Comprehensive analysis of early T cell responses to acute Zika Virus infection during the first epidemic in Bahia, Brazil.

BACKGROUND: In most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and eliminating virus-infected cells during the early stages of infection. AIM: To test the hypothesis that circulating T cells exhibit phenotypic and functional activation characteristics during the viremic phase of ZIKV infection. METHODS: A comprehensive analysis using mass cytometry was performed on peripheral blood mononuclear cells obtained from patients with acute ZIKV infection (as confirmed by RT-PCR) and compared with that from healthy donors (HD). The frequency of IFN-γ-producing T cells in response to peptide pools covering immunogenic regions of structural and nonstructural ZIKV proteins was quantified using an ELISpot assay. RESULTS: Circulating CD4+ and CD8+ T lymphocytes from ZIKV-infected patients expressed higher levels of IFN-γ and pSTAT-5, as well as cell surface markers associated with proliferation (Ki-67), activation ((HLA-DR, CD38) or exhaustion (PD1 and CTLA-4), compared to those from HD. Activation of CD4+ and CD8+ memory T cell subsets, including Transitional Memory T Cells (TTM), Effector Memory T cells (TEM), and Effector Memory T cells Re-expressing CD45RA (TEMRA), was prominent among CD4+ T cell subset of ZIKV-infected patients and was associated with increased levels of IFN-γ, pSTAT-5, Ki-67, CTLA-4, and PD1, as compared to HD. Additionally, approximately 30% of ZIKV-infected patients exhibited a T cell response primarily directed against the ZIKV NS5 protein. CONCLUSION: Circulating T lymphocytes spontaneously produce IFN-γ and express elevated levels of pSTAT-5 during the early phase of ZIKV infection whereas recognition of ZIKV antigen results in the generation of virus-specific IFN-γ-producing T cells.

Detection of encephalitis-causing viruses reveals predominance of chikungunya virus in the state of Bahia, Brazil.

OBJECTIVES: Encephalitis is a severe neurological syndrome for which herpesvirus and enteroviruses are the most common etiological agents. Arboviruses, a wildly diverse group of pathogens, are also critical epidemiological agents associated with encephalitis. In Brazil, little is known about the causative agents of encephalitis. METHODS: We conducted a hospital surveillance for encephalitis between 2020 and 2022. Molecular (RT-PCR and qPCR) and serological (virus-specific IgM and viral antigens) techniques were performed in cerebrospinal fluid and serum samples obtained from study participants. RESULTS: In the 43 participants evaluated, the etiologic agent or the presence of IgM was detected in 16 (37.2%). Nine (20.9%) cases were positive for chikungunya virus (CHIKV), three (7.0%) for dengue virus, two (4.7%) for human adenovirus, one (2.3%) for varicella-zoster virus, and one (2.3%) for enterovirus. Whole-genome sequencing revealed that the CHIKV identified belongs to the East/Central/South African lineage. CONCLUSION: Herein, CHIKV is a common pathogen identified in encephalitis cases. Our results reinforce previous evidence that chikungunya represents a significant cause of encephalitis during CHIKV outbreaks and epidemics and add to existing information on the epidemiology of encephalitis in Brazil.

Seroprevalence Of SARS-COV-2 infection in asymptomatic indigenous from the largest Brazilian periurban area.

This study assessed the seroprevalence of SARS-CoV-2 in 496 asymptomatic individuals from Mato Grosso do Sul, located in Dourados, the largest periurban indigenous area in Brazil, from January 25 to February 4, 2021. The volunteers participated before receiving their first dose of the CoronaVac inactivated vaccine. For screening, blood samples were collected and analyzed using SARS-CoV-2 rapid tests and the enzyme-linked immunosorbent assay (ELISA). We observed varying trends in total anti-SARS-CoV-2 antibodies across different variables. Seropositivity among the participants tested was 63.70% (316/496) using the rapid test and 52.82% (262/496) were positive using the ELISA method. The majority of participants identified with the Guarani-Kaiowá ethnic group, with 66.15% (217/328), and other ethnic groups with 58.84% (193/328). The median age of the subjects was 30.5 years, with 79.57% (261/328) being femaleThis research showed the elevated seroprevalence of SARS-CoV-2 antibodies in asymptomatic Brazilians. The findings indicate a high seropositivity rate among the asymptomatic indigenous population of Midwest Brazil. This underscores the overlooked status of these communities and underscores the need for targeted national initiatives that emphasize the protection of vulnerable ethnic groups in the fight against COVID-19.

MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study.

BACKGROUND: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. OBJECTIVE: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. METHODS: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. RESULTS: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. CONCLUSIONS: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.

Heterologous DNA Prime- Subunit Protein Boost with Chikungunya Virus E2 Induces Neutralizing Antibodies and Cellular-Mediated Immunity.

Chikungunya virus (CHIKV) has become a significant public health concern due to the increasing number of outbreaks worldwide and the associated comorbidities. Despite substantial efforts, there is no specific treatment or licensed vaccine against CHIKV to date. The E2 glycoprotein of CHIKV is a promising vaccine candidate as it is a major target of neutralizing antibodies during infection. In this study, we evaluated the immunogenicity of two DNA vaccines (a non-targeted and a dendritic cell-targeted vaccine) encoding a consensus sequence of E2CHIKV and a recombinant protein (E2*CHIKV). Mice were immunized with different homologous and heterologous DNAprime-E2* protein boost strategies, and the specific humoral and cellular immune responses were accessed. We found that mice immunized with heterologous non-targeted DNA prime- E2*CHIKV protein boost developed high levels of neutralizing antibodies, as well as specific IFN-γ producing cells and polyfunctional CD4+ and CD8+ T cells. We also identified 14 potential epitopes along the E2CHIKV protein. Furthermore, immunization with recombinant E2*CHIKV combined with the adjuvant AS03 presented the highest humoral response with neutralizing capacity. Finally, we show that the heterologous prime-boost strategy with the non-targeted pVAX-E2 DNA vaccine as the prime followed by E2* protein + AS03 boost is a promising combination to elicit a broad humoral and cellular immune response. Together, our data highlights the importance of E2CHIKV for the development of a CHIKV vaccine.

Analyses of Early ZIKV Genomes Are Consistent with Viral Spread from Northeast Brazil to the Americas.

The Americas, particularly Brazil, were greatly impacted by the widespread Zika virus (ZIKV) outbreak in 2015 and 2016. Efforts were made to implement genomic surveillance of ZIKV as part of the public health responses. The accuracy of spatiotemporal reconstructions of the epidemic spread relies on the unbiased sampling of the transmission process. In the early stages of the outbreak, we recruited patients exhibiting clinical symptoms of arbovirus-like infection from Salvador and Campo Formoso, Bahia, in Northeast Brazil. Between May 2015 and June 2016, we identified 21 cases of acute ZIKV infection and subsequently recovered 14 near full-length sequences using the amplicon tiling multiplex approach with nanopore sequencing. We performed a time-calibrated discrete phylogeographic analysis to trace the spread and migration history of the ZIKV. Our phylogenetic analysis supports a consistent relationship between ZIKV migration from Northeast to Southeast Brazil and its subsequent dissemination beyond Brazil. Additionally, our analysis provides insights into the migration of ZIKV from Brazil to Haiti and the role Brazil played in the spread of ZIKV to other countries, such as Singapore, the USA, and the Dominican Republic. The data generated by this study enhances our understanding of ZIKV dynamics and supports the existing knowledge, which can aid in future surveillance efforts against the virus.

Production and Characterization of Two Specific ZIKV Antigens Based on Bioinformatic Analysis and Serological Screening.

BACKGROUND: The high structural similarity between the Zika virus (ZIKV) and other flaviviruses, such as Dengue Virus (DENV), complicates the identification of the infecting virus due to the occurrence of cross-reactions in serological assays. This phenomenon has increased the demand for more specific antigens for immunodiagnostic applications. METHODS: The present work aimed to identify specific regions of ZIKV and produce unique antigens through computational methods, molecular and microbiological techniques. RESULTS: Based on the computational analysis we successfully expressed two recombinant proteins derived from specific regions of the ZIKV. Through serological assays using characterized sera, we observed that the region 146-182 of ZIKV's E protein, expressed in tandem, was not reactive despite the predictive sensitivity and specificity observed by computer analyses. On the other hand, the non-denatured fraction 220-352 of ZIKV's NS1 showed greater specificity to IgG+ sera of ZIKV by dot blot and western blot, which highlights its properties as a possible tool in the diagnosis of ZIKV. CONCLUSION: These findings demonstrate that ZIKV NS1 fraction 220-352 is a potential tool that may be applied in the development of serological diagnosis. We also provided data that suggest the non-applicability of the region 146-182 of ZIKV's protein E in serological assays despite previous indications about its potential based on computational analysis.

Genomic monitoring unveils a high prevalence of severe acute respiratory syndrome coronavirus 2 Omicron variant in vaccine breakthrough cases in Bahia, Brazil.

