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Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.

Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.

Quality of life of head and neck cancer patients before and after cancer-directed treatment - A longitudinal study

Context: Head-and-neck cancer (HNC) is a major health problem worldwide and even disproportionately bigger in India. Their diagnosis and treatment create severe impact on the quality of life (QOL). We chose to study such patients because we were already reporting these cancers to the Indian Council of Medical Research as part of project titled "Pattern of care and survival studies." Aims: The aim of the study is to assess and compare QOL of H and N cancer patients before and after the completion of cancer-directed treatment (CDT). Settings and Design: The present study was a hospital-based study conducted in the tertiary care hospital of Jammu with longitudinal study design. Subjects and Methods: All newly diagnosed HNC patients registered with the Department of Radiotherapy and ENT on inpatient or outpatient basis were included over a period of 6 months. Each patient was followed for 4-6 weeks after the completion of CDT. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ C30) (general) and EORTC QLQ H and N-35 (specific) questionnaires. Statistical Analysis: Paired t-test was calculated to compare pre- and postmean scores. Pre- and post-Cronbach alpha reliability coefficient was also calculated. Results: The most frequent site was larynx followed by the oral cavity. Regarding both EORTC QLQ C-30 questionnaire and Global health status and EORTC H and N-35 specific questionnaires, the mean scores across all domains showed worsening of QoL from their baseline. The worsening was more severe in emotional function (functional scale), while physical, cognitive, and social functions were comparatively less affected. Pain, swallowing, speech, and mouth problems were most worsened. Conclusions: QoL showed worsening after CDT in all domains due to acute and subacute adverse effects of chemotherapy and radiotherapy in treatment course.

Recomendaciones para la atención oftalmológica durante el estado de alarma por la pandemia de enfermedad por coronavirus COVID-19./ Recomendaciones para la atención oftalmológica durante el estado de alarma por la pandemia de enfermedad por coronavirus COVID-19./ Recommendations for eye care during the alarm state by the coronavirus disease pandemic COVID-19

OBJECTIVE: Minimize exposure to the SARS-CoV-2, reduce the chances of cross-transmission between patients and healthcare personnel, and prevent the development of postoperative complications from the management of patients with eye diseases during the 2019 coronavirus disease pandemic (COVID-19). METHODS: COVID-19 literature review and consensus establishment between different Spanish ophthalmology societies in order to provide guidelines and recommendations of maximum resources primarily conditioned by the state of alert, confinement and social distancing that occurs in Spain since March 16, 2020. RESULTS: The recommendations will promote the adoption of action and protection measures for eye care in outpatient clinics, surgical areas and hospitalization, for unconfirmed (asymptomatic and symptomatic) and confirmed COVID-19 patients. Measures must be adapted to the circumstances and availability of personal protective equipment in each of the centers and Autonomous Communities, which will be updated according to the pandemic phases and the measures adopted by the Spanish Government. CONCLUSIONS: During the COVID-19 pandemic, attention to the potential health risks to the population caused by coronavirus should prevail over the possible progression of the common eye diseases. Ophthalmologists and other eye care professionals must assume a possible progression of these diseases due to the impossibility of adequate patient follow-up.

Individualized Prediction of COVID-19 Adverse outcomes with MLHO

The COVID-19 pandemic has devastated the world with health and economic wreckage. Precise estimates of the COVID-19 adverse outcomes on individual patients could have led to better allocation of healthcare resources and more efficient targeted preventive measures. We developed MLHO (pronounced as melo) for predicting patient-level risk of hospitalization, ICU admission, need for mechanical ventilation, and death from patients' past (before COVID-19 infection) medical records. MLHO is an end-to-end Machine Learning pipeline that implements iterative sequential representation mining and feature and model selection to predict health outcomes. MLHO's architecture enables a parallel and outcome-oriented calibration, in which different statistical learning algorithms and vectors of features are simultaneously tested and leveraged to improve prediction of health outcomes. Using clinical data from a large cohort of over 14,000 patients, we modeled the four adverse outcomes utilizing about 600 features representing patients' before-COVID health records. Overall, the best predictions were obtained from extreme and gradient boosting models. The median AUC ROC for mortality prediction was 0.91, while the prediction performance ranged between 0.79 and 0.83 for ICU, hospitalization, and ventilation. We broadly describe the clusters of features that were utilized in modeling and their relative influence on predicting each outcome. As COVID-19 cases are re-surging in the U.S. and around the world, a Machine Learning pipeline like MLHO is crucial to improve our readiness for confronting the potential future waves of COVID-19, as well as other novel infectious diseases that may emerge in the near future.

Sisters with No Pain, No Tears: A Report of a New Variant of Hereditary Sensory and Autonomic Neuropathy (Type IX) Caused by a Novel SCN11A Mutation

Lack of pain sensation in children involves a rare group of heritable disorders; hereditary sensory and autonomic neuropathy (HSAN). Till date, eight types of HSAN have been described depending on the clinical phenotype and the underlying gene mutation. We report a new variant of HSAN (Type IX) in two siblings (of Indian origin) with a novel mutation of SCN11A gene and a distinct clinical phenotype.

Postoperative radiotherapy improves overall survival in patients with primary squamous cell carcinoma of the breast

BACKGROUND: Primary squamous cell carcinoma of the breast (PSCCB) is a rare clinical classification of breast tumors. Little is known about its clinicopathological features, prognosis and potential therapeutic strategies. The purpose of this study is to evaluate the effect of postoperative radiotherapy (PORT) on patients with squamous cell carcinoma (SCC) of the breast. METHODS: We retrospectively analyzed patients diagnosed with PSCCB in our center. All pathological slides were reviewed by an experienced pathologist to confirm the diagnosis. Furthermore, we searched the public database for patients with SCC of the breast. Then, we analyzed the clinicopathological features, treatment methods and patient outcomes. RESULTS: We identified 14 patients with primary SCC of the breast in our center. Additionally, 739 patients with SCC of the breast from the Surveillance, Epidemiology and End Results (SEER) database were diagnosed between 1975 and 2016. Only 453 patients who underwent surgery were included in this study. Patients from the SEER database had a more advanced tumor node metastasis (TNM) stage than patients from our center. The median overall survival (OS) of all patients was 104 months (95% confidence interval [CI], 87.2-120.8 months), and the 5-year OS was 60.8% (95% CI, 56.1%-65.5%). Most of the patients (58%) tested negative for hormonal receptor expression. Multivariate analysis showed that PORT was an independent prognostic factor for OS. CONCLUSION: The results of our study demonstrate that SCC of the breast presents aggressive behavior with unique clinical characteristics. PORT improved OS significantly in patients with SCC of the breast. Longer-term studies are needed to confirm our findings.

Intratonsillar detection of 27 distinct viruses: A cross-sectional study

Palatine tonsils have been observed to harbor several distinct respiratory and herpesviruses in separate studies. In this study, the presence of these viruses in palatine tonsils was comprehensively studied in both children and adults. A cross-sectional analysis of 181 patients (median age 22 years; range, 2.6-66) operated for a benign tonsillar disease was conducted. Real-time polymerase chain reaction was performed to detect 27 distinct viruses in all: eight human herpesviruses, 16 respiratory viruses, parvo B19, and polyoma BK/JC viruses. Clinical characteristics of the patients and underlying conditions were evaluated. In total, 92% of patients had virus detected in tonsils (Epstein-Barr virus 72%, human herpesvirus 7, and 6B 54% and 16%, respectively, enterovirus 18%, parvovirus B19 7% and the rest <4%). No herpes simplex virus 2, varicella zoster virus, polyoma JC virus, parainfluenza-, metapneumo-, or coronaviruses were found. Enterovirus was more common in children and was frequently observed in the presence of HHV6B. None of the viruses showed a positive association to the tonsillar disease. Respiratory symptoms were not associated with the prevalence of viruses. This study comprehensively reports a cross-sectional view of intratonsillar virus infections in elective tonsillectomy patients in a wide age range cohort. Tonsils are a major virus reservoir for distinct herpes and respiratory viruses without a positive association with tonsillar disease or respiratory symptoms.

A historical insight into an announced tragedy: COVID-19 pandemic

The wet markets in southern China have long been supposed to be a time bomb. A new type of pneumonia was diagnosed by doctors in November, 2019 in Wuhan, southern China. The delay in recognizing the human transmission of the disease, and the delay to take actions to curb the spread of the disease, particularly the long delay to stop flights inside and abroad when the disease had already been detected in three different continents, facilitate the spread of the new disease, later on called COVID-19.

COVID-19 pandemic impacts to dentistry/ Impactos da pandemia causada pela COVID-19 na odontologia

Objective: To achieve a literature review on the impacts of COVID-19 on dentistry. Methods: Analysis of scientific articles contained in the LILACS and PubMed platforms that fulfill the informative purpose of the research. Results: The production of aerosols during dental procedures could be highlighted as the most dangerous agent, the literature recommends restricting the type of service only to emergencies and reducing the use of rotating instruments or cough-inducing equipaments. New protective measures must be taken, such as the type of PPE used and the frequency of asepsis of the workplace, since any surface that has been exposed to oral or pharyngeal secretions may contain a load of viral particles, an online triage is also recommended before any assistance. Due to the easy spreading of this disease and the possibility of asymptomatic patients, the current best measure is avoiding the execution of procediments. Conclusion: COVID-19 will be a milestone for the current generations of health professionals, it could also be an advance for use distance technologies and integration of new biosafety techniques.

Impact of the first month of Covid-19 lockdown on oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments

OBJECTIVE: To evaluate the impact of the first month of lockdown related to the Covid-19 epidemic on the oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments. MATERIAL AND METHODS: A multicenter prospective observational assessment was conducted in 6 university hospital otorhinolaryngology departments (Paris Centre, Nord, Est and Sorbonne) during the 1-month periods before (Month A) and after (Month B) lockdown on March 17, 2020. The main goal was to evaluate lockdown impact on oncologic surgical activity in the departments. Secondary goals were to report population characteristics, surgery conditions, postoperative course, progression of Covid status in patients and surgeons, and adverse events. RESULTS: 224 procedures were performed. There was 10.9% reduction in overall activity, without significant difference between departments. Squamous cell carcinoma and larynx, hypopharynx, oropharynx, oral cavity and nasal cavity and sinus locations were predominant, at 79% and 75.8% of cases respectively, with no significant differences between months. T3/4 and N2/3 tumors were more frequent in Month B (P=.002 and .0004). There was no significant difference between months regarding surgical approach, type of reconstruction, postoperative course, tracheotomy and nasogastric feeding-tube time, intensive care stay or hospital stay. None of the Month A patients were Covid-19-positive, versus 3 in Month B, without adverse events. None of the otorhinolaryngologists involved in the procedures developed symptoms suggesting Covid-19 infestation. CONCLUSION: The present study underscored the limited impact of the Covid-19 epidemic and lockdown on surgical diagnosis and cancer surgery in the Ile de France university otorhinolaryngology departments, maintaining chances for optimal survival without spreading the virus.

COVID-19 and obesity: The intersection between a pandemic and an epidemic in a developing country

We have read with great interest the prospective cohort study published by Czernichow et al (1) , wherein they found that obesity doubles mortality in patients hospitalized with coronavirus disease (COVID-19), using as an indicator anthropometric, the body mass index (BMI) Despite BMI being recognized as an anthropometric index of obesity and various studies confirming that it predicts cardiovascular events, the lack of information it provides on the distribution of body fat is considered its main limitation The use of abdominal circumference and waist-height ratio are better measures of visceral fat distribution, which is more closely associated with cardiometabolic risk;(2) however, those measures demand greater contact with COVID-19 patients

The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19

Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19). Research has indicated that patients with pneumonia and sepsis have low vitamin C status and elevated oxidative stress. Administration of vitamin C to patients with pneumonia can decrease the severity and duration of the disease. Critically ill patients with sepsis require intravenous administration of gram amounts of the vitamin to normalize plasma levels, an intervention that some studies suggest reduces mortality. The vitamin has pleiotropic physiological functions, many of which are relevant to COVID-19. These include its antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions. Preliminary observational studies indicate low vitamin C status in critically ill patients with COVID-19. There are currently a number of randomized controlled trials (RCTs) registered globally that are assessing intravenous vitamin C monotherapy in patients with COVID-19. Since hypovitaminosis C and deficiency are common in low-middle-income settings, and many of the risk factors for vitamin C deficiency overlap with COVID-19 risk factors, it is possible that trials carried out in populations with chronic hypovitaminosis C may show greater efficacy. This is particularly relevant for the global research effort since COVID-19 is disproportionately affecting low-middle-income countries and low-income groups globally. One small trial from China has finished early and the findings are currently under peer review. There was significantly decreased mortality in the more severely ill patients who received vitamin C intervention. The upcoming findings from the larger RCTs currently underway will provide more definitive evidence. Optimization of the intervention protocols in future trials, e.g., earlier and sustained administration, is warranted to potentially improve its efficacy. Due to the excellent safety profile, low cost, and potential for rapid upscaling of production, administration of vitamin C to patients with hypovitaminosis C and severe respiratory infections, e.g., COVID-19, appears warranted.

