Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α.

The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.

Smartphone-based evaluation of static balance and mobility in long-lasting COVID-19 patients.

Background: SARS-CoV-2 infection can lead to a variety of persistent sequelae, collectively known as long COVID-19. Deficits in postural balance have been reported in patients several months after COVID-19 infection. The purpose of this study was to evaluate the static balance and balance of individuals with long COVID-19 using inertial sensors in smartphones. Methods: A total of 73 participants were included in this study, of which 41 had long COVID-19 and 32 served as controls. All participants in the long COVID-19 group reported physical complaints for at least 7 months after SARS-CoV-2 infection. Participants were evaluated using a built-in inertial sensor of a smartphone attached to the low back, which recorded inertial signals during a static balance and mobility task (timed up and go test). The parameters of static balance and mobility obtained from both groups were compared. Results: The groups were matched for age and BMI. Of the 41 participants in the long COVID-19 group, 22 reported balance impairment and 33 had impaired balance in the Sharpened Romberg test. Static balance assessment revealed that the long COVID-19 group had greater postural instability with both eyes open and closed than the control group. In the TUG test, the long COVID-19 group showed greater acceleration during the sit-to-stand transition compared to the control group. Conclusion: The smartphone was feasible to identify losses in the balance motor control and mobility of patients with long-lasting symptomatic COVID-19 even after several months or years. Attention to the balance impairment experienced by these patients could help prevent falls and improve their quality of life, and the use of the smartphone can expand this monitoring for a broader population.

Tratamento de queloides e cicatrizes hipertróficas: Uma revisão descritiva / Treatment of keloids and hypertrophic scars: A descriptive review

Queloides e cicatrizes hipertróficas são lesões formadas a partir da resposta fibroproliferativa anormal ao processo de cicatrização de feridas, gerando uma proliferação excessiva do colágeno nas lesões. Geralmente, predominam em pacientes do sexo feminino e em indivíduos com tons de pele mais escuros. A abordagem terapêutica dessas cicatrizes pode ser indicada de acordo com alguns critérios, como déficit funcional, tamanho e tempo de cicatrização da ferida. Nesse sentido, o presente estudo objetivou realizar uma revisão descritiva da literatura, buscando as evidências de tratamento dos últimos cinco anos neste tema. A revisão foi realizada com base no guideline PRISMA, utilizando as bases de dados PubMed, LILACS, Cochrane Library, SCOPUS, Web of Science e Grey Literature, entre os anos de 2018 e 2022. Foram encontrados 740 artigos, dos quais 16 ensaios clínicos randomizados foram selecionados. Foi evidenciado que manejo do queloide apresenta abordagem multimodal, não havendo um padrão-ouro de tratamento, com taxa de recorrência baixa. Além disso, a terapia combinada de diferentes agentes pareceu ser superior ao uso isolado de métodos terapêuticos no tratamento dessas lesões.

Keloids and hypertrophic scars are lesions formed from the abnormal fibroproliferative response to the wound healing process, generating excessive collagen proliferation in the lesions. They generally predominate in female patients and individuals with darker skin tones. The therapeutic approach to these scars can be indicated according to criteria such as functional deficit, size, and wound healing time. In this sense, the present study aimed to conduct a descriptive review of the literature, seeking evidence of treatment over the last five years. The review was carried out based on the PRISMA guideline, using the databases PubMed, LILACS, Cochrane Library, SCOPUS, Web of Science, and Grey Literature between 2018 and 2022. Seven hundred forty articles were found, of which 16 randomized clinical trials were selected. It was demonstrated that keloid management presents a multimodal approach, with no gold standard of treatment with a low recurrence rate. Furthermore, combined therapy with different agents appeared superior to the isolated therapeutic methods in treating these injuries.

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions.

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-ß, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

Monocytes subpopulations pattern in the acute respiratory syndrome coronavirus 2 virus infection and after long COVID-19.

INTRODUTION AND OBJECTIVE: The present study sought to characterize the pattern of monocyte subpopulations in patients during the course of the infections caused by SARS-CoV-2 virus or who presented long COVID-19 syndrome compared to monocytes from patients with zika virus (Zika) or chikungunya virus (CHIKV). CASUISTRY: Study with 89 peripheral blood samples from patients, who underwent hemogram and serology (IgG and IgM) for detection of Zika (Control Group 1, n = 18) or CHIKV (Control Group 2, n = 9), and from patients who underwent hemogram and reverse transcription polymerase chain reaction for detection of SARS-CoV-2 at the acute phase of the disease (Group 3, n = 19); and of patients who presented long COVID-19 syndrome (Group 4, n = 43). The monocyte and subpopulations counts were performed by flow cytometry. RESULTS: No significant difference was observed in the total number of monocytes between the groups. The classical (CD14++CD16-) and intermediate (CD14+CD16+) monocytes counts were increased in patients with acute infection or with long COVID-19 syndrome. The monocytes subpopulations counts were lower in patients with infection Zika or CHIKV. CONCLUSION: Increase in the monocyte subpopulations in patients with acute infection or with long COVID-19 syndrome may be an important finding of differentiated from the infection Zika or CHIKV.

Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers.

Long COVID is characterized by persistent signs and symptoms that continue or develop for more than 4 weeks after acute COVID-19 infection. Patients with Long COVID experience a cardiovascular autonomic imbalance known as dysautonomia. However, the underlying autonomic pathophysiological mechanisms behind this remain unclear. Current hypotheses include neurotropism, cytokine storms, and inflammatory persistence. Certain immunological factors indicate autoimmune dysfunction, which can be used to identify patients at a higher risk of Long COVID. Heart rate variability can indicate autonomic imbalances in individuals suffering from Long COVID, and measurement is a non-invasive and low-cost method for assessing cardiovascular autonomic modulation. Additionally, biochemical inflammatory markers are used for diagnosing and monitoring Long COVID. These inflammatory markers can be used to improve the understanding of the mechanisms driving the inflammatory response and its effects on the sympathetic and parasympathetic pathways of the autonomic nervous system. Autonomic imbalances in patients with Long COVID may result in lower heart rate variability, impaired vagal activity, and substantial sympathovagal imbalance. New research on this subject must be encouraged to enhance the understanding of the long-term risks that cardiovascular autonomic imbalances can cause in individuals with Long COVID.

Relationship between Determinants of Food Choices and Socioeconomic and Demographic Factors of Individuals with Hepatitis B and C in the Amazon Region.

Knowing the determinants of food choices allows the nutritionist to develop more assertive guidelines considering biopsychosocial factors to produce effective changes in eating practices. This cross-sectional, descriptive, and analytical study aimed to test the correlation between the determinants of food choices and the socioeconomic and demographic factors of individuals with hepatitis B and C. Patients with hepatitis B and/or C aged between 20 and 74 years were evaluated from August 2020 to August 2021. Their socioeconomic and demographic data and clinical data were collected, and The Eating Motivation Survey (TEMS) was applied. A total of 145 individuals were evaluated, with a mean age of 53.54 ± 12.14 years. There were positive weak correlations between gender (p2 = 0.193; p = 0.020) and age (p2 = 0.177; p = 0.033) with the scale "preference"; negative correlations between age and the scales "price" (p2 = -0.204; p = 0.014) and "emotion control" (p2 = -0.168; p = 0.044); negative correlations between education and the scales "convenience" (p2 = -0.172; p = 0.039) and "social norms" (p2 = -0.206; p = 0.013); and income showed a negative correlation with "price" (p2 = -0.208; p = 0.012) and a positive correlation with "weight control" (p2 = 0.186; p = 0.025). These findings contribute to the development of more realistic and feasible eating strategies that favor food autonomy.

Comparative Analysis of Human Hepatic Lesions in Dengue, Yellow Fever, and Chikungunya: Revisiting Histopathological Changes in the Light of Modern Knowledge of Cell Pathology.

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.

Persistent olfactory dysfunction associated with poor sleep quality and anxiety in patients with long COVID.

Introduction: Poor sleep quality have been widely reported in patients with long COVID. Determining the characteristics, type, severity, and relationship of long COVID with other neurological symptoms is essential for the prognosis and management of poor sleep quality. Methods: This cross-sectional study was conducted at a public university in the eastern Amazon region of Brazil between November 2020 and October 2022. The study involved 288 patients with long COVID with self-report neurological symptoms. One hundred thirty-one patients were evaluated by using standardised protocols: Pittsburgh sleep quality index (PSQI), Beck Anxiety Inventory, Chemosensory Clinical Research Center (CCRC), and Montreal Cognitive Assessment (MoCA). This study aimed to describe the sociodemographic and clinical characteristics of patients with long COVID with poor sleep quality and their relationship with other neurological symptoms (anxiety, cognitive impairment, and olfactory disorder). Results: Patients with poor sleep quality were mainly women (76.3%), 44.04 ± 12.73 years old, with >12 years of education (93.1%), and had monthly incomes of up to US $240.00 (54.2%). Anxiety and olfactory disorder were more common in patients with poor sleep quality. Discussion: Multivariate analysis shows that the prevalence of poor sleep quality was higher in patients with anxiety, and olfactory disorder is associated with poor sleep quality. In this cohort of patients with long COVID, the prevalence of poor sleep quality was highest in the group tested by PSQI and were associated with other neurological symptoms, such as anxiety and olfactory dysfunction. A previous study indicates a significant association between poor sleep quality and psychological disorders over time. Recent studies involving neuroimaging found functional and structural changes in Long COVID patients with persistent olfactory disfunction. Poor sleep quality are integral part of complex changes related to Long COVID and should be part of patient's clinical management.

