Molecular docking used as an advanced tool to determine novel compounds on emerging infectious diseases: A systematic review.

Emerging infectious diseases (EID) as well as reappearing irresistible infections are expanding worldwide. Utmost of similar cases, it was seen that the EIDs have long been perceived as a predominant conclusion of host-pathogen adaption. Here, one should get to analyze their host-pathogen interlink and their by needs to look ways, as an example, by exploitation process methodology particularly molecular docking and molecular dynamics simulation, have been utilized in recent time as the most outstanding tools. Hence, we have overviewed some of important factors that influences on EIDs especially HIV/AIDs, H1N1 and coronavirus. Moreover, here we specified the importance of molecular docking applications especially molecular dynamics simulations approach to determine novel compounds on the emerging infectious diseases. Additionally, in vivo and in vitro studies approach to determine novel compounds on the emerging infectious diseases that has implemented to evaluate the limiting affinities between small particles as well as macromolecule that can further, used as a target of HIV/AIDs, H1N1, and coronavirus were also discussed. These novel drug molecules approved in vivo and in vitro studies with reaffirm results and hence, it is clear that the computational methods (mainly molecular docking and molecular dynamics) are found to be more effective technique for drug discovery and medical practitioners.

Statistical Modeling of Deaths from COVID-19 Influenced by Social Isolation in Latin American Countries.

Social isolation is extremely important to minimize the effects of a pandemic. Latin American countries have similar socioeconomic characteristics and health system infrastructures. These countries face difficulties in dealing with the COVID-19 pandemic, and some of them have very high death rates. The government stringency index (GSI) of 12 Latin American countries was gathered from the Oxford COVID-19 Government Response Tracker project. The GSI is calculated by considering nine social distancing and isolation measures. Population data from the United Nations Population Fund and number-of-deaths data were collected from the dashboard of the WHO. We performed an analysis of the data collected from March through December 2020 using a mixed linear model. Peru, Brazil, Chile, Bolivia, Colombia, Argentina, and Ecuador had the highest death rates, with an increasing trend over time. Suriname, Venezuela, Uruguay, Paraguay, and Guyana had the lowest death rates, and these rates remained steady. The GSI in most countries followed the same pattern during the months analyzed. In other words, high indices at the beginning of the pandemic and lower indices in the latter months, whereas the number of deaths increased during the entire period. Almost no country kept its GSI high for a long time, especially from October to December. Time and GSI, as well as their interaction, were highly significant. As their interaction increases, the death rate decreases. In conclusion, a greater GSI at the start of the COVID-19 pandemic was associated with a decrease in the number of deaths over time in Latin American countries.

COVID-19-Associated Pulmonary Aspergillosis in a Series of Complete Autopsies from the Brazilian Amazon.

Between April and July 2020, and, therefore, prior to the broad recommendation of corticosteroids for severe COVID-19, a total of 50 full autopsies were performed in Manaus. We confirmed two invasive cases of aspergillosis through histopathology and gene sequencing (4%) in our autopsy series. The confirmed invasive aspergillosis incidence seems much lower than expected based on the "probable and possible" definitions, and an individualized approach should be considered for each country scenario. Interestingly, a prolonged length of stay in the intensive care unit was not observed in any of the cases. Timely diagnosis and treatment of fungal infection can reduce mortality rates.

A prenylated dsRNA sensor protects against severe COVID-19.

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2'-5'-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.

Hemorrhagic and thrombotic manifestations in the central nervous system in COVID-19: A large observational study in the Brazilian Amazon with a complete autopsy series.

SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.

Correlation Between Clinical and Pathological Findings of Liver Injury in 27 Patients With Lethal COVID-19 Infections in Brazil.

Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID-19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID-19 in Manaus, Brazil. There was a high prevalence of liver injury (elevated alanine aminotransferase and aspartate aminotransferase in 44% and 48% of patients, respectively) in these patients. Histological analysis showed sinusoidal congestion and ischemic necrosis in more than 85% of the cases, but these appeared to be secondary to systemic rather than intrahepatic thrombotic events, as only 14% and 22% of samples were positive for CD61 (marker of platelet activation) and C4d (activated complement factor), respectively. Furthermore, the extent of these vascular findings did not correlate with the extent of transaminase elevations. Steatosis was present in 63% of patients, and portal inflammation was present in 52%. In most cases, hepatocytes expressed angiotensin-converting enzyme 2 (ACE2), which is responsible for binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), even though this ectoenzyme was minimally expressed on hepatocytes in normal controls. However, SARS-CoV-2 staining was not observed. Most hepatocytes also expressed inositol 1,4,5-triphosphate receptor 3 (ITPR3), a calcium channel that becomes expressed in acute liver injury. Conclusion: The hepatocellular injury that commonly occurs in patients with severe COVID-19 is not due to the vascular events that contribute to pulmonary or cardiac damage. However, new expression of ACE2 and ITPR3 with concomitant inflammation and steatosis suggests that liver injury may result from inflammation, metabolic abnormalities, and perhaps direct viral injury.

