Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation.

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin-proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.

Pathogenicity of the Canadian Delmarva (DMV/1639) Infectious Bronchitis Virus (IBV) on Female Reproductive Tract of Chickens.

Infectious bronchitis virus (IBV) infection causes significant economic losses to various sectors of the poultry industry worldwide. Over the past few years, the incidence of false layer syndrome in Eastern Canadian layer flocks has been associated with the increased prevalence of the IBV Delmarva (DMV)/1639 strain. In this study, 1-day-old specific-pathogen-free (SPF) hens were infected with the Canadian DMV/1639 strain and observed until 16 weeks of age in order to determine if the IBV DMV/1639 strain is causing false layer syndrome. Early after infection, the virus showed a wide tissue distribution with characteristic gross and histopathological lesions in the respiratory tract and kidney. Around 60-70% of the infected hens demonstrated continuous cloacal viral shedding until the end of the experiment (at 16 weeks) which was associated with high IBV genome loads detected in the cecal tonsils. The experiment confirmed the field observations that the Canadian DMV/1639 strain is highly pathogenic to the female reproductive tract causing marked cystic lesions in the oviduct. Moreover, significant histopathological damage was observed in the ovary. Our study provides a detailed description of the pathological consequences of the IBV DMV/1639 strain circulating in an important poultry production sector.

Decreased NHE3 activity in intestinal epithelial cells in TGEV and PEDV-induced piglet diarrhea.

Transmissible gastroenteritis (TGE) and porcine epidemic diarrhea (PED) are highly transmissible intestinal infections caused by transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), respectively. They are clinically associated with vomiting, diarrhea, and dehydration in piglets. An imbalance in Na+ uptake by intestinal epithelial cells causes TGEV/PEDV-induced diarrhea. However, the mechanism by which TGEV/PEDV-infection in piglets causes Na+ imbalance diarrhea has not been elucidated. In the present study, we demonstrated that specific inhibition of NHE3 activity caused small intestinal bulging, intestinal wall thinning and severe diarrhea in piglets, consistent with the signs of TGEV/PEDV infection. This study further elucidated the role of NHE3 in TGEV/PEDV-induced diarrhea. In this study, small intestinal epithelial cells (IPEC-J2) were used as a model of infection. The results showed that TGEV/PEDV infection reduced NHE3 activity and Na+ uptake in IPEC-J2 cells. Further studies revealed that the use of NHE3-specific inhibitors could reduce the amount of cell membrane NHE3, thereby decreasing Na+ uptake and ultimately leading to diarrhea. Transcriptomic studies performed on obtained jejunal tissues were also consistent with pre-laboratory results. This study will provide a basis for understanding Na+ imbalance diarrhea caused by TGEV/PEDV, as well as for elucidating the diarrheal pathogenesis of other members of α-animal coronaviruses.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

Disfunción endotelial. Mecanismos e implicancias en Covid-19 / Endothelial dysfunction. Mechanisms and implications on Covid-19

Endothelium is the inner layer of vessels that separates circulating blood from the rest of the body tissues. Since its discovery, it has been involved in various functions, both systemic and organ specific. Currently, endothelial damage and failure in its functions is considered a key element in pathophysiology of various clinical scenarios, among which we may find COVID-19.Hence, it has been a target in development of strategies that seek to maintain, enhance or repair its function. The purpose of the following review is to describe what an endothelial function is about, its relation with current medical practice, and its implications in the SARS- CoV-2 pandemic. (AU)

Clinical-epidemiological relation between sars-cov-2 and kawasaki disease: an integrative literature / Relação clínico-epidemiológica entre sars-cov-2 e doença de kawasaki: uma revisão integrativa da literatura

ABSTRACT Objective: To analyze the current scientific literature to document, in an integrative review, the main findings that correlate Kawasaki disease (KD) to COVID-19. Data sources: The search was carried out in June 2020 in the following databases: Biblioteca Virtual em Saúde (BVS), periódico da CAPES and U.S National Library of Medicine (PubMed). The combination of descriptors used was [(COVID-19 OR SARS-CoV-2) AND (Kawasaki disease)], and the inclusion criteria stipulated were studies published from January 2019 to June 2020, without restriction of language or location, and available online in full. News, editorials, comments, and letters, as well as duplicates and articles that did not answer the guiding question were excluded. Data synthesis: A total of 97 articles were identified, of which seven comprised this review. The association of KD to the new coronavirus appears to trigger a severe clinical condition of vasculitis. Different from the usual, in this inflammatory syndrome, patients are older, and prevalence is higher in children from African or Caribbean ancestry; clinical and laboratory manifestations are also atypical, with a predominance of abdominal complaints and exaggerated elevation of inflammatory markers. In addition, there was a greater report of rare complications and greater resistance to the recommended treatment for KD. Conclusions: Pediatric COVID-19 and its potential association to severe KD, still unfamiliar to health professionals, reinforces the importance of testing patients with vasculitis for the new coronavirus and the need to wage high surveillance and preparation of the health system during the current pandemic.