OBJECTIVE: Genome sequencing has been proved to be an excellent tool to monitor the molecular epidemiology of the disease caused by severe acute respiratory syndrome coronavirus 2, i.e., coronavirus disease 2019. Some reports of infected, vaccinated individuals have aroused great interest because they are primarily being infected with circulating variants of concern. To investigate the cases of infected, vaccinated individuals in Salvador, Bahia, Brazil, we performed genomic monitoring to estimate the magnitude of the different variants of concern in these cases. METHODS: Nasopharyngeal swabs from infected (symptomatic and asymptomatic), vaccinated or unvaccinated individuals (n=29), and quantitative reverse transcription polymerase chain reaction cycle threshold value (Ct values) of ≤30 were subjected to viral sequencing using nanopore technology. RESULTS: Our analysis revealed that the Omicron variant was found in 99% of cases and the Delta variant was found in only one case. Infected, fully vaccinated patients have a favorable clinical prognosis; however, within the community, they become viral carriers with the aggravating factor of viral dissemination of variants of concern not neutralized by the currently available vaccines. CONCLUSION: It is important to acknowledge the limitations of these vaccines and to develop new vaccines to emergent variants of concern, as is the case of influenza vaccine; going through new doses of the same coronavirus vaccines is "more of the same."

Genomic monitoring unveils a high prevalence of severe acute respiratory syndrome coronavirus 2 Omicron variant in vaccine breakthrough cases in Bahia, Brazil

SUMMARY OBJECTIVE: Genome sequencing has been proved to be an excellent tool to monitor the molecular epidemiology of the disease caused by severe acute respiratory syndrome coronavirus 2, i.e., coronavirus disease 2019. Some reports of infected, vaccinated individuals have aroused great interest because they are primarily being infected with circulating variants of concern. To investigate the cases of infected, vaccinated individuals in Salvador, Bahia, Brazil, we performed genomic monitoring to estimate the magnitude of the different variants of concern in these cases. METHODS: Nasopharyngeal swabs from infected (symptomatic and asymptomatic), vaccinated or unvaccinated individuals (n=29), and quantitative reverse transcription polymerase chain reaction cycle threshold value (Ct values) of ≤30 were subjected to viral sequencing using nanopore technology. RESULTS: Our analysis revealed that the Omicron variant was found in 99% of cases and the Delta variant was found in only one case. Infected, fully vaccinated patients have a favorable clinical prognosis; however, within the community, they become viral carriers with the aggravating factor of viral dissemination of variants of concern not neutralized by the currently available vaccines. CONCLUSION: It is important to acknowledge the limitations of these vaccines and to develop new vaccines to emergent variants of concern, as is the case of influenza vaccine; going through new doses of the same coronavirus vaccines is "more of the same."

Development of monoclonal antibodies against prM of Dengue virus 4 / Desenvolvimento de anticorpos monoclonais para prM de Dengue vírus 4

Introduction: dengue is a most common mosquito-borne viral disease in the Americas and tropical countries. Objective: in this work, mice were hyperimmunized with DENV 4 antigen to produce monoclonal antibodies (mAbs). Methodology: DENV 4 (GenBank KC806069) was inoculated in C6/36 cell monolayers cultivated in Leibovitz's 15 medium supplemented with 5% fetal bovine serum and incubated at 28 oC. The virus stock was submitted to concentration and ultracentrifugation and stored at -80 oC until use (VC DENV 4). Balb/c mice were injected intraperitoneally with 50µg of DENV-4 and successive intraperitoneal injections of 25 µg of VCDENV 4 with Freund's incomplete adjuvant were performed. The spleen cells were fused to SP2/0 myeloma cells with PEG 1540 and distributed in 96-well microplates with Iscove's modified medium with Hipoxantina­Aminopterina­Timidina. Hybridoma screening by indirect ELISA showed positive results for six mAbs, and their characterization was performed by Western blotting and Indirect Immunofluorescence (IFI) techniques. Results: the six mAbs showed strong recognition of prM (24/29 kDa), and minor reaction to E protein (66 kDa), E/E protein dimer (105 kDa), and NS1 (49 kDa) protein in two mAbs. The use of mAbs anti-prM as a diagnostic tool using IFI has been demonstrated to detect DENV-4 antigen in infected cells or tissues. Conclusion: DENV 4 generate mAbs with strong reactivity to prM with potential use to confirm the presence of DENV 4 antigen in tissues or infected cells.