Cytokine Storm Induced New Onset Depression In Patients With COVID-19. A New Look Into The Association Between Depression and Cytokines -Two Case Reports

Background Depression appears to be a common complication in patients during and post–COVID-19 infection Understanding the mechanism of action of cytokines such as interleukin-6, interleukin-10 and others in depression and in cytokine storm syndrome, the core component of COVID- 19, could shine a new light on future treatment options for both disorders Objective This review demonstrates the role of interleukins in COVID-19 pathogenesis and their role in depression Results We described cases we have treated as an example for the dual role interleukins have in COVID-19 infection and depression and reviewed approximately 70 articles focusing on the role of interleukins in cytokine storm syndrome and depression Conclusion This review highlights the key features of cytokines in both diseases As the scientific community has more time to recover and process the effect of the current pandemic, we believe that additional research will pave the way to diverse pathways to treat depression in these patient and others

ACE2 imbalance as a key player for the poor outcomes in COVID-19 patients with age-related comorbidities - Role of gut microbiota dysbiosis

Coronavirus disease 19 (COVID-19) is a pandemic condition caused by the new coronavirus SARS-CoV-2. The typical symptoms are fever, cough, shortness of breath, evolving to a clinical picture of pneumonia and, ultimately, death. Nausea and diarrhea are equally frequent, suggesting viral infection or transmission via the gastrointestinal-enteric system. SARS-CoV-2 infects human cells by using angiotensin converting enzyme 2 (ACE2) as a receptor, which is cleaved by transmembrane proteases during host cells infection, thus reducing its activities. ACE2 is a relevant player in the renin-angiotensin system (RAS), counterbalancing the deleterious effects of angiotensin II. Furthermore, intestinal ACE2 functions as a chaperone for the aminoacid transporter B0AT1. It has been suggested that B0AT1/ACE2 complex in the intestinal epithelium regulates gut microbiota (GM) composition and function, with important repercussions on local and systemic immune responses against pathogenic agents, namely virus. Notably, productive infection of SARS-CoV-2 in ACE2+ mature human enterocytes and patients' GM dysbiosis was recently demonstrated. This review outlines the evidence linking abnormal ACE2 functions with the poor outcomes (higher disease severity and mortality rate) in COVID-19 patients with pre-existing age-related comorbidities and addresses a possible role for GM dysbiosis. The article culminates with the therapeutics opportunities based on these pathways.

Practical Guidelines for Collection, Manipulation and Inactivation of SARS-CoV-2 and COVID-19 Clinical Specimens

SARS-CoV-2 is a novel coronavirus that causes the acute respiratory disease-Coronavirus disease 2019 (COVID-19)-which has led to a global health crisis. Currently, no prophylactics or therapies exist to control virus spread or mitigate the disease. Thus, the risk of infection for physicians and scientists is high, requiring work to be conducted in Biosafety Level-3 (BSL-3) facilities if virus will be isolated or propagated. However, inactivation of the virus can enable safe handling at a reduced biosafety level, making samples accessible to a diverse array of institutions and investigators. Institutions of all types have an immediate need for guidelines that outline safe collection, handling, and inactivation of samples suspected to contain active virus. Here we provide a practical guide for physicians and researchers wishing to work with materials from patients who are COVID-19 positive or suspected positive. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Practical guidelines for the safe collection and handling of specimens collected from COVID-19 and suspected COVID-19 patients Basic Protocol 2: Inactivating SARS-CoV-2.

Practical Guidelines for Collection, Manipulation and Inactivation of SARS-CoV-2 and COVID-19 Clinical Specimens

SARS-CoV-2 is a novel coronavirus that causes the acute respiratory disease-Coronavirus disease 2019 (COVID-19)-which has led to a global health crisis. Currently, no prophylactics or therapies exist to control virus spread or mitigate the disease. Thus, the risk of infection for physicians and scientists is high, requiring work to be conducted in Biosafety Level-3 (BSL-3) facilities if virus will be isolated or propagated. However, inactivation of the virus can enable safe handling at a reduced biosafety level, making samples accessible to a diverse array of institutions and investigators. Institutions of all types have an immediate need for guidelines that outline safe collection, handling, and inactivation of samples suspected to contain active virus. Here we provide a practical guide for physicians and researchers wishing to work with materials from patients who are COVID-19 positive or suspected positive. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Practical guidelines for the safe collection and handling of specimens collected from COVID-19 and suspected COVID-19 patients Basic Protocol 2: Inactivating SARS-CoV-2.

Systematic screening for SARS-CoV-2 in pregnant women admitted for delivery in a Portuguese maternity

Objectives The burden of undocumented SARS-Cov-2 infections in Portuguese pregnant women is unknown. At our institution, routine COVID-19 testing was implemented from 19th of March on to all pregnant women who were admitted for delivery. The purpose of the study was to estimate the SARS-CoV-2 infection rate in our obstetric population admitted for delivery. Mathods Between 19th March and May 4th, 184 pregnant women were screened for SARS-CoV-2 infection upon admission. Results Eleven women were positive for SARS-CoV-2, corresponding to a global prevalence of 6.0%. Of these, only two reported symptoms at admission. The prevalence of asymptomatic infection was 4.9%. We report a lower rate of positive cass than other studies. Eighty-two percent of our cases had no symptoms at admission. Conclusions The proportion of asymptomatic infection highlights the importance of universal laboratory screening for all women admitted for delivery as opposed to symptom-based screening.

Precaution strategy toward the COVID-19 pandemic in the operating room of a tertiary hospital in Taiwan

BACKGROUND: The pandemic of SARS-CoV-2 (COVID-19), that began in December 2019, spread mostly from person to person through respiratory droplets. A recommendation was issued to postpone all elective surgical practices. However, some confirmed or suspected COVID-19 patients required life-saving emergent surgeries. METHODS: To facilitate emergent surgical interventions for these patients, we have reviewed the current literature and established an algorithm of precautions to be taken by operating room team members during the COVID-19 pandemic. RESULTS: The initial algorithm of preparation for surgical intervention during the COVID-19 pandemic was relatively simple. However, the abrupt increase of confirmed COVID-19 cases due to returned overseas travelers since mid-March, 2020, disrupted the routine hospital clinical service. Due to the large number of febrile patients, the algorithm was therefore revised according to travel history, occupation, contact and cluster history (TOCC), unexplained fever/symptoms and emergent/non-emergent surgery. TOCC (+) patients presenting with otherwise unexplained fever/symptoms would be regarded as belonging to the fifth category of "severe special infectious pneumonia." If the patient requires emergent surgery to relieve the non-life-threatening disorders, two times of negative COVID-19 tests are necessary before the operation is approved. For life-threatening situations without two negative results of COVID-19 tests, the operation schedule should be approved by the Chairman of Surgery Management Committee. CONCLUSION: The application of a clear and integrated algorithm for operating room team members aids in effective personal protective equipment facilitation to keep both healthcare providers and patients safe as well as to prevent hospital-based transmission of COVID-19.

Potential role of statins in COVID-19

Patients with COVID-19 infection have an increased risk of cardiovascular complications and thrombotic events. Statins are known for their pleiotropic anti-inflammatory, antithrombotic and immunomodulatory effects. They may have a potential role as adjunctive therapy to mitigate endothelial dysfunction and dysregulated inflammation in patients with COVID-19 infection.

Transfusion support in COVID-19 patients: Impact on hospital blood component supply during the outbreak

BACKGROUND: During the COVID-19 outbreak, most hospitals deferred elective surgical procedures to allow space for the overwhelming number of COVID-19 patient admissions, expecting a decrease in routine blood component requirements. However, because transfusion support needs of COVID-19 patients are not well known, its impact on hospital blood supply is uncertain. The objective of this study was to assess the effect of the COVID-19 pandemic on transfusion demand. STUDY DESIGN AND METHODS: Transfusion records during the peak of the COVID-19 pandemic (March 1-April 30, 2020) were reviewed in our center to assess changes in blood requirements. RESULTS: During this period 636 patients received a total of 2934 blood components, which reflects a 17.6% reduction in transfusion requirements with regard to the same period of 2019, and blood donations in Madrid dropped by 45%. The surgical blood demand decreased significantly during the outbreak (50.2%). Blood usage in the hematology and oncology departments remained unchanged, while the day ward demand halved, and intensive care unit transfusion needs increased by 116%. A total of 6.2% of all COVID inpatients required transfusion support. COVID-19 inpatients consumed 19% of all blood components, which counterbalanced the savings owed to the reduction in elective procedures. CONCLUSION: Although only a minority of COVID-19 inpatients required transfusion, the expected reduction in transfusion needs caused by the lack of elective surgical procedures is partially offset by the large number of admitted patients during the peak of the pandemic. This fact must be taken into account when planning hospital blood supply.

An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies

Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to more than 200 countries or territories. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood laboratory profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.

Prevalence of Metabolic Syndrome According to Causes of Physical Activity Limitation

Purpose: One cause of metabolic syndrome (MetS) is inactivity. This study analyzed the prevalence of MetS due to causes of activity limitation (AL) in adults over 40 years old. Paticipants and Methods: Participants included 2885 people aged 40-79 (1198 men and 1687 women) who completed the Korean National Health and Nutrition Survey (KNHANES) conducted between 2013 and 2017. They were divided into two groups based on age: the middle age group (MA) included 1148 total participants, 515 men and 633 women from 40-59 years old; the older age group (OA) included 1737 total participants, 683 men and 1054 women from 60-79 years old. MetS was diagnosed according to the Third Report of the National Cholesterol Education Program and the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III). Logistic regression was conducted to calculate the odds ratio for MetS prevalence. Results: The prevalence of MetS in people with AL increased 1.432-fold in the MA men group, 1.511-fold in the OA men group, 1.546-fold in the MA women group, and 1.565-fold in the OA women group. There were several causes of AL; people with physical activity for diabetes mellitus and hypertension increased MetS prevalence in both sexes and all age groups: MA men group (OR=3.216, 95% CI=1.852-7.354, P=0.034), MA women group (OR=2.159, 95% CI=1.854-5.346, P=0.032), OA men group (OR=3.200, 95% CI=1.235-7.841, P=0.009), and OA women group (OR=3.444, 95% CI=1.310-6.627, P=0.008). Also, mental problems in the MA men group (OR=2.284, 95% CI=1.591-4.986, P=0.012) and OA men group (OR=1.149, 95% CI=1.017-2.941, P=0.012), and musculoskeletal problems in the MA women group (OR=1.784, 95% CI=1.102-2.902, P=0.021) and OA women group (OR=1.459, 95% CI=1.054-1.993, P=0.004) increased the prevalence. Conclusion: The prevalence of MetS due to activity limitation was increased in MA and OA groups. Activity limitation increased the MetS prevalence from 1.4- to 1.5-times, Therefore, to prevent metabolic syndrome, physical activity should be increased, and guidelines should be presented according to the activity limitation causes, age, and sex.

Melatonin down-regulates steroidal hormones, thymocyte apoptosis and inflammatory cytokines in middle-aged T. cruzi infected rats

Chagas disease, triggered by the flagellate protozoan Trypanosoma cruzi (T. cruzi) plays a potentially threat to historically non-endemic areas. Considerable evidence established that the immuno-endocrine balance could deeply influence the experimental T. cruzi progression inside the host's body. A high-resolution multiple reaction monitoring approach (MRMHR) was used to study the influence of melatonin on adrenal and plasma steroidal hormones profile of T. cruzi infected Wistar rats. Young (5 weeks) and middle-aged (18 months) male Wistar rats received melatonin (5 mg/Kg, orally) during the acute Chagas disease. Corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, progesterone and melatonin concentration were evaluated. Interleukin-1 alpha and ß (IL-1&#945; and ß), IL-6 and transforming growth factor beta (TGF-ß) were also analyzed. Our results revealed an increased production of corticosterone, cortisone, cortisol and aldosterone in middle-aged control animals, thus confirming the aging effects on the steroidal hormone profile. Serum melatonin levels were reduced with age and predominantly higher in young and middle-aged infected rats. Melatonin treatment reduced the corticosterone, 11-DHC, cortisol, cortisone, aldosterone and progesterone in response to T. cruzi infection. Decreased IL-1 &#945; and ß concentrations were also found in melatonin treated middle-aged infected animals. Melatonin treated middle-aged control rats displayed reduced concentrations of TGF-ß. Melatonin levels were significantly higher in all middle-aged rats treated animals. Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats. Finally, our results show a link between the therapeutic and biological effects of melatonin controlling steroidal hormones pathways as well as inflammatory mediators.

Molecular docking analysis of selected phytochemicals against SARS-CoV-2 Mpro receptor

Presently world is on a war with the novel coronavirus and with no immediate treatments available the scourge caused by the SARS-CoV-2 is increasing day by day. A lot of researches are going on for the potential drug candidate that could help the healthcare system in this fight. Plants are a natural data bank of bioactive compounds. Many phytochemicals are being studied for various ailments including cancer, bacterial and viral infections, etc. The present study aims to screen 38 bioactive compounds from 5 selected plants viz., Azadirachta indica, Curcuma longa, Zingiber officinale, Ocimum basilicum and Panax ginseng against SARS-CoV-2. Lipinski's rule was taken as the foundation for initial screening. Shortlisted compounds were subjected to molecular docking study with Mpro receptor present in SARS-CoV-2. The study identified that gedunin, epoxyazadiradione, nimbin and ginsenosides have potential to inhibit Mpro activity and their binding energies are - 9.51 kcal/mol, - 8.47 kcal/mol, - 8.66 kcal/mol and - 9.63 kcal/mol respectively. Based on bioavailability radar studies gedunin and epoxyazadiradione are the two most potent compounds which are used for molecular dynamics simulation studies. Molecular dynamics studies showed that gedunin is more potent than epoxyazadiradione. To find the effectiveness and to propose the exact mechanism, in-vitro studies can be further performed on gedunin.