RESUMO Objetivo: Analisar a literatura científica atual a fim de documentar, por meio de revisão integrativa, os principais achados que associam a doença de Kawasaki (DK) à doença do coronavírus (COVID-19). Fonte de dados: A busca ocorreu em junho de 2020, nas bases de dados: Biblioteca Virtual em Saúde (BVS), periódico da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e U.S. National Library of Medicine (PubMed). Os descritores utilizados foram [(COVID-19 OR SARS-CoV-2) AND (Kawasaki Disease)], e os critérios de inclusão estipulados compreenderam estudos publicados de janeiro de 2019 a junho de 2020, sem restrição de idioma ou localização e disponíveis online integralmente. Foram excluídos notícias, editoriais, comentários e cartas de apresentação, assim como duplicatas e artigos que não respondiam à pergunta norteadora. Síntese dos dados: Identificaram-se 97 artigos, dos quais sete compuseram esta revisão. A associação da DK com o novo coronavírus parece desencadear um quadro de vasculite grave. Diferentemente do usual, nessa síndrome inflamatória, os pacientes são mais velhos e a descendência prevalente é africana ou caribenha; as manifestações clínicas e laboratoriais também são atípicas, com predomínio de queixas abdominais e elevação exagerada de marcadores inflamatórios. Além disso, houve maior relato de complicações raras e maior resistência ao tratamento preconizado para DK. Conclusões: A COVID-19 pediátrica e sua potencial associação com uma DK grave, ainda pouco conhecida pelos profissionais da saúde, reforçam a importância da testagem de pacientes com vasculite para o novo coronavírus e a necessidade de empreender alta vigilância e preparação do sistema de saúde durante a atual pandemia.

Obesidade como fator agravante da COVID-19 em adultos hospitalizados: revisão integrativa / Obesidad como factor agravante de COVID-19 en adultos hospitalizados: revisión integradora / Obesity as an aggravating factor of COVID-19 in hospitalized adults: an integrative review

Resumo Objetivo: Identificar, na literatura científica, a relação da obesidade como fator de risco agravante para a morbidade por COVID-19. Métodos: Trata-se de um estudo bibliográfico, tipo revisão integrativa de literatura, nos idiomas português, inglês e espanhol, por meio da estratégia PICo, em cinco bases de dados,PubMed, Scopus, Web of Science, Embasee BVS, realizada de maio a junho de 2020. Os critérios de inclusão adotados foram: artigos primários realizados com adultos; disponíveis na íntegra; publicados durante o período de 2019 a 2020; nos idiomas português, inglês e espanhol. Os critérios de exclusão foram: relato de casos; casos clínicos; dissertações; teses; os já selecionados na busca em outra base de dados e que não respondessem à questão da pesquisa. Resultados: A seleção resultou em noveestudos, sendo que quatro estudos - 44,4% (E3, E5, E6 e E7) - apresentaram a prevalência de obesidade em adultos hospitalizados por COVID-19, dois estudos - 22,2% (E6, E9) - associaram a obesidade ao desenvolvimento da COVID-19 grave, três estudos - 33,3% (E1, E4 e E7) - associaram a obesidade à necessidade de ventilação mecânica e três estudos - 33,3% (E2, E4 e E8) - associaram a obesidade à mortalidade por COVID-19. Conclusão: A obesidade trata-se de uma doença crônica não transmissível, sendo um fator de risco considerado importante para o agravamento da doença COVID-19, no entanto, é passível de prevenção, pois hábitos saudáveis de vida podem reduzir o quadro grave de infecção por COVID-19.

