Inflammatory and cytotoxic mediators in COVID-19 patients and in ChAdOx1 nCoV-19 (AZD1222) vaccine recipients.

Immunological and cytotoxic mediators are induced in natural infection and are essential for the effectiveness of vaccination. Vaccination is useful to prevent the spread of SARS-CoV-2 and limit the morbidity/mortality of COVID-19. ChAdOx1 nCoV-19 is one of the most widespread vaccines in the world. We compared the detection of anti-S1 SARS-CoV2 IgG and the profile of inflammatory and cytotoxic responses of patients who developed different clinical outcomes of COVID-19 with individuals previously exposed or not to the virus received the first and booster doses of ChAdOx1 nCoV-19. Plasma from 35 patients with COVID-19 and 11 vaccinated were evaluated by multiplex assay. Here, no vaccinated subjects had serious adverse effects. Those vaccinated with a booster dose had higher anti-S1 IgG than mild/moderate and recovered patients. Critically ill and deceased patients had IgG levels like those immunized. By univariate analysis, IL-2, IL-17, and perforin do not differentiate between patients and vaccinated individuals. Granzyme A increased at dose 1, while patients had their levels reduced. High levels of granulysin, sFas, and IL-6 were detected in the deaths, but after vaccination, all were declined. The multivariate analysis supports the role of IL-6 and granulysin as associated and non-confounding variables related to the worst clinical outcome of COVID-19, but not sFas. Our data confirm the ability of the ChAdOx1 vaccine to produce specific antibody levels up to booster time. Furthermore, our data suggest that the vaccine can regulate both the hyper-production and the kinetics of the production of inflammatory and cytotoxic mediators involved in the cytokine storm, such as granulysin and IL-6.

Frequency of pleural effusion in dengue patients by severity, age and imaging modality: a systematic review and meta-analysis.

BACKGROUND: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality. METHODS: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue. RESULTS: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023). CONCLUSIONS: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection.

Morphological Aspects and Viremia Analysis of BALB/c Murine Model Experimentally Infected with Dengue Virus Serotype 4.

Ever since its brief introduction in the Brazilian territory in 1981, dengue virus serotype 4 (DENV-4) remained absent from the national epidemiological scenario for almost 25 years. The emergence of DENV-4 in 2010 resulted in epidemics in most Brazilian states. DENV-4, however, remains one of the least studied among the four DENV serotypes. Despite being known as a mild serotype, DENV-4 is associated with severe cases and deaths and deserves to be investigated; however, the lack of suitable experimental animal models is a limiting factor for pathogenesis studies. Here, we aimed to investigate the susceptibility and potential tropism of DENV-4 for liver, lung and heart of an immunocompetent mice model, and to evaluate and investigate the resulting morphological and ultrastructural alterations upon viral infection. BALB/c mice were inoculated intravenously with non-neuroadapted doses of DENV-4 isolated from a human case. The histopathological analysis of liver revealed typical alterations of DENV, such as microsteatosis, edema and vascular congestion, while in lung, widespread areas of hemorrhage and interstitial pneumonia were observed. While milder alterations were present in heart, characterized by limited hemorrhage and discrete presence of inflammatory infiltrate, the disorganization of the structure of the intercalated disc is of particular interest. DENV-4 RNA was detected in liver, lung, heart and serum of BALB/c mice through qRT-PCR, while the NS3 viral protein was observed in all of the aforementioned organs through immunohistochemistry. These findings indicate the susceptibility of the model to the serotype and further reinforce the usefulness of BALB/c mice in studying the many alterations caused by DENV.

Chikungunya virus Detection in Aedes aegypti and Culex quinquefasciatus during an Outbreak in the Amazon Region.

Chikungunya virus (CHIKV) was first reported in Brazil in 2014 and, after it spread countrywide, an outbreak of febrile illness with reports of arthralgia happened in the municipality of Xinguara, Pará, Brazil in 2017, indicating the virus' circulation. Here, we aimed to investigate CHIKV in mosquito vectors collected during an active surveillance of virus isolation in cell culture by using molecular detection and viral genome sequencing. A total of 492 Aedes, Culex and Mansonia mosquitoes were collected and separated in 36 pools according to the species and sex, and 22.2% (8/36) were positive. CHIKV was indentified in pools of Ae. aegypti females (n = 5), an Ae. aegypti male (n = 1) and in Culex quinquefasciatus females (n = 2). However, as the mosquitoes' whole bodies were macerated and used for detection, one cannot suggest the role of the latter in the viral transmission. Despite this, vector competence studies must be carried out in the different species to investigate long-term adaptations. Viral genome sequencing has characterized the East-Central-South-African (ECSA) genotype in all positive pools analyzed, corroborating previous reports for the Amazon region.