A Novel Strategy for COVID-19 Classification from Chest X-ray Images Using Deep Stacked-Ensembles

The issue of COVID-19, increasing notably with a massive mortality rate has led to the WHO declaring it as a pandemic. The unavailability of an antiviral drug has also led to dismay world-wide. The diagnostic tests are performed by collecting samples inserting a swab into the nasal or oral cavity. These collected samples and then sent to laboratories for viral-tests. Recently, chest radiographs are used to observe the proportion of virus in the lungs at various section-scans. As laboratory testing is time-consuming with a lot of human effort, diagnosis using chest radiographs is considered to be a befitting choice. In this research, a stacked-ensemble model is designed to classify whether a patient is infected with COVID-19, viral-pneumonia or has a healthy profile by considering chest X-ray images. A lot of complications were observed from existing literature in classifying COVID-19 radiographic images and are eliminated using our methodology. A training algorithm is constructed to speed up the training process which acquired good generalisations. The proposed model resulted in state-of-the-art outcomes with an accuracy score of 99.48% for binary classification and 97.4% for tri-class classification. Additionally, visualisations are illustrated for a detailed comprehension of the model's perception for the information provided to it.

Impact of the COVID-19 pandemic on cardiovascular mortality and catherization activity during the lockdown in central Germany: an observational study

AIMS: During the COVID-19 pandemic, hospital admissions for cardiac care have declined However, effects on mortality are unclear Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths Simultaneously we looked at catheterization activities in the same region METHODS AND RESULTS: Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019 Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2 6% [incidence rate ratio (IRR) 1 03, 95% confidence interval (CI) 0 99-1 06;p = 0 16] Cardiovascular and cardiac mortality increased significantly by 7 6% (IRR 1 08, 95%-CI 1 01-1 14;p = 0 02) and by 11 8% (IRR 1 12, 95%-CI 1 05-1 19;p &lt; 0 001), respectively During the same period, our data revealed a drop in cardiac catherization procedures CONCLUSION: During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality

COVID-19: a perspective for lifting lockdown in Zimbabwe

The Coronavirus disease 2019 (Covid-19) scourge has challenged the world's health systems and presented multiple socio-economic and public health challenges to the states it has affected. Zimbabwe has been affected by the pandemic, and in response, the government has set up an array of measures, including a national lockdown, to curb transmission. While it is critical to maintain such vigorous containment measures, socio-economic pressures in Zimbabwe will challenge the sustainability of the lockdown. Given the potential for lift of the lockdown before the Covid-19 pandemic ends, we discuss the Covid-19 pandemic situation in Zimbabwe and viewpoints on important considerations and strategies for lifting the lockdown.

COVID-19: a perspective for lifting lockdown in Zimbabwe

The Coronavirus disease 2019 (Covid-19) scourge has challenged the world's health systems and presented multiple socio-economic and public health challenges to the states it has affected. Zimbabwe has been affected by the pandemic, and in response, the government has set up an array of measures, including a national lockdown, to curb transmission. While it is critical to maintain such vigorous containment measures, socio-economic pressures in Zimbabwe will challenge the sustainability of the lockdown. Given the potential for lift of the lockdown before the Covid-19 pandemic ends, we discuss the Covid-19 pandemic situation in Zimbabwe and viewpoints on important considerations and strategies for lifting the lockdown.

COVID-19 and the academy: It is time for going digital

In many countries, the lock-down due to the COVID-19 pandemic triggered discussions on the use of digital interaction formats for academic exchange The pace with which researchers adopted digital formats for conferences, lectures, and meetings revealed that currently available tools can substitute many of the physical interactions in the workplace It also showed that academics are willing to use digital tools for scientific exchange This article sheds light on scholars' experiences with digital formats and tools during the pandemic We argue that digital interaction formats increase the inclusivity of knowledge exchange, reduce time and costs of organizing academic interactions, and enable more diverse workspaces with geographical and temporal flexibility However, we also observe that digital interaction formats struggle to reproduce social interactions such as informal discussions, raise new concerns on data security, and can induce higher stress levels due to the blurring of the boundaries between work and private spaces We argue that digital formats are not meant to substitute physical interactions entirely, but rather reshape how research communities operate and how academics socialize We expect hybrid formats to emerge, which combine digital and physical interaction formats, and an increase in digital interactions between geographically distant working groups We conclude that the time has come for digital interaction formats to be part of a new regime in the field of academic exchange

DNA nanoscaffold-based SARS-CoV-2 detection for COVID-19 diagnosis

COVID-19 pandemic outbreak is the most astounding scene ever experienced in the 21st century. It has been determined to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the global pandemic, the lack of efficient rapid and accurate molecular diagnostic testing tools has hindered the public opportunely response to the emerging viral threat. Herein, a DNA nanoscaffold hybrid chain reaction (DNHCR)-based nucleic acid assay strategy is reported for rapid detection of SARS-CoV-2 RNA. In this method, the DNA nanoscaffolds have been first constructed by the self-assembly of long DNA strands and self-quenching probes (H1). Then, the SARS-CoV-2 RNA will initiate the hybridization of H1 and free H2 DNA probes along the nanoscaffold, and an illuminated DNA nanostring is instantly obtained. By taking advantages of the localization design of the H1 probes and the temperature tolerance of the isothermal amplification, the proposed DNHCR method can detect target at short responding time (within 10 min) and mild condition (15 °C-35 °C). Moreover, the reliability of DNHCR method in serum and saliva samples have also been validated. Therefore, DNHCR-based method is expected to provide a simple and faster alternative to the traditional SARS-CoV-2 qRT-PCR assay.

COVID 19 diagnostic multiplicity and its role in community surveillance and control

Diagnosis of persons exposed to/infected with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is central to controlling the global pandemic of COVID-19 Currently, several diagnostic modalities are available for COVID-19, each with its own pros and cons Although there is a global consensus to increase the testing capacity, it is also essential to prudently utilize these tests to control the pandemic In this paper, we have reviewed the current array of diagnostics for SARS-CoV-2, highlighted the gaps in current diagnostic modalities, and their role in community surveillance and control of the pandemic The different modalities of COVID-19 diagnosis discussed are: clinical and radiological, molecular based (laboratory based and point-of-care), Immunoassay based (ELISA, rapid antigen and antibody detection tests) and digital diagnostics (artificial intelligence based algorithms) The role of rapid antigen/antibody detection tests in community surveillance has also been described here These tests can be used to identify asymptomatic persons exposed to the virus and in community based seroprevalence surveys to assess the epidemiology of spread of the virus However, there are few concerns about the accuracy of these tests which needs to evaluated beforehand

COVID-19 and Flu Pandemics Follow a Pattern: A possible Cross-immunity in the Pandemic Origin and Graver Disease in Farther Regions

So far, the COVID-19 pandemic has caused less casualty in Eastern Asia areas compared to the other parts of the world The pattern of less casualty in the pandemic origin has also been observed in the three main flu pandemics in the last century It is reasonable to speculate that less casualty of COVID-19/flu in the pandemic origin is likely due to the preexisting cross-immunity to some close viruses being more prevalent in those regions Experts and modelers should scale up the severity of a flu-like viral epidemic to predict its real severity for the rest of the world

Point-of-Use Rapid Detection of SARS-CoV-2: Nanotechnology-Enabled Solutions for the COVID-19 Pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic that has been spreading around the world since December 2019 More than 10 million affected cases and more than half a million deaths have been reported so far, while no vaccine is yet available as a treatment Considering the global healthcare urgency, several techniques, including whole genome sequencing and computed tomography imaging have been employed for diagnosing infected people Considerable efforts are also directed at detecting and preventing different modes of community transmission Among them is the rapid detection of virus presence on different surfaces with which people may come in contact Detection based on non-contact optical techniques is very helpful in managing the spread of the virus, and to aid in the disinfection of surfaces Nanomaterial-based methods are proven suitable for rapid detection Given the immense need for science led innovative solutions, this manuscript critically reviews recent literature to specifically illustrate nano-engineered effective and rapid solutions In addition, all the different techniques are critically analyzed, compared, and contrasted to identify the most promising methods Moreover, promising research ideas for high accuracy of detection in trace concentrations, via color change and light-sensitive nanostructures, to assist fingerprint techniques (to identify the virus at the contact surface of the gas and solid phase) are also presented

COVID-19 pneumonia in lung transplant recipients: Report of 2 cases

Coronavirus disease 2019 (COVID-19) has been declared pandemic since March 2020. In Europe, Italy was the first nation affected by this infection. We report anamnestic data, clinical features, and therapeutic management of 2 lung transplant recipients with confirmed COVID-19 pneumonia. Both patients were in good clinical condition before the infection and were receiving immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil, and corticosteroids. Whereas mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS-CoV-2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions, and had a fatal outcome. Further insight into SARS-CoV-2 infection is eagerly awaited to improve the outcome of transplant recipients affected by COVID-19 pneumonia.

COVID-19 pneumonia in lung transplant recipients: Report of 2 cases

Coronavirus disease 2019 (COVID-19) has been declared pandemic since March 2020. In Europe, Italy was the first nation affected by this infection. We report anamnestic data, clinical features, and therapeutic management of 2 lung transplant recipients with confirmed COVID-19 pneumonia. Both patients were in good clinical condition before the infection and were receiving immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil, and corticosteroids. Whereas mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS-CoV-2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions, and had a fatal outcome. Further insight into SARS-CoV-2 infection is eagerly awaited to improve the outcome of transplant recipients affected by COVID-19 pneumonia.

COVID-19 pneumonia in lung transplant recipients: Report of 2 cases

Coronavirus disease 2019 (COVID-19) has been declared pandemic since March 2020. In Europe, Italy was the first nation affected by this infection. We report anamnestic data, clinical features, and therapeutic management of 2 lung transplant recipients with confirmed COVID-19 pneumonia. Both patients were in good clinical condition before the infection and were receiving immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil, and corticosteroids. Whereas mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS-CoV-2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions, and had a fatal outcome. Further insight into SARS-CoV-2 infection is eagerly awaited to improve the outcome of transplant recipients affected by COVID-19 pneumonia.

Web tools to fight pandemics: the COVID-19 experience

The current outbreak of COVID-19 has generated an unprecedented scientific response worldwide, with the generation of vast amounts of publicly available epidemiological, biological and clinical data. Bioinformatics scientists have quickly produced online methods to provide non-computational users with the opportunity of analyzing such data. In this review, we report the results of this effort, by cataloguing the currently most popular web tools for COVID-19 research and analysis. Our focus was driven on tools drawing data from the fields of epidemiology, genomics, interactomics and pharmacology, in order to provide a meaningful depiction of the current state of the art of COVID-19 online resources.

Lesson from COVID-19: restructuring the current health system and policies in Nepal

Although COVID-19 pandemic has created a state of alarm worldwide, the downfall in health and economy is rather paramount in low income countries Nepal, due to its inadequate health resources and poor health system, is more vulnerable to the plight But on a positive note, the weaknesses that have been exposed can be taken as lessons to learn With the policies committed to achieving health as the fundamental right of people as per the constitution, capacity building, intersectoral coordination, preventive, promotive and curative facilities, and appropriate strategies and preparedness plan, Nepal can combat the pandemic and develop a resilient and well-functioning health system in future Now is a moment of historic opportunity Public health program must be strengthened as soon as possible by ensuring that at least minimum requirement are in place at the province and municipality levels and media partnership should be created to prevent societal fear Furthermore, this is an opportunity to implement the power devolution in federal republic of Nepal

Factors associated with incorrect facemask use among individuals visiting high-risk locations during covid-19 pandemic

In December 2019, an outbreak of a novel coronavirus disease (COVID-19, previously known as 2019-nCoV) was determined to be transmitted via respiratory droplets Thus, health agencies have recommended the use of facemasks as a protective measure The current study investigated the prevalence and factors contributing to incorrect facemask use among individuals visiting high risk public locations A cross-sectional observational study of facemask use among individuals visiting high risk public facilities was conducted during a local COVID-19 outbreak from end of April to middle of May 2020 in Sitiawan, Perak, Malaysia Enrolment in the study included any individuals entering the selected study facilities via a dedicated entry point Suitable study locations were identified as a local wet market selling freshly slaughtered animals and a district specialist hospital Trained data collectors were stationed at the entry points to observe individuals entering the selected facilities for the type, category, and correct facemask use Individuals were categorized into two groups, correct and incorrect facemask users, based on visual observation of facemask use The Pearson chi-square test was used for differences in investigated variables Both binary and multiple logistic regression models were used in this study The study protocol was approved by the institutional review board The main outcome measure was facemask use (either correct or incorrect) A total of 3322 individuals with a high prevalence of facemask use (98 2%) consisting of a large proportion of medical-grade face masks (75 5%) were included in this study Male individuals, Malay ethnic people, high-risk age groups, and those wearing a medical grade facemask were more likely to present incorrect facemask use A high prevalence of facemask use among individuals visiting public facilities was observed However, incorrect facemask use raises the need for of targeted public health strategy to mitigate the impact of COVID-19 epidemic © 2020, Mahidol University - ASEAN Institute for Health Development All rights reserved

pH-sensitive deoxycholic acid dimer for improving doxorubicin delivery and antitumor activity in vivso

To develop simple and effective nano-drug delivery systems remains a major challenge in cancer treatment. Herein, we synthesized an ortho ester-linked deoxycholic acid dimer (DCA-OE), which could effectively self-assemble with doxorubicin (DOX) to form stable nanoparticles (DCA-OE/DOX NPs) by a single emulsion method. DCA-based nanoparticles had a desirable size (∼200 nm), morphology (spherical shape), and high drug encapsulation (drug loading content of ∼18.0 %, drug loading efficiency of ∼77.6 %). DCA-OE could improve the stability and solubility of DOX in physiological environment, while pH-sensitive ortho ester linkage endowed the ability to release DOX quickly in cancer cells. In vitro cytotoxicity and apoptosis verified drug-loaded dimer nanoparticles had similar toxicity with free DOX. Besides, these particles could efficiently accumulate and penetrate into human liver carcinoma cell line (HepG2) multicellular spheroids, thus resulting in enhanced antitumor effect. In vivo tests further exhibited that DCA-OE/DOX NPs had lower systemic toxicity and higher tumor inhibition effect, and its tumor inhibition rate was 84.1 %, which was far more than free DOX (49.3 %). Therefore, the strategy to link functional small molecules with ortho ester has great potentials in specific delivery of anticancer drugs.