Resumen Objetivo: Identificar en la literatura científica la relación de la obesidad como factor de riesgo agravante para la morbilidad por COVID-19. Métodos: Se trata de un estudio bibliográfico, tipo revisión integradora de literatura, en idioma portugués, inglés y español, por medio de la estrategia PICO, en cinco bases de datos: PubMed, Scopus, Web of Science, Embase y BVS, realizada de mayo a junio de 2020. Los criterios de inclusión adoptados fueron: artículos primarios realizados con adultos, con texto completo disponible, publicados durante el período de 2019 a 2020, en idioma portugués, inglés y español. Los criterios de exclusión fueron: relato de casos, casos clínicos, tesis de maestría y doctorado, los artículos ya seleccionados en la búsqueda en otra base de datos y los que no respondieran la pregunta de investigación. Resultados: La selección tuvo como resultado nueve estudios, de los cuales cuatro — 44,4% (E3, E5, E6 y E7) — presentaron prevalencia de obesidad en adultos hospitalizados por COVID-19; en dos estudios — 22,2% (E6, E9) — se relacionó la obesidad con el desarrollo de COVID-19 grave; en tres estudios — 33,3% (E1, E4 y E7) — se relacionó la obesidad con la necesidad de ventilación mecánica; y en tres estudios — 33,3% (E2, E4 y E8) — se relacionó la obesidad con la mortalidad por COVID-19. Conclusión: La obesidad se trata de una enfermedad crónica no transmisible y es considerada un factor de riesgo importante para el agravamiento de la enfermedad COVID-19. Sin embargo, la prevención es posible, ya que los hábitos de vida saludables pueden reducir el cuadro grave de infección por COVID-19.

Abstract Objective: To identify, in scientific literature, the relationship of obesity as an aggravating risk factor for morbidity by COVID-19. Methods: This is a bibliographic and integrative literature review study, in Brazilian Portuguese, English and Spanish languages, through PICo strategy, in the PubMed, Scopus, Web of Science, Embase and VHL databases, held from May to June 2020. Primary articles conducted with adults, available in full, published during the period 2019 to 2020, in Brazilian Portuguese, English and Spanish were included. Case reports, clinical cases, dissertations, theses, the already selected in the search in another database and that did not answer the question of the search were excluded. Results: The selection resulted in nine studies. Four studies - 44.4% (E3, E5, E6 and E7) - presented the prevalence of obesity in adults hospitalized by COVID-19. Two studies - 22.2% (E6, E9) - associated obesity with the development of severe COVID-19. Three studies - 33.3% (E1, E4 and E7) - associated obesity with the need for mechanical ventilation. Three studies - 33.3% (E2, E4 and E8) - associated obesity with mortality due to COVID-19. Conclusion: Obesity is a chronic non-communicable disease, being a risk factor considered important for the worsening of COVID-19 disease, however, it is preventable, because healthy lifestyle habits can reduce the severe picture of COVID-19 infection.

Recomendaciones para el manejo inicial del síndrome inflamatorio multisistémico relacionado temporalmente con COVID-19, en niños y adolescentes / Recommendations for the initial management of multisystem inflammatory syndrome temporally related to COVID-19, in children and adolescents

El síndrome inflamatorio multisistémico en niños y adolescentes temporalmente relacionado con COVID-19 es una presentación clínica de la infección por SARS-CoV-2. Comparte algunas características con la enfermedad de Kawasaki, el shock tóxico, la sepsis, el síndrome de activación macrofágica y la miocarditis. Son escasas las publicaciones que abordan su manejo inicial, que tiene semejanzas con el propuesto para el shock séptico. Esta revisión analiza dicho abordaje basado en las características propias del síndrome inflamatorio multisistémico relacionado con COVID-19, de acuerdo con el paradigma de construcción de una "guía de práctica institucional", y sugiere estrategias de aproximación terapéutica, que incluyen detección temprana, estabilización, referencia, tratamiento específico y análisis de proceso

Multisystem inflammatory syndrome temporally related to COVID-19 in children and adolescents is a clinical presentation of SARS-CoV-2 infection. It shares some features with Kawasaki disease, toxic shock, sepsis, macrophage activation syndrome, and myocarditis. Few publications have addressed its initial management, which is similar to that proposed for septic shock. This review analyzes such approach based on the characteristics typical of multisystem inflammatory syndrome related to COVID-19 in accordance with the paradigm of an "institutional practice guideline" and suggests therapeutic approach strategies, including early detection, stabilization, referral, specific treatment, and process analysis.

Recent Clinical and Preclinical Studies of Hydroxychloroquine on RNA Viruses and Chronic Diseases: A Systematic Review.