Healthcare system capacity of the municipalities in the State of Rio de Janeiro: infrastructure to confront COVID-19

Considering the growing number of cases requiring emergency care as a result of SARS-CoV-2 in the Brazilian State of Rio de Janeiro, this study focuses on mapping the health infrastructure of the municipalities of the state, comparing the Structure Efficiency Index (IEE) before (2016) and after the COVID-19 pandemic. The article fills a gap in the academic literature, informing public health policies specialists and technicians, as well as policy and decision-makers, about the capacity of municipalities to face the problem. We calculated the Structure Efficiency Index (IEE) of the states'92 municipalities and positioned them on the pandemic curve. It was possible to verify that the government of the State of Rio de Janeiro needs to start acting to suppress COVID-19, maintaining the policy of providing more hospital beds, and purchasing equipment. However, it is also necessary to consider the particularities and deficiencies of each region, as the policy to transfer patients to places with available beds can contribute to the spread of the disease. Resumen Considerando el número creciente de casos de atención de emergencia procedentes del SARS-CoV-2, en el estado de Río de Janeiro, este estudio se centra en el mapeo de la infraestructura de salud en los municipios de dicho estado, con el fin de informar a los especialistas, técnicos, formuladores y tomadores de decisiones de políticas de salud pública sobre la capacidad de cada localidad para enfrentar el problema. Para esto, calculamos el índice de eficiencia de estructura (IEE) colocando los 92 municipios del estado en la curva de la pandemia. Se pudo verificar que el Gobierno del Estado de Río de Janeiro debe comenzar a actuar para suprimir la COVID-19 manteniendo la política de apertura o reapertura de camas y adquisición de equipos. Sin embargo, también se deben considerar las particularidades y deficiencias de cada región, ya que la política de traslado de pacientes postrados a otras regiones con camas disponibles puede propagar la enfermedad. Resumo Considerando um número crescente de casos de atendimento de emergência, provenientes do SARS-CoV-2, no Estado do Rio de Janeiro, o presente estudo se concentra no mapeamento da infraestrutura de saúde nos municípios do Estado, comparando o Índice de Eficiência em Estrutura antes (2016) e após a pandemia da COVID-19. O artigo preenche uma lacuna acadêmica ao informar aos especialistas, técnicos, formuladores e tomadores de decisão de políticas públicas de saúde, sobre a capacidade de cada localidade para enfrentar o problema. Para isso, calculamos o Índice de Eficiência da Estrutura (IEE), alocando os 92 municípios do Estado na curva de pandemia. Foi possível verificar que o Governo do Estado do Rio de Janeiro precisa começar a atuar na supressão da COVID-19, mantendo a política de abertura, ou reabertura, de leitos e aquisição de equipamentos. No entanto, também é necessário considerar as particularidades e deficiências de cada região, pois a política de transferência dos acamados para outras regiões com leitos disponíveis pode espalhar a doença.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management

We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

Case Report: Adrenal Pathology Findings in Severe COVID-19: An Autopsy Study.

Although high mortality has been reported in many COVID-19 studies, very limited postmortem information from complete autopsies is available. We report the findings in the adrenal glands in 28 autopsies with confirmed SARS-CoV-2 infection. Microscopic lesions were identified in the adrenal glands in 12/28 patients (46%). Seven cases showed necrosis, generally ischemic; four showed cortical lipid degeneration; two showed hemorrhage; and one unspecific focal adrenalitis. Vascular thrombosis in one patient and focal inflammation in association with other findings in three patients were observed. No case presented adrenal insufficiency. In conclusion, adrenal lesions are frequent in patients with severe COVID-19. The lesions are mild but could contribute to the lethal outcome.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management.

We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

Description of Covid-19 Cases in Brazil and Italy.

The emergence of Covid-19 started in China and has rapidly spread across the globe, notably in Italy and more recently to Brazil. This is a very worrying situation for the affected countries. This Brief Communication aims to describe and correlate the number of confirmed cases and deaths of Covid-19 in Brazil and Italy. This is a descriptive and retrospective study that used data collated on the World Health Organization (WHO) online platform between 21 January and 19 April 2020. After analyzing the data, it was observed that the number of confirmed cases and deaths in Brazil is lower than that in Italy. There are certain factors in Brazil which see it in a lower risk position than Italy; however, despite the current slow spread of the virus, the situation in Brazil is difficult to predict.