SARS-CoV-2 infection serology: a useful tool to overcome lockdown?

The outbreak of 2019 novel coronavirus disease (Covid-19) caused by SARS-CoV-2 has spread rapidly, inducing a progressive growth in infected patients number. Social isolation (lockdown) has been assessed to prevent and control virus diffusion, leading to a worldwide financial and political crisis. Currently, SARS-CoV-2 RNA detection in nasopharyngeal swab takes place by real-time PCR (RT-qPCR). However, molecular tests can give some false-negative results. In this context, serological assays can be useful to detect IgG/IgM antibodies, to assess the degree of immunization, to trace the contacts, and to support the decision to re-admit people at work. A lot of serological diagnostic kits have been proposed on the market but validation studies have not been published for many of them. The aim of our work was to compare and to evaluate different assays analytical performances (two different immunochromatographic cards, an immunofluorescence chromatographic card, and a chemiluminescence-automated immunoassay) on 43 positive samples with RT-qPCR-confirmed SARS-CoV-2 infection and 40 negative control subjects. Our data display excellent IgG/IgM specificities for all the immunocromatographic card tests (100% IgG and 100% IgM) and for the chemiluminescence-automated assay (100% IgG and 94% IgM); IgG/IgM sensitivities are moderately lower for all methods, probably due to the assay viral antigen's nature and/or to the detection time of nasopharyngeal swab RT-qPCR, with respect to symptoms onset. Given that sensitivities (around 94% and 84% for IgG and IgM, respectively) implicate false-negative cases and given the lack of effective vaccines or treatments, the only currently available procedure to reduce SARS-CoV-2 transmission is to identify and isolate persons who are contagious. For this reason, we would like to submit a flowchart in which serological tests, integrated with nasopharyngeal swab RT-qPCR, are included to help social and work activities implementation after the pandemic acute phase and to overcome lockdown.

SARS-CoV-2 infection serology: a useful tool to overcome lockdown?

The outbreak of 2019 novel coronavirus disease (Covid-19) caused by SARS-CoV-2 has spread rapidly, inducing a progressive growth in infected patients number. Social isolation (lockdown) has been assessed to prevent and control virus diffusion, leading to a worldwide financial and political crisis. Currently, SARS-CoV-2 RNA detection in nasopharyngeal swab takes place by real-time PCR (RT-qPCR). However, molecular tests can give some false-negative results. In this context, serological assays can be useful to detect IgG/IgM antibodies, to assess the degree of immunization, to trace the contacts, and to support the decision to re-admit people at work. A lot of serological diagnostic kits have been proposed on the market but validation studies have not been published for many of them. The aim of our work was to compare and to evaluate different assays analytical performances (two different immunochromatographic cards, an immunofluorescence chromatographic card, and a chemiluminescence-automated immunoassay) on 43 positive samples with RT-qPCR-confirmed SARS-CoV-2 infection and 40 negative control subjects. Our data display excellent IgG/IgM specificities for all the immunocromatographic card tests (100% IgG and 100% IgM) and for the chemiluminescence-automated assay (100% IgG and 94% IgM); IgG/IgM sensitivities are moderately lower for all methods, probably due to the assay viral antigen's nature and/or to the detection time of nasopharyngeal swab RT-qPCR, with respect to symptoms onset. Given that sensitivities (around 94% and 84% for IgG and IgM, respectively) implicate false-negative cases and given the lack of effective vaccines or treatments, the only currently available procedure to reduce SARS-CoV-2 transmission is to identify and isolate persons who are contagious. For this reason, we would like to submit a flowchart in which serological tests, integrated with nasopharyngeal swab RT-qPCR, are included to help social and work activities implementation after the pandemic acute phase and to overcome lockdown.

Acute ischemic stroke and COVID-19

Ischemic stroke may be a presenting feature of COVID-19. Its etiology remains unclear, but severe COVID-19 disease might increase the risk of large-artery strokes. More evidence is needed to substantiate the current reports and provide insights for optimal management.

Acute ischemic stroke and COVID-19

Ischemic stroke may be a presenting feature of COVID-19. Its etiology remains unclear, but severe COVID-19 disease might increase the risk of large-artery strokes. More evidence is needed to substantiate the current reports and provide insights for optimal management.

Iron overload and Hepcidin overexpression could play a key role in COVID infection, and may explain vulnerability in elderly, diabetics, and obese patients

BACKGROUND: The COVID epidemic hit like a tsunami worldwide. At the time of its arrival in Italy, available literary data were meager, and most of them concerned its epidemiology. World Health Organization proposed guidelines in march 2020, a strategy of treatment has been developed, and a significant number of subsequent articles have been published to understand, prevent, and cure COVID patients. METHODS: From the observation of two patients, we performed a careful analysis of scientific literature to unearth the relation between COVID infection, clinical manifestations as pneumonia and thrombosis, and to find out why it frequently affects obese, diabetics, and elderly patients. RESULTS: The analysis shows that hepcidin could represent one of such correlating factors. Hepcidin is most elevated in older age, in non-insulin diabetics patients and in obese people. It is the final target therapy of many medicaments frequently used. Viral disease, and in particular SARS-CoV19, could induce activation of the hepcidin pathway, which in turn is responsible for an increase in the iron load. Excess of iron can lead to cell death by ferroptosis and release into the bloodstream, such as free iron, which in turn has toxic and pro-coagulative effects. CONCLUSIONS: Overexpression of hepcidin and iron overload might play a crucial role in COVID infection, becoming potential targets for treatment. Hepcidin could also be considered as a biomarker to measure the effectiveness of our treatments and the restoration of iron homeostasis the final intent. (www.actabiomedica.it).

Forecasting the effect of social distancing on COVID-19 autumn-winter outbreak in the metropolitan area of Buenos Aires

Forecasting the extent of the domestic health risk of epidemics by mathematical modeling is a useful tool for evaluating the feasibility of policies for controlling outbreaks The objective of this study was to develop a time-dependent dynamic simulation model to forecast the COVID-19 autumn-winter outbreak in the metropolitan area of Buenos Aires, and to assess the effect of social distancing on epidemic spread The model used was the "Susceptible-Exposed-Infectious-Recovered" framework which incorporated appropriate compartments relevant to interventions such as quarantine, isolation and treatment In a low-intervention scenario including only 2-week isolation for international travelers and their contacts, the model estimated a maximum peak of nearly 90 000 symptomatic cases for early May For an intervention scenario with mandatory quarantine during a 5-month period, the curve of cases flattened and receded as the proportion of quarantined individuals increased The maximum peak was expected to appear between May 8 and Jul 8 depending on the quarantine strategy, and the average number of infectious symptomatic cases were 46 840, 30 494, 23 164, 16 179, and 13 196 when 10%, 20%, 30%, 40%, and 50% of the population remained in a 5-month-term continuous quarantine, respectively Only mandatory quarantine was able to delay the maximum peak of infection and significantly reduce the total number of infected individuals and deaths at a 150-day term The interruption of the quarantine before 120 days of its beginning could generate an even more serious outbreak 30 days later, and surpass the scarce medical resources available for the intensive care of critically-ill patients

Mean-Field Game Analysis of SIR Model with Social Distancing

The current COVID-19 pandemic has proven that proper control and prevention of infectious disease require creating and enforcing the appropriate public policies. One critical policy imposed by the policymakers is encouraging the population to practice social distancing (i.e. controlling the contact rate among the population). Here we pose a mean-field game model of individuals each choosing a dynamic strategy of making contacts, given the trade-off of gaining utility but also risking infection from additional contacts. We compute and compare the mean-field equilibrium (MFE) strategy, which assumes each individual acting selfishly to maximize its own utility, to the socially optimal strategy, which maximizes the total utility of the population. We prove that the optimal decision of the infected is always to make more contacts than the level at which it would be socially optimal, which reinforces the important role of public policy to reduce contacts of the infected (e.g. quarantining, sick paid leave). Additionally, we include cost to incentivize people to change strategies, when computing the socially optimal strategies. We find that with this cost, policies reducing contacts of the infected should be further enforced after the peak of the epidemic has passed. Lastly, we compute the price of anarchy (PoA) of this system, to understand the conditions under which large discrepancies between the MFE and socially optimal strategies arise, which is when intervening public policy would be most effective.

COVID-19 Associated With Life-Threatening Apnea in an Infant Born Preterm: A Case Report

A pandemic linked to the new coronavirus strain (SARS-CoV-2) has been raging for several months. Pediatric populations are less impacted than adults, and critical respiratory diseases seem rare (1, 2). We report the case of an infant, who presented with life-threatening apneas at home requiring basic life support. SARS-CoV-2 was subsequently identified in the patient's nasopharyngeal aspirate. He did not present with bronchiolitis or hypoxic failure as described in severe forms of COVID−19. The outcome was favorable in a few hours. The occurrence of apneas is not uncommon during viral respiratory infections in early infancy; however, there are very few descriptions related to a documented SARS-CoV-2 respiratory tract infection. In light of this clinical case, it seems necessary to quickly bring up a potential COVID-19 contamination in infants admitted for life-threatening apnea, in order to properly report and isolate these patients to avoid further nosocomial dissemination of SARS-CoV-2.

Tunicamycin anticancer drug may reliable to treat coronavirus disease-19

BACKGROUND: SARS-CoV-2 outbreaks remains a medical and economic challenge, due to the lack of a suitable drug or vaccine The glycan in some proteins plays an important role in protein folding, sorting, transport, and oligomerization, so the hindering of N-linked glycosylation of glycoproteins will prevent assembly of the virion Tunicamycin anticancer drug inhibits the N-linked glycan AIM: This study aimed to find out the mechanism action of tunicamycin on the viral glycoproteins RESULTS: The growth of the virus in the presence of tunicamycin conducted in the production of non-infectious and absence of spike protein (spikeless virions) Tunicamycin inhibits E2, S, and M glycoproteins of coronaviruses Tunicamycin has also diminished glycosylation of PTMs such as HE, and 8ab of SARS-CoV Finally, CONCLUSION: This study recommends using this drug to treat the SARS-CoV-2 © 2020 Ali Adel Dawood, Haitham Abdul-Malik Alnori

HIV-1 infection among women in Israel, 2010-2018

INTRODUCTION: Although women comprise 33% of the HIV-1-carriers in Israel, they have not previously been considered a risk group requiring special attention. Immigration waves from countries in Africa and in East Europe may have changed the local landscape of women diagnosed with HIV-1. Here, we aimed to assess viral and demographic characteristics of HIV-1-positive women identified in Israel between 2010 and 2018. METHODS: All > 16 year-old, HIV-1-infected women, diagnosed in Israel in 2010-2018, (n = 763) registered in the National HIV reference laboratory were included in this cross-sectional study. Demographic and clinical characteristics were extracted from the database. Viral subtypes and transmitted drug resistance mutations (TDRM) were determined in 337 (44.2%) randomly selected samples collected from treatment-naive women. RESULTS: Median age at diagnosis was 38 years. Most (73.3%) women were immigrants from the former Soviet Union (FSU) (41.2%, 314) or sub-Saharan Africa (SSA) (32.2%, 246) and carried subtype A (79.7%) or C (90.3%), respectively. Only 11.4% (87) were Israeli-born women. Over the years, the prevalence of women from SSA decreased while that of women from FSU increased significantly (p < 0.001). The median CD4+ cell count was 263 cells/mm3, and higher (391 cells/mm3) in Israeli-born women. TDRM were identified in 10.4% of the tested samples; 1.8, 3 and 7.1% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively. The prevalence of women with NNRTI TDRM significantly increased from 4.9% in 2010-2012 to 13.3% in 2016-2018. Israeli-born women had the highest prevalence (16.3%) of NNRTI TDRM (p = 0.014). NRTI A62 (5.6%), NNRTI E138 and K103 (5.6 and 4.2%, respectively) were the most prominent mutated sites. CONCLUSIONS: Most HIV-1-positive women diagnosed in Israel in 2010-2018 were immigrants, with the relative ratio of FSU immigrants increasing in recent years. The high proportion of women diagnosed with resistance mutations, particularly, the yearly increase in the frequency of NNRTI mutations, support the national policy of resistance testing at baseline.

