Cognitive dysfunctions in the course of SARS­CoV­2 virus infection, including NeuroCOVID, frontal syndrome and cytokine storm (Review).

During the coronavirus disease 2019 (COVID-19) pandemic, cognitive impairment of varying degrees of severity began to be observed in a significant percentage of patients. The present study discussed the impact of immunological processes on structural and functional changes in the central nervous system and the related cognitive disorders. The purpose of the present review was to analyse and discuss available information from the scientific literature considering the possible relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection and cognitive impairment, including NeuroCOVID, frontal syndrome and cytokine storm. A systematic literature review was conducted using: Google Scholar, Elsevier and the PubMed database. When searching for materials, the following keywords were used: 'cognitive dysfunctions', 'SARS-CoV-2', 'COVID-19', 'Neuro-SARS2', 'NeuroCOVID', 'frontal syndrome', 'cytokine storm', 'Long COVID-19'. A total of 96 articles were included in the study. The analysis focused on the characteristics of each study's materials, methods, results and conclusions. SARS-CoV-2 infection may induce or influence existing cognitive disorders of various nature and severity. The influence of immunological factors related to the response against SARS-CoV-2 on the disturbance of cerebral perfusion, the functioning of nerve cells and the neuroprotective effect has been demonstrated. Particular importance is attached to the cytokine storm and the related difference between pro- and anti-inflammatory effects, oxidative stress, disturbances in the regulation of the hypothalamic-pituitary-adrenal axis and the stress response of the body.

A high-throughput response to the SARS-CoV-2 pandemic.

Four years after the beginning of the COVID-19 pandemic, it is important to reflect on the events that have occurred during that time and the knowledge that has been gained. The response to the pandemic was rapid and highly resourced; it was also built upon a foundation of decades of federally funded basic and applied research. Laboratories in government, pharmaceutical, academic, and non-profit institutions all played roles in advancing pre-2020 discoveries to produce clinical treatments. This perspective provides a summary of how the development of high-throughput screening methods in a biosafety level 3 (BSL-3) environment at Southern Research Institute (SR) contributed to pandemic response efforts. The challenges encountered are described, including those of a technical nature as well as those of working under the pressures of an unpredictable virus and pandemic.

The impact of COVID-19 on healthcare booking and cancellation patterns: time series analysis of private healthcare service utilisation in Finland.

BACKGROUND: COVID-19 has had wide-reaching effects on healthcare services beyond the direct treatment of the pandemic. Most current studies have reported changes in realised service usage, but the dynamics of how patients engage with healthcare services are less well understood. We analysed the effects of COVID-19 on healthcare bookings and cancellations for various service channels between January 2020 and July 2021. METHODS: Our data includes 7.3 million bookings, 11.0 million available appointments, and 405.1 thousand cancellations by 900.6 thousand individual patients between the ages of 18 and 65 years. The data were collected from electronic health record data, including laboratory and imaging services as well as inpatient stays, between January 2017 and July 2021. The patients were Finnish private and occupational healthcare customers in the capital region of Finland. We fitted an autoregressive moving average (ARIMA) model on data between 2017 and 2019 to predict the expected numbers of bookings, available appointments, and cancellations, which were compared to observed time series data between 2020 and 2021. RESULTS: Utilisation of physical, in-person primary care physician appointments decreased by up to 50% during the first 18 months of the pandemic. At the same time, digital care channels experienced a rapid, multi-fold increase in service usage. Simultaneously, the number of bookings for laboratory and imaging services decreased by 50% below the pre-pandemic projections. The number of specialist and hospital service bookings remained at the predicted level during the study period. Cancellations for most health services increased sharply by up to three times the pre-COVID levels during the first weeks of the pandemic but returned to the pre-pandemic levels for the rest of the study period. CONCLUSIONS: The reduction in in-person appointments and the increase in the utilisation of digital services was likely a contributing factor in the decrease of the utilisation of diagnostic and imaging services throughout the study period. Utilisation of specialist care and hospital services were not affected. Cancellations contributed to the changes in service utilisation only during the first weeks of the pandemic.

Comparable outcomes of outpatient remdesivir and sotrovimab among high-risk patients with mild to moderate COVID-19 during the omicron BA.1 surge.

