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12 | rme85fwo | what are best practices in hospitals and at home in maintaining quarantine? | Global Spread (October 2014) As the Ebola outbreak continued to rage in West Africa, Western countries began to be directly affected by the disease. On the last day of September 2014, the first active Ebola case was diagnosed in the United States. Officials in Dallas, Texas, scrambled to contain the virus. A few weeks later, tension rose dramatically when two of the nurses who treated the initial US patient developed Ebola. One of the nurses traveled to Ohio and back before becoming sick. She flew by plane and had contact with other travelers. Officials were very worried that Ebola flare-ups would start to occur across the country. On October 6, 2014, a nursing assistant in Spain was diagnosed with Ebola. Like the US nurses, she had helped treat a repatriated Ebola victim. On October 23, 2014, a new US case was identified. A doctor was diagnosed with Ebola in New York City after returning from Guinea. On the same day, an Ebola case was discovered in the West African country of Mali. The Ebola outbreak seemed out of control and poised to start a major international epidemic. In West Africa, however, a corner had been turned. Healthcare efforts had shifted from treating all Ebola patients in medical facilities to providing families with supplies to take care of sick patients at home. Toward the end of October 2014, reports started to surface about there being fewer cases in West Africa, especially in Liberia. These reports were initially treated with caution. As time progressed, however, it became clear that the drop in cases was real. |
21 | 0uzma5vr | what are the mortality rates overall and in specific populations | Estimate of the development of the epidemic reproduction number Rt from Coronavirus SARS-CoV-2 case data and implications for political measures based on prognostics The novel Coronavirus SARS-CoV-2 (CoV) has induced a world-wide pandemic and subsequent non-pharmaceutical interventions (NPI) in order to control the spreading of the virus. NPIs are considered to be critical in order to at least delay the peak number of infected individuals and to prevent the health care system becoming overwhelmed by the number of patients to treat in hospitals or in intensive care units (ICUs). However, there is also increasing concern that the NPIs in place would increase mortality because of other diseases, increase the frequency of suicide and increase the risk of an economic recession with unforeseeable implications. It is therefore instrumental to evaluate the necessity of NPIs and to monitor the progress of containment of the virus spreading. We used a data-driven estimation of the evolution of the reproduction number for viral spreading in Germany as well as in all its federal states. Based on an extended infection-epidemic model, parameterized with data from the Robert Koch-Institute and, alternatively, with parameters stemming from a fit to the initial phase of CoV spreading in different regions of Italy, we consistently found that the reproduction number was turned down to a range near 1 in all federal states. We used the latest reproduction number as a starting point for the simulation of epidemic progression and varied the reproduction number, mimicking either release or strengthening of NPIs. Germany is currently, April 3rd, 2020, at the border line of a reproduction number between the scenarios of major immunisation of the population or eradication of the virus. We strongly recommend to keep all NPIs in place and suggest to even strengthen the measures in order to accelerate reaching the state of full control, thus, also limiting collateral damage of the NPIs in time. |
24 | sc8q1rox | what kinds of complications related to COVID-19 are associated with diabetes | Paying close attention to diabetic patients with novel coronavirus infection/ 中华内分泌代谢杂志 A major infectious disease associated with severe acute respiratory syndrome coronavirus 2 (2019-nCoV)has emerged in Wuhan, China. Current clinical studies have shown that diabetes is commonly complicated with this disorder. Hyperglycemia is a risk factor for severe infection, and also an independent risk factor for the progression of mild infection to severe infection. This may be related to the immune deficiency of diabetics. Besides, virus may cause direct damage to the islets and induce acute stress hyperglycemia. Special attention should be payed to diabetics with 2019-nCoV infection. Systemic steroid hormones should be used with particular caution in patients with 2019-nCoV infection, especially those with diabetes. |