Being responsible for someone else: a shared duty for parents and heart failure specialists during the COVID-19 pandemic

A pandemic by a novel coronavirus disease (COVID-19) has been declared by the World Health Organization Lombardy, the region of our tertiary referral centre for heart diseases in Northern Italy, has been particularly hit by the pandemic According to the government's prescriptions, all elective activities and procedures in the last months were suspended in order to concentrate our efforts on COVID-19 patients' care Entire departments have been turned into 'COVID-19 units', where healthcare professionals are daily involved in supporting critically ill patients On a personal level, this was a period of special feelings and peculiar unexpected events People close to healthcare workers have been affected, and our lives have been turned upside down Furthermore, right in this period, few colleagues (and friends) are facing entirely new events in their lives, such as fatherhood with its load of joy and concern Through the case of a young woman recently admitted to our department with a severe heart failure due to a peripartum cardiomyopathy, described in narrative form, this manuscript would help all those involved in the front line in the fight against the pandemic in these difficult times

Reflexões sobre a gestão do Sistema Único de Saúde para a coordenação no enfrentamento da COVID-19/ Reflections on the management of Brazilian Unified Health System for the coordination in facing COVID-19/ Reflexiones sobre la gestión del Sistema Unico de Salud de Brasil para la coordinación en el enfrentamiento a la COVID-19

Objetivo: Refletir acerca da gestão em saúde do Sistema Único de Saúde (SUS), na perspectiva de desafios e possibilidades para superar lacunas de coordenação no enfrentamento da COVID-19. Método: Trata-se de estudo reflexivo, fundamentado na formulação discursiva sobre a gestão em saúde no SUS organizado nas seguintes seções: introdução com a contextualização da temática, macrodesafios no âmbito do SUS na coordenação da atenção à saúde no enfrentamento da COVID-19, aspectos para subsidiar ações de coordenação da gestão e considerações finais. Resultados: Constatam-se desafios na coordenação entre os entes federativos, de financiamento, de consolidação da vigilância em saúde, da regulação, da capacidade instalada e gestão de pessoas que remetem à importância de estabelecer estratégias para o fortalecimento do SUS, principalmente, na coordenação da gestão em saúde. Conclusões e implicações para a prática: Destaca-se a relevância da autoridade da gestão regulatória no SUS para a coordenação e sua potencialidade de organização em prover melhores condições de atenção, porém, entende-se que é necessário revistar a territorialidade, o planejamento e o processo de trabalho, como elementos constituintes da vigilância em saúde.

Molecular docking and pharmacokinetic screening of eucalyptol (1,8 cineole) from eucalyptus essential oil against SARS-CoV-2

SARS-CoV-2 (COVID-19), member of corona virus family, is a positive single stranded RNA virus Due to lack of drugs it is spreading its tentacles across the world Being associated with cough, fever, and respiratory distress, this disease caused more than 15% mortality worldwide Mpro/3CLpro has recently been regarded as a suitable target for drug design due to its vital role in virus replication The current study focused on the inhibitory activity of eucalyptol (1,8 cineole), an essential oil component from eucalyptus oil, against Mpro/3CLpro from SARS-CoV-2 Till date there is no work is undertaken on in-silico analysis of this compound against Mpro/3CLpro of SARS-CoV-2 Molecular docking studies were conducted by using 1-click dock tool and Patchdock analysis In-silico absorpt ion, distribution, metabolism, excretion and toxicity (ADMET) profile were also studied The calculated parameters such as docking score indicated effective binding of eucalyptol to COVID-19 Mpro protein Active site prediction revealed the involvement of active site residues in ligand binding Interactions results indicated that, Mpro/3CLpro/eucalyptol complexes forms hydrophobic interactions ADMET studies provided guidelines and mechanistic scope for identification of potent anti-COVID 19 drug Therefore, eucalyptol may represent potential herbal treatment to act as COVID-19 Mpro/3CLpro inhibitor, a finding which must be validated in vivo

Use of remdesivir for patients with Covid-19: a review article

The etiological agent of COVID-19, which causes severe respiratory diseases such as pneumonia and pulmonary insufficiency, has been confirmed as a new coronavirus, now known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) There is currently no authorized medication for the treatment of COVID-19 No vaccines have been authorized Thus, this study aimed at conducting a review of the use of Remdesivir in patients with COVID-19 The following electronic databases were used MEDLINE, SCIELO, LILACS, and PUBMED On May 1, Remdesivir received emergency use authorization from the Food and Drug Administration Remdesivir is currently the most promising molecule in the treatment of COVID-19, taking into account its broad antiviral spectrum (considering the genetic sequences of the virus, it is expected to maintain activity against SARS-CoV-2) There is in vitro and in vivo information available for coronaviruses, as well as an extensive clinical safety database (from a clinical trial of the Ebola virus and in the context of the Monitored Emergency Use of Unregistered and Investigational Interventions - MEURI) Further studies are relevant as available data on the efficacy and safety of Remdesivir against SARS-nCoV-2 are limited

Establishing and comparing energy security trends in resource-rich exporting nations (Russia and the Caspian Sea region)

In the international arena, it is often the case that in countries which largely depend on foreign resources, energy security, and its key components i e security of energy supply, environment, technology, geopolitical and economic factors, is a subject of concern However, due to the abundance of fossil fuel resources in resource-rich exporting nations, there is a lack of understanding of the risks around energy security and accordingly often a policy vacuum Conceptualising energy security from different geopolitical vantage points will allow future concerns around energy supply security, climate change, and regional economic crises to be evaluated By using policy documents and developing a time series approach and normalized z-scores for a range of comparable metrics this article compares the energy security performance in six Caspian Sea countries individually and collectively The article results show that Azerbaijan, Iran, Kazakhstan made significant progress in energy security since 1990, while energy security indicators in Russia, Uzbekistan, and Turkmenistan regressed Iran has a leading position in energy security performance, while Uzbekistan and Turkmenistan have the lowest level of the energy security indicators compare to other region countries This article both contributes a replicable definition of energy security that can be undertaken for other global regions, and begins to incorporate diversification and renewables development to enhance domestic energy security assessment

Anti-SARS-Cov-2 IgA Response in Tears of COVID-19 Patients

The pandemic virus SARS-CoV-2 has been reported to be able to enter the body via the eye conjunctiva, but the presence of antiviral response in the eye remains poorly known Our study was thus aimed to analyze the presence of secretory mucosal anti-SARS-CoV-2 type A immunoglobulins (IgA) in the conjunctival fluid of COVID-19 patients The tears of 28 COVID-19 patients and 20 uninfected controls were collected by the Schirmer test and analyzed by a specific ELISA assay detecting anti-spike (S1) virus protein IgA The results showed that 35 7% of COVID-19 subjects have specific antiviral IgA at the ocular level, persisting till 48 days post disease onset Most of the IgA positive subjects presented mild symptoms The collected data indicate a prolonged persistence of anti-SARS-CoV-2 IgA at the eye level and suggest that IgA detection may be extremely helpful in clarifying virus pathology and epidemiology

A multiplex microsphere IgG assay for SARS-CoV-2 using ACE2-mediated inhibition as a surrogate for neutralization

The COVID-19 pandemic has highlighted the challenges inherent to the serological detection of a novel pathogen such as SARS-CoV-2. Serological tests can be used diagnostically and for surveillance, but their usefulness depends on their throughput, sensitivity and specificity. Here, we describe a multiplex fluorescent microsphere-based assay, 3Flex, that can detect antibodies to three major SARS-CoV-2 antigens-spike (S) protein, the spike ACE2 receptor-binding domain (RBD), and nucleocapsid (NP). Specificity was assessed using 213 pre-pandemic samples. Sensitivity was measured and compared to the Abbott⃝ ARCHITECT⃝ SARS-CoV-2 IgG assay using serum samples from 125 unique patients equally binned (n = 25) into 5 time intervals (&#8804;5, 6 to 10, 11 to 15, 16 to 20, and &#8805;21 days from symptom onset). With samples obtained at &#8804;5 days from symptom onset, the 3Flex assay was more sensitive (48.0% vs. 32.0%), but the two assays performed comparably using serum obtained &#8805;21 days from symptom onset. A larger collection (n = 534) of discarded sera was profiled from patients (n = 140) whose COVID-19 course was characterized through chart review. This revealed the relative rise, peak (S, 23.8; RBD, 23.6; NP, 16.7; in days from symptom onset), and decline of the antibody response. Considerable interperson variation was observed with a subset of extensively sampled ICU patients. Using soluble ACE2, inhibition of antibody binding was demonstrated for S and RBD, and not for NP. Taken together, this study described the performance of an assay built on a flexible and high-throughput serological platform that proved adaptable to the emergence of a novel infectious agent.

Development of SARS-CoV-2 Nucleocapsid Specific Monoclonal Antibodies

The global COVID-19 pandemic has caused massive disruptions in every society around the world To help fight COVID-19, new molecular tools specifically targeting critical components of the causative agent of COVID-19, SARS-Coronavirus-2 (SARS-CoV-2), are desperately needed The SARS-CoV-2 nucleocapsid protein is a major component of the viral replication processes, integral to viral particle assembly, and is a major diagnostic marker for infection and immune protection Currently available antibody reagents targeting the nucleocapsid protein were primarily developed against the related SARS-CoV virus and are not specific to SARS-CoV-2 nucleocapsid protein Therefore, in this work we developed and characterized a series of new mouse monoclonal antibodies against the SARS-CoV-2 nucleocapsid protein The anti-nucleocapsid monoclonal antibodies were tested in ELISA, western blot, and immunofluorescence analyses The variable regions from the heavy and light chains from five select clones were cloned and sequenced, and preliminary epitope mapping of the sequenced clones was performed Overall, the new antibody reagents described here will be of significant value in the fight against COVID-19

Triage during the COVID-19 epidemic in Spain: better and worse ethical arguments

The COVID-19 pandemic has generated an imbalance between the clinical needs of the population and the effective availability of advanced life support (ALS) resources. Triage protocols have thus become necessary. Triage decisions in situations of scarce resources were not extraordinary in the pre-COVID-19 era; these protocols abounded in the context of organ transplantation. However, this prior experience was not considered during the COVID-19 outbreak in Spain. Lacking national guidance or public coordination, each hospital has been forced to put forth independent and autonomous triage protocols, most of which were, nonetheless, based on common ethical principles and clinical criteria. However, controversial, non-clinical criteria have also been defended by Spanish scientific societies and public institutions, including setting an age cut-off value for unilaterally withholding ALS, using 'social utility' criteria, prioritising healthcare professionals or using 'first come, first served' policies. This paper describes the most common triage criteria used in the Spanish context during the COVID-19 epidemic. We will highlight our missed opportunities by comparing these criteria to those used in organ transplantation protocols. The problems posed by subjective, non-clinical criteria will also be discussed. We hope that this critical review might be of use to countries at earlier stages of the epidemic while we learn from our mistakes.

Fighting fake news in the COVID-19 era: policy insights from an equilibrium model

The COVID-19 crisis has revealed structural failures in governance and coordination on a global scale. With related policy interventions dependent on verifiable evidence, pandemics require governments to not only consider the input of experts but also ensure that science is translated for public understanding. However, misinformation and fake news, including content shared through social media, compromise the efficacy of evidence-based policy interventions and undermine the credibility of scientific expertise with potentially longer-term consequences. We introduce a formal mathematical model to understand factors influencing the behavior of social media users when encountering fake news. The model illustrates that direct efforts by social media platforms and governments, along with informal pressure from social networks, can reduce the likelihood that users who encounter fake news embrace and further circulate it. This study has implications at a practical level for crisis response in politically fractious settings and at a theoretical level for research about post-truth and the construction of fact.

Data-Driven Insights on the Effects of COVID-19 on Public Interest in Medical Aesthetics: Part II (Active Analysis)

BACKGROUND: The COVID-19 pandemic significantly affected financial and psychosocial factors that influence plastic surgery demand. OBJECTIVES: The authors sought to actively assess public interest changes and the reasons underlying these shifts. METHODS: Using Amazons' Mechanical Turk, we crowdsourced public opinions regarding aesthetic interventions from April 30 to May 3, 2020. The survey assessed prior experience with and interest in 6 aesthetic interventions before and during the pandemic and reasons for changing interest. United States residents aged 18 years and over who passed the attention check were included. RESULTS: We included 704 of 838 total responses. One-half of respondents were female; the median age group was 25 to 34 years. During the pandemic, 21% of respondents had increased and 33% decreased interest in at least one intervention. Non-invasive procedures (7.3%), facial aesthetic surgery (6.6%), and medical-grade skincare (5.9%) elicited the greatest interest increase. Seeing themselves in the mirror more often (43.2%), desire to look better after the crisis (41.8%), and increased time on social media (40.4%) were the top reasons for increased interest. The most common reasons for decreased interest were changing spending priorities (58%), focusing on other health aspects (49.8%), and worrying about infection in medical facilities (46.3%). Almost one-half of respondents considered virtual consultations for interventions of increased interest. CONCLUSIONS: The COVID-19 pandemic significantly affected interest in medical aesthetics. Offering telemedicine and discussing detailed COVID-19 infection control policies with patients will be critical to address patient needs and concerns. These findings can be used to improve patient outreach, advertisement, and counseling as practices focus on reopening.