Studies conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness has not been directly compared. This study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Among 3257 patients, 2158 received sotrovimab and 1099 received remdesivir. Patients treated with sotrovimab were younger and had lower comorbidity but were more likely to be immunocompromised than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine. COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab, respectively, p = .15) and mortality within 28 days (0.4% in both groups, p = .82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the outcomes between the two groups. We demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab.

Does a Low Score in the Respiratory Visual Triage Tool Predict a Negative COVID-19 Test in an Admitted Patient?

Background: Fast and accurate COVID-19 identification is important to population and epidemic monitoring in hospitals. Visual triage or respiratory triage should be efficient and utilized as visual clues to alert HCWs on the case definitions. Objective: This study aims to evaluate the diagnostic value of the respiratory triage for COVID-19 infections and to evaluate the efficacy of the MOH triage tool in identifying low risk patients. Methods: A single-center retrospective chart review that was conducted at King Fahd Hospital of the University (KFHU), Khober, KSA on all adult patients admitted to the hospital through the ED. The visual triage checklist comprises two main sections, with one focused on the risk of exposure and the other related to patient clinical signs and symptoms, each with a defined score where any score ≥ 4 will need to isolate and assessed by the physician while a score of less than 4 means that the patient can be admitted with other patients. The hospital swabbed all admitted patients regardless of their score. We compared their PCR result with their case definition score. The collected data was entered and analyzed using the Statistical Package for the Social Science (SPSS Inc. Chicago, IL, USA) version 23. Results: The study included 7258 participants. 20% of participants aged between 21 to 30 years old, 52.2% of sample were females, and 78% were Saudi nationality. Visual triage score was less than 4 in n= 4745 participants (65.4%) and 4 or more in n= 2513 (34.6%). The test had sensitivity of 75% and specificity 21%. Conclusion: Most studies shows that COVID 19 has an infectivity rate of 18 to 30%. Based on this low sensitivity result, using the screening tool alone puts patients and HCWs at risk of getting infected with COVID 19.

Prevalence and Impact of Gastrointestinal Manifestations in COVID-19 Patients: A Systematic Review.

Background and objective: The aim of this study is to systematically analyze and summarize the implications of COVID-19 on the digestive system by quantitatively evaluating the prevalence of gastrointestinal symptoms such as nausea, vomiting, abdominal pain, constipation, diarrhea, anorexia. reported in COVID-19 cases. We simultaneously investigated other variables to determine the association of such symptoms in COVID-19 patients which can potentially influence the disease prognosis and outcome. This systematic review presents an updated literature on the issue as it requires more scientific discussion in order to better inform the medical community and authorities so that appropriate measures can be taken to control the virus outbreak. Methods: MEDLINE database was searched to identify relevant articles. Data was analyzed and synthesized from the 16 eligible studies which exclusively reported GI symptoms in COVID-19 patients along with the disease prognosis. A meta-analysis of studies having adequate information regarding the prevalence of specific GI symptoms in association with other relevant independent variables was performed. Results: From the search strategy, we identified 16 articles which fit our eligibility criteria comprising of 10 cross-sectional studies, 2 cohort study, 1 RCT and 3 observational studies. From these pooled studies, 6 articles exclusively talked about COVID-19 patients in which GI symptoms were reported and adequately discussed. In a total of 3646 patients, GI symptoms were documented in (16.2%-10.1%) patients. The most prevalent GI symptom was diarrhea (47%) but the most common clinical manifestation reported was fever (77.4%). Among the adult patients, hypertension (11.6%) was the most frequently reported comorbidity. Presence of viral RNA in stool sample was noted in 16.7% patients with GI symptom. In patients who complained of having GI symptoms, an abnormal liver function was largely observed, with an elevated ALT level in (10.9%) and an elevated AST in (8.8%) of the patients. Evidence of vertical transmission (14.2%) was reported in one study which highlights the extent and mode of viral transmission. It was observed that a great majority of the patients in the 6 studies reporting specifically on patients with GI symptoms were on antiviral therapy (68.6%) as the standard disease management protocol but the eventual disease outcome as in this case died (8.4%), discharged (45.6%) was not linked to just one therapeutic factor but other indicators of disease severity such as positive chest CT findings (87.82%) have led to a poor disease prognosis which was noted in (28.9%) severe patients with GI symptoms compared to (71.1%) non-severe COVID-19 patients with GI symptom. Conclusion: Presence of GI symptoms in COVID-19 patients has shown to have a positive association with the poor disease prognosis likely as a result of direct viral toxicity. It is important for the physicians to recognize digestive symptoms as an important characteristic in COVID-19 patients. Hence, precise and targeted documentation of GI symptoms and viral stool sample investigations should be performed in order to understand the rapidly evolving disease symptomology.