24 | 2ftw85xw | what kinds of complications related to COVID-19 are associated with diabetes | Facing the COVID‐19 outbreak: What should we know and what could we do? A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province in China in December 2019 and caused a serious type of pneumonia called coronavirus disease 2019 or COVID-19. This epidemic quickly spread across China and extended to more than 20 other countries. This commentary discusses the reasons for the fast spread of SARS-CoV-2 in three aspects: the infectious sources, including the biological nature of the virus; the susceptible population; and the transmission routes. The current situations and suggestions regarding the control of the disease are summarized. This article is protected by copyright. All rights reserved. |
24 | 5caapdld | what kinds of complications related to COVID-19 are associated with diabetes | Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma Abstract We have produced transgenic mouse strains harboring class II major histocompatibility complex or interferon-gamma genes linked to the human insulin promoter. These experiments were designed to investigate the consequences of the expression of immunological effector molecules by nonimmunological cells. In both of these studies we observed the disappearance from the pancreas of the insulin-producing β cells coinciding with the development of insulin-dependent diabetes mellitus. Transgenic mice expressing both chains of the I-A gene showed progressive atrophy of the islets of Langerhans, whereas mice expressing interferon-gamma suffered an inflammatory destruction of the islets. |
17 | x6dr6rsh | are there any clinical trials available for the coronavirus | Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6, IL-6 receptor and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome. TRIAL DESIGN: A phase 3 prospective, multi-center, interventional, open label, 6-arm 2x2 factorial design study. PARTICIPANTS: Subjects will be recruited at the specialized COVID-19 wards and/or ICUs at 16 Belgian participating hospitals. Only adult (≥18y old) patients will be recruited with recent (≤16 days) COVID-19 infection and acute hypoxia (defined as PaO2/FiO2 below 350mmHg or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation) and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those, who have not been on mechanical ventilation for more than 24 hours before randomisation. Patients should have had a chest X-ray and/or CT scan showing bilateral infiltrates within the last 2 days before randomisation. Patients with active bacterial or fungal infection will be excluded. INTERVENTION AND COMPARATOR: Patients will be randomized to 1 of 5 experimental arms versus usual care. The experimental arms consist of Anakinra alone (anti-IL-1 binding the IL-1 receptor), Siltuximab alone (anti-IL-6 chimeric antibody), a combination of Siltuximab and Anakinra, Tocilizumab alone (humanised anti-IL-6 receptor antibody) or a combination of Anakinra with Tocilizumab in addition to standard care. Patients treated with Anakinra will receive a daily subcutaneous injection of 100mg for a maximum of 28 days or until hospital discharge, whichever comes first. Siltuximab (11mg/kg) or Tocilizumab (8mg/kg, with a maximum dose of 800mg) are administered as a single intravenous injection immediately after randomization. MAIN OUTCOMES: The primary end point is the time to clinical improvement defined as the time from randomization to either an improvement of two points on a six-category ordinal scale measured daily till day 28 or discharge from the hospital or death. This ordinal scale is composed of (1) Death; (2) Hospitalized, on invasive mechanical ventilation or ECMO; (3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, not requiring supplemental oxygen; (6) Not hospitalized. RANDOMISATION: Patients will be randomized using an Interactive Web Response System (REDCap). A 2x2 factorial design was selected with a 2:1 randomization regarding the IL-1 blockade (Anakinra) and a 1:2 randomization regarding the IL-6 blockade (Siltuximab and Tocilizumab). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 342 participants will be enrolled: 76 patients will receive usual care, 76 patients will receive Siltuximab alone, 76 patients will receive Tocilizumab alone, 38 will receive Anakinra alone, 38 patients will receive Anakinra and Siltuximab and 38 patients will receive Anakinra and Tocilizumab. TRIAL STATUS: COV-AID protocol version 3.0 (15 Apr 2020). Participant recruitment is ongoing and started on April 4(th) 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 1st, 2020 (ClinicalTrials.gov Identifier: NCT04330638) and on EudraCT on April 3rd 2020 (Identifier: 2020-001500-41). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
