Síndrome inflamatória multissistêmica em crianças infectadas por coronavírus: uma revisão integrativa / Multisystemic inflamatory syndrome in children infected by coronavirus: an integrative review / Síndrome inflamatorio multisistémico en niños infectados por coronavirus: una revisión integradora

Durante a pandemia de COVID-19, foram observadas manifestações atípicas em pacientes pediátricos em diversas regiões do mundo, e o conjunto desses sintomas caracterizou uma nova patologia denominada Síndrome Inflamatória Multissistêmica em Crianças (MIS-C), ou Síndrome Inflamatória Multissistêmica Pediátrica Temporariamente associada ao COVID-19 (PIMS- TS). O objetivo desta revisão foi analisar as manifestações clínicas e as possíveis complicações relacionadas a tal quadro inflamatório. Foi realizada uma busca por artigos científicos nas bases de dados Embase, PubMed e Web of Science, por meio da combinação dos descritores "MIS-C", "PIMS- TS" e "COVID-19". Após a análise dos artigos encontrados, e considerando critérios de inclusão e exclusão, foram selecionados 15 estudos para compor esta revisão. A maioria dos estudos mencionaram complicações gastrointestinais, cardiovasculares, respiratórias e mucocutâneas. Ademais, foram encontrados marcadores que indicavam estado inflamatório generalizado e coagulopatia. Assim, concluiu-se que MIS-C provavelmente é uma síndrome manifestada após a infecção por SARS-CoV-2, podendo ocasionar quadros mais graves, mas com baixas taxas de mortalidade.

During the COVID-19 pandemic, atypical manifestations were observed in pediatric patients in different regions of the world, and the set of these symptoms characterized a new pathology called Multisystemic Inflammatory Syndrome in Children (MIS-C), or Pediatric Multisystemic Inflammatory Syndrome Temporarily associated with COVID-19 (PIMS-TS). The purpose of this review was to analyze the clinical manifestations and possible complications related to such an inflammatory condition. A search for scientific articles was carried out in the databases Embase, PubMed and Web of Science, by combining the descriptors "MIS-C", "PIMS-TS" and "COVID-19". After analyzing the articles found, and considering inclusion and exclusion criteria, 15 studies were selected to compose this review. Most studies mentioned gastrointestinal, cardiovascular, respiratory and mucocutaneous complications. In addition, markers were found that indicated generalized inflammatory status and coagulopathy. Thus, it was concluded that MIS-C is probably a syndrome manifested after infection by SARS-CoV-2, which can cause more severe conditions, but with low mortality rates.

Durante la pandemia de COVID-19 se observaron manifestaciones atípicas en pacientes pediátricos de diferentes regiones del mundo, y el conjunto de estos síntomas caracterizó una nueva patología denominada Síndrome Inflamatorio Multisistémico en Niños (SMI-C), o Síndrome Inflamatorio Multisistémico Pediátrico Asociado Temporalmente a COVID-19 (SIPM-TS). El propósito de esta revisión fue analizar las manifestaciones clínicas y las posibles complicaciones relacionadas con dicha condición inflamatoria. Se realizó una búsqueda de artículos científicos en las bases de datos Embase, PubMed y Web of Science, combinando los descriptores "MIS-C", "PIMS- TS" y "COVID-19". Tras analizar los artículos encontrados, y teniendo en cuenta los criterios de inclusión y exclusión, se seleccionaron 15 estudios para componer esta revisión. La mayoría de los estudios mencionaron complicaciones gastrointestinales, cardiovasculares, respiratorias y mucocutáneas. Además, se encontraron marcadores que indicaban un estado inflamatorio generalizado y coagulopatía. Así pues, se concluyó que el SMI-C es probablemente un síndrome que se manifiesta tras la infección por el SARS-CoV-2, que puede causar cuadros más graves, pero con bajas tasas de mortalidad.