Impact of COVID-19 lockdown on injury risk in Qatar's professional football.

OBJECTIVES: To compare injury incidence, burden and characteristics between the pre- and post-COVID-19 lockdown periods in Qatari professional football. DESIGN: Prospective cohort study. METHODS: Injury and exposure data for two post-COVID-19 lockdown periods [early post-lockdown period: short-term ~2 months (54 matches) and late post-lockdown period: long-term 8-months (183 matches)] were compared to the benchmark of the same periods from the three previous seasons (2017/18-2019/20). RESULTS: We observed no difference in overall, training or match incidence between early post-lockdown period and the benchmark reference. However, this short-term period resulted in lower burden for overall- (RR 0.80, P < 0.0001), training- (RR 0.73, P < 0.0001) and match-injuries (RR 0.40, P < 0.0001) compared to the benchmark. During late post-lockdown period match injury incidence (RR 0.72, P = 0.0010) and match injury burden (RR 0.69, P < 0.001) were lower than the benchmark. In contrast, both overall- (RR 1.30, P < 0.001) and training-injury burden (RR 1.65, P < 0.001) were higher. A significant increase in adductor strains in both post-lockdown periods was observed. CONCLUSIONS: Immediately after the COVID-19 lockdown (short-term effect), there was no difference in injury incidence but a lower injury burden compared to benchmark. Moreover, the rapid return to competition for the successive season (long-term effect) was associated with a higher overall- and training-injury burden, but a lower match-injury burden compared to the benchmark.

Electrogenic Staphylococcus epidermidis colonizes nasal cavities and alleviates IL-6 progression induced by the SARS2-CoV nucleocapsid protein.

AIM: Certain probiotic bacteria have been shown to possess an immunomodulatory effect and a protective effect on influenza infections. Using the Staphylococcus epidermidis K1 colonized mice model, we assessed the effect of nasal administration of glycerol or flavin mononucleotide (FMN) on the production of interleukin (IL)-6 mediated by the severe acute respiratory syndrome coronavirus 2 (SARS2-CoV) nucleocapsid protein (NPP). METHODS AND RESULTS: FMN, one of the key electron donors for the generation of electricity facilitated by S. epidermidis ATCC 12228, was detected in the glycerol fermentation medium. Compared to the S. epidermidis ATCC 12228, the S. epidermidis K1 isolate showed significant expression of the electron transfer genes, including pyruvate dehydrogenase (pdh), riboflavin kinase (rk), 1,4-dihydroxy-2-naphthoate octaprenyltransferase (menA), and type II NADH quinone oxidoreductase (ndh2). Institute of cancer research (ICR) mice were intranasally administered with S. epidermidis K1 with or without pretreatment with riboflavin kinase inhibitors, then nasally treated with glycerol or FMN before inoculating the NPP. Furthermore, J774A.1 macrophages were exposed to NPP serum and then treated with NPP of SARS2-CoV. The IL-6 levels in the bronchoalveolar lavage fluid (BALF) of mice and macrophages were quantified using a mouse IL-6 enzyme-linked immunosorbent assay kit. CONCLUSIONS: Here, we report that nasal administration of NPP strongly elevates IL-6 levels in both BALF and J774A.1 macrophages. It is worth noting that NPP-neutralizing antibodies can decrease IL-6 levels in macrophages. The nasal administration of glycerol or FMN to S. epidermidis K1-colonized mice results in a reduction of NPP-induced IL-6 production.

Application of thermography to estimate respiratory rate in the emergency room: The journal Temperature toolbox.