Introdução: a dengue é uma doença viral transmitida por mosquitos comumente das Américas e países tropicais. Objetivo: neste trabalho, camundongos foram hiperimunizados com antígeno DENV 4 para produzir anticorpos monoclonais (mAbs). Metodologia: DENV 4 (GenBank KC806069) foi inoculado em monocamadas de células C6 / 36 cultivadas em meio Leibovitz 15 suplementado com 5% de soro fetal bovino e incubadas a 28oC. O estoque viral foi submetido à concentração, ultracentrifugação e armazenado a -80 oC (VC DENV 4). Camundongos Balb / c foram injetados intraperitonealmente com 50 µg de VC DENV-4 e injeções intraperitoneais sucessivas de 25 µg de antigeno com adjuvante incompleto de Freund. As células do baço foram misturadas a células SP2/0 com PEG 1540 e distribuídas em microplacas de 96 poços com meio Iscove Modificado em presença de Hipoxantina ­ Aminopterina ­ Timidina. A triagem de hibridomas por ELISA indireto apresentou resultados positivos para seis mAbs, e sua caracterização foi realizada por técnicas de Western blotting e Imunofluorescência Indireta (IFI). Resultados: os seis mAbs mostraram forte reconhecimento de prM (24/29 kDa) e reação menor à proteína E (66 kDa), dímero de proteína E / E (105 kDa) e proteína NS1 (49 kDa) em dois mAbs. O uso de mAbs anti-prM como uma ferramenta de diagnóstico utilizando IFI demonstrou eficacia em detectar o antígeno DENV-4 em células ou tecidos infectados. Conclusão: o mAbs produzidos para DENV 4 demonstraram uma forte reatividade contra prM, e poderiam ser uma ferramenta de uso potencial no diagnóstico de DENV 4 .

Acute-Phase Levels of CXCL8 as Risk Factor for Chronic Arthralgia Following Chikungunya Virus Infection.

The immunopathogenesis of chikungunya virus (CHIKV) infection and the role of acute-phase immune response on joint pain persistence is not fully understood. We investigated the profile of serum chemokine and cytokine in CHIKV-infected patients with acute disease, compared the levels of these biomarkers to those of patients with other acute febrile diseases (OAFD) and healthy controls (HC), and evaluated their role as predictors of chronic arthralgia development. Chemokines and cytokines were measured by flow Cytometric Bead Array. Patients with CHIKV infection were further categorized according to duration of arthralgia (≤ 3 months vs >3 months), presence of anti-CHIKV IgM at acute-phase sample, and number of days of symptoms at sample collection (1 vs 2-3 vs ≥4). Patients with acute CHIKV infection had significantly higher levels of CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1ß, IL-6, IL-12, and IL-10 as compared to HC. CCL2, CCL5, and CXCL10 levels were also significantly higher in patients with CHIKV infection compared to patients with OAFD. Patients whose arthralgia lasted > 3 months had increased CXCL8 levels compared to patients whose arthralgia did not (p<0.05). Multivariable analyses further indicated that high levels of CXCL8 and female sex were associated with arthralgia lasting >3 months. Patients with chikungunya and OAFD had similar cytokine kinetics for IL-1ß, IL-12, TNF, IFN-γ, IL-2, and IL-4, although the levels were lower for CHIKV patients. This study suggests that chemokines may have an important role in the immunopathogenesis of chronic chikungunya-related arthralgia.

SARS-CoV-2 infection in pregnant women and newborns in two maternity hospitals in Salvador-Bahia, Brazil.

The outbreak of the new coronavirus (SARS-CoV-2) causing the coronavirus disease (COVID-19) has spread globally. As of June 18, 2020, a high maternal mortality rate due to SARS-CoV-2 infections was identified in Brazil, representing most of the world cases at that time. An observational, cross-sectional study was performed with pregnant women admitted in two maternity hospitals located in Salvador/Bahia and their newborns, from May 24th up to July 17th of 2020. Among 329 pregnant women enrolled at hospital admission, a high prevalence (n=28; 8.5%) of pregnant women with COVID-19 was observed, as well as a high proportion of asymptomatic cases (n=19; 67.9%). Two newborns had detectable SARS-CoV-2 but evolved without abnormalities. This data highlight the importance of identifying pregnant women with COVID-19 for proper isolation measures to prevent in-hospital transmission.

Meningoencephalitis Associated with Zika Virus and Chikungunya Virus Infection.