Perfil epidemiológico de óbitos decorrentes da Covid-19 em um município do sudoeste do Paraná / Epidemiological profile of death resulting from Covid-19 in a municipality in southwest of Paraná / Perfil epidemiológico de las muertes por Covid-19 en un municipio del suroeste de Paraná

Introdução: No final do ano de 2019 surgiu na China uma doença infectocontagiosa de característica respiratória e alto grau de disseminação até então desconhecida. No Brasil o primeiro caso de Covid-19 foi confirmado no final de fevereiro de 2020 e a primeira morte em meados de março. Segundo dados da plataforma Coronavírus Brasil, em 17 de março de 2021, houve registro de 11.603.535 casos confirmados e 282.127 óbitos. Objetivo: Descrever o perfil de pessoas que morreram tendo como causa básica do óbito a Covid-19, em um município do Sudoeste do Paraná, entre os anos de 2020 e 2021. Metodologia: Trata-se de um estudo transversal, descritivo, documental de caráter quantitativo que foi realizado na prefeitura municipal de Francisco Beltrão. Resultados: Houve prevalência de óbitos em pacientes do sexo masculino, idosos, com presença de alguma comorbidade associada, sendo hipertensão a mais citada (50,8%). Os sintomas mais prevalentes foram tosse (74,4%), dispneia (56,3%) e saturação < 95% (48,3%), necessitando ainda de hospitalização em algum período da doença (94,1%), sendo os leitos de Sistema Único de Saúde os mais procurados (74,4%). Quanto à taxa de ocupação 49,6% dos casos necessitou apenas de leitos de enfermaria e 42% unidades de terapia intensiva. Discussão: Diversas pesquisas apontam que o sexo masculino é o mais acometido por condições graves de saúde, devido à demora na busca de assistência médica. No que se refere à idade, neste estudo, a prevalência de óbitos se deu entre 71 e 75 anos (15,1%) o que justifica que o envelhecimento é um fator de risco elevado para complicações da doença. Durante a análise dos dados, notou- se que grande parte dos pacientes que tiveram como desfecho o óbito, possuíam algum fator associado, dentre os mais citados, verificou-se a Hipertensão Arterial Sistêmica (50,8%) Diabetes Mellitus (24,8%), doenças cardiovasculares (23,9%) e obesidade (14,7%). No que diz respeito à hospitalização, nesse estudo notou-se que 74,4% da amostra foram hospitalizadas em leitos de SUS, 18,5% em hospitais particulares e 7,1% não possuíam essa informação. Conclusão: É possível observar a importância do estudo epidemiológico para identificar o perfil da população em risco, podendo auxiliar no planejamento do atendimento, rastreamento e controle da doença, além de conhecer a evolução da patologia, a fim de buscar ações adequadas para seu enfrentamento.

Introduction: At the end of 2019, a previously unknown infectious disease with respiratory characteristics and a high degree of dissemination emerged in China. In Brazil the first case of Covid-19 was confirmed in late February 2020 and the first death in mid-March. According to data from the Coronavirus Brazil platform, as of March 17, 2021, 11,603,535 confirmed cases and 282,127 deaths were recorded. Objective: To describe the profile of people who died with Covid-19 as the underlying cause of death in a city in southwestern Paraná between the years 2020 and 2021. Methodology: This is a cross-sectional, descriptive, documental, quantitative study carried out at the Francisco Beltrão City Hall. Results: There was a prevalence of deaths in male patients, elderly, with the presence of some associated comorbidity, hypertension being the most cited (50.8%). The most prevalent symptoms were cough (74.4%), dyspnea (56.3%) and saturation < 95% (48.3%), requiring hospitalization in some period of the disease (94.1%), and the Unified Health System beds were the most sought (74.4%). As for the occupancy rate, 49.6% of the cases required only ward beds and 42% intensive care units. Discussion: Several studies show that men are the most affected by serious health conditions, due to the delay in seeking medical assistance. Regarding age, in this study, the prevalence of deaths was between 71 and 75 years (15.1%), which justifies that aging is a high risk factor for disease complications. During data analysis, it was noted that most patients who died had some associated factor, among the most cited were systemic arterial hypertension (50.8%), diabetes mellitus (24.8%), cardiovascular diseases (23.9%) and obesity (14.7%). Regarding hospitalization, in this study it was noted that 74.4% of the sample were hospitalized in SUS beds, 18.5% in private hospitals, and 7.1% did not have this information. Conclusion: It is possible to observe the importance of the epidemiological study to identify the profile of the population at risk, which can help in planning care, tracking and control of the disease, besides knowing the evolution of the pathology in order to seek appropriate actions for its confrontation