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.

Respiratory Virus Infections in Asthma: Research Developments and Therapeutic Advances.

In this review, we discuss the latest developments in research pertaining to virus-induced asthma exacerbations and consider recent advances in treatment options. Asthma is a chronic disease of the airways that continues to impose a substantial clinical burden worldwide. Asthma exacerbations, characterised by an acute deterioration in respiratory symptoms and airflow obstruction, are associated with significant morbidity and mortality. These episodes are most commonly triggered by respiratory virus infections. The mechanisms underlying the pathogenesis of virus-induced exacerbations have been the focus of extensive biomedical research. Developing a robust understanding of the interplay between respiratory viruses and the host immune response will be critical for developing more efficacious, targeted therapies for exacerbations. CONCLUSION: There has been significant recent progress in our understanding of the mechanisms underlying virus-induced airway inflammation in asthma and these advances will underpin the development of future clinical therapies.

Differences in terms of presentation and outcomes between patients with lung cancer as opposed to other solid organ cancer after infection with SARS-CoV-2: protocol for a systematic review.

INTRODUCTION: Scholars believe that COVID-19 can be particularly lethal for patients with cancer. Some studies found that COVID-19 appears to be more lethal in patients with lung cancer than in other cancer patients. In order to take appropriate measures to balance a delay in lung cancer treatment against the risk for a potential COVID-19 exposure, we first need to know whether patients with lung cancer have special risks. We aim to conduct a systematic review and meta-analysis to examine differences in terms of presentation and outcomes between patients with lung cancer as opposed to other solid organ cancer after infection with SARS-CoV-2. METHODS AND ANALYSIS: A comprehensive search of published original research studies will be performed in Embase, MEDLINE, Web of Science, WangFangData, CQVIP, COMPENDEX and CNKI. The medRxiv preprint server will also be searched for applicable studies (grey literature). Original research studies will be included if they include patients with: (A) laboratory-confirmed SARS-CoV-2 infection and (B) confirmed solid cancer, and (C) measurable clinical presentation or outcome, such as mortality rate, intensive care unit admission rate, incidence of pneumonia. One author will conduct the electronic database searches, two authors will independently screen studies, two will extract data and two will assess study quality. If I² exceeds 60% for the pooled analysis, we will explore sources of heterogeneity in subgroups of studies. We will use fixed-effect, random-effects or mixed-effects models to estimate the relative risk or OR. If the data reporting allows, a subgroup analysis between non-small cell lung cancer and small cell lung cancer patients will be performed. ETHICS AND DISSEMINATION: The proposed study will not collect individual-level data and, therefore, does not require ethical approval. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42020190118.

Characteristics, complications and outcomes among 1549 patients hospitalised with COVID-19 in a secondary hospital in Madrid, Spain: a retrospective case series study.

OBJECTIVES: To describe demographic, clinical, radiological and laboratory characteristics, as well as outcomes, of patients admitted for COVID-19 in a secondary hospital. DESIGN AND SETTING: Retrospective case series of sequentially hospitalised patients with confirmed SARS-CoV-2, at Infanta Leonor University Hospital (ILUH) in Madrid, Spain. PARTICIPANTS: All patients attended at ILUH testing positive to reverse transcriptase-PCR on nasopharyngeal swabs and diagnosed with COVID-19 between 1 March 2020 and 28 May 2020. RESULTS: A total of 1549 COVID-19 cases were included (median age 69 years (IQR 55.0-81.0), 57.5% men). 78.2% had at least one underlying comorbidity, the most frequent was hypertension (55.8%). Most frequent symptoms at presentation were fever (75.3%), cough (65.7%) and dyspnoea (58.1%). 81 (5.8%) patients were admitted to the intensive care unit (ICU) (median age 62 years (IQR 51-71); 74.1% men; median length of stay 9 days (IQR 5-19)) 82.7% of them needed invasive ventilation support. 1393 patients had an outcome at the end of the study period (case fatality ratio: 21.2% (296/1393)). The independent factors associated with fatality (OR; 95% CI): age (1.07; 1.06 to 1.09), male sex (2.86; 1.85 to 4.50), neurological disease (1.93; 1.19 to 3.13), chronic kidney disease (2.83; 1.40 to 5.71) and neoplasia (4.29; 2.40 to 7.67). The percentage of hospital beds occupied with COVID-19 almost doubled (702/361), with the number of patients in ICU quadrupling its capacity (32/8). Median length of stay was 9 days (IQR 6-14). CONCLUSIONS: This study provides clinical characteristics, complications and outcomes of patients with COVID-19 admitted to a European secondary hospital. Fatal outcomes were similar to those reported by hospitals with a higher level of complexity.