The etiology of viral meningoencephalitis is frequently unidentified. Chikungunya virus (CHIKV) and Zika virus (ZIKV) are known to affect the central nervous system and should therefore be considered in the diagnosis of meningoencephalitis, as its outcome may be influenced by the etiologic agent, age, and immunological condition of the patient. In this study, we aimed to determine whether CHIKV and ZIKV were the etiological agents of viral encephalitis in patients with meningoencephalitis admitted to the main hospital of infectious diseases in the city of Salvador, Brazil. Of the 1,049 patients with neurological symptoms who were admitted to the hospital during the study period, 149 were enrolled and 20 (13.34%) tested positive for ZIKV (12%) or CHIKV (1.34%). No specific clinical manifestations were observed to be associated with ZIKV or CHIKV infections. Determination of the etiological agent of meningitis and encephalitis is important for patient management and appropriate treatment.

Seroprevalence of Chikungunya virus and living conditions in Feira de Santana, Bahia-Brazil.

BACKGROUND: Chikungunya is an arbovirus, transmitted by Aedes mosquitoes, which emerged in the Americas in 2013 and spread rapidly to almost every country on this continent. In Brazil, where the first cases were detected in 2014, it currently has reached all regions of this country and more than 900,000 cases were reported. The clinical spectrum of chikungunya ranges from an acute self-limiting form to disabling chronic forms. The purpose of this study was to estimate the seroprevalence of chikungunya infection in a large Brazilian city and investigate the association between viral circulation and living condition. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based ecological study in selected Sentinel Areas (SA) through household interviews and a serologic survey in 2016/2017. The sample was of 1,981 individuals randomly selected. The CHIKV seroprevalence was 22.1% (17.1 IgG, 2.3 IgM, and 1.4 IgG and IgM) and varied between SA from 2.0% to 70.5%. The seroprevalence was significantly lower in SA with high living conditions compared to SA with low living condition. There was a positive association between CHIKV seroprevalence and population density (r = 0.2389; p = 0.02033). CONCLUSIONS/SIGNIFICANCE: The seroprevalence in this city was 2.6 times lower than the 57% observed in a study conducted in the epicentre of the CHIKV epidemic of this same urban centre. So, the herd immunity in this general population, after four years of circulation of this agent is relatively low. It indicates that CHIKV transmission may persist in that city, either in endemic form or in the form of a new epidemic, because the vector infestation is persistent. Besides, the significantly lower seroprevalences in SA of higher Living Condition suggest that beyond the surveillance of the disease, vector control and specific actions of basic sanitation, the reduction of the incidence of this infection also depends on the improvement of the general living conditions of the population.

Risk of chronic arthralgia and impact of pain on daily activities in a cohort of patients with chikungunya virus infection from Brazil.

OBJECTIVES: To investigate risk factors for persistent arthralgia in patients with chikungunya, and describe its impact on daily activities. METHODS: From September 2014 to July 2016, a surveillance study enrolled patients with acute febrile illness in Salvador, Brazil, and detected those with chikungunya virus infection using IgM enzyme-linked immunosorbent assay or reverse transcriptase polymerase chain reaction. Telephone follow-ups were performed to ascertain the progression of disease. RESULTS: Of 153 followed cases, 65 (42.5%) reported chronic arthralgia that lasted >3 months, and 47 (30.7%) were still symptomatic at the time of the interview (approximately 1.5 years after symptom onset). Limitations in daily activities and mental distress were reported by 93.8% and 61.5% of those with chronic arthralgia, respectively. Female sex [risk ratio (RR) 1.79, 95% confidence interval (CI) 1.95-2.69] and age (RR 1.02 for each 1-year increase, 95% CI 1.01-1.03) were independent risk factors for chronic arthralgia. Chronic arthralgia was not associated with co-infection with dengue virus (RR 0.97, 95% CI 0.48-1.94) or chikungunya viral load at diagnosis (median chikungunya virus RNA of 5.60 and 5.52 log10 copies/µL for those with and without chronic arthralgia, respectively; P = 0.75). CONCLUSIONS: These findings reinforce the high frequency of chronic chikungunya arthralgia, and highlight the substantial disability associated with the persistence of pain. Development of novel strategies to mitigate the transmission of chikungunya virus and to provide long-term medical assistance for patients with chikungunya are needed urgently.

Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers.