Introducción: A finales del año 2019 apareció en China una enfermedad infecto- contagiosa de característica respiratoria y alto grado de diseminación desconocida hasta entonces. En Brasil se confirmó el primer caso de Covid-19 a finales de febrero de 2020 y la primera muerte a mediados de marzo. Según los datos de la plataforma Coronavirus Brasil, hasta el 17 de marzo de 2021, había 11.603.535 casos confirmados y 282.127 muertes. Objetivo: Describir el perfil de las personas fallecidas con Covid-19 como causa subyacente de muerte en una ciudad del sudoeste de Paraná entre los años 2020 y 2021. Metodología: Se trata de un estudio transversal, descriptivo, documental de carácter cuantitativo que se realizó en la prefectura municipal de Francisco Beltrão. Resultados: Hubo una prevalencia de muertes en pacientes masculinos, de edad avanzada, con presencia de alguna comorbilidad asociada, siendo la hipertensión la más citada (50,8%). Los síntomas más prevalentes fueron la tos (74,4%), la disnea (56,3%) y la saturación < 95% (48,3%), requiriendo hospitalización en algún periodo de la enfermedad (94,1%), siendo las camas del Sistema Único de Salud las más solicitadas (74,4%). En cuanto a la tasa de ocupación, el 49,6% de los casos sólo necesitaban camas de sala y el 42% unidades de cuidados intensivos. Discusión: Varias investigaciones señalan que el género masculino es el más afectado por las condiciones de salud graves, debido al retraso en la búsqueda de asistencia médica. En cuanto a la edad, en este estudio, la prevalencia de muertes se produjo entre los 71 y los 75 años (15,1%), lo que justifica que el envejecimiento sea un factor de riesgo elevado para las complicaciones de la enfermedad. Durante el análisis de los datos, se observó que la mayoría de los pacientes que fallecieron tenían algún factor asociado, entre los más citados estaban la Hipertensión Arterial Sistémica (50,8%), la Diabetes Mellitus (24,8%), las enfermedades cardiovasculares (23,9%) y la obesidad (14,7%). En lo que respecta a la hospitalización, en este estudio se observó que el 74,4% de la muestra estaba hospitalizada en camas del SUS, el 18,5% en hospitales privados y el 7,1% no tenía esta información. Conclusión: Es posible observar la importancia del estudio epidemiológico para identificar el perfil de la población en riesgo, pudiendo ayudar en la planificación de la atención, el rastreo y el control de la enfermedad, además de conocer la evolución de la patología, con el fin de buscar las acciones adecuadas para su enfrentamiento.

Systemic administration of glucocorticoids, cardiovascular complications and mortality in patients hospitalised with COVID-19, SARS, MERS or influenza: A systematic review and meta-analysis of randomised trials.

BACKGROUND: Administration of glucocorticoids might reduce mortality in patients with severe COVID-19 but have adverse cardiometabolic effects. OBJECTIVES: to investigate the effect of systemic administration of glucocorticoids on cardiovascular complications and all-cause mortality in patients hospitalised with respiratory viral infections, including COVID-19, SARS, MERS and influenza. METHODS: We identified randomised trials published prior to July 28th, 2021. The Mantel-Haenszel random effects method and the Hartung and Knapp adjustment were used to obtain pooled estimates of treatment effect with 95% confidence intervals. RESULTS: No randomised trials of glucocorticoids for SARS, MERS or influenza reported relevant outcomes. We included eleven COVID-19 randomised trials (8109 patients). Overall, compared to placebo or standard care, glucocorticoids were not associated with a reduction of in-hospital mortality (p = 0.09). In a pre-specified sub-analysis, in-hospital mortality was reduced by 19% when follow-up was restricted to 14 days from randomisation (5/11 trials, 1329 patients, p = 0.02). With longer follow-up (9/11 trials, 7874 patients), administration of glucocorticoids was associated with a trend to benefit for those requiring mechanical ventilation (RR 0.86; 95% CI 0.57-1.27) but possible harm for those not receiving oxygen at randomisation (RR 1.27; 95% CI 1.00 - 1.61), an effect that was significantly different amongst subgroups (p = 0.0359). Glucocorticoids reduced the risk of worsening renal function by 37% (4/11 trials); reported rate of other cardiovascular complications was low. CONCLUSIONS: Administration of systemic glucocorticoids to patients hospitalised with COVID-19 does not lower mortality overall but may reduce it in those requiring respiratory support and increase it in those who do not.

Viral burden and diversity in acute respiratory tract infections in hospitalized children in wet and dry zones of Sri Lanka.