Among the vital signs collected during hospital triage, respiratory rate is an important parameter associated with physiological, pathophysiological, and emotional changes. In recent years, the importance of its verification in emergency centers due to the severe acute respiratory syndrome 2 (SARS2) pandemic has become very clear, although it is still one of the least evaluated and collected vital signs. In this context, infrared imaging has been shown to be a reliable estimator of respiratory rate, with the advantage of not requiring physical contact with patients. The objective of this study was to evaluate the potential of analyzing a sequence of thermal images as an estimator of respiratory rate in the clinical routine of an emergency room. We used an infrared thermal camera (T540, Flir Systems) to obtain the respiratory rate data of 136 patients, based on nostrils' temperature fluctuation, during the peak of the COVID-19 pandemic in Brazil and compared it with the chest incursion count method, commonly employed in the emergency screening procedures. We found a good agreement between both methods, with Bland-Altman limits of agreement ranging from -4 to 4 min-1, no proportional bias (R2 = 0.021, p = 0.095), and a strong correlation between them (r = 0.95, p < 0.001). Our results suggest that infrared thermography has potential to be a good estimator of respiratory rate in the routine of an emergency room.

Identification and characterization of 7-azaindole derivatives as inhibitors of the SARS-CoV-2 spike-hACE2 protein interaction.

The COVID-19 pandemic, caused by SARS-CoV-2, has become a global public health crisis. The entry of SARS-CoV-2 into host cells is facilitated by the binding of its spike protein (S1-RBD) to the host receptor hACE2. Small molecule compounds targeting S1-RBD-hACE2 interaction could provide an alternative therapeutic strategy sensitive to viral mutations. In this study, we identified G7a as a hit compound that targets the S1-RBD-hACE2 interaction, using high-throughput screening in the SARS2-S pseudovirus model. To enhance the antiviral activity of G7a, we designed and synthesized a series of novel 7-azaindole derivatives that bind to the S1-RBD-hACE2 interface. Surprisingly, ASM-7 showed excellent antiviral activity and low cytotoxicity, as confirmed by pseudovirus and native virus assays. Molecular docking and molecular dynamics simulations revealed that ASM-7 could stably bind to the binding interface of S1-RBD-hACE2, forming strong non-covalent interactions with key residues. Furthermore, the binding of ASM-7 caused alterations in the structural dynamics of both S1-RBD and hACE2, resulting in a decrease in their binding affinity and ultimately impeding the viral invasion of host cells. Our findings demonstrate that ASM-7 is a promising lead compound for developing novel therapeutics against SARS-CoV-2.

Clinical outcomes of COVID-19 treated with remdesivir across the continuum of care.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results: Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p < 0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

Structural patterns of SARS-CoV-2 variants of concern (alpha, beta, gamma, delta) spike protein are influenced by variant-specific amino acid mutations: A computational study with implications on viral evolution.

SARS-CoV-2 (SARS2) regularly mutates resulting to variants of concern (VOC) which have higher virulence and transmissibility rates while concurrently evading available therapeutic strategies. This highlights the importance of amino acid mutations occurring in the SARS2 spike protein structure since it may affect virus biology. However, this was never fully elucidated. Here, network analysis was performed based on the COVID-19 genomic epidemiology network between December 2019-July 2021. Representative SARS2 VOC spike protein models were generated and quality checked, protein model superimposition was done, and common contact based on contact mapping was established. Throughout this study, we found that: (1) certain individual variant-specific amino acid mutations can affect the spike protein structural pattern; (2) certain individual variant-specific amino acid mutations had no affect on the spike protein structural pattern; and (3) certain combination of variant-specific amino acids are putatively epistatic mutations that can potentially influence the VOC spike protein structural pattern. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Network analysis of the autophagy biochemical network in relation to various autophagy-targeted proteins found among SARS-CoV-2 variants of concern.

Autophagy is an important cellular process that triggers a coordinated action involving multiple individual proteins and protein complexes while SARS-CoV-2 (SARS2) was found to both hinder autophagy to evade host defense and utilize autophagy for viral replication. Interestingly, the possible significant stages of the autophagy biochemical network in relation to the corresponding autophagy-targeted SARS2 proteins from the different variants of concern (VOC) were never established. In this study, we performed the following: autophagy biochemical network design and centrality analyses; generated autophagy-targeted SARS2 protein models; and superimposed protein models for structural comparison. We identified 2 significant biochemical pathways (one starts from the ULK complex and the other starts from the PI3P complex) within the autophagy biochemical network. Similarly, we determined that the autophagy-targeted SARS2 proteins (Nsp15, M, ORF7a, ORF3a, and E) are structurally conserved throughout the different SARS2 VOC suggesting that the function of each protein is preserved during SARS2 evolution. Interestingly, among the autophagy-targeted SARS2 proteins, the M protein coincides with the 2 significant biochemical pathways we identified within the autophagy biochemical network. In this regard, we propose that the SARS2 M protein is the main determinant that would influence autophagy outcome in regard to SARS2 infection.

Death caused by covid-19 in top ten countries in Asia affected by covid-19 pandemic with special reference to Pakistan / Morte causada por covid-19 nos dez principais países da Ásia afetados pela pandemia de covid-19, com referência especial ao Paquistão

Abstract The COVID-19 is a contagious viral disease, was first emerged in Wuhan, China in December 2019 and became the whole world on alert. The mortality rate in top most countries in Asia with special reference to Pakistan has been focused. Since February 26 to September 2020 the total confirmed cases and mortality rate was measured through Wikipedia and the notable journals. Iran is the only country having highest number of deaths (5.73%) followed by Indonesia (3.77%) while Saudi Arabia shows the lowest number of deaths as 1.39%. In Pakistan the first case was confirmed in 26th February, 2020. The nCov-19 has closely related to severe acute respiratory syndrome (SARS) hence SARS COV-2 was named. This virus is responsible for more than 33.9 million deaths in over all the world as of 20th September, 2020. The number of new cases is increasing time to time. Sindh province of Pakistan has reported the highest number of cases till September, 20, 2020 as compared to other parts of the country and has the highest number of death followed by Khyber Pakhtunkhwa. Because of the person to person contact the disease is spreading rapidly. The individuals who has already infected with other diseases like cancer or diabetic etc. are vulnerable. The nCOV-19 is the most contagious due to its mode of transmission. There is still no vaccine is available for the treatment of disease caused by nCoV-2019. It is therefore the only option to control this pandemic is to adopt effective preventive measures.

Resumo A covid-19 é uma doença viral contagiosa, que surgiu pela primeira vez em Wuhan, China, em dezembro de 2019, e deixou o mundo todo em alerta. A taxa de mortalidade na maioria dos principais países da Ásia, com referência especial ao Paquistão, foi enfocada. De 26 de fevereiro a setembro de 2020, o total de casos confirmados e a taxa de mortalidade foram medidos por meio da Wikipedia e de periódicos notáveis. O Irã é o único país com maior número de mortes (5,73%), seguido pela Indonésia (3,77%), enquanto a Arábia Saudita mostra o menor número de mortes, 1,39%. No Paquistão, o primeiro caso foi confirmado em 26 de fevereiro de 2020. O nCov-19 está intimamente relacionado à síndrome respiratória aguda grave (SARS), daí o nome SARS COV-2. Esse vírus é responsável por mais de 33,9 milhões de mortes em todo o mundo em 20 de setembro de 2020. O número de novos casos está aumentando de tempos em tempos. A província de Sindh, no Paquistão, registrou o maior número de casos até 20 de setembro de 2020, em comparação com outras partes do país, e tem o maior número de mortes, seguida por Khyber Pakhtunkhwa. Por causa do contato pessoa a pessoa, a doença está se espalhando rapidamente. Indivíduos que já foram diagnosticados com outras doenças, como câncer ou diabetes, etc. são mais vulneráveis. O nCOV-19 é o mais contagioso devido ao seu modo de transmissão. Ainda não há vacina disponível para o tratamento da doença causada pelo nCoV-2019. Portanto, a única opção para controlar essa pandemia é a adoção de medidas preventivas eficazes.

