

Human milk is a dynamic biological fluid whose composition varies throughout lactation, adapting to meet the physiological needs of the newborn. This study investigated how the breastfeeding time (foremilk, middle milk, hindmilk) affects energy, fatty acid, and tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) contents in mature human milk from five distinct donors (M1-M5), using creamatocrit, gas chromatography, and enzyme-linked immunosorbent assays, respectively. The results progressively increased in energy values, with the highest values in hindmilk. Fatty acid composition exhibited distinct individual profiles, with palmitic acid predominating in M1 and M5, and oleic acid more prominent in M2, M3, and M4. The duration of breastfeeding significantly influences the caloric and lipid composition of mature human milk. Principal component analysis (PCA) accounted for 59.6% of the variance, indicating the clustering of fatty acid profiles according to collection times from the same donor. No consistent pattern was observed for the immunological factors throughout the lactation. TNF-α was undetectable in some samples, possibly due to its low concentration in mature human milk, while IL-10 was consistently detected. These findings suggest that individual factors such as maternal diet, body composition, and lifestyle may influence the nutritional and immunological composition of human milk.

The Gamma and Delta variants of concern (VOCs) of SARS-CoV-2 drove the second and third wave in Brazil and significantly intensified the number of cases and deaths. In this study, we investigate the timeline and origins of the Gamma and Delta variants using a spatiotemporal analysis based on 1508 genomes collected between March and September 2021 from health administrative regions in Paraná state, Brazil. Our findings indicate that community transmission of Gamma-P.1 began in late 2020, with substantial contributions from the Northeast and North regions. In contrast, our analysis of the Delta-AY.101 genomes underscored the crucial role of Paraná in national-level transmission dynamics beginning in late March 2021. At a local level, the movement estimates inferred from the monophyletic clades showed that the Curitiba health region was the primary source for Gamma-P.1, with a substantial contribution from Londrina. This health-region also emerged as an important hub for Delta-AY.101. Our phylogeographical GLM analysis demonstrates that air travel fluxes and population size at the origin of locations were the strongest predictors of shaping SARS-CoV-2 dispersal dynamics within Paraná. In addition, viral load analysis suggests that Gamma-P.1 and Delta-AY.101 may have maintained a similarly high transmissibility potential throughout the evaluated months, providing insights into the prolonged co-circulation dynamics. Our study underscores the relevance of understanding SARS-CoV-2 introductions and regional circulation contributions at the country level to enhance public health preparedness and strengthen local surveillance programs.

ABSTRACT The novel HLA‐C*01:283 allele differs from C*01:02:01:01 by change of C → T in exon 4.

BACKGROUND:Zika virus (ZIKV) is an emergent pathogen known for the outbreak in early 2015, causing significant consequences, of which congenital ZIKV syndrome is the most severe manifestation. Toll-like receptors (TLRs) are important for the appropriate function of the innate immune response against pathogens. The presence of mutations in TLR genes can potentially result in altered susceptibility to diseases. Thus, this study aimed to investigate the influence of TLR2 rs5743708, TLR3 rs3775291, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810 and TLR7 rs179008 polymorphisms in ZIKV infection in a case-control study. METHODS:The study enrolled 142 patients with ZIKV that sought medical care with ZIKV-related symptoms during the ZIKV outbreak and 142 controls. Genotyping was carried out by PCR-RFLP. Multivariate and χ2 analyses were performed to assess associations between polymorphisms and disease. RESULTS:The dominant inheritance model revealed an increased risk for patients who were carriers of the TLR3 rs3775291 T allele. The C/T-T/T genotypes were significantly increased in patients rather than controls compared with the C/C genotype (OR=1.76, 95% CI 1.05 to 2.94; p=0.03). CONCLUSIONS:Our data support the literature and suggest that the variant rs3775291 in TLR3 may confer susceptibility to ZIKV infection in the Brazilian population.

The novel HLA-DQB1*04:107 allele differs from DQB1*04:01:01:03 by a change of A>G in exon 2.

The high variability of human leukocyte antigen (HLA) genes results in each molecule having distinct antigenic peptide binding capacities, potentially influencing the immune response to SARS-CoV-2. This study aimed to investigate associations between HLA class I (A, B) and class II (DRB1) polymorphisms and COVID-19 severity in a South Brazilian population, and to evaluate the binding affinity of alleles to viral peptides. A cross-sectional study included 503 unvaccinated patients with RT-qPCR-confirmed COVID-19: 145 non-severe, 129 severe, and 229 critical. HLA typing was performed using PCR-SSO and Luminex™ technology. The DRB1*11 allelic group was significantly associated with protection against severe and critical cases, while DRB1*15 was associated with increased risk; both remained significant after Bonferroni correction. Other allelic groups were associated with disease outcomes but lost significance after correction: B*49 and B*08 (risk); and B*37, B*50, and A*03 (protection). In silico analysis revealed that the DRB1*15 allele group showed a higher proportion of strong binders, mostly from non-structural proteins, while DRB1*11:01 binders, though fewer in number, were concentrated in the M protein. These results suggest functional differences in antigen presentation and reinforce the relevance of class II HLA, particularly DRB1, in modulating COVID-19 severity.

The novel HLA-DRB1*11:341 allele differs from DRB1*11:01:01:01 by change of C → A in exon 4.

The new HLA‐DRB3*03:69 allele differs from DRB3*03:01:01:03 by change of C → G in exon 3.

We identified two new HLA-DRB3 alleles in Brazilian individuals using next generation sequencing.

The Natural Killer cells are innate lymphoid cells that play essential roles in defense against viral and parasitic infections, elimination of tumor cells, regulation of adaptive immunity through cytotoxicity, and cytokine secretion. Fundamental knowledge about the regulation of Natural Killer cells can be applied to study their function in patients undergoing hematopoietic stem cell transplantation, with or without Cytomegalovirus reactivation. The function of Natural Killer cells is governed by a repertoire of receptors responsible for initiating intracellular activating or inhibitory signaling. The balance of this signaling directs the cytotoxic activity of these cells, as well as cell proliferation and cytokine release.Understanding the interaction of receptors expressed on the surface of Natural Killer cells with their ligands expressed on target cells is a topic of discussion in the context of alloreactivity and the graft-versus-leukemia effect in transplant patients. Recent investigations have shown that KIR/HLA interactions go beyond affinity and describe that many of them depend on the peptide being presented by the HLA at that moment. Analysis of the peptidome (HLA class I + bound peptide) has demonstrated that some Natural Killer cell receptors are peptide-dependent. Therefore, understanding these interactions by considering the entire Natural Killer cell receptor + HLA class I + peptide complex is crucial in the reestablishment of immune cells after hematopoietic stem cell transplantation, especially in the context of Cytomegalovirus reactivation, which is very common in these patients. Hence, the aim of this study is to deepen our understanding of the specificity of interactions between human Natural Killer cell KIR receptors and the peptidome in the context of Cytomegalovirus reactivation after allogeneic, related, HLA-compatible hematopoietic stem cell transplantation without T-cell depletion. For the analysis of interactions between Natural Killer cell receptors and peptidomes, specific peptide libraries for HLA class I alleles will be created to evaluate the specificities of interactions between KIR + HLA class I + peptide.

The new HLA-DPA1*01:182 allele differs from HLA-DPA1*01:03:01:04 by a single mismatch in exon 4.