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation.

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV-V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1ß induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

Characteristics of COVID-19 at a non-COVID tertiary pulmonary care centre in Delhi, India.

The pandemic of COVID-19 has emerged as a serious health crisis globally and India too has been extensively affected with 604,641 active cases reported, till date. The present study focuses on the demographic, clinical and laboratory profile of such patients from a tertiary level non-COVID respiratory care hospital. This is a retrospective observational study. Seventy-seven sick patients fulfilling COVID suspect criteria were admitted to the isolation area. Their RT-PCR test was done from the designated laboratory and 35 of them  were confirmed to be COVID-19 patients. The detailed demographic, clinical and laboratory profile of these COVID-19 patients was studied. The mean age was 46±17 years with male predominance (57%). Majority  of the cases (83%) were symptomatic. The most common symptom was cough (66%) followed by breathlessness and fever. Nineteen (54.3%) patients had one or the other co-morbidity and 16 (45.7%) had chronic lung diseases as one of the comorbidities. Nearly half of the patients (51%) required supplementary oxygen on presentation. Two patients were put on invasive mechanical ventilation while 4 patients required non-invasive ventilation before being shifted to the COVID hospital. Hence, it can be concluded that COVID-19 in patients of chronic respiratory diseases  manifests with higher prevalence of symptoms and also higher severity of disease. Further, the  symptomatology of COVID-19 closely mimics the acute exacerbation of chronic lung diseases, so cautious screening and testing should be done, especially at the pulmonary department.

COVID-19 Transmission in a Psychiatric Long-Term Care Rehabilitation Facility: An Observational Study.

OBJECTIVE: To report the clinical characteristics and transmission rate of coronavirus disease 2019 (COVID-19) in a community inpatient long-term care psychiatric rehabilitation facility designed for persons with serious mental illness to provide insight into transmission and symptom patterns and emerging testing protocols, as well as medical complications and prognosis. METHODS: This study examined a cohort of 54 residents of a long-term care psychiatric rehabilitation program from March to April 2020. Baseline demographics, clinical diagnoses, and vital signs were examined to look for statistical differences between positive versus negative severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) groups. During the early phase of the pandemic, the facility closely followed the local shelter-in-place order (starting March 19, 2020) and symptom-based testing. RESULTS: Of the residents, the primary psychiatric diagnoses were schizoaffective disorder: 28 (51.9%), schizophrenia: 21 (38.9%), bipolar I disorder: 3 (5.5%), and unspecified psychotic disorder: 2 (3.7%). Forty (74%) of 54 residents tested positive for SARS-COV-2, with a doubling time of 3.9 days. There were no statistical differences between the positive SARS-COV-2 versus negative groups for age or race/ethnicity. Psychiatric and medical conditions were not significantly associated with contracting SARS-COV-2, with the exception of obesity (n = 17 [43%] positive vs n = 12 [86%] negative, P = .01). Medical monitoring of vital signs and symptoms did not lead to earlier detection. All of the residents completely recovered, with the last resident no longer showing any symptoms 24 days from the index case. CONCLUSION: Research is needed to determine optimal strategies for long-term care mental health settings that incorporate frequent testing and personal protective equipment use to prevent rapid transmission of SARS-COV-2.

Bilateral, vertical supranuclear gaze palsy following unilateral midbrain infarct.

A 60-year-old man recently admitted for bipedal oedema, endocarditis and a persistently positive COVID-19 swab with a history of anticoagulation on rivaroxaban for atrial fibrillation, transitional cell carcinoma, cerebral amyloid angiopathy, diabetes and hypertension presented with sudden onset diplopia and vertical gaze palsy. Vestibulo-ocular reflex was preserved. Simultaneously, he developed a scotoma and sudden visual loss, and was found to have a right branch retinal artery occlusion. MRI head demonstrated a unilateral midbrain infarct. This case demonstrates a rare unilateral cause of bilateral supranuclear palsy which spares the posterior commisure. The case also raises a question about the contribution of COVID-19 to the procoagulant status of the patient which already includes atrial fibrillation and endocarditis, and presents a complex treatment dilemma regarding anticoagulation.