40 | tcrxm7jy | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Transmission Cycle of SARS-CoV and SARS-CoV-2 Severe acute respiratory syndrome (SARS) is a pandemic that has shocked the world twice over the last two decades caused by a highly transmissible and pathogenic coronavirus (CoV). It causes disease in the lower respiratory tract in humans that was first reported in late 2002 in Guangdong province, China, and later on in December 2019 in Wuhan, China. The two viruses designated as SARS-CoV and SARS-CoV-2, respectively, originated probably from the bat and infected humans via carrier animals. The constant recombination and evolution in the CoV genome may have facilitated their cross-species transmission resulting in recurrent emergence as a pandemic. This chapter intends to accumulate recent findings related to CoV transmission and tentative molecular mechanisms governing the process. |
16 | zhmuzv7z | how long does coronavirus remain stable on surfaces? | Airborne Infectious Microorganisms Inhalation exposes the upper and lower respiratory tracts of humans to a variety of airborne particles and vapors. Airborne transmission of pathogenic microorganisms to humans from the environment, animals, or other humans can result in disease. Inhalation is an important route of exposure as the lung is more susceptible to infection than the gastrointestinal tract. Ingested microorganisms must past through the acidic environment of the stomach before they can colonize tissue while inhaled microorganisms are deposited directly on the moist surfaces of the respiratory tract. Inhalation of microbial aerosols can elicit adverse human health effects including infection, allergic reaction, inflammation, and respiratory disease. Following inhalation, infectious viruses, bacteria, and fungi can establish in host cells of the respiratory tract. Some are translocated and infect the gastrointestinal tract and other tissues. This chapter discusses human viral, bacterial, and fungal diseases transmitted via aerosols. Viral diseases presented are influenza, severe acute respiratory syndrome (SARS), Norwalk-like viruses (NLVs) and hantavirus disease, measles, and varicella. Bacterial diseases are Legionnaires' disease, tuberculosis, and nontubercule mycobacterial disease. Exposure to some Gram-negative and Gram-positive bacteria, endotoxin, and actinomycetes when dispersed through the air can result in disease following inhalation. Fungal diseases included are histoplasmosis, coccidiomycosis, blastomycosis, cryptococcosis, and aspergillosis. The threat of bioterrorism with airborne infectious agents is also briefly presented. |
24 | u6uqroi0 | what kinds of complications related to COVID-19 are associated with diabetes | Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression Abstract Background and aims Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. Methods Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. Results There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I2: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I2: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I2: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I2: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I2: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age ≥55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension ≥25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) Conclusion DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19. |
11 | xxc7vdnt | what are the guidelines for triaging patients infected with coronavirus? | Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus infection in Saudi Arabia Abstract Background The rapid and accurate identification of individuals who are at high risk of Middle East respiratory syndrome coronavirus (MERS-CoV) infection remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who have developed pneumonia. Methods A two-center, retrospective case–control study was performed. A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. According to the rRT-PCR results, 135 patients were positive for MERS-CoV and 225 were negative. Demographic characteristics, clinical presentations, and radiological and laboratory findings were collected for each subject. Results A risk prediction model to identify pneumonia patients at increased risk of MERS-CoV was developed. The model included male sex, contact with a sick patient or camel, diabetes, severe illness, low white blood cell (WBC) count, low alanine aminotransferase (ALT), and high aspartate aminotransferase (AST). The model performed well in predicting MERS-CoV infection (area under the receiver operating characteristics curves (AUC) 0.8162), on internal validation (AUC 0.8037), and on a goodness-of-fit test (p =0.592). The risk prediction model, which produced an optimal probability cut-off of 0.33, had a sensitivity of 0.716 and specificity of 0.783. Conclusions This study provides a simple, practical, and valid algorithm to identify pneumonia patients at increased risk of MERS-CoV infection. This risk prediction model could be useful for the early identification of patients at the highest risk of MERS-CoV infection. Further validation of the prediction model on a large prospective cohort of representative patients with pneumonia is necessary. |
15 | ajpcpzdp | how long can the coