Effect of a Structured Multilevel Telehealth Service on Hospital Admissions and Mortality During COVID-19 in a Resource-Limited Region in Brazil: Retrospective Cohort Study.

BACKGROUND: The COVID-19 pandemic represented a great stimulus for the adoption of telehealth and many initiatives in this field have emerged worldwide. However, despite this massive growth, data addressing the effectiveness of telehealth with respect to clinical outcomes remain scarce. OBJECTIVE: The aim of this study was to evaluate the impact of the adoption of a structured multilevel telehealth service on hospital admissions during the acute illness course and the mortality of adult patients with flu syndrome in the context of the COVID-19 pandemic. METHODS: A retrospective cohort study was performed in two Brazilian cities where a public COVID-19 telehealth service (TeleCOVID-MG) was deployed. TeleCOVID-MG was a structured multilevel telehealth service, including (1) first response and risk stratification through a chatbot software or phone call center, (2) teleconsultations with nurses and medical doctors, and (3) a telemonitoring system. For this analysis, we included data of adult patients registered in the Flu Syndrome notification databases who were diagnosed with flu syndrome between June 1, 2020, and May 31, 2021. The exposed group comprised patients with flu syndrome who used TeleCOVID-MG at least once during the illness course and the control group comprised patients who did not use this telehealth service during the respiratory illness course. Sociodemographic characteristics, comorbidities, and clinical outcomes data were extracted from the Brazilian official databases for flu syndrome, Severe Acute Respiratory Syndrome (due to any respiratory virus), and mortality. Models for the clinical outcomes were estimated by logistic regression. RESULTS: The final study population comprised 82,182 adult patients with a valid registry in the Flu Syndrome notification system. When compared to patients who did not use the service (n=67,689, 82.4%), patients supported by TeleCOVID-MG (n=14,493, 17.6%) had a lower chance of hospitalization during the acute respiratory illness course, even after adjusting for sociodemographic characteristics and underlying medical conditions (odds ratio [OR] 0.82, 95% CI 0.71-0.94; P=.005). No difference in mortality was observed between groups (OR 0.99, 95% CI 0.86-1.12; P=.83). CONCLUSIONS: A telehealth service applied on a large scale in a limited-resource region to tackle COVID-19 was related to reduced hospitalizations without increasing the mortality rate. Quality health care using inexpensive and readily available telehealth and digital health tools may be delivered in areas with limited resources and should be considered as a potential and valuable health care strategy. The success of a telehealth initiative relies on a partnership between the involved stakeholders to define the roles and responsibilities; set an alignment between the different modalities and levels of health care; and address the usual drawbacks related to the implementation process, such as infrastructure and accessibility issues.

A new paradigm for leprosy diagnosis based on host gene expression.

Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 (IDO1) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.

COVID-19 Telehealth Service Can Increase Access to the Health Care System and Become a Cost-Saving Strategy.

Introduction: Data addressing the economic aspects of telehealth initiatives are incipient. This study aimed to evaluate the labor costs for running a COVID-19 telehealth system and its potential incremental access to health care service. Methods: From July 2020 to July 2021, data from a Brazilian teleconsultation service were analyzed. Labor costs were estimated by time-driven activity-based costing. A Generalized Reduced Gradient solving method was coded to maximize the mean incremental access rate and two scenarios were considered to compare the teleconsultation with the in-person consultation: (1) only the length of time that patients spent with a clinician in an in-person consultation was accounted and (2) in addition to the medical consultation, nursing screening was accounted. The mean incremental access rate of the teleconsultation service was defined as a maximization objective in the model. Results: Mean labor costs per medical and nursing teleconsultations are Int$ 24 and Int$ 10, based on data analyses from 25,258 patients. Telemonitoring a patient with a daily call for 7 days costs, on average, Int$ 14. COVID-19 teleconsultation service represents, on average, an incremental access to medical consultation rate of 35% to 52% (min 23% max 63%) for the scenarios (1) and (2), respectively, and considering the current consumed budget for this service. Discussion: A COVID-19 telehealth service contributes to increasing access to the health care system without increasing costs. These services can be included in the bundle of care strategies offered in a national public health care system that looks for more sustainable strategies to provide care.

Elevated Pentraxin-3 Concentrations in Patients With Leprosy: Potential Biomarker of Erythema Nodosum Leprosum.

Background: Leprosy, the leading infectious cause of disability worldwide, remains a major public health challenge in the most severely affected countries despite the sharp decline in new cases in recent years. The search for biomarkers is essential to achieve a better understanding of the molecular and cellular mechanisms underlying the disease. Methods: Pentraxin-3 (PTX3) analyses of sera from 87 leprosy patients with or without reactions were conducted via enzyme-linked immunosorbent assay. In situ identification of PTX3 in skin lesion was confirmed by quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and immunofluorescence assays. Results: We found that PTX3 serum levels were higher in multibacillary patients when evaluated before the onset of acute erythema nodosum leprosum (ENL) and persistently elevated during reaction. Thalidomide treatment reduced PTX3 in the serum 7 days after starting treatment. In situ analyses have also demonstrated enhancement of PTX3 in ENL lesions and showed that treatment with thalidomide reduced its expression and the prominent neutrophilic infiltrate, a hallmark of the disease. Conclusions: In summary, our study provides in vivo evidence that PTX3 is enhanced during ENL but not in reversal reaction and provides a new molecular target in ENL pathogenesis.

Diversity and associations between Drosophilidae (Diptera) species and Basidiomycetes in a Neotropical forest.

Drosophilidae is one of the most representative families of insects that occurs in fungal fruiting bodies of Basidiomycetes; however, the diversity and community structure of mycophagous Drosophilidae in the Neotropical region is poorly known. The aims of the present study were to describe the diversity of mycophagous Drosophilidae and to investigate its colonization of fungal hosts in a forest of southern Brazil. From 120 fungal samples (patches of mushrooms) of 17 Basidiomycetes genera, flies were recorded emerging from 70 samples and collected in adult stages of 25 fungal samples, for a total of 4897 drosophilids belonging to 31 species and 5 genera. Drosophila Fallén was the most species-rich genus, whereas Hirtodrosophila Duda was the dominant genus. Studies performed in the Holarctic region indicate that mycophagous drosophilid have generalist habits; however, our results showed that most drosophilids use fewer than two fungal hosts, and most species of Hirtodrosophila and Leucophenga were restricted to abundant fungal species, suggesting a specialization for these resources. The most specialized fauna emerged from Auricularia, which was the most frequent fungal genus in our collection, and this result supports the assumption that specialization depends on the availability of fungal resources over time.

Whole blood transcriptomics reveals the enrichment of neutrophil activation pathways during erythema nodosum leprosum reaction.

Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.

Clinical and electrocardiographic outcomes evaluated by telemedicine of outpatients with clinical suspicion of COVID-19 treated with chloroquine compounds in Brazil†.

Aims: To evaluate clinical and electrocardiographic outcomes of patients with COVID-19, comparing those using chloroquine compounds (chloroquine) to individuals without specific treatment. Methods: Outpatients with suspected COVID-19 in Brazil who had at least one tele-electrocardiography (ECG) recorded in a telehealth system were enrolled in two arms (Group 1: chloroquine and Group 2: without specific treatment) and one registry (Group 3: other treatments). Outcomes were assessed through follow-up calls (phone contact, days 3 and 14) and linkage to national mortality and hospitalization databases. The primary outcome was composed of: hospitalization, intensive care admission, mechanical ventilation, and all-cause death, and the ECG outcome was the occurrence of major abnormalities by the Minnesota code. Significant variables in univariable logistic regression were included in 4 models: 1-unadjusted; 2-adjusted for age and sex; 3-model 2 + cardiovascular risk factors and 4-model 3 + COVID-19 symptoms. Results: In 303 days, 712 (10.2%) patients were allocated in group 1, 3,623 (52.1%) in group 2 and 2,622 (37.7%) in group 3; 1,969 had successful phone follow-up (G1: 260, G2: 871, and G3: 838). A late follow-up ECG was obtained for 917 (27.2%) patients [group 1: 81 (11.4%), group 2: 512 (14.1%), group 3: 334 (12.7%)]. In adjusted models, chloroquine was independently associated with greater chance of the composite clinical outcome: phone contact (model 4): OR = 3.24 (95% CI 2.31-4.54), p < 0.001. Chloroquine was also independently associated with higher mortality, assessed by phone + administrative data (model 3): OR = 1.67 (95% CI 1.20-2.28). However, chloroquine did not associate with the occurrence of major ECG abnormalities [model 3; OR = 0.80 (95% CI 0.63-1.02, p = 0.07)]. Abstracts with partial results of this work was accepted in the American Heart Association Scientific Sessions, November 2022, in Chicago, IL, USA. Conclusion: Chloroquine was associated with a higher risk of poor outcomes in patients suspected to have COVID-19 when compared to those who received standard care. Follow-up ECGs were obtained in only 13.2% of patients and did not show any significant differences in major abnormalities amongst the three groups. In the absence of early ECG changes, other side effects, late arrhythmias or deferral of care may be hypothesized to explain the worse outcomes.

Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy.

Peripheral neuropathy is the main cause of physical disability in leprosy patients. Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

Gene expression patterns associated with multidrug therapy in multibacillary leprosy.

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

Oligomeric α-Synuclein induces skin degeneration in reconstructed human epidermis.

Aged and photoaged skin exhibit fine wrinkles that are signs of epidermal inflammation and degeneration. It has been shown that healthy elderly skin expresses amyloidogenic proteins, including α-Synuclein, which are known to oligomerize and trigger inflammation and neurodegeneration. However, little is known about their putative role in skin physiology and sensitivity. To unravel this possible role, we investigated the impact of oligomeric α-Synuclein (Oα-Syn) in 2D and 3D keratinocyte human models. Exogenous Oα-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. Oα-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1ß and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1ß inhibitor partially diminished RHE degeneration caused by Oα-Syn. These findings suggest that Oα-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging.

Arginase 1 is a marker of protection against illness in contacts of leprosy patients.

Leprosy household contacts are generally more prone to develop the disease compared to the general population. Previous studies have demonstrated that genes related to the alternative activation (M2) profile in macrophages are associated with the increased bacillary load in multibacillary leprosy patients (MB), and that contacts of MB patients have a higher risk of contracting the disease. In addition, positive serological responses to PGL-1 or LID-1 are associated with a higher risk of disease. We performed a 5-year follow-up of contacts of leprosy patients and evaluated the pattern of gene and protein expression in cells from contacts that developed leprosy during this period. Leprosy household contacts had decreased soluble CD163 and heme oxygenase 1 (HO-1) serum levels when compared with healthy donors and leprosy patients. In contrast, arginase 1 activities were higher in contacts when compared with both healthy donors and leprosy patients. Of the contacts, 33 developed leprosy during the follow-up. Gene expression analysis revealed reduced ARG1 expression in these contacts when compared with contacts that did not develop disease. Arginase activity was a good predictive marker of protection in contacts (sensitivity: 90.0%, specificity: 96.77%) and the association with serology for anti-PGL-1 and anti-LID-1 increased the sensitivity to 100%. Altogether, the data presented here demonstrate a positive role of arginase against leprosy and suggest that the evaluation of arginase activity should be incorporated into leprosy control programs in order to aid in the decision of which contacts should receive chemoprophylaxis.

The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum.

In leprosy patients, acute inflammatory episodes, known as erythema nodosum leprosum (ENL), are responsible for high morbidity and tissue damage that occur during the course of Mycobacterium leprae infection. In a previous study, we showed evidence implicating DNA-sensing via TLR9 as an important inflammatory pathway in ENL. A likely important consequence of TLR9 pathway activation is the production of type I interferons (IFN-I) by plasmacytoid dendritic cells (pDCs), also implicated in the pathogenesis of several chronic inflammatory diseases. In this study, we investigated whether the IFN-I pathway is activated during ENL. Blood samples and skin lesions from multibacillary patients diagnosed with ENL were collected and the expression of genes of the IFN-I pathway and interferon-stimulated genes were compared with samples collected from non-reactional multibacillary (NR) patients. Whole blood RNAseq analysis suggested higher activation of the IFN-I pathway in ENL patients, confirmed by RT-qPCR. Likewise, significantly higher mRNA levels of IFN-I-related genes were detected in ENL skin biopsies when compared to NR patient lesions. During thalidomide administration, the drug of choice for ENL treatment, a decrease in the mRNA and protein levels of some of these genes both in the skin and blood was observed. Indeed, in vitro assays showed that thalidomide was able to block the secretion of IFN-I by peripheral blood mononuclear cells in response to M. leprae sonicate or CpG-A, a TLR9 ligand. Finally, the decreased frequencies of peripheral pDCs in ENL patients, along with the higher TLR9 expression in ENL pDCs and the enrichment of CD123+ cells in ENL skin lesions, suggest the involvement of these cells as IFN-I producers in this type of reaction. Taken together, our data point to the involvement of the pDC/type I IFN pathway in the pathogenesis of ENL, opening new avenues in identifying biomarkers for early diagnosis and new therapeutic targets for the better management of this reactional episode.