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19.

Introduction: Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19. Methods: Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively. Results: The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed. Discussion: The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.

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.

Headache in long COVID as disabling condition: A clinical approach.

Background and purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can exacerbate previous headache disorders or change the type of pain experienced from headaches. This study aimed to investigate the clinical features of Long COVID headaches. Method: This was a cross-sectional, descriptive, and analytical observational study that included 102 patients (with previous headache, n = 50; without previous headache, n = 52) with long COVID and headache complaints. The Migraine Disability Assessment Test and Visual Analog Pain Scale were used to collect participants' headache data according to a standardized protocol. Results: The patients in this study who reported experiencing headaches before COVID-19 had longer headache duration in the long COVID phase than that in the pre-long COVID phase (p = 0.031), exhibited partial improvement in headache symptoms with analgesics (p = 0.045), and had a duration of long COVID of <1 year (p = 0.030). Patients with moderate or severe disability and those classified as having severe headaches in the long COVID phase were highly likely to develop chronic headaches. Hospital admission [odds ratio (OR) = 3.0082; 95% confidence interval (95% CI): 1.10-8.26], back pain (OR = 4.0017; 95% CI: 1.13-14.17), insomnia (OR = 3.1339; 95% CI: 1.39-7.06), and paraesthesia (OR = 2.7600; 95% CI: 1.20-6.33) were associated with headache in these patients. Conclusion: Headache is a disabling condition in patients with long COVID-19, exacerbating the conditions of those with headaches prior to contracting COVID-19.

Liver Function in Patients with Long-Term Coronavirus Disease 2019 of up to 20 Months: A Cross-Sectional Study.

The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.

Evaluation of the Hematological Patterns from Up to 985 Days of Long COVID: A Cross-Sectional Study.

Long COVID affects many individuals following acute coronavirus disease 2019 (COVID-19), and hematological changes can persist after the acute COVID-19 phase. This study aimed to evaluate these hematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a 'long COVID' clinical care program in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected to quantify erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalized in the acute phase had higher mean red/white blood cell, platelet, and plateletcrit levels and red blood cell distribution width. Furthermore, hematimetric parameters were higher in shorter periods of long COVID than in longer periods. Patients with more than six concomitant long COVID symptoms had a higher white blood cell count, a shorter prothrombin time (PT), and increased PT activity. Our results indicate there may be a compensatory mechanism for erythrogram-related markers within 985 days of long COVID. Increased levels of leukogram-related markers and coagulation activity were observed in the worst long COVID groups, indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.

Thrombophilia and Immune-Related Genetic Markers in Long COVID.

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development.

Antibody Response to the SARS-CoV-2 Spike and Nucleocapsid Proteins in Patients with Different COVID-19 Clinical Profiles.

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.

Metabolic Profile of Patients with Long COVID: A Cross-Sectional Study.

A significant proportion of patients experience a wide range of symptoms following acute coronavirus disease 2019 (COVID-19). Laboratory analyses of long COVID have demonstrated imbalances in metabolic parameters, suggesting that it is one of the many outcomes induced by long COVID. Therefore, this study aimed to illustrate the clinical and laboratory markers related to the course of the disease in patients with long COVID. Participants were selected using a clinical care programme for long COVID in the Amazon region. Clinical and sociodemographic data and glycaemic, lipid, and inflammatory screening markers were collected, and cross-sectionally analysed between the long COVID-19 outcome groups. Of the 215 participants, most were female and not elderly, and 78 were hospitalised during the acute COVID-19 phase. The main long COVID symptoms reported were fatigue, dyspnoea, and muscle weakness. Our main findings show that abnormal metabolic profiles (such as high body mass index measurement and high triglyceride, glycated haemoglobin A1c, and ferritin levels) are more prevalent in worse long COVID presentations (such as previous hospitalisation and more long-term symptoms). This prevalence may suggest a propensity for patients with long COVID to present abnormalities in the markers involved in cardiometabolic health.

Identification of risk areas for arboviruses transmitted by Aedes aegypti in northern Brazil: A One Health analysis.