Anticoagulant treatment in COVID-19: a narrative review

The actual Coronavirus Disease (COVID 19) pandemic is due to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the coronavirus family. Besides the respiratory involvement, COVID 19 patients frequently develop a pro-coagulative state caused by virus-induced endothelial dysfunction, cytokine storm and complement cascade hyperactivation. It is common to observe diffuse microvascular thrombi in multiple organs, mostly in pulmonary microvessels. Thrombotic risk seems to be directly related to disease severity and worsens patients' prognosis. Therefore, the correct understanding of the mechanisms underlying COVID-19 induced prothrombotic state can lead to a thorough assessment of the possible management strategies. Hence, we review the pathogenesis and therapy of COVID 19-related thrombosis disease, focusing on the available evidence on the possible treatment strategies and proposing an algorithm for the anticoagulation strategy based on disease severity.

Defining a regulatory strategy for ATMP/aerosol delivery device combinations in the treatment of respiratory disease

Advanced Therapeutic Medicinal Products (ATMP) are a heterogenous group of investi-gational medicinal products at the forefront of innovative therapies with direct applicability in respiratory diseases ATMPs include, but are not limited to, stem cells, their secretome, or extracellular vesicles, and each have shown some potential when delivered topically within the lung This review focuses on that subset of ATMPs One key mode of delivery that has enabling potential in ATMP validation is aerosol-mediated delivery The selection of the most appropriate aerosol generator technology is influenced by several key factors, including formulation, patient type, patient inter-vention, and healthcare economics The aerosol-mediated delivery of ATMPs has shown promise for the treatment of both chronic and acute respiratory disease in pre-clinical and clinical trials;however, in order for these ATMP device combinations to translate from the bench through to com-mercialization, they must meet the requirements set out by the various global regulatory bodies In this review, we detail the potential for ATMP utility in the lungs and propose the nebulization of ATMPs as a viable route of administration in certain circumstances Further, we provide insight to the current regulatory guidance for nascent ATMP device combination product development within the EU and US

The Future of Global Great Power Competition after the Coronavirus

Due to the COVID-19 pandemic, the domestic and foreign policy agendas of all countries have been turned upside down The pandemic has brought new problems and competition areas to states and to the international system While the pandemic politically calls to mind the post-World War II era, it can also be compared with the 2008 crisis due to its economic effects such as unemployment and the disruption of global supply chains A debate immediately began for a new international system;however, it seems that the current international system will be affected, but will not experience a radical change That is, a new international order is not expected, while disorder is most likely in the post-pandemic period In an atmosphere of global instability where debates on the U S -led international system have been worn for a while, in the post-pandemic period states will invest in self-sufficiency and redefine their strategic areas, especially in health security The decline of U S leadership, the challenging policies of China, the effects of Chinese policies on the U S -China relations and the EU's deepening crisis are going to be the main discussion topics that will determine the future of the international system

A conceptual framework for incorporating competitiveness into network-level transit quality metrics

In today’s mobility context, people have more mode choices than in the past, and many of those new choices are auto-based This has led to a resurgence of transit agencies rethinking their networks and how well they connect people to opportunities This paper proposes a new theoretical framework, Competitive Access, for transportation researchers and practitioners to use in describing and measuring regional transit access The Competitive Access framework incorporates the concept of competitiveness between auto-based modes and transit, and is flexible enough to capture the varying contexts in which accessibility can change between and within regions Using this framework, we propose two measures that describe the trip coverage and regional access provided by a transit network These measures better reflect the realities experienced by riders in comparison to traditional access measures Additionally, this paper includes a guide for practitioners to implement the framework and its associated measures in a network redesign context

Ensuring the Sustainability of University Learning: Case Study of a Leading Chinese University

The spread of the novel coronavirus at the start of 2020 shocked higher education across China then around the rest of the world To ensure sustainability of learning, this required an unprecedented shift from campus-based to emergency online education This created an urgent need to learn more about the quality of online education, the provision of global education, and the transformation potential of universities This paper analyses these matters, presenting insights from large-scale research conducted on a leading Chinese university, the first ever major research university to make this substantial transition This research applied a mixed methods design, which combines quantitative and qualitative approaches The results provide important insight into the nature, quality, and outcomes of online learning in major Asian research universities They signal critical areas that require reform to ensure the sustainability of future higher education

Nanoparticle-Based Strategies to Combat COVID-19

Coronavirus disease 2019 (COVID-19) is the worst pandemic disease of the current millennium This disease is caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first exhibited human-to-human transmission in December 2019 and has infected millions of people within months across 213 different countries Its ability to be transmitted by asymptomatic carriers has put a massive strain on the currently available testing resources Currently, there are no clinically proven therapeutic methods that clearly inhibit the effects of this virus, and COVID-19 vaccines are still in the development phase Strategies need to be explored to expand testing capacities, to develop effective therapeutics, and to develop safe vaccines that provide lasting immunity Nanoparticles (NPs) have been widely used in many medical applications, such as biosensing, drug delivery, imaging, and antimicrobial treatment SARS-CoV-2 is an enveloped virus with particle-like characteristics and a diameter of 60–140 nm Synthetic NPs can closely mimic the virus and interact strongly with its proteins due to their morphological similarities Hence, NP-based strategies for tackling this virus have immense potential NPs have been previously found to be effective tools against many viruses, especially against those from the Coronaviridae family This Review outlines the role of NPs in diagnostics, therapeutics, and vaccination for the other two epidemic coronaviruses, the 2003 severe acute respiratory syndrome (SARS) virus and the 2012 Middle East respiratory syndrome (MERS) virus We also highlight nanomaterial-based approaches to address other coronaviruses, such as human coronaviruses (HCoVs);feline coronavirus (FCoV);avian coronavirus infectious bronchitis virus (IBV);coronavirus models, such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and transmissible gastroenteritis virus (TGEV);and other viruses that share similarities with SARS-CoV-2 This Review combines the salient principles from previous antiviral studies with recent research conducted on SARS-CoV-2 to outline NP-based strategies that can be used to combat COVID-19 and similar pandemics in the future

A Major Issue Related to the Death Caused by Novel Corona Virus

Novel coronavirus (COVID-19) disease is an infectious viral disease that is caused by a coronavirus The people suffering from these viral diseases (COVID-19) g

Traversable wormhole without interaction

We show that strong quantum entanglement can support a stable traversable wormhole without any explicit interaction or tunnelling term between the two boundary theories of the wormhole. Specifically we work with two complex SYK models. The entangled state is prepared using a tunnelling term in imaginary time but the tunnelling term is removed from the time evolution operator so the two complex SYK models are not coupled. Low temperature states show revival dynamics which is the hallmark of a traversable wormhole geometry. To send any meaningful information from one system to the other, one only needs to turn on a very small interaction term. The technique that we are employing can be applied to other systems to study aspects of quantum entanglement.

Disentangling Types of Liquidity & Testing Limits-to-Arbitrage Theories in the CDS-Bond Basis

We disentangle asset-specific, market, and funding liquidity in the CDS-Bond basis outside and during the 07/09 Global Financial Crisis Our findings stress the importance of separating different types of liquidity, since all three measures have independently negative impacts on the basis Funding liquidity emerges as the economically most important liquidity metric While asset-specific liquidity is cross-correlated in both the cash and derivative markets, funding and market liquidity only matter for the cash market We exploit the decomposition of the basis to test predictions of limits-to-arbitrage theories We find strong evidence in favor of margin-based asset pricing and flight-to-quality effects This article is protected by copyright All rights reserved

Coronaviruses seven outbreaks associated with OC43, 229E, severe acute respiratory syndrome-CoV1, NL63, HKU1, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome-CoV2

Background: Coronaviruses (CoVs) responsible for seven outbreaks during a period of six decades Started with infection of hCov-229E at 1966 and hope to stop with severe acute respiratory syndrome-CoV2 at 2020 They have a wide range of host animal and can transmit to human causing illness mainly concerned with respiratory tract infections They originated from animal reservoirs such as bats, Chinese ferret masked palm civets, raccoon dogs, and domestic cats and can transmit the infection to human Methodology: CT imaging, CBC, CRP, liver function, and coagulation assays were used as primary tests for suspected patients whose confirmed using real-time PCR assay along with serological test such as rapid test, ELISA, and other techniques based on antiviral specific Abs Results: The results reveal symptoms of patients ranged from rhinorrhea, fever, cough to wide range of upper respiratory tract infections, and, occasionally, lower respiratory tract infections, including pneumonia and bronchiolitis The results of diagnosis showed that CT imaging is helpful along with CBC and CRP assays as a primary screening test The real-time PCR assay was the gold standard and sometime gives false negative may be due to inefficiency of sample collection and must be confirmed with a rapid test of ELISA IgM and IgG, especially after symptoms development Wide range of antiviral was used for treatment success to cure the CoVs infections Conclusions: CoVs seem to be having tendency for animal-human transmission along with targeting a special type of cells like those of respiratory tract to cause asymptomatic to severe infections easy to treat with prominent antiviral agents [ABSTRACT FROM AUTHOR] Copyright of Drug Invention Today is the property of Journal of Pharmacy Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Data and cooperation required for Venezuela's refugee crisis during COVID-19

The deteriorating political and economic situation in Venezuela has ramifications far beyond the Latin American country's borders as almost five million Venezuelans fled and migrated into countries in the region due to the crisis at home. The scarcity of health services, the lack of information sharing, and the absence of reliable data in Venezuela create challenges for confronting developing health emergencies and disease outbreaks. The need for accurate data is especially dire given the current COVID-19 pandemic and evolving movement of refugees. While countries and international organizations came together to form a coordinated response to Venezuela's political and humanitarian crisis, this geopolitical progress is threatened by the rapid spread of COVID-19, and the instinct for countries to focus inwards on domestic response priorities, rather than engage in regional cooperation. It is critical that the international community set aside geopolitical differences and cooperate to seek an accurate picture of the conditions on the ground to improve the welfare of Venezuelan migrants and to provide a more robust response to the current pandemic.

Changing workplace geographies in the COVID-19 crisis

COVID-19 has fundamentally changed workplace geographies with large proportions of people working at home during the ‘Great Lockdown’. This commentary argues that working at home has emerged as a key policy response and one in which inequalities are embedded. We outline the nature of these social and spatial inequalities by examining existing evidence and data for the Global North, and consider some of the economic and policy challenges ahead.

Framing a Needed Discourse on Health Disparities and Social Inequities: Drawing Lessons from a Pandemic

COVID-19 provides numerous opportunities for policymakers to consider matters of social equity in relation to the field of public health. Specifically, by reflecting on health disparities in relation to the disproportionate impact of COVID-19 on minority and historically underserved populations, we can leverage a needed discourse on health outcomes for many communities. Grounded in the social determinants of health conceptual framework, this article explores the application of the disproportionate impact of COVID-19 on vulnerable populations and communities of color for a discussion on strategies for minimizing health disparities. This article is protected by copyright. All rights reserved.

Immune Response to COVID-19: Can We Benefit from the SARS-CoV and MERS-CoV Pandemic Experience?

The global range and high fatality rate of the newest human coronavirus (HCoV) pandemic has made SARS-CoV-2 the focus of the scientific world. Next-generation sequencing of the viral genome and a phylogenetic analysis have shown the high homology of SARS-CoV-2 to other HCoVs that have led to local epidemics in the past. The experience acquired in SARS and MERS epidemics may prove useful in understanding the SARS-CoV-2 pathomechanism and lead to effective treatment and potential vaccine development. This study summarizes the immune response to SARS-CoV, MERS-CoV, and SARS-CoV-2 and focuses on T cell response, humoral immunity, and complement system activation in different stages of HCoVs infections. The study also presents the quantity and frequency of T cell responses, particularly CD4+ and CD8+; the profile of cytokine production and secretion; and its relation to T cell type, disease severity, and utility in prognostics of the course of SARS, MERS, and COVID-19 outbreaks. The role of interferons in the therapy of these infections is also discussed. Moreover, the kinetics of specific antibody production, the correlation between humoral and cellular immune response and the immunogenicity of the structural HCoVs proteins and their utility in the development of a vaccine against SARS, MERS, and COVID-19 has been updated.

Optimizing Access to Heart Failure Care in Canada During the COVID-19 Pandemic

The traditional model of heart failure (HF) care in Canada, which relies upon a multidisciplinary team and clinic-based care processes, has been undermined as a result of the COVID-19 pandemic. As the pandemic continues, we will be challenged to improve or maintain the health status of those with HF by optimizing guideline-directed care despite physical distancing constraints and a reduction in the health care workforce. This will require development of new strategies specifically targeted at decreasing the risk of decompensation and resultant HF hospitalization. As such, we must quickly pivot to the adoption and application of novel technologies and revise usual care models, processes, and workflow. The unprecedented COVID-19 crisis has delivered the Canadian HF community a burning platform for the design and implementation of innovative approaches to support the vulnerable population we serve; born out of necessity, we now have the opportunity to explore innovative approaches that might inform the future of HF care delivery in Canada. Herein, we provide perspectives from leadership within the Canadian Heart Failure Society on how to optimize HF care during the COVID-19 pandemic.

Impact of Maternal Demographic and Socioeconomic Factors on the Association Between Particulate Matter and Adverse Birth Outcomes: a Systematic Review and Meta-analysis

BACKGROUND: Numerous studies conducted in the United States found associations between prenatal exposure to particulate matter (PM) and adverse birth outcomes, and some studies identified vulnerable populations, including certain racial/ethnic groups and people with low-socioeconomic status. However, their findings are not always consistent. In this review, we compared the risk of adverse birth outcomes due to PM exposures among subpopulations and investigated whether any particular population is more vulnerable. METHODS: We selected U.S. studies examining associations between PM exposure during pregnancy and birth outcomes that included results for effect modification by race/ethnicity and/or maternal education. We summarized the findings for various sizes of PM and birth outcomes. Meta-analysis was conducted to quantify vulnerable race/ethnicity for the association between fine PM (PM2.5) and birthweight. RESULTS: In total, 19 studies were assessed, and PM-related risks of adverse birth outcomes, particularly those related to fetal growth, likely differ across subpopulations. A meta-analysis from five studies showed that a 10 µg/m3 increase of PM2.5 during the full-gestation reduced birthweight by 21.9 g (95% confidence interval 11.7, 32.0), 15.7 g (10.1, 21.4), 9.3 g (2.7, 15.8), and 5.8 g (- 9.0, 20.7) for Black, White, Hispanic, and Asian mothers, respectively. CONCLUSION: Our review indicated that Black mothers and mothers with low educational attainment are more vulnerable subpopulations. More investigation is needed for effect modification by other maternal factors, such as household income. Characterizing and quantifying vulnerable subpopulations are essential for addressing environmental justice since it can help regulatory agencies allocate resources and design policy interventions.

A dynamic nomenclature proposal for SARS-CoV-2 to assist genomic epidemiology

The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of thousands of virus genome sequences The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2 We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and declassifying virus lineages that become unobserved and hence are likely inactive By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2 ### Competing Interest Statement The authors have declared no competing interest

Maintenance oncohematological patients and new coronavirus infection: Experience of the City Clinical Hospital NO 52

Justification Oncological diseases, along with diabetes, hypertension, cardiovascular and chronic obstructive pulmonary diseases, are associated with severe course and worst prognosis of the new coronavirus infection - COVID-19 Due to the limited number of the international studies and the lack of the domestic publications on the analysis of the course of COVID-19 in patients with oncohematological pathology and the patient management tactics, this work seems extremely topical Materials and methods 24 04 2020-31 05 2020, 110 patients with oncohematological pathology associated with new coronavirus infection were observed on the basis of the hematology service of City Clinical Hospital No 52: 59 women and 51 men, mean age 58 (18-90) years Results Currently, 24 (22%) patients among 110 are continuing treatment The outcome of the disease is observed in 86 (78%) patients: 50 (58%) patients were discharged from hospital with complete or partial resolution of pneumonia, 36 (42%) of the 86 patients died The groups did not differ in gender The median age was higher in the group of deceased patients (66 vs 54 years in patients who had a favorable outcome after COVID-19) The somatic status ECOG 3-4 was an independent predictive factor determining the adverse outcome of the disease The third part of the patients from the group with a fatal cases due to a severe condition in the debut of the disease immediately were hospitalized in the intensive care unit (ICU), 2 (6%) of them had died within the first day Disposition, according to the nosology showed a significant predominance among patients with an adverse outcome associated with acute leukemia (18% vs 39%) Patients with resistant course of hemoblastosis accounted for 50% of deceased patients Severe form of the course of COVID-19 infection was twice as frequently (46% vs 84%) among patients with an adverse outcome of the disease, that was associated with both the initial more severe group of patients (33% were hospitalized in the ICU), and less curability of pneumonia against the background of the adverse prognostic factors: the older age group, the predominance of patients with acute leukemia and resistant course of oncohematological diseases Specific anticancer therapy and COVID-19 therapy were comparable in both groups Conclusions Identification of new coronavirus infection against a backdrop of oncohematological disease is associated with a severe course of COVID-19 and high death rate - 42% According to the preliminary obtained results, the adverse prognostic factors of COVID-19 in patients with oncohematological diseases include: elderly age, the poor somatic status (ECOG 3-4), relapse or progression of hemoblastosis and nosological affiliation to acute leukemia © 2020 Journal of Modern Oncology All rights reserved

Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells

COVID-19 affects vulnerable populations including elderly individuals and patients with cancer Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells Chloroquine or hydroxychloroquine increase cleaved active SP-domain of TMPRSS2, and this is potentiated by MEKi In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi We show elevated cytokines in COVID-19- (+) patient plasma (N=9) versus control (N=11) TMPRSS2, inflammatory cytokines G-CSF, M- CSF, IL-1a, IL-6 and MCP-1 are suppressed by MEKi alone or in combination with remdesivir MEKi enhance NK cell (but not T-cell) killing of target-cells, without suppressing TRAIL-mediated cytotoxicity We generated a pseudotyped SARS-CoV-2 virus with a lentiviral core but with the SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope and used VSV-G lentivirus as a negative control Our results show infection of human bronchial epithelial cells or lung cancer cells and that MEKi suppress infectivity of the SARS-CoV-2-S pseudovirus following infection We show a drug class-effect with MEKi to promote immune responses involving NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells in a model system MEKi may attenuate coronavirus infection to allow immune responses and antiviral agents to control COVID-19 disease progression and severity

Micro-macro dynamics of the online opinion evolution: An asynchronous network model approach

This article investigates the complex relationship between endogenous and exogenous, deterministic and stochastic stimulating factors in public opinion dynamics. An asynchronous multiagent network model is proposed to explore the interaction mechanism between individual opinions and the public opinion in online multiagent network community, including both the micro and the macro patterns of opinion evolution. In addition, based on random network models, a novel algorithm is provided for opinion evolution prediction. The model property analysis and numerical experiments show that the proposed asynchronous multiagent network model can assimilate and explain some interesting phenomena that are observed in the real world. Further case studies with numerical simulation and real-world applications confirm the feasibility and flexibility of the proposed model in public opinion analysis. The results challenge the common perception that mass media or opinion facilitators play the fundamental role in controlling the development trends of public opinion. This study shows that the formation and evolution of public opinion in the presence of opinion leaders depend also on an individual's emotional inertia and conformity pressures from peers in the same topic group.

Data-driven Simulation and Optimization for Covid-19 Exit Strategies

The rapid spread of the Coronavirus SARS-2 is a major challenge that led almost all governments worldwide to take drastic measures to respond to the tragedy. Chief among those measures is the massive lockdown of entire countries and cities, which beyond its global economic impact has created some deep social and psychological tensions within populations. While the adopted mitigation measures (including the lockdown) have generally proven useful, policymakers are now facing a critical question: how and when to lift the mitigation measures? A carefully-planned exit strategy is indeed necessary to recover from the pandemic without risking a new outbreak. Classically, exit strategies rely on mathematical modeling to predict the effect of public health interventions. Such models are unfortunately known to be sensitive to some key parameters, which are usually set based on rules-of-thumb.In this paper, we propose to augment epidemiological forecasting with actual data-driven models that will learn to fine-tune predictions for different contexts (e.g., per country). We have therefore built a pandemic simulation and forecasting toolkit that combines a deep learning estimation of the epidemiological parameters of the disease in order to predict the cases and deaths, and a genetic algorithm component searching for optimal trade-offs/policies between constraints and objectives set by decision-makers. Replaying pandemic evolution in various countries, we experimentally show that our approach yields predictions with much lower error rates than pure epidemiological models in 75% of the cases and achieves a 95% R2 score when the learning is transferred and tested on unseen countries. When used for forecasting, this approach provides actionable insights into the impact of individual measures and strategies.

Preparedness and Reorganization of Care for Coronavirus Disease 2019 Patients in a Swiss ICU: Characteristics and Outcomes of 129 Patients

Objectives: In many countries, large numbers of critically ill patients with coronavirus disease 2019 are admitted to the ICUs within a short period of time, overwhelming usual care capacities. Preparedness and reorganization ahead of the wave to increase ICU surge capacity may be associated with favorable outcome. The purpose of this study was to report our experience in terms of ICU organization and anticipation, as well as reporting patient characteristics, treatment, and outcomes. Design: A prospective observational study. Setting: The division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). Patients: All consecutive adult patients with acute respiratory failure due to coronavirus disease 2019 admitted in the ICU between March 9, 2020, and May 19, 2020, were enrolled. Patients' demographic data, comorbidities, laboratory values, treatments, and clinical outcomes were collected. Interventions: None. Measurements and Main Results: The ICU was reorganized into cells of six to eight patients under the care of three physicians and five nurses. Its capacity increased from 30 to 110 beds, fully equipped and staffed, transforming the surgical intermediate care unit, the postoperative care facility, and operating theaters into ICUs. Surge capacity has always exceeded the number of patients hospitalized. Among 129 critically ill patients with severe acute hypoxemic respiratory failure, 96% required invasive mechanical ventilation. A total of 105 patients (81%) were discharged alive and 24 died, corresponding to a mortality of 19%. Patients who died were significantly older, with higher severity scores at admission, had higher levels of d-dimers, plasma creatinine, high-sensitive troponin T, C-reactive protein, and procalcitonin, and required more frequent prone sessions. Conclusions: A rapid increase in ICU bed capacity, including adequate equipment and staffing, allowed for a large number of critically ill coronavirus disease 2019 patients to be taken care of within a short period of time. Anticipation and preparedness ahead of the wave may account for the low mortality observed in our center. These results highlight the importance of resources management strategy in the context of the ongoing coronavirus disease 2019 pandemic.

Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study

BACKGROUND: Fecal microbiota transplantation (FMT) can be a life-saving treatment against recurrent Clostridioides difficile infection (CDI). It is therefore necessary to maintain this procedure available for these patients during the COVID-19 pandemic while keeping high efficacy and safety standards. AIMS: To report outcomes of a FMT service that has adapted its operational workflow during COVID-19 pandemic to continue offering FMT to patients with CDI. METHODS: All patients with CDI referred to our center for FMT during pandemic were prospectively included. Each step of the FMT working protocol was adapted with specific security measures to prevent the transmission of SARS-CoV-2. RESULTS: Of 26 patients evaluated for FMT, 21 were treated for recurrent or refractory CDI. Eighteen patients completed the 8-week follow-up, and no one recurred after FMT. Follow-up is ongoing in 3 patients, although in all of them diarrhea disappeared after the first procedure. No serious adverse events were reported. Two patients had also COVID-19-related pneumonia, and were cured both from CDI and COVID-19. CONCLUSION: This is the first report to show that it is possible to maintain standard volumes, efficacy and safety of FMT for recurrent CDI during the COVID-19 pandemic, by adopting specific changes in the operational workflow.

Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study

BACKGROUND: Fecal microbiota transplantation (FMT) can be a life-saving treatment against recurrent Clostridioides difficile infection (CDI). It is therefore necessary to maintain this procedure available for these patients during the COVID-19 pandemic while keeping high efficacy and safety standards. AIMS: To report outcomes of a FMT service that has adapted its operational workflow during COVID-19 pandemic to continue offering FMT to patients with CDI. METHODS: All patients with CDI referred to our center for FMT during pandemic were prospectively included. Each step of the FMT working protocol was adapted with specific security measures to prevent the transmission of SARS-CoV-2. RESULTS: Of 26 patients evaluated for FMT, 21 were treated for recurrent or refractory CDI. Eighteen patients completed the 8-week follow-up, and no one recurred after FMT. Follow-up is ongoing in 3 patients, although in all of them diarrhea disappeared after the first procedure. No serious adverse events were reported. Two patients had also COVID-19-related pneumonia, and were cured both from CDI and COVID-19. CONCLUSION: This is the first report to show that it is possible to maintain standard volumes, efficacy and safety of FMT for recurrent CDI during the COVID-19 pandemic, by adopting specific changes in the operational workflow.

