The diagnostic of arbovirus-related obstetric complications in high-risk pregnancy and childbirth care is challenging, especially in endemic areas. We conducted a prospective study to track active or recent Zika (ZIKV), dengue (DENV), or chikungunya (CHIKV) virus infection among hospitalized pregnant women (PW) with obstetric complications in a hospital at the epicenter of Zika outbreak and ZIKV-related microcephaly in Brazil. Clinical data and blood samples were collected at enrollment and 10 days after the admission of study participants, between October 2018 and May 2019. Further clinical data were extracted from medical records. Samples were screened by molecular and serological tests. Out of 780 participants, 93.1% (95% CI: 91.1–94.7%) presented previous DENV exposure (IgG). ZIKV, CHIKV, and/or DENV laboratory markers of recent or active infection were detected in 130 PW, yielding a prevalence of 16.6% (95% CI: 14.2–19.5%); 9.4% (95% CI: 7.4–11.7%), 7.4% (95% CI: 5.7–9.7%), and 0.38% (95% CI: 0.1–1.2%) of CHIKV, ZIKV, and DENV infections, respectively. Most ZIKV infections were detected by molecular assays (89.6%), while CHIKV infections were detected by serology (95.9%). Our findings highlight the need for arbovirus infections screening in PW with obstetrical complications, potentially associated to these infections in endemic areas regardless of the signs or symptoms suggestive of arboviral disease.

The mannose-binding lectin (MBL) plays an important role in innate immunity. Genetically determined variations in serum levels of MBL may influence the susceptibility and clinical outcome of dengue infection in early life. We investigated the MBL2 gene polymorphisms and serum levels of MBL (total and functional) in children with asymptomatic (n=17) and symptomatic (n=29) primary dengue infections and age-matched uninfected children (n=84) enrolled in a birth cohort with dengue in Brazil. Polymorphisms of the MBL2 gene were assessed by reverse transcription-polymerase chain reaction (RT-PCR), whereas the enzyme-linked immunosorbent assay (ELISA) was used to quantify serum levels of MBL. We found that the X allele and YX genotype in the MBL2 were more frequent in the dengue cases than in the control group. Likewise, the LXPA haplotype was exclusively found in dengue cases, thus probably related to dengue infection in our setting. Moreover, we found a higher frequency of the O allele and AO genotype in the control group. Serum levels of total and functional MBL were higher in dengue naïve infants than in dengue cases. MBL2 variants related to lower production of serum MBL were associated with dengue infection in infants, whereas intermediate to high levels of total and functional serum MBL were associated with protection against dengue infection. These findings highlight the role of MBL2 variants and serum levels of MBL in the susceptibility of children to dengue disease at early ages.

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to find the optimal loci classification subset, followed by a support vector machine with the linear kernel (SVM-LK) to classify patients into the severe COVID-19 group. The best features that were selected by the SVM-RFE method included 12 SNPs in 12 genes: PD-L1, PD-L2, IL10RA, JAK2, STAT1, IFIT1, IFIH1, DC-SIGNR, IFNB1, IRAK4, IRF1, and IL10. During the COVID-19 prognosis step by SVM-LK, the metrics were: 85% accuracy, 80% sensitivity, and 90% specificity. In comparison, univariate analysis under the 12 selected SNPs showed some highlights for individual variant alleles that represented risk (PD-L1 and IFIT1) or protection (JAK2 and IFIH1). Variant genotypes carrying risk effects were represented by PD-L2 and IFIT1 genes. The proposed complex classification method can be used to identify individuals who are at a high risk of developing severe COVID-19 outcomes even in uninfected conditions, which is a disruptive concept in COVID-19 prognosis. Our results suggest that the genetic context is an important factor in the development of severe COVID-19.