The present study was done to identify the viral diversity, seasonality and burden associated with childhood acute respiratory tract infection (ARTI) in Sri Lanka. Nasopharyngeal aspirates (NPA) of hospitalized children (1 month-5 years) with ARTI were collected in 2 centers (wet and dry zones) from March 2013 to August 2014. Respiratory viral antigen detection by immunofluorescence assay (IFA) was used to identify the infecting viruses. IFA negative 100 NPA samples were tested for human metapeumovirus (hMPV), human bocavirus and corona viruses by polymerase chain reaction. Of the 443 and 418 NPAs, 37.2% and 39.4% were positive for any of the 8 different respiratory viruses tested from two centers studied. Viral co-infection was detected with respiratory syncytial virus (RSV) in both centers. Peak viral detection was noted in the wet zone from May-July 2013 and 2014 and in the dry zone from December-January 2014 suggesting a local seasonality for viral ARTI. RSV showed a clear seasonality with a direct correlation of monthly RSV infections with rainy days in the wet zone and an inverse correlation with temperature in both centers. The case fatality rate was 2.7% for RSV associated ARTI. The overall disability adjusted life years was 335.9 and for RSV associated ARTI it was 241.8. RSV was the commonly detected respiratory virus with an annual seasonality and distribution in rainy seasons in the dry and wet zones of Sri Lanka. Identifying the virus and seasonality will contribute to employ preventive measures and reduce the empirical use of antibiotics in resource limited settings.

Boletim Epidemiológico COVID-2019 (RS): semana epidemiológica (SE) 49 de 2021 / Epidemiological Bulletin COVID-2019 (RS): epidemiological week (SE) 49, 2021

Neste boletim são apresentados: situação mundial, ocorrência de hospitalizações confirmadas para sars-cov-2, perfil das pessoas, distribuição espacial, Síndrome Inflamatória Multissistêmica Pediátrica (SIM-P), povos indígenas, descrição de surtos, trabalhadores da saúde, Vigilância sentinela de síndrome gripal e tabelas de descrição do surto. (AU)

Kinetics of antibody response in critically ill patients with Middle East respiratory syndrome and association with mortality and viral clearance.

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1-3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.

25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses.

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.

Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19.

Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7-8 exhibit severe lung inflammation, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions.

Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality.

The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.

The lethal internal face of the coronaviruses: Kidney tropism of the SARS, MERS, and COVID19 viruses.

The kidney is one of the main targets attacked by viruses in patients with a coronavirus infection. Until now, SARS-CoV-2 has been identified as the seventh member of the coronavirus family capable of infecting humans. In the past two decades, humankind has experienced outbreaks triggered by two other extremely infective members of the coronavirus family; the MERS-CoV and the SARS-CoV. According to several investigations, SARS-CoV causes proteinuria and renal impairment or failure. The SARS-CoV was identified in the distal convoluted tubules of the kidney of infected patients. Also, renal dysfunction was observed in numerous cases of MERS-CoV infection. And recently, during the 2019-nCoV pandemic, it was found that the novel coronavirus not only induces acute respiratory distress syndrome (ARDS) but also can induce damages in various organs including the liver, heart, and kidney. The kidney tissue and its cells are targeted massively by the coronaviruses due to the abundant presence of ACE2 and Dpp4 receptors on kidney cells. These receptors are characterized as the main route of coronavirus entry to the victim cells. Renal failure due to massive viral invasion can lead to undesirable complications and enhanced mortality rate, thus more attention should be paid to the pathology of coronaviruses in the kidney. Here, we have provided the most recent knowledge on the coronaviruses (SARS, MERS, and COVID19) pathology and the mechanisms of their impact on the kidney tissue and functions.

Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.

GABAA-Receptor Agonists Limit Pneumonitis and Death in Murine Coronavirus-Infected Mice.

There is an urgent need for new approaches to limit the severity of coronavirus infections. Many cells of the immune system express receptors for the neurotransmitter γ-aminobutyric acid (GABA), and GABA-receptor (GABA-R) agonists have anti-inflammatory effects. Lung epithelial cells also express GABA-Rs, and GABA-R modulators have been shown to limit acute lung injuries. There is currently, however, no information on whether GABA-R agonists might impact the course of a viral infection. Here, we assessed whether clinically applicable GABA-R agonists could be repurposed for the treatment of a lethal coronavirus (murine hepatitis virus 1, MHV-1) infection in mice. We found that oral GABA administration before, or after the appearance of symptoms, very effectively limited MHV-1-induced pneumonitis, severe illness, and death. GABA treatment also reduced viral load in the lungs, suggesting that GABA-Rs may provide a new druggable target to limit coronavirus replication. Treatment with the GABAA-R-specific agonist homotaurine, but not the GABAB-R-specific agonist baclofen, significantly reduced the severity of pneumonitis and death rates in MHV-1-infected mice, indicating that the therapeutic effects were mediated primarily through GABAA-Rs. Since GABA and homotaurine are safe for human consumption, they are promising candidates to help treat coronavirus infections.