Inequalities in awareness and availability of bereavement services in North-East England

OBJECTIVES: National guidance recommends equality in access to bereavement services;despite this, awareness and availability appears inconsistent The aim of this study was to explore availability and accessibility of bereavement services across the North-East of England and to highlight issues potentially applicable across the UK, at a time of unprecedented need due to the impact of COVID-19 METHODS: Phase 1: an eight item, web-based survey was produced A survey link was cascaded to all GP practices (General Practitioners) in the region Phase 2: an email was sent to all services identified in phase 1, requesting details such as referral criteria and waiting times RESULTS: All 392 GP practices in the region were invited to participate The response rate was 22% (85/392) Twenty-one per cent (18/85) of respondents reported that they do not refer patients, comments included 'not aware of any services locally' A total of 36 services were contacted with 72% responding with further information Most bereavement specific support was reliant on charity-funded services including hospices, this sometimes required a pre-existing link with the hospice Waiting times were up to 4 months CONCLUSIONS: Although multiple different, usually charity-funded services were identified, awareness and accessibility were variable This survey was conducted prior to the COVID-19 pandemic, where complex situations surrounding death is likely to impact on the usual grieving process and increase the need for bereavement support Meanwhile, charities providing this support are under severe financial strain There is an urgent need to bridge the gap between need and access to bereavement services

How mobility habits influenced the spread of the COVID-19 pandemic: Results from the Italian case study

Starting from December 2019 the world has faced an unprecedented health crisis caused by the new Coronavirus (COVID-19) due to the SARS-CoV-2 pathogen. Within this topic, the aim of the paper was to quantify the effect of mobility habits in the spread of the Coronavirus in Italy through a multiple linear regression model. Estimation results showed that mobility habits represent one of the variables that explains the number of COVID-19 infections jointly with the number of tests/day and some environmental variables (i.e. PM pollution and temperature). Nevertheless, a proximity variable to the first outbreak was also significant, meaning that the areas close to the outbreak had a higher risk of contagion, especially in the initial stage of infection (time-decay phenomena). Furthermore, the number of daily new cases was related to the trips performed three weeks before. This threshold of 21 days could be considered as a sort of positivity detection time, meaning that the mobility restrictions quarantine commonly set at 14 days, defined only according to incubation-based epidemiological considerations, is underestimated (possible delays between contagion and detection) as a containment policy and may not always contribute to effectively slowing down the spread of virus worldwide. This result is original and, if confirmed in other studies, will lay the groundwork for more effective containment of COVID-19 in countries that are still in the health emergency, as well as for possible future returns of the virus.

National Institute for the Infectious Diseases "L. Spallanzani", IRCCS. Recommendations for COVID-19 clinical management

On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a disease (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The "L. Spallanzani" National Institute for the Infectious Diseases, IRCCS, Rome, Italy, has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; they should be considered as expert opinions, which may be modified according to newly produced literature data.

National Institute for the Infectious Diseases "L. Spallanzani", IRCCS. Recommendations for COVID-19 clinical management

On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a disease (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The "L. Spallanzani" National Institute for the Infectious Diseases, IRCCS, Rome, Italy, has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; they should be considered as expert opinions, which may be modified according to newly produced literature data.

A shift towards the annual habit in selfing Arabidopsis lyrata

An annual life history is often associated with the ability to self-fertilize. However, it is unknown whether the evolution of selfing commonly precedes the evolution of annuality, or vice versa. Using a 2-year common garden experiment, we asked if the evolution of selfing in the normally perennial Arabidopsis lyrata was accompanied by a shift towards the annual habit. Despite their very recent divergence from obligately outcrossing populations, selfing plants exhibited a 39% decrease in over-winter survival after the first year compared with outcrossing plants. Our data ruled out the most obvious underlying mechanism: differences in reproductive investment in the first year did not explain differences in survival. We conclude that transitions to selfing in perennial A. lyrata may be accompanied by a shift towards annuality, but drivers of the process require further investigation.

Occupational risk prevention, education and support in black, Asian and ethnic minority health worker in the COVID-19 pandemic

The onset of the COVID-19 in the UK has resulted in an inordinate amount of deaths affecting Black, Asian and Ethnic Minority (BAME) healthcare workers. The occupational risk to this group is thought to be a contributory factor, but other factors include race, genetics, medical co-morbidities, socio-economic status, and access to personal protection equipment. Why COVID-19 appears to be more deadly in BAME members remains unknown, but the UK government is investigating this now. It does appear that certain factors may worsen the disease process in BAME members, but which ones are pertinent to prevention remain to be determined, until a vaccine is available. Thus, the onus should rest on risk prevention, education, and support for all. Some of the safety strategies that may be instituted to help guide those in the workplace include education, treating potential therapeutic targets and ensuring protection in the working environment. The consideration of a compensation scheme, for families of healthcare workers that have suffered because of COVID-19, would go some way to support the recovery process.

Human permanent tooth sizes are associated with genes encoding oestrogen receptors

OBJECTIVE: To evaluate if genetic polymorphisms in the oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) genes encoded for oestrogen receptors alpha (ER&#945;) and beta (ERß) are involved in permanent tooth size. DESIGN: Cross-sectional study. SETTING: Orthodontic Clinic at School of Dentistry of Ribeirão Preto, University of São Paulo. PARTICIPANTS: A total of 108 orthodontic patients. MATERIALS AND METHODS: Pre-treatment orthodontic records were evaluated. Dental casts were used to determine the maximum crown measurements of fully erupted permanent teeth in the mesiodistal dimensions. Second and third molars were not included in the analysis. Genomic DNA samples were used for the genotyping of four genetic polymorphisms: ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938). The associations between tooth size and sex were evaluated using t test. The associations between tooth size and genotype were analysed with linear regression and adjusted by sex at an alpha of P⩽0.05. RESULTS: Female patients presented smaller tooth size than male patients. A statistically significant difference was observed in almost all teeth (P<0.05). The genetic polymorphisms in rs9340799, rs2234693, rs1256049 and rs4986938 were associated with some tooth sizes in both the maxilla and mandible (P<0.05). CONCLUSION: This study provides evidence that genetic polymorphisms in ESR1 and ESR2 could be associated with tooth size in permanent teeth.

Analysis of the Anti-Vaccine Movement in Social Networks: A Systematic Review

The aim of this study was to analyze social networks' information about the anti-vaccine movement. A systematic review was performed in PubMed, Scopus, CINAHL and CUIDEN databases. The search equations were: "vaccine AND social network" and "vaccine AND (Facebook[title] OR Twitter[title] OR Instagram[title] OR YouTube[title])". The final sample was n = 12, including only articles published in the last 10 years, in English or Spanish. Social networks are used by the anti-vaccine groups to disseminate their information. To do this, these groups use different methods, including bots and trolls that generate anti-vaccination messages and spread quickly. In addition, the arguments that they use focus on possible harmful effects and the distrust of pharmaceuticals, promoting the use of social networks as a resource for finding health-related information. The anti-vaccine groups are able to use social networks and their resources to increase their number and do so through controversial arguments, such as the economic benefit of pharmaceuticals or personal stories of children to move the population without using reliable or evidence-based content.

The GTPase Arl8B plays a principle role in the positioning of interstitial axon branches by spatially controlling autophagosome and lysosome location

Interstitial axon branching is an essential step during the establishment of neuronal connectivity. However, the exact mechanisms on how the number and position of branches are determined are still not fully understood. Here, we investigated the role of Arl8B, an adaptor molecule between lysosomes and kinesins. In chick retinal ganglion cells, downregulation of Arl8B reduces axon branch density and shifts their location more proximally, while Arl8B overexpression leads to increased density and more distal positions of branches. These alterations correlate with changes in the location and density of lysosomes and autophagosomes along the axon shaft. Diminishing autophagy directly by knockdown of atg7, a key autophagy gene, reduces branch density, while induction of autophagy by rapamycin increases axon branching, indicating that autophagy plays a prominent role in axon branch formation. In vivo, local inactivation of autophagy in the retina using a mouse conditional knockout approach disturbs retino-collicular map formation which is dependent on the formation of interstitial axon branches. These data suggest that Arl8B plays a principal role in the positioning of axon branches by spatially controlling autophagy, thus directly controlling formation of neural connectivity in the brain.SIGNIFICANCE STATEMENTThe formation of interstitial axonal branches plays a prominent role in numerous places of the developing brain during neural circuit establishment. We show here that the GTPase Arl8B controls density and location of interstitial axon branches, and at the same time controls also density and location of the autophagy machinery. Up- or down-regulation of autophagy in vitro promotes or inhibits axon branching. Local disruption of autophagy in vivo disturbs retino-collicular mapping. Our data suggest that Arl8B controls axon branching by controlling locally autophagy. This work is one of the first reports showing a role of autophagy during early neural circuit development and suggests that autophagy in general plays a much more prominent role during brain development than previously anticipated.

Angiotensin II receptors: Impact for COVID-19 severity

COVID-19 is an outbreak of viral pneumonia which became a global health crisis, and the risk of morbidity and mortality of people with obesity are higher. SARS-CoV-2, the pathogen of COVID-19, enters into cells through binding to the Angiotensin Converting Enzyme (ACE) homolog-2 (ACE2). ACE2 is a regulator of two contrary pathways in renin angiotensin system (RAS): ACE-Ang-II-AT1R axis and ACE2-Ang 1-7-Mas axis. Viral entry process eventuates in downregulation of ACE2 and subsequent activation of ACE-Ang-II-AT1R axis. ACE-Ang II-AT1R axis increases lipid storage, reduces white-to-beige fat conversion and plays role in obesity. Conversely, adipose tissue is an important source of angiotensin, and obesity results in increased systemic RAS. ACE-Ang-II-AT1R axis, which has proinflammatory, profibrotic, prothrombotic, and vasoconstrictive effects, is potential mechanism of more severe SARS-CoV-2 infection. The link between obesity and severe COVID-19 may be attributed to ACE2 consumption and subsequent ACE-Ang-II-AT1R axis activation. Therefore, patients with SARS-CoV-2 infection may benefit from therapeutic strategies that activate ACE2-Ang 1-7-Mas axis, such as Ang II receptor blockers (ARBs), ACE inhibitors (ACEIs), Mas receptor agonists and ACE2.

Angiotensin II Receptors - Impact for COVID-19 Severity

COVID-19 is an outbreak of viral pneumonia which became a global health crisis, and the risk of morbidity and mortality of people with obesity are higher. SARS-CoV-2, the pathogen of COVID-19, enters into cells through binding to the Angiotensin Converting Enzyme (ACE) homolog-2 (ACE2). ACE2 is a regulator of two contrary pathways in renin angiotensin system (RAS): ACE-Ang-II-AT1R axis and ACE2-Ang 1-7-Mas axis. Viral entry process eventuate in downregulation of ACE2 and subsequent activation of ACE-Ang-II-AT1R axis. ACE-Ang II-AT1R axis increases lipid storage, reduces white-to-beige fat conversion and plays role in obesity. Conversely, adipose tissue is an important source of angiotensin, and obesity results in increased systemic RAS. ACE-Ang-II-AT1R axis, which has proinflammatory, profibrotic, prothrombotic and vasoconstrictive effects, is potential mechanism of more severe SARS-CoV-2 infection. The link between obesity and severe COVID-19 may be attributed to ACE2 consumption and subsequent ACE-Ang-II-AT1R axis activation. Therefore, patients with SARS-CoV-2 infection may benefit from therapeutic strategies that activate ACE2-Ang 1-7-Mas axis, such as Ang II reseptor blockers (ARBs), ACE inhibitors (ACEIs), Mas receptor agonists and ACE2. This article is protected by copyright. All rights reserved.

Impact of COVID-19 on the Hong Kong Youth Quitline Service and Quitting Behaviors of Its Users

Tobacco use is a possible risk factor for contracting and spreading COVID-19. We aimed to describe the impact of the COVID-19 pandemic on the Youth Quitline service and quitting behaviors of its users in Hong Kong. We conducted a telephone survey involving 201 participants of the Youth Quitline service, and retrospectively analyzed the operation and use of Quitline since the COVID-19 outbreak in Hong Kong. The number of incoming calls to the Youth Quitline and the participants' quit rate has increased since the COVID-19 outbreak in Hong Kong. Many participants (68%) did not realize that tobacco use potentially increased their risk for developing and spreading COVID-19; however, 43% agreed that the pandemic motivated their intention to quit, and 83% changed their smoking habits during the pandemic. These changes were mainly due to wearing masks (30%), closure of bars/pubs (25%), suspension of classes (14%), and being unable to socialize with friends (24%). Overall, 58% reduced their tobacco use; of these participants, 66% reported a &#8805;50% reduction in daily cigarette consumption. The participants reduced their smoking during the COVID-19 pandemic despite lacking knowledge about the potentially increased risk for contracting COVID-19 from continued smoking. The pandemic could create new opportunities to motivate young smokers to quit smoking, especially those seeking support for smoking cessation, and may further contribute to reducing the risks posed by COVID-19.

Coronavirus Disease 2019-related dyspnea cases difficult to interpret using chest computed tomography

Patients with Coronavirus Disease 2019 (COVID-19) often have clinical characteristics, such as chest tightness and dyspnea. Continuous, unresolved dyspnea often indicates the progression of lung lesions. The mechanism that underlies the chest distress and dyspnea in patients with COVID-19 is still unclear. Chest CT has a higher sensitivity and can play an essential role in the diagnosis and treatment of the disease. However, our clinical observations showed that although some patients had significant chest distress and dyspnea, the lesions that were observed in the lungs during computed tomography were milder and not completely consistent with clinical symptoms. We analyzed the clinical characteristics, laboratory test results, and imaging findings of these patients. We found that extensive inflammation of the bilateral and respiratory bronchioles in patients with COVID-19 due to excessive activation of proinflammatory cytokines and chemotactic aggregation of T-lymphocytes at the site of inflammation are possible mechanisms underlying chest distress and dyspnea in patients with COVID-19. Short-time and lose-dose use of corticosteroid may be helpful to treat chest tightness and dyspnea in mild COVID-19 patients. Through this study, we aimed to improve our understanding of the pathogenesis of COVID-19.

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually led to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the ß-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.