O Município do Rio de Janeiro é uma das cidades mais afetadas pela circulação simultânea dos vírus chikungunya (CHIKV), Zika (ZIKV) e dengue (DENV) no Brasil. Apesar de os testes rápidos estarem disponíveis comercialmente no país, ainda existem dúvidas sobre seu desempenho em cenários de cocirculação de flavivírus. O objetivo deste estudo foi avaliar o desempenho e melhor ponto de corte do teste rápido de CHIKV em cenário de cocirculação de Zika e dengue no Município do Rio de Janeiro. Foram incluídos 2.120 voluntários que residiam em domicílios particulares permanentes no Rio de Janeiro e que foram testados pelo teste rápido plataforma imunocromatográfica de duplo percurso (DPP, acrônimo em inglês) para CHIKV. Deste total, 769 participantes tiveram amostras de sangue venoso coletadas para confirmação diagnóstica pelo padrão ouro (teste de neutralização por redução de placas - PRNT) e testadas para CHIKV, DENV e ZIKV. Utilizou-se a curva ROC (receiver operating characteristic) para os cálculos de sensibilidade, especificidade, valores preditivos positivo e negativo e melhor ponto de corte. Das amostras analisadas, 15,5% foram identificadas com exposição prévia para CHIKV pelo teste rápido e 20,4% tiveram exposição prévia ao CHIKV pelo PRNT. Identificou-se exposição prévia para DENV em 89,2% das amostras testadas pelo PRNT e 67,8% para ZIKV. A sensibilidade e especificidade encontrada para o ponto de corte do fabricante foi de 96,1% e 97,5%, respectivamente. O melhor ponto de corte encontrado para o teste rápido foi de ≥ 14, para este resultado a acurácia foi de 97,7%, com especificidade e sensibilidade de 97,9% e 96,8%, respectivamente. Conclui-se que o teste rápido tem alto desempenho para detectar infecção por CHIKV em cenário de cocirculação de Zika e dengue.

Cellular components and inflammatory mediators involved in the transmigration of HTLV-1-infected cells across the blood–brain barrier (BBB) are not fully understood. This study proposes a BBB model to identify the immunological mechanisms associated with HTLV-1 pathogenesis. PBMCs from individuals with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (n = 4) or HTLV-1-infected individuals without HAM/TSP (n = 4) were isolated. An indirect cell co-culture was performed between human brain microvascular endothelial (hBMEC) cells and neuroblastoma (SH-SY5Y) cells. PBMCs from healthy individuals (n = 4) were used as a negative control, and MT-2 cells were used as a positive control. Supernatants and cells were collected to quantify inflammatory cytokines and assess cell death after 24, 48, and 72 h. Multiple comparisons were performed using the Kruskal–Wallis test, followed by Fisher’s LSD post hoc analysis. We observed that the production of cytokines IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, as well as the rate of neuronal death, was higher in co-cultures mimicking HAM/TSP carriers compared to HTLV-1-infected individuals without HAM/TSP and controls. Our results suggest that the HAM/TSP condition induces the release of IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, along with the infiltration of mononuclear cells, which may lead to neuronal death.

Background: Arboviruses, including dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV), pose serious threats to neonatal health; however, the consequences of maternal peripartum infections, particularly those that are asymptomatic, remain poorly characterized. Methods: This hospital-based cross-sectional study investigated the adverse neonatal outcomes associated with maternal arbovirus infection among pregnant women hospitalized for obstetric complications in Northeast Brazil (October 2018 to May 2019). Maternal and neonatal data were collected through interviews and reviewing medical records. Acute/recent maternal infections were confirmed by molecular or serological assays. Associations between maternal infection (categorized as any arbovirus, ZIKV-only, or CHIKV-only) and neonatal outcomes were assessed using Poisson’s regression with robust variance, yielding adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs), controlled for maternal covariates. Results: Among 806 neonates, 131 (16.3%) were born to arbovirus-infected mothers and had a higher prevalence of prematurity (aPR=1.25, 95% CI: 1.00-1.56) and sepsis (aPR=1.74, 95% CI: 1.07-2.83) compared with those born to non-infected mothers. Neonates of ZIKV-infected mothers had a two-fold higher prevalence of sepsis (aPR=2.02, 95% CI: 1.00-4.11) than neonates of non-infected mothers, and a trend was observed for CHIKV (aPR=1.76, 95% CI: 0.97-3.20). Conclusions: In this hyperendemic region, a high frequency of newborns were exposed to maternal arbovirus infection during the inter-epidemic period, which was associated with increased premature births and neonatal sepsis. These findings underscore the need for increased clinical vigilance and routine screening in endemic areas, necessitating further longitudinal studies to confirm causality and guide management.