Senolytics reduce coronavirus-related mortality in old mice.

The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein-1, increasing expression of viral entry proteins and reducing antiviral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse ß-coronavirus experienced increased senescence and inflammation, with nearly 100% mortality. Targeting SnCs by using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased antiviral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality after viral infection, including that of SARS-CoV-2.

Interferon therapy in patients with SARS, MERS, and COVID-19: A systematic review and meta-analysis of clinical studies.

Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR = -0.05, 95% CI: (-0.71,0.62), I2 = 44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR = -0.44, 95% CI: (-1.13,0.25), I2 = 31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.

Letalidade da COVID-19 entre profissionais de saúde no Pará, Brasil / Lethality of COVID-19 among healthcare professionals in Pará, Brazil / Letalidad por COVID-19 entre profesionales de salud en Pará, Brasil

Objetivo: analisar a letalidade da COVID-19 por sexo e idade entre os profissionais de saúde do Estado Pará, Brasil. Método: estudo epidemiológico e observacional, com utilização de dados secundários públicos sobre casos e óbitos acumulados por COVID-19 e dados demográficos, entre março e outubro de 2020. O número de casos e óbitos por COVID-19 ocorridos entre profissionais de saúde foram comparados em relação à idade e ao sexo pelo teste qui-quadrado, seguido por regressão logística pelo método Backward Stepwise de Wald. Resultados: entre os 15.332 casos confirmados de COVID-19, 70,3% eram do sexo feminino e 61,3% com idade entre 30 a 49 anos (39,2±11,6 anos). Registraram-se 97 óbitos, com uma taxa de letalidade de 0,6%. A probabilidade de óbito foi 52,8 vezes (20,7-134,5) e 4,0 vezes (2,5-6,2) maior entre jovens e homens quando comparados às demais notificações. Conclusão: a taxa de letalidade entre os profissionais de saúde é alta, especialmente entre homens jovens. Este é um alerta sobre os impactos da doença entre os trabalhadores da saúde e suscita ao poder público, especificamente ao setor saúde melhores condições de trabalho e políticas de saúde do trabalhador.(AU)

Objective: to analyze the lethality of COVID-19 by sex and age among health professionals in the state of Pará, Brazil. Method: epidemiological and observational study, using public secondary data on cases and deaths accumulated by COVID-19 and demographic data, between March and October 2020. The number of cases and deaths by COVID-19 that occurred among health professionals were compared in relation to age and sex using the chi-square test, followed by logistic regression using Wald's Backward Stepwise method. Results: among the 15,332 confirmed cases of COVID-19, 70.3% were female and 61.3% aged between 30 and 49 years (39.2 ± 11.6 years). 97 deaths were recorded, with a fatality rate of 0.6%. The probability of death was 52.8 times (20.7-134.5) and 4.0 times (2.5-6.2) higher among young men and men when compared to other reports. Conclusion: the lethality rate among health professionals is high, especially among young men. This is an alert about the impacts of the disease among health workers and raises the public authorities, specifically the health sector, better working conditions and worker health policies.(AU)

Objetivo: analizar la letalidad de COVID-19 por sexo y edad en profesionales de la salud en el estado de Pará, Brasil. Método: estudio epidemiológico y observacional, utilizando datos secundarios públicos sobre casos y defunciones acumulados por COVID-19 y datos demográficos, entre marzo y octubre de 2020. Se comparó el número de casos y defunciones por COVID-19 ocurridos entre profesionales de la salud en relación con edad y sexo usando la prueba de chi-cuadrado, seguida de regresión logística usando el método de Wald Backward Stepwise. Resultados: entre los 15.332 casos confirmados de COVID-19, el 70,3% eran mujeres y el 61,3% tenían entre 30 y 49 años (39,2 ± 11,6 años). Se registraron 97 muertes, con una tasa de letalidad del 0,6%. La probabilidad de muerte fue 52,8 veces (20,7-134,5) y 4,0 veces (2,5-6,2) más grande entre hombres y jóvenes en comparación con otros informes. Conclusión: la tasa de letalidad entre los profesionales de la salud es alta, especialmente entre los hombres jóvenes. Se trata de una alerta sobre los impactos de la enfermedad entre los trabajadores de la salud y plantea a las autoridades públicas, específicamente al sector salud, mejores condiciones laborales y políticas de salud laboral.(AU)

