Neurological Sequelae of COVID-19.

BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients. RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

In Silico Drug Repositioning to Target the SARS-CoV-2 Main Protease as Covalent Inhibitors Employing a Combined Structure-Based Virtual Screening Strategy of Pharmacophore Models and Covalent Docking.

The epidemic caused by the SARS-CoV-2 coronavirus, which has spread rapidly throughout the world, requires urgent and effective treatments considering that the appearance of viral variants limits the efficacy of vaccines. The main protease of SARS-CoV-2 (Mpro) is a highly conserved cysteine proteinase, fundamental for the replication of the coronavirus and with a specific cleavage mechanism that positions it as an attractive therapeutic target for the proposal of irreversible inhibitors. A structure-based strategy combining 3D pharmacophoric modeling, virtual screening, and covalent docking was employed to identify the interactions required for molecular recognition, as well as the spatial orientation of the electrophilic warhead, of various drugs, to achieve a covalent interaction with Cys145 of Mpro. The virtual screening on the structure-based pharmacophoric map of the SARS-CoV-2 Mpro in complex with an inhibitor N3 (reference compound) provided high efficiency by identifying 53 drugs (FDA and DrugBank databases) with probabilities of covalent binding, including N3 (Michael acceptor) and others with a variety of electrophilic warheads. Adding the energy contributions of affinity for non-covalent and covalent docking, 16 promising drugs were obtained. Our findings suggest that the FDA-approved drugs Vaborbactam, Cimetidine, Ixazomib, Scopolamine, and Bicalutamide, as well as the other investigational peptide-like drugs (DB04234, DB03456, DB07224, DB7252, and CMX-2043) are potential covalent inhibitors of SARS-CoV-2 Mpro.

Usefulness of PCR Screening in the Initial Triage of Trauma Patients During COVID-19 Pandemic.

BACKGROUND: Hospitals worldwide have postponed all nonessential surgery during the COVID-19 pandemic, but non-COVID-19 patients are still in urgent need of care. Uncertainty about a patient's COVID-19 status risks infecting health care workers and non-COVID-19 inpatients. We evaluated the use of quantitative reverse transcription polymerase chain reaction (RT-qPCR) screening for COVID-19 on admission for all patients with fractures. METHODS: We conducted a retrospective cohort study of patients older than 18 years admitted with low-energy fractures who were tested by RT-qPCR for SARS-CoV-2 at any time during hospitalization. Two periods based on the applied testing protocol were defined. During the first period, patients were only tested because of epidemiological criteria or clinical suspicion based on fever, respiratory symptoms, or radiological findings. In the second period, all patients admitted for fracture treatment were screened by RT-qPCR. RESULTS: We identified 15 patients in the first period and 42 in the second. In total, 9 (15.8%) patients without clinical or radiological findings tested positive at any moment. Five (33.3%) patients tested positive postoperatively in the first period and 3 (7.1%) in the second period (P = 0.02). For clinically unsuspected patients, postoperative positive detection went from 3 of 15 (20%) during the first period to 2 of 42 (4.8%) in the second (P = 0.11). Clinical symptoms demonstrated high specificity (92.1%) but poor sensitivity (52.6%) for infection detection. CONCLUSIONS: Symptom-based screening for COVID-19 has shown to be specific but not sensitive. Negative clinical symptoms do not rule out infection. Protocols and separated areas are necessary to treat infected patients. RT-qPCR testing on admission helps minimize the risk of nosocomial and occupational infection. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Efectividad del plan de contingencia de la unidad de enfermedad inflamatoria intestinal ante la infección de COVID-19

OBJETIVO: La toma de decisiones en los hospitales y en sus propios servicios asistenciales apenas está referenciada en la literatura. Durante el período de pandemia por Covid-19, los servicios asistenciales han puesto en marcha planes de contingencia para minimizar las consecuencias del coronavirus en los profesionales y pacientes. Sin embargo, apenas se comparte el despliegue de esos planes de contingencia, ni sus resultados, privando de referencias para refutar, comparar o emular los citados planes a otros servicios asistenciales u hospitales. El objetivo del trabajo fue la descripción de la puesta en marcha de dichos planes ante la pandemia de Covid-19 en la Unidad de Enfermedad Inflamatoria Intestinal de un Servicio de Digestivo en el Área Sanitaria de Pontevedra e O Salnés (Galicia). MÉTODOS: Un equipo de directivos y profesionales adaptaron al entorno sanitario las 10 medidas recomendadas por Deloitte para afrontar una pandemia. A continuación, se formularon las medidas como listado de comprobación. A partir del ciclo de mejora Plan-Do-Check-Act, se agruparon las 10 medidas en las siguientes categorías: gestión del riesgo, gestión organizacional y toma de decisiones. Por último, un equipo externo realizó una evaluación cualitativa de la puesta en marcha del plan de contingencia realizado. RESULTADOS: La Unidad de Enfermedad Inflamatoria Intestinal del Servicio de Digestivo realizó un plan de contingencia que presenta un cumplimiento de las 10 medidas recomendadas para hacer frente a la pandemia de Covid-19 con garantías. CONCLUSIONES: Compartir el despliegue del plan de contingencia y sus resultados es útil para identificar buenas prácticas. Este trabajo ofrece un método para evaluar las tomas de decisiones en los plantes de contingencia en situaciones de pandemia. Los resultados sitúan a la Unidad de Enfermedad Inflamatoria Intestinal en el rango de la excelencia OBJECTIVE: Decision making in hospitals, and especially in their own healthcare services, is hardly referenced in the literature. During the pandemic period, healthcare services have put in place contingency plans to minimize the consequences of the coronavirus on professionals and patients. However, the deployment of contingency plans and results are hardly shared, depriving other services of references to refute, compare or emulate the aforementioned plans. The objective of this work was the description of the implementation and evaluation of Contingency Plans in the Covid-19 pandemic in a unit of inflammatory bowel disease of a Digestive Service in the Sanitary Area of Pontevedra and O Salnés. METHODS: A team of managers and professionals adapted the 10 measures recommended by Deloitte to face a pandemic to the healthcare environment. The measures were then formulated as a checklist. From the Plan-Do-Check-Act improvement cycle, they were grouped into categories: risk management, organizational management and decision-making. Finally, an external team carried out a qualitative evaluation of the implementation of the contingency plan carried out. RESULTS: The Intestinal Inflammatory Disease Unit of the Digestive Service has obtained an assessment of compliance with the 10 recommended measures to confidently face a pandemic. CONCLUSIONS: Sharing the deployment of the contingency plan and its results is useful to identify good practices. This article shows a method to evaluate decision-making in pandemic situations. The outcomes faces the The Intestinal Inflammatory Disease Unit in an excelent position

Access to Care Matters: Remote Health Care Needs During COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic is straining health care worldwide with >31 million confirmed cases. Currently, 1 in every 100 U.S. residents and 245,000 in New York City are confirmed positive. The Bronx, with high-risk comorbidities, due in part to socioeconomic factors, has seen disproportionately higher rates of COVID-19-related complications. Poor health care access is exacerbated as in-person visits now pose viral transmission risk. There has been limited discourse regarding widespread disparities underlying transitions to telemedicine. Methods: We review perspectives in recent literature on telemedicine and its potential within neurology. Results: While telemedicine has reduced strain on in-person visits, preliminary reflections highlight implementation successes and challenges. Conclusions: To provide effective care beyond this crisis, fundamental changes in training, technological accessibility, and health care policy are needed. We propose open access to telehealth training, screening of patient's potential technological inequities and socioeconomic insecurities, and advocacy to secure broad long-term access to telehealth care.