Synchronous Teleconsultation and Monitoring Service Targeting COVID-19: Leveraging Insights for Postpandemic Health Care.

BACKGROUND: Although a great number of teleconsultation services have been developed during the COVID-19 pandemic, studies assessing usability and health care provider satisfaction are still incipient. OBJECTIVE: This study aimed to describe the development, implementation, and expansion of a synchronous teleconsultation service targeting patients with symptoms of COVID-19 in Brazil, as well as to assess its usability and health care professionals' satisfaction. METHODS: This mixed methods study was developed in 5 phases: (1) the identification of components, technical and functional requirements, and system architecture; (2) system and user interface development and validation; (3) pilot-testing in the city of Divinópolis; (4) expansion in the cities of Divinópolis, Teófilo Otoni, and Belo Horizonte for Universidade Federal de Minas Gerais faculty and students; and (5) usability and satisfaction assessment, using Likert-scale and open-ended questions. RESULTS: During pilot development, problems contacting users were solved by introducing standardized SMS text messages, which were sent to users to obtain their feedback and keep track of them. Until April 2022, the expanded system served 31,966 patients in 146,158 teleconsultations. Teleconsultations were initiated through chatbot in 27.7% (40,486/146,158) of cases. Teleconsultation efficiency per city was 93.7% (13,317/14,212) in Teófilo Otoni, 92.4% (11,747/12,713) in Divinópolis, and 98.8% (4981/5041) in Belo Horizonte (university campus), thus avoiding in-person assistance for a great majority of patients. In total, 50 (83%) out of 60 health care professionals assessed the system's usability as satisfactory, despite a few system instability problems. CONCLUSIONS: The system provided updated information about COVID-19 and enabled remote care for thousands of patients, which evidenced the critical role of telemedicine in expanding emergency services capacity during the pandemic. The dynamic nature of the current pandemic required fast planning, implementation, development, and updates in the system. Usability and satisfaction assessment was key to identifying areas for improvement. The experience reported here is expected to inform telemedicine strategies to be implemented in a postpandemic scenario.

Endoluminal vacuum therapy for the treatment of complete dehiscence of low colorectal anastomosis.

Video 1Endoluminal vacuum therapy Endo-SPONGE for the treatment of complete dehiscence of low colorectal anastomosis.

Two new species and a new species group of Mycodrosophila Oldenberg, 1914 (Diptera: Drosophilidae) from the Amazon.

There are 130 described species in the genus Mycodrosophila Oldenberg, 1914, distributed across all biogeographic regions. Most of these species show essential mycophagy. Currently, ten species are known from the Neotropical Region, nine of which are found in the Amazon, Atlantic Forest, Cerrado and Pampa biomes of Brazil. In this study, we describe the adult external morphology and structures of male and/or female terminalia for two new species from the Amazon Biome of Brazil. In addition, we propose a new species group, the Mycodrosophila neoprojectans group, encompassing the two new species described here, together with three previously described species from the Neotropics.

SARS-CoV-2 infection of the central nervous system in a 14-month-old child: A case report of a complete autopsy.