Dengue Virus Serotype 2 Established in Northern Mozambique (2015-2016).

After the report of an outbreak of dengue virus serotype 2 in 2014 in Nampula and Pemba cities, northern Mozambique, a surveillance system was established by the National Institute of Health. A study was performed during 2015-2016 to monitor the trend of the outbreak and confirm the circulating serotype of dengue virus (DENV). After the inclusion of consenting patients who met the case definition, samples from 192 patients were tested for the presence of nonstructural protein 1 antigen, and 60/192 (31%) samples were positive. Further analysis included DENV IgM antibodies, with 39 (20%) IgM positive cases. Reverse transcriptase (RT) PCR was performed for identification of the prevailing DENV serotype; 21/23 tested samples were DENV-2 positive, with DENV-2 present in both affected cities. When sequencing DENV, phenotype Cosmopolitan was identified. The surveillance indicates ongoing spread of DENV-2 in northern Mozambique 2 years after the first report of the outbreak.

Analysis of Clinical and Laboratory Alterations Related to Dengue Case Severity: Comparison between Serotypes 2 and 4 in Brazil.

The increase in severe dengue (SD) cases has caused great impact on public health and has concerned authorities of countries where the disease is endemic and epidemics reach high proportions. The recognition of progression signs of this severe disease during the initial febrile phase can be difficult, since the symptoms are often indistinguishable from other febrile diseases. The aim of this study was to evaluate the clinical manifestations and laboratory findings in patients from two dengue outbreaks and their association with the disease. The study was conducted in patients (n = 153) with signs and symptoms consistent with dengue occurred during two distinct epidemics, 2010 and 2013, in the city of Campos dos Goytacazes, Rio de Janeiro, Brazil. According to the 2009 World Health Organization criteria, patients were classified as dengue without warning signs ([DwoWS] 60.6%, 57/94), dengue with warning signs ([DwWS] 30.9%, 29/94), and SD (4.25%, 4/94). Patients with DwWS/SD presented lower platelet and leukocyte counts and higher transaminase levels when compared with the DwoWS ones. Interestingly, patients from the epidemic of 2010 caused by dengue virus 2 (DENV-2) had lower platelet counts than patients of the 2013 epidemic caused by DENV-4. Furthermore, plasma leakage, gastrointestinal bleeding, and pleural effusion, hallmarks for a more severe disease, were also more frequently observed in those cases. Although previous studies may have extensively reported the wide range of the clinical aspects of dengue, the characterization of DENV-4 is desirable considering the burden of the disease during epidemics, especially for the health units and hospitals performing patient's management.

Dengue in Latin America: Systematic Review of Molecular Epidemiological Trends.

Dengue, the predominant arthropod-borne viral disease affecting humans, is caused by one of four distinct serotypes (DENV-1, -2, -3 or -4). A literature analysis and review was undertaken to describe the molecular epidemiological trends in dengue disease and the knowledge generated in specific molecular topics in Latin America, including the Caribbean islands, from 2000 to 2013 in the context of regional trends in order to identify gaps in molecular epidemiological knowledge and future research needs. Searches of literature published between 1 January 2000 and 30 November 2013 were conducted using specific search strategies for each electronic database that was reviewed. A total of 396 relevant citations were identified, 57 of which fulfilled the inclusion criteria. All four dengue virus serotypes were present and co-circulated in many countries over the review period (with the predominance of individual serotypes varying by country and year). The number of countries in which more than one serotype circulated steadily increased during the period under review. Molecular epidemiology data were found for Argentina, Bolivia, Brazil, the Caribbean region, Colombia, Ecuador, Mexico and Central America, Paraguay, Peru and Venezuela. Distinct lineages with different dynamics were found in each country, with co-existence, extinction and replacement of lineages occurring over the review period. Despite some gaps in the literature limiting the possibility for comparison, our review has described the molecular epidemiological trends of dengue infection. However, several gaps in molecular epidemiological information across Latin America and the Caribbean were identified that provide avenues for future research; in particular, sequence determination of the dengue virus genome is important for more precise phylogenetic classification and correlation with clinical outcome and disease severity.