Pesquisa aponta que obesidade como fator de risco para Covid-19 fica mais evidente nos mais jovens

De acordo com os dados da pesquisa Covid-19 and Obesity: An Epidemiologic Analysis of the Brazilian Data (Covid-19 e obesidade: uma análise epidemiológica dos dados brasileiros), desenvolvida pela pesquisadora da Universidade Federal de Juiz de Fora (UFJF), Jacy Gameiro, o vírus potencializa que pacientes com obesidade cheguem a óbito mais novos que indivíduos sem a comorbidade. O estudo também mostra que o fator de risco está associado a um aumento na necessidade da internação nas Unidades de Terapia Intensivas (UTIs) e do uso do suporte ventilatório para quem está hospitalizado.

An application of slow feature analysis to the genetic sequences of coronaviruses and influenza viruses.

BACKGROUND: Mathematical approaches have been for decades used to probe the structure of DNA sequences. This has led to the development of Bioinformatics. In this exploratory work, a novel mathematical method is applied to probe the DNA structure of two related viral families: those of coronaviruses and those of influenza viruses. The coronaviruses are SARS-CoV-2, SARS-CoV-1, and MERS. The influenza viruses include H1N1-1918, H1N1-2009, H2N2-1957, and H3N2-1968. METHODS: The mathematical method used is the slow feature analysis (SFA), a rather new but promising method to delineate complex structure in DNA sequences. RESULTS: The analysis indicates that the DNA sequences exhibit an elaborate and convoluted structure akin to complex networks. We define a measure of complexity and show that each DNA sequence exhibits a certain degree of complexity within itself, while at the same time there exists complex inter-relationships between the sequences within a family and between the two families. From these relationships, we find evidence, especially for the coronavirus family, that increasing complexity in a sequence is associated with higher transmission rate but with lower mortality. CONCLUSIONS: The complexity measure defined here may hold a promise and could become a useful tool in the prediction of transmission and mortality rates in future new viral strains.

Relação da COVID-19 com o Índice de Desenvolvimento Humano / Relationship of COVID-19 with the Human Development Index

Síntese de evidências e análise exploratória acerca da relação entre IDHs e a evolução da pandemia da COVID-19 nos municípios do estado de Goiás. Para essa análise utilizou-se dados referentes à situação da COVID-19 nos municípios de Goiás, utilizando-se de IDH dos Municipíos de Goiás no site do IBGE, IDH dos Bairros de Goiânia, Populações estimadas para 2019, números de casos e óbitos por município do Estado de Goiás, Painel de Acompanhamento da Covid da Secretaria de Estado da Saúde de Goiás (SES-GO); números de internações nas unidades do SUS pelo Argos, agrupado por município, residência dos paciente; números de internações pelo SIVEP, agrupado por município de residência dos pacientes. Para calcular a precisão utilizou-se a métrica Coeficiente de Determinação (r²). No que se refere à correlação, obteve-se os índices de correlação do IDH com as diferentes variáveis apresentadas no gráfico de calor. Conclui que não há, até o momento, consonância da literatura científica acerca da relação entre o IDH e indicadores epidemiológicos da COVID-19. Serão necessários mais estudos e metodologias diferentes de modo a aferir a influência das diferentes variáveis

Evidence synthesis and exploratory analysis on the relationship between HDIs and the evolution of the COVID-19 pandemic in the municipalities of the state of Goiás. For this analysis, data referring to the situation of COVID-19 in the municipalities of Goiás were used, using HDI of the Municipalities of Goiás on the IBGE website, HDI of the Neighborhoods of Goiânia, Estimated populations for 2019, number of cases and deaths by municipality of the State of Goiás, Covid Monitoring Panel of the State Health Department of Goiás (SES-GO ); number of admissions to SUS units by Argos, grouped by municipality, patient residence; number of admissions by SIVEP, grouped by municipality of residence of patients. To calculate the precision, the Coefficient of Determination (r²) metric was used. With regard to the correlation, we obtained the correlation indices of the HDI with the different variables presented in the heat graph. It concludes that, to date, there is no consonance in the scientific literature on the relationship between the HDI and COVID-19 epidemiological indicators. More studies and different methodologies will be needed in order to assess the influence of different variables

The presence of care homes and excess deaths during the COVID-19 pandemic: Evidence from Italy.