BACKGROUND: Neurological and other systemic complications occur in adults with severe COVID-19. Here we describe SARS-CoV-2 infection complicated by neuroinvasion in the post-mortem tissues of a child. METHODS: We performed a complete autopsy of a 14-month-old child who died of COVID-19 pneumonitis. Histological sections of multiple organs were stained with haematoxylin and eosin. Luxol fast blue staining for myelin and immunohistochemistry were performed in selected areas of the brain. The presence of SARS-CoV-2 was investigated by immunostaining with anti-spike protein antibody and by RT-qPCR. FINDINGS: Lesions included microthrombosis, pulmonary congestion, interstitial oedema, lymphocytic infiltrates, bronchiolar injury, collapsed alveolar spaces, cortical atrophy, and severe neuronal loss. SARS-CoV-2 staining was observed along the apical region of the choroid plexus (ChP) epithelium and in ependymal cells of the lateral ventricle, but was restricted to ChP capillaries and vessels in some regions. SARS-CoV-2 infection of brain tissue was confirmed by RT-qPCR in fragments of the ChP, lateral ventricle, and cortex. INTERPRETATION: Our results show multisystemic histopathological alterations caused by SARS-CoV-2 infection and contribute to knowledge regarding the course of fatal COVID-19 in children. Furthermore, our findings of ChP infection and viral neurotropism suggest that SARS-CoV-2 may invade the central nervous system by blood-cerebrospinal fluid barrier disruption. FUNDING: Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ); the National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES), in addition to intramural grants from D'Or Institute for Research and Education. EDITOR'S NOTE: This translation in Portuguese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. RESUMO: Complicações sistêmicas e neurológicas foram descritas em adultos com COVID-19 grave. Neste trabalho, descrevemos a infecção por SARS-CoV-2, incluindo sua neuroinvasão, nos tecidos post-mortem de uma criança. MÉTODOS: Realizamos a autópsia completa de uma criança de 14 meses que morreu de pneumonite por COVID-19. Cortes histológicos de múltiplos órgãos foram corados com Hematoxilina e Eosina. A coloração de Luxol Fast Blue para mielina e imuno-histoquímica foram realizadas em áreas selecionadas do cérebro. A presença de SARS-CoV-2 foi investigada por imunomarcação com anticorpo anti-proteína spike e por RT-qPCR. ACHADOS: As lesões incluíram microtrombose, congestão pulmonar, edema intersticial, infiltrados linfocíticos, lesão bronquiolar, colapso dos espaços alveolares, atrofia cortical e perda neuronal grave. A presença de SARS-CoV-2 foi observada ao longo da região apical do epitélio do plexo coróide (PC) e nas células ependimárias do ventrículo lateral, mas ficou restrita aos capilares e vasos do PC em outras regiões. A infecção do tecido cerebral por SARS-CoV-2 foi confirmada por RT-qPCR em fragmentos do PC, ventrículo lateral e cortex cerebral. INTERPRETAÇÃO: Nossos resultados mostram alterações histopatológicas multissistêmicas causadas pela infecção por SARS-CoV-2 e contribuem para ampliar o conhecimento sobre a evolução da COVID-19 fatal em crianças. Além disso, nossos achados sobre a infecção no PC e neurotropismo viral sugerem que o SARS-CoV-2 pode invadir o sistema nervoso central pela ruptura da barreira sangue-líquido cefalorraquidiano. FINANCIAMENTO: Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) e Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), além de financiamento intramural do Instituto D'Or de Pesquisa e Educação.

Potential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients.

The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.

Spatial analysis of leisure-time physical activity in an urban area.

OBJECTIVE: To analyze the spatial distribution of the prevalence of leisure-time physical activity (LTPA) in a Brazilian urban area and its association with the characteristics of the physical and social environments. METHODS: A cross-sectional study conducted with data from the Surveillance System for Risk and Protective Factors for Chronic Diseases from the years 2008-2010, in Belo Horizonte, state of Minas Gerais, Brazil. The outcome was the practice of LTPA and the independent variables were residential and population density, the density of places for physical activity, homicide rates, average family income, and health vulnerability index. The spatial scanning technique was employed to identify clusters with a high prevalence of PA at leisure time. The Mann-Whitney test was used to compare variables inside and outside the cluster. RESULTS: The sample included 5,779 participants, 33.3% (SE = 0.73) of whom reported sufficient PA during leisure time. We identified a significant cluster of a high prevalence of LTPA. After adjustments, the cluster presented a radius of 3,041.99 meters and 603 individuals, and 293 (48.6%) of them reported sufficient LTPA. The probability of performing sufficient LTPA in the cluster was 27% higher (PR = 1.27; p = 0.002) than in the coverage areas of primary healthcare units outside the cluster. There was a higher density of places for LTPA practice, higher population and residential density, and higher family income in the cluster. CONCLUSION: The results evidenced a cluster of high prevalence of LTPA in a privileged physical and socioeconomic environment in Belo Horizonte, even after adjustments, demonstrating that reducing inequalities can increase LTPA.

Presence of Senescent and Memory CD8+ Leukocytes as Immunocenescence Markers in Skin Lesions of Elderly Leprosy Patients.

Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.