Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos, artículos en preprint y noticias científicas actualizado al 23 de Abril de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos, artículos en preprint y revisiones sistemáticas actualizado al 24 de Abril de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos, revisiones sistemáticas y noticias científicas actualizado al 27 de Abril de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 01 de Junio de 2020.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 02 de Junio de 2020.

INTRODUCTION: SARS-CoV-2 is a novel virus from the coronavirus family that emerged in the Hubei province of China in December 2019 and rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared a global pandemic. Infection with SARS-CoV-2 causes coronavirus disease 19 (COVID19) which can be fatal. There is an obvious and pressing need for research surrounding SARS-CoV-2 that will aid in eradication of this pandemic. OBJECTIVE: The goal of this study was to absolve the dire need for small animal models of human disease that demonstrate hallmark pathological features of infection. Due to ethical and financial obstacles, the use of animals that closely resemble human immunity, such as non-human primates, is often not a viable option. For this reason, there is a push to develop small animal models that can mimic human disease responses, particularly those in viral infections that have a narrow species tropism. To achieve this in the context of the novel coronavirus, SARS-CoV-2, we studied various mouse models and their capacity to become infected with and mount an immune response to SARS-CoV-2. Our goal was to identify a model that sufficiently mimics severe COVID19 seen in humans as well as provide molecular insight into pathways that prevent the development of severe disease. METHODS: NRG-L and HIS-NRGF-L mice were subcutaneously implanted with human fetal lung xenografts and infected with SARS-CoV-2. Tissues were stained with H&E for histopathological scoring. NRG-L and HIS-NRGF-L tissues were fluorescently labeled using 2 different multiplex immunohistochemistry panels. Slides were digitized by a Vectra Polaris™ fluorescent whole slide scanner and digital analysis was completed using HALO™. Statistical analysis was conducted using GraphPad Prism™ 9.0.1. RESULTS: Infected NRG-L mice present extensive histopathological manifestations when compared to uninfected controls. Cumulative histology scores at both 2 and 7DPI were increased when compared to uninoculated fLX. Neutrophil influx, intra-airspace necrosis, capillary fibrin thrombi, and presence of syncytial cells were the most significant independent observations that contributed to the increased cumulative score. Together these findings indicate that fLX inoculated with SARS-CoV-2 faithfully recapitulate several features of diffuse alveolar damage (DAD) described in severe COVID-19. HIS-NRGF-L mice displayed decreased influx of neutrophils, intra-airway necrosis, and syncytial cells when compared to NRG-L fLX. Hemorrhage was decreased at both 2 and 7 DPI for HIS-NRGF-L fLX compared to NRG-L fLX. Cumulative histology scores were decreased in HIS-NRGF-L fLX at 7 DPI when compared to NRG-L fLX. Taken together these findings support the hypothesis that human myeloid and lymphoid infiltrates suppress or prevent the disparate host response observed in NRGL-L fLX that manifested in pronounced diffuse alveolar damage. CONCLUSION: Using digital image analysis of multiplex immunohistochemistry paired with semi-quantitative histopathological scoring, this study characterized important hallmark lesions observed in severe COVID19 as seen in small animal models. NRG-L and HIS-NRGF-L mice that are subcutaneously implanted with human fetal lung xenografts are susceptible to infection with SARS-CoV-2 and can produce severe and moderate disease phenotypes respectively. Co-engraftment with human fetal lung tissue and human immune system components in HIS-NRGF-L mice suppresses the divergent host response that is observed in NRG-L mice. For this reason, NRG-L mice engrafted with fLX are an ideal small animal model of severe COVID19, whereas HIS-NRGF-L mice severe as a valuable and informative model for deciphering molecular mechanisms driving severe COVID-19 that will serve as targets for therapeutic development.

This work details the inhibition of BACE1, BACE2, and SARS-CoV-2 3CLpro through several novel and potent protease inhibitors. Nanomolar potency of BACE1 and BACE2 is achieved with all tested inhibitors, and the S2 subsite has been identified as a BACE2 selectivity determinant. This is supported by the observation that the novel BACE2 mutant, BACE2 L246N, displays increased potency and selectivity over BACE1 against this peptidomimetic scaffold. Nanomolar to micromolar potency of SARS-CoV-2 3CLpro is achieved with the compounds tested in this study. Kinetic data illustrates the allowed substitutions at the P1’, P1, P2, and P4 positions on two scaffolds: ML188 and GC376. Finally, this work presents the high-resolution crystal structures of four inhibitors bound to BACE1 and 12 inhibitors bound to SARS-CoV-2 3CLpro. These structural data help to explain the selectivity determinants of BACE1 and BACE2 and further enable structure-based drug design against these two enzymes for the treatments of Alzheimer's Disease and Type II Diabetes, respectively. Additionally, these structural data illustrate the flexibility of the GC376 scaffold at the P3/P4 position, providing a structural rationale for the observed differences in potency across the different analogs. These structural data further enable structure-based drug design against SARS-CoV-2 3CLpro for the treatment of COVID-19.

Användandet av e-hälsa har ökat både nationellt och internationellt de senaste åren. Under SARS-CoV-2-pandemin har nyttjandet i Sverige varit explosionsartat, då icke-fysiska möten minimerar risken för smittspridning. Tidigare forskning visar att e-hälsa har positiva effekter, men ses också som ett hot av distriktssköterskor. Studien belyser därför distriktssköterskans upplevelse av arbetet med e-hälsa under den pågående pandemin och är en kvantitativ enkätstudie med induktiv ansats. Deltagarna rekryterades med hjälp av bekvämlighetsurval och begränsades till legitimerade sjuksköterskor och specialistsjuksköterskor inom primärvården. Den totala svarsfrekvensen var 48 %. Analysen av enkäterna genomfördes med hjälp av IBM SPSS Statistics. De analyser som utfördes var Spearmans rangkorrelation och Kruskal-Wallis icke-parametriska test. Resultatet visade att det fanns en brist i utbildning kring e-hälsa hos informanterna. E-hälsotjänsterna var inte användarvänliga och de var tidskrävande för informanterna. Tid avsattes inte heller för arbetet med e-hälsa på arbetsplatserna. Det fanns potential för minskad smittspridning av SARS-CoV-2 genom arbetet med e-hälsa förutsatt att den vård som gavs genom e-hälsa var av god kvalitet. Ytterligare studier bör genomföras för att få en djupare förståelse för vad som kan och bör förbättras med e-hälsotjänsterna.

El SARS-CoV-2 es un virus ARN monocatenario de la familia de los coronavirus, causante de la COVID-19 (Coronavirus Disease 2019). Este virus es responsable de la pandemia actual que, desde su aparición a finales de 2019, ha provocado la muerte de millones de personas y ha tenido un impacto global no solo a nivel sanitario sino también económico y social. Por ello, el presente artículo tiene como objetivo revisar la información más actualizada sobre el SARS-CoV-2, empezando por describir los mecanismos de transmisión del virus, su fisiopatología y filogenética. Asimismo, presentará a las variantes emergentes del SARS-CoV-2, su relevancia para la salud pública local y global, su epidemiología en Perú, y finalmente, el rol y la importancia de las vacunas en este contexto. / SARS-CoV-2 is a single-stranded RNA virus of the coronavirus family, which causes COVID-19 (Coronavirus Disease 2019). This virus is responsible for the current pandemic, which, since its emergence in late 2019, has caused millions of deaths and has had a global impact not only on public health but also on social and economic areas. Therefore, this article aims to review the most up-to-date information on SARS-CoV-2, beginning with the description of the pathophysiology and phylogenetics of the virus. Also, we will present the emerging SARS-CoV-2 variants, their relevance for local and global public health, their epidemiology in Peru, and finally, the role and importance of vaccines in this context.

Se realizó un estudio descriptivo en el que se evaluaron las características clínicas y laboratoriales en la evolución de pacientes con diagnóstico de síndrome de distrés respiratorio agudo (SDRA) secundario a infección por SARS-CoV-2 y que recibieron Tocilizumab. Veinticuatro pacientes recibieron Tocilizumab, la mayoría eran varones (95,8 %), la comorbilidad más frecuente fue obesidad (33,3 %), al momento de recibir Tocilizumab la mediana de PaO2/FiO2 fue 159,5 (RIC 114,5-255,3). Veintiún (87,5 %) pacientes presentaron mejoría clínica y 3 (12,5 %) fallecieron. Quince pacientes (62,5 %) desarrollaron hepatotoxicidad, la mayoría de grado 3 (33,3 %) y tres (12,5 %) pacientes presentaron injuria hepática grado 4. Once pacientes (45,8 %) presentaron sobreinfección bacteriana, siendo el germen más frecuente Acinetobacter baumannii. Luego de la administración de Tocilizumab más de la mitad de los pacientes presentó una reacción adversa, a pesar de ello la mortalidad fue baja y la mayoría tuvo una mejora clínica. / A descriptive study was carried out, in which clinical and laboratory characteristics were evaluated in patients with a diagnosis of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection and who received Tocilizumab. Twentyfour patients received Tocilizumab, the majority were male (95.8%), the most frequent comorbidity was obesity (33.3%). At the time of receiving Tocilizumab the median PAO2 / FiO2 was 159.5 (IQR 114.5-255, 3). Twenty-one (87.5%) patients presented clinical improvement and 3 (12.5%) died. Fifteen patients (62.5%) developed hepatotoxicity, the majority grade 3 (33.3%) and three (12.5%) patients presented grade 4 liver injury. Eleven patients (45.8%) presented bacterial superinfection, the more common organism being Acinetobacter baumannii. After the administration of Tocilizumab, more than half of the patients presented an adverse reaction; despite this, mortality was low, and the majority had a clinical improvement.