Introduction: The complex and growing problem generated by the rapid expansion of unplanned urban areas includes high population density and increased infestation by vectors responsible for the transmission of several diseases. This requires interdisciplinary and intersectoral interventions due to the burden of diseases, especially those caused by arboviruses, which can present severe forms and generate significant pressure on health systems, especially in more vulnerable regions. The objective of this study was to analyze the spatial distribution of arboviruses transmitted by Aedes aegypti (dengue, Zika, and chikungunya) and assess their correlations with demographic, social, and environmental data from the state of Tocantins, Brazil. Methods: This was an ecological time series study of the dengue, Zika, and chikungunya arboviruses in the state of Tocantins. Local Moran's indices were used to observe the spatial autocorrelation of cases and to delimit clusters of high and low risks, correlating them with socioenvironmental indicators, in addition to analyses to detect case clusters. Results: The state reported a mean incidence of 591 annual cases of arbovirus infections per 100,000 inhabitants and a stationary trend with seasonal pattern. Female Pardo individuals aged 20-39 years, with an education level of below college education, were the most affected; Palmas and Araguaína, the two largest cities in the state in terms of economy and population, were the most affected. Conclusion: A better understanding of the interaction between social characteristics, the environment, and ecology of wild animals and vectors is important for the development of mechanisms to predict outbreaks as well as to develop strategies to reduce and/or mitigate recurring arboviral epidemics and other diseases.

Dengue fever ophthalmic manifestations: A review and update.

Dengue fever, the most common arbovirus disease, affects an estimated 390 million people annually. Dengue virus (DENV) is an RNA virus of the Flaviviridae family with four different serotypes. Dengue haemorrhagic fever is the deadliest form of dengue infection and is characterised by thrombocytopaenia, hypotension, and the possibility of multi-system organ failure. The mechanism hypothesised for DENV viral replication is intrinsic antibody-dependent enhancement, which refers to Fcγ receptor-mediated viral amplification. This hypothesis suggests that the internalisation of DENV through the Fcγ receptor inhibits antiviral genes by suppressing type-1 interferon-mediated antiviral responses. DENV NS1 antibodies can promote the release of various inflammatory mediators in the nuclear transcription factor pathway (NF-κB-dependent), including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-8. As a result, MCP-1 increases ICAM-1 expression and facilitates leukocyte transmigration. In addition, anti-DENV NS1 antibodies induce endothelial cell apoptosis via a nitric oxide-regulated pathway. A chain reaction involving pre-existing DENV heterotypic antibodies and innate immune cells causes dysfunction in complement system activity and contributes to the action of autoantibodies and anti-endothelial cells, resulting in endothelial cell dysfunction, blood-retinal barrier breakdown, haemorrhage, and plasma leakage. A spectrum of ocular diseases associated with DENV infection, ranging from haemorrhagic to inflammatory manifestations, has been reported in the literature. Although rare, ophthalmic manifestations can occur in both the anterior and posterior segments and are usually associated with thrombocytopenia. The most common ocular complication is haemorrhage. However, ophthalmic complications, such as anterior uveitis and vasculitis, suggest an immune-mediated pathogenesis.

New Insights into the Mechanism of Immune-Mediated Tissue Injury in Yellow Fever: The Role of Immunopathological and Endothelial Alterations in the Human Lung Parenchyma.

Yellow fever (YF) may cause lesions in different organs. There are no studies regarding the in situ immune response in the human lung and investigating immunopathological aspects in fatal cases can help to better understand the evolution of the infection. Lung tissue samples were collected from 10 fatal cases of human yellow fever and three flavivirus-negative controls who died of other causes and whose lung parenchymal architecture was preserved. In YFV-positive fatal cases, the main histopathological changes included the massive presence of diffuse alveolar inflammatory infiltrate, in addition to congestion and severe hemorrhage. The immunohistochemical analysis of tissues in the lung parenchyma showed significantly higher expression of E-selectin, P-selectin, ICAM-1, VCAM-1 in addition to cytokines such as IL-4, IL-10, IL-13, TNF- α, IFN-γ and TGF-ß compared to the negative control. The increase in immunoglobulins ICAM-1 and VCAM-1 results in strengthening of tissue transmigration signaling. E-selectin and P-selectin actively participate in this process of cell migration and formation of the inflammatory infiltrate. IFN-γ and TNF-α participate in the process of cell injury and viral clearance. The cytokines IL-4 and TGF-ß, acting in synergism, participate in the process of tissue regeneration and breakdown. The anti-inflammatory cytokines IL-4, IL-10 and IL-13 also act in the reduction of inflammation and tissue repair. Our study indicates that the activation of the endothelium aggravates the inflammatory response by inducing the expression of adhesion molecules and cytokines that contribute to the rolling, recruitment, migration and eliciting of the inflammatory process in the lung parenchyma, contributing to the fatal outcome of the disease.