Pronóstico de pacientes hospitalizados por COVID-19 en un centro terciario en Chile: estudio de cohorte / Prognosis of patients with COVID-19 admitted to a tertiary center in Chile: a cohort study

Introducción Desde el comienzo de la pandemia de COVID-19, se han desarrollado diversas investigaciones sobre el pronóstico de pacientes con SARS-CoV-2 asociado a factores como edad, condiciones biodemográficas, comorbilidades, factores sociales, parámetros clínicos, hematológicos, marcadores inflamatorios, de coagulación, bioquímicos y gasométricos, entre otros. Hasta ahora, existen escasos estudios que hayan abordado el tema en América Latina, por lo que es de interés conocer el comportamiento de la enfermedad en la región. Objetivo Evaluar el curso del COVID-19 en pacientes ingresados en un centro terciario en Chile y analizar factores predictores, medidos en el período cercano a la admisión, que se asocien al pronóstico vital y al uso de ventilación mecánica invasiva. Métodos Estudio de cohorte retrospectivo realizado en Clínica Indisa de Santiago, Chile. Participaron todos los pacientes de 15 años o más hospitalizados entre el 11 de marzo y el 25 de julio de 2020. Se analizó la letalidad hospitalaria, la complejidad de los casos y se aplicaron modelos de regresión logística para identificar predictores de las variables de resultado definidas. Resultados La muestra estuvo constituida por 785 sujetos. La edad media fue 59 años, 59% fueron hombres y 61,3% tenía comorbilidades. El 45% requirió cuidados intensivos y 24% ventilación mecánica invasiva. La letalidad hospitalaria global fue de 18,7%. En pacientes de unidad de cuidados intensivos fue 32,1% y en quienes recibieron ventilación mecánica invasiva 59,4%. Los factores de riesgo independientes de morir incluyeron la edad (Odds ratio 1,09; intervalo de confianza 95%: 1,07 a 1,12), diabetes (1,68; 1,06 a 2,67), enfermedad pulmonar crónica (2,80; 1,48 a 5,28) y mayores niveles de proteína C reactiva, creatinina y ferritina. No se demostró asociación con el sexo, pertenencia al seguro público de salud, antecedente de cardiopatía, obesidad, ni dímero D. Similares factores fueron predictores de ventilación mecánica invasiva. Conclusiones El pronóstico y factores predictores en esta cohorte de pacientes hospitalizados en Chile por COVID-19 fueron comparables en su mayoría a los reportados en estudios similares de países de mayores ingresos. El sexo masculino no fue un factor de mal pronóstico en este grupo de pacientes.

Introduction Since the beginning of the COVID-19 pandemic, extensive research has been done on the prognosis of patients with SARS-CoV-2 associated with age, biodemographic conditions, comorbidities, social factors, clinical parameters, inflammatory blood markers, coagulation, biochemical and blood gas parameters, among others. Few studies have addressed this problem in Latin America, so it is of interest to know how the disease plays out in this region. Objective The purpose of our study is to evaluate the course of COVID-19 in patients admitted to a tertiary center in Chile and to assess factors measured close to hospital admission that may be associated with death and the need for invasive mechanical ventilation. Methods We did a retrospective cohort study at Indisa Clinic in Santiago, Chile. We included all patients aged 15 years and older hospitalized between March 11 and July 25, 2020. Hospital mortality and severity of the cases were analyzed, and logistic regression models were applied to identify predictors of outcome variables. Results The sample included 785 subjects. The mean age was 59 years, 59% were men, and 61.3% had comorbidities. Forty five per cent required intensive care, and 24% invasive mechanical ventilation. The overall hospital fatality rate was 18.7%. In intensive care patients, the case fatality was 32.1%, and in those who received invasive mechanical ventilation, it was 59.4%. Independent risk factors for death included age (odds ratio 1.09; 95% confidence interval: 1.07 to 1.12), diabetes (1.68; 1.06 to 2.67), chronic lung disease (2.80; 1.48 to 5.28), increased C-reactive protein, creatinine, and ferritin. No association with sex, public health insurance, history of heart disease, oxygen saturation upon admission, or D-dimer was found. Similar factors were predictors of invasive mechanical ventilation. Discussion The prognosis and predictive factors in this cohort of patients hospitalized in Chile for COVID-19 were comparable to those reported in similar studies from higher-income countries. Male sex was not associated with a poor prognosis in this group of patients.