This paper explores the relationship between the spatial distribution of excess deaths and the presence of care home facilities during the first wave of the COVID-19 outbreak in Italy. Using registry-based mortality data for Lombardy, one of the areas most severely hit by the pandemic we show that the presence of a care home in a municipality is associated with significantly higher excess death rates in the population. This effect appears to be driven by excess mortality in the elderly population of 70 years old and older. Our results are robust to controlling for the number of residents in each care home, suggesting that the presence of such facilities may have acted as one of factors contributing to the diffusion of COVID-19 at the local level.

Aplicación de un modelo cubano predictivo de mortalidad en pacientes graves por covid-19 en Lombardía, Italia / Application of a Cuban mortality-predictive model in seriously-ill patients with Covid-19 in Lombardy, Italy

RESUMEN Introducción: la neumonía por covid-19 es la enfermedad infecciosa que ha revolucionado al mundo en los últimos meses. El diagnóstico pasa por varios momentos: el cuadro clínico, la analítica sanguínea y las imágenes. La estratificación del riesgo de muerte es muy importante para optimizar los recursos. Objetivos: validar un modelo matemático cubano predictivo de mortalidad en pacientes ingresados por covid-19. Materiales y métodos: estudio de cohorte con 191 pacientes, que ingresaron graves en el Hospital Mayor de Crema, en la provincia de Cremona, región de Lombardía (Italia), en el período de abril a mayo de 2020. El universo estuvo constituido por 191 pacientes, y no se tomó muestra alguna. Las variables fueron: edad, estado del paciente, niveles de creatinina plasmática, frecuencia respiratoria, frecuencia cardiaca, presión arterial, niveles de oxígeno y de dióxido de carbono en sangre, valor del sodio y de hemoglobina. Resultados: mortalidad del 22 % en pacientes graves y críticos, con media de la edad (grupo 1: 59 años) (grupo 2: 73 años); t-Student = 0,00. Test de Hosmer-Lemenshow (0,766) con elevado ajuste. Sensibilidad = 93 %. Área bajo la curva = 0,957. Porcentaje de aciertos en la regresión logística de 86,4 % y en la red neuronal de 91,2 %. Media del modelo por grupos (grupo 1: 4 458) (grupo 2: 2 911) t-Student = 0,00. Conclusiones: el modelo demostró ser muy útil en el flujograma de pacientes atendidos con la covid-19. Permitió detectar tempranamente (a los cinco días del ingreso) los pacientes con alto riesgo de muerte y discriminar aquellos que no tendrían este riesgo, de manera que pudieran ser tratados en unidades de cuidados mínimos (AU).

ABSTRACT Introduction: COVID-19 pneumonia is an infectious disease that has revolutionized the world in the last months. The diagnosis goes thought several moments: clinical features, blood analytic and images. Death risk stratification is very important to optimize resources. Objective: to validate the Cuban mathematic predictive model of mortality in patients admitted due to COVID-19. Materials and methods: cohort study with 191 seriously-ill patients who were admitted to Maggiore di Crema Hospital, Cremona, Lombardy region, Italy, in the period April-May 2020. The universe were 191 patients and no sample was chosen. The variables were: age; patient's status; plasma creatinine levels; respiratory rate; heart rate; arterial pressure; blood oxygen and carbon dioxide levels; values of sodium and hemoglobin. Results: 22 % of mortality in seriously-ill and critical patients, with average age in Group 1: 59 years, in Group 2: 73 years; t-Student = 0.00. Hosmer-Lemenshow test (0.766) with high adjustment. Sensitivity= 93 %. Area below the curve=0.957. Success percentage in logistic regression of 86.4 % and 91.2 % in the neuronal net. Model media per groups: Group 1= 4 458; Group 2= 2 911, t-Student = 0.00. Conclusions: the model showed to be very useful in the flow chart of patients attended with COVID-19. It allowed to early detect the patients at high death risk five days from admission and discriminating those who were not at risk, in a way that they could be treated in minimal care units (AU).