Death caused by covid-19 in top ten countries in Asia affected by covid-19 pandemic with special reference to Pakistan / Morte causada por covid-19 nos dez principais países da Ásia afetados pela pandemia de covid-19, com referência especial ao Paquistão

The COVID-19 is a contagious viral disease, was first emerged in Wuhan, China in December 2019 and became the whole world on alert. The mortality rate in top most countries in Asia with special reference to Pakistan has been focused. Since February 26 to September 2020 the total confirmed cases and mortality rate was measured through Wikipedia and the notable journals. Iran is the only country having highest number of deaths (5.73%) followed by Indonesia (3.77%) while Saudi Arabia shows the lowest number of deaths as 1.39%. In Pakistan the first case was confirmed in 26th February, 2020. The nCov-19 has closely related to severe acute respiratory syndrome (SARS) hence SARS COV-2 was named. This virus is responsible for more than 33.9 million deaths in over all the world as of 20th September, 2020. The number of new cases is increasing time to time. Sindh province of Pakistan has reported the highest number of cases till September, 20, 2020 as compared to other parts of the country and has the highest number of death followed by Khyber Pakhtunkhwa. Because of the person to person contact the disease is spreading rapidly. The individuals who has already infected with other diseases like cancer or diabetic etc. are vulnerable. The nCOV-19 is the most contagious due to its mode of transmission. There is still no vaccine is available for the treatment of disease caused by nCoV-2019. It is therefore the only option to control this pandemic is to adopt effective preventive measures.

A covid-19 é uma doença viral contagiosa, que surgiu pela primeira vez em Wuhan, China, em dezembro de 2019, e deixou o mundo todo em alerta. A taxa de mortalidade na maioria dos principais países da Ásia, com referência especial ao Paquistão, foi enfocada. De 26 de fevereiro a setembro de 2020, o total de casos confirmados e a taxa de mortalidade foram medidos por meio da Wikipedia e de periódicos notáveis. O Irã é o único país com maior número de mortes (5,73%), seguido pela Indonésia (3,77%), enquanto a Arábia Saudita mostra o menor número de mortes, 1,39%. No Paquistão, o primeiro caso foi confirmado em 26 de fevereiro de 2020. O nCov-19 está intimamente relacionado à síndrome respiratória aguda grave (SARS), daí o nome SARS COV-2. Esse vírus é responsável por mais de 33,9 milhões de mortes em todo o mundo em 20 de setembro de 2020. O número de novos casos está aumentando de tempos em tempos. A província de Sindh, no Paquistão, registrou o maior número de casos até 20 de setembro de 2020, em comparação com outras partes do país, e tem o maior número de mortes, seguida por Khyber Pakhtunkhwa. Por causa do contato pessoa a pessoa, a doença está se espalhando rapidamente. Indivíduos que já foram diagnosticados com outras doenças, como câncer ou diabetes, etc. são mais vulneráveis. O nCOV-19 é o mais contagioso devido ao seu modo de transmissão. Ainda não há vacina disponível para o tratamento da doença causada pelo nCoV-2019. Portanto, a única opção para controlar essa pandemia é a adoção de medidas preventivas eficazes.

Death caused by covid-19 in top ten countries in Asia affected by covid-19 pandemic with special reference to Pakistan

Abstract The COVID-19 is a contagious viral disease, was first emerged in Wuhan, China in December 2019 and became the whole world on alert. The mortality rate in top most countries in Asia with special reference to Pakistan has been focused. Since February 26 to September 2020 the total confirmed cases and mortality rate was measured through Wikipedia and the notable journals. Iran is the only country having highest number of deaths (5.73%) followed by Indonesia (3.77%) while Saudi Arabia shows the lowest number of deaths as 1.39%. In Pakistan the first case was confirmed in 26th February, 2020. The nCov-19 has closely related to severe acute respiratory syndrome (SARS) hence SARS COV-2 was named. This virus is responsible for more than 33.9 million deaths in over all the world as of 20th September, 2020. The number of new cases is increasing time to time. Sindh province of Pakistan has reported the highest number of cases till September, 20, 2020 as compared to other parts of the country and has the highest number of death followed by Khyber Pakhtunkhwa. Because of the person to person contact the disease is spreading rapidly. The individuals who has already infected with other diseases like cancer or diabetic etc. are vulnerable. The nCOV-19 is the most contagious due to its mode of transmission. There is still no vaccine is available for the treatment of disease caused by nCoV-2019. It is therefore the only option to control this pandemic is to adopt effective preventive measures.

Resumo A covid-19 é uma doença viral contagiosa, que surgiu pela primeira vez em Wuhan, China, em dezembro de 2019, e deixou o mundo todo em alerta. A taxa de mortalidade na maioria dos principais países da Ásia, com referência especial ao Paquistão, foi enfocada. De 26 de fevereiro a setembro de 2020, o total de casos confirmados e a taxa de mortalidade foram medidos por meio da Wikipedia e de periódicos notáveis. O Irã é o único país com maior número de mortes (5,73%), seguido pela Indonésia (3,77%), enquanto a Arábia Saudita mostra o menor número de mortes, 1,39%. No Paquistão, o primeiro caso foi confirmado em 26 de fevereiro de 2020. O nCov-19 está intimamente relacionado à síndrome respiratória aguda grave (SARS), daí o nome SARS COV-2. Esse vírus é responsável por mais de 33,9 milhões de mortes em todo o mundo em 20 de setembro de 2020. O número de novos casos está aumentando de tempos em tempos. A província de Sindh, no Paquistão, registrou o maior número de casos até 20 de setembro de 2020, em comparação com outras partes do país, e tem o maior número de mortes, seguida por Khyber Pakhtunkhwa. Por causa do contato pessoa a pessoa, a doença está se espalhando rapidamente. Indivíduos que já foram diagnosticados com outras doenças, como câncer ou diabetes, etc. são mais vulneráveis. O nCOV-19 é o mais contagioso devido ao seu modo de transmissão. Ainda não há vacina disponível para o tratamento da doença causada pelo nCoV-2019. Portanto, a única opção para controlar essa pandemia é a adoção de medidas preventivas eficazes.

Tryptophan Metabolism 'Hub' Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease.

The epithelial barrier's primary role is to protect against entry of foreign and pathogenic elements. Both COVID-19 and Inflammatory Bowel Disease (IBD) show commonalities in symptoms and treatment with sensitization of the epithelial barrier inviting an immune response. In this study we use a multi-omics strategy to identify a common signature of immune disease that may be able to predict for more severe patient outcomes. Global proteomic approaches were applied to transcriptome and proteome. Further semi- and relative- quantitative targeted mass spectrometry methods were developed to substantiate the proteomic and metabolomics changes in nasal swabs from healthy, COVID-19 (24 h and 3 weeks post infection); serums from Crohn's disease patients (scored for epithelial leak), terminal ileum tissue biopsies (patient matched inflamed and non-inflamed regions, and controls). We found that the tryptophan/kynurenine metabolism pathway is a 'hub' regulator of canonical and non-canonical transcription, macrophage release of cytokines and significant changes in the immune and metabolic status with increasing severity and disease course. Significantly modified pathways include stress response regulator EIF2 signaling (p = 1 × 10-3); energy metabolism, KYNU (p = 4 × 10-4), WARS (p = 1 × 10-7); inflammation, and IDO activity (p = 1 × 10-6). Heightened levels of PARP1, WARS and KYNU are predictive at the acute stage of infection for resilience, while in contrast, levels remained high and are predictive of persistent and more severe outcomes in COVID disease. Generation of a targeted marker profile showed these changes in immune disease underlay resolution of epithelial barrier function and have the potential to define disease trajectory and more severe patient outcomes.

Stakeholders analysis of COVID-19 management and control: a case of Iran.

BACKGROUND: The COVID-19 pandemic is a multi-faceted phenomenon with many political, economic and social consequences. Success in managing and controlling this pandemic depends on the coordinated efforts of many organizations and institutions. Therefore, this study aimed to identify and analyze the actors and stakeholders related to managing and controlling this pandemic in Iran. METHODS: This mix-method stakeholder analysis was conducted in 2021 nationwide as retrospectively. The purposive sampling method was applied when inviting eligible participants to participate in the study. Our study was conducted in two phases. In the qualitative phase, data were collected using a semi-structured interview. An interview guide was developed based on the WHO stakeholder analysis framework. In the quantitative phase, we used a questionnaire developed based on the study framework. Each question was scored on a 5-point Likert scale, with a score greater than 4 was considered as high, 3-4 was considered as moderate, and 1-3 was considered as low. Data were analyzed using framework analysis, WHO stakeholders' analysis framework and MENDELOW matrix. MAXQDA qualitative data analysis software Version 11 and Policy Maker software (Version. 4) were used for data analysis. RESULTS: A total of 48 stakeholders were identified. Ministry of Health (MoH), National Headquarters for Coronavirus Control (NHCC) had the highest participation level, high supportive position, and knowledge of the subject. The Parliament of Iran (PoI), Islamic Revolutionary Guard Corps (IRGC), and Islamic Republic of Iran Broadcasting (IRIB) had the highest power/influence during the Covid-19 epidemic. Only two stakeholders (6.06%) had high participation, and 18.18% had moderate participation. All stakeholders except for the NHCC and the MoH lacked appropriate knowledge of the subject. Furthermore, only three stakeholders (9.09%) had high power/influence. CONCLUSION: Given the multidimensional nature of Covid-19, most institutions and organizations were involved in managing this pandemic. Stakeholders with high power/authority and resources had a low/moderate participation level and a moderate supportive position. Moreover, organizations with a high supportive position and participation had low power/authority and resources to cope with COVID-19.

Antibiotic Resistance during COVID-19: A Systematic Review.

One of the public health issues faced worldwide is antibiotic resistance (AR). During the novel coronavirus (COVID-19) pandemic, AR has increased. Since some studies have stated AR has increased during the COVID-19 pandemic, and others have stated otherwise, this study aimed to explore this impact. Seven databases-PubMed, MEDLINE, EMBASE, Scopus, Cochrane, Web of Science, and CINAHL-were searched using related keywords to identify studies relevant to AR during COVID-19 published from December 2019 to May 2022, according to PRISMA guidelines. Twenty-three studies were included in this review, and the evidence showed that AR has increased during the COVID-19 pandemic. The most commonly reported resistant Gram-negative bacteria was Acinetobacterbaumannii, followed by Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. A. baumannii and K. pneumonia were highly resistant to tested antibiotics compared with E. coli and P. aeruginosa. Moreover, K. pneumonia showed high resistance to colistin. Commonly reported Gram-positive bacteria were Staphylococcus aureus and Enterococcus faecium. The resistance of E. faecium to ampicillin, erythromycin, and Ciprofloxacin was high. Self-antibiotic medication, empirical antibiotic administration, and antibiotics prescribed by general practitioners were the risk factors of high levels of AR during COVID-19. Antibiotics' prescription should be strictly implemented, relying on the Antimicrobial Stewardship Program (ASP) and guidelines from the World Health Organization (WHO) or Ministry of Health (MOH).

The mitochondrial seryl-tRNA synthetase SARS2 modifies onset in spastic paraplegia type 4.

PURPOSE: Hereditary spastic paraplegia type 4 is extremely variable in age at onset; the same variant can cause onset at birth or in the eighth decade. We recently discovered that missense variants in SPAST, which influences microtubule dynamics, are associated with earlier onset and more severe disease than truncating variants, but even within the early and late-onset groups there remained significant differences in onset. Given the rarity of the condition, we adapted an extreme phenotype approach to identify genetic modifiers of onset. METHODS: We performed a genome-wide association study on 134 patients bearing truncating pathogenic variants in SPAST, divided into early- and late-onset groups (aged ≤15 and ≥45 years, respectively). A replication cohort of 419 included patients carrying either truncating or missense variants. Finally, age at onset was analyzed in the merged cohort (N = 553). RESULTS: We found 1 signal associated with earlier age at onset (rs10775533, P = 8.73E-6) in 2 independent cohorts and in the merged cohort (N = 553, Mantel-Cox test, P < .0001). Western blotting in lymphocytes of 20 patients showed that this locus tends to upregulate SARS2 expression in earlier-onset patients. CONCLUSION: SARS2 overexpression lowers the age of onset in hereditary spastic paraplegia type 4. Lowering SARS2 or improving mitochondrial function could thus present viable approaches to therapy.