BACKGROUND: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term. METHODS: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database. RESULTS: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p <0.0001)), and blood type A (OR 4.8 (p = 0.002)). SARS-CoV-2 antibodies were signifcantly lower in recurrent patients after initial COVID-19  (2.4 ±â€¯0.610; p<0.0001) and after recurrence (6.4 ±â€¯11.34; p = 0.007).  Virus genome sequencing identified reinfection by a different isolate in one patient. CONCLUSIONS: This is the first detailed case series showing COVID-19 recurrence with qRT-PCR positivity. For one individual detection of phylogenetically distinct genomic sequences in the first and second episodes confirmed bona fide renfection, but in most cases the data do not formally distinguish between reinfection and re-emergence of a chronic infection reservoir. These episodes were significantly associated with reduced Ab response during initial disease and argue the need for ongoing vigilance without an assumption of protection after a first episode.

SARS-CoV-2 infection in pregnant women and newborns in two maternity hospitals in Salvador-Bahia, Brazil

ABSTRACT The outbreak of the new coronavirus (SARS-CoV-2) causing the coronavirus disease (COVID-19) has spread globally. As of June 18, 2020, a high maternal mortality rate due to SARS-CoV-2 infections was identified in Brazil, representing most of the world cases at that time. An observational, cross-sectional study was performed with pregnant women admitted in two maternity hospitals located in Salvador/Bahia and their newborns, from May 24th up to July 17th of 2020. Among 329 pregnant women enrolled at hospital admission, a high prevalence (n=28; 8.5%) of pregnant women with COVID-19 was observed, as well as a high proportion of asymptomatic cases (n=19; 67.9%). Two newborns had detectable SARS-CoV-2 but evolved without abnormalities. This data highlight the importance of identifying pregnant women with COVID-19 for proper isolation measures to prevent in-hospital transmission.

Betulinic Acid Exerts Cytoprotective Activity on Zika Virus-Infected Neural Progenitor Cells.

Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barré syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2+ NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2+ and Casp3+ NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs.

Clinical and laboratory findings of acute Zika virus infection in patients from Salvador during the first Brazilian epidemic

Abstract Several major epidemics of Zika fever, caused by the ZIKA virus (ZIKV), have emerged in Brazil since early 2015, eventually spreading to other countries on the South American continent. The present study describes the clinical manifestations and laboratory findings of patients with confirmed acute ZIKV infection during the first epidemic that occurred in Salvador, Brazil. All included patients were seen at the emergency room of a private tertiary hospital located in Salvador, Brazil from 2015 through 2017. Patients were considered eligible if signs of systemic viral febrile disease were present. All individuals were tested for ZIKV and Chikungunya infection using PCR, while rapid test was used to detect Dengue virus antibodies or, alternatively, the NS1 antigen. A diagnosis of acute ZIKV infection was confirmed in 78/434 (18%) individuals with systemic viral febrile illness. Positivity was mainly observed in blood, followed by saliva and urine. Coinfection with Chikungunya and/or Dengue virus was detected in 5% of the ZIKV-infected patients. The most frequent clinical findings were myalgia, arthralgia and low-grade fever. Laboratory analysis demonstrated normal levels of hematocrit, platelets and liver enzymes. In summary, in acute settings where molecular testing remains unavailable, clinicians face difficulties to confirm the diagnosis of ZIKV infection, as they rely only on clinical examinations and conventional laboratory tests.

Clinical and laboratory findings of acute Zika virus infection in patients from Salvador during the first Brazilian epidemic.

Several major epidemics of Zika fever, caused by the ZIKA virus (ZIKV), have emerged in Brazil since early 2015, eventually spreading to other countries on the South American continent. The present study describes the clinical manifestations and laboratory findings of patients with confirmed acute ZIKV infection during the first epidemic that occurred in Salvador, Brazil. All included patients were seen at the emergency room of a private tertiary hospital located in Salvador, Brazil from 2015 through 2017. Patients were considered eligible if signs of systemic viral febrile disease were present. All individuals were tested for ZIKV and Chikungunya infection using PCR, while rapid test was used to detect Dengue virus antibodies or, alternatively, the NS1 antigen. A diagnosis of acute ZIKV infection was confirmed in 78/434 (18%) individuals with systemic viral febrile illness. Positivity was mainly observed in blood, followed by saliva and urine. Coinfection with Chikungunya and/or Dengue virus was detected in 5% of the ZIKV-infected patients. The most frequent clinical findings were myalgia, arthralgia and low-grade fever. Laboratory analysis demonstrated normal levels of hematocrit, platelets and liver enzymes. In summary, in acute settings where molecular testing remains unavailable, clinicians face difficulties to confirm the diagnosis of ZIKV infection, as they rely only on clinical examinations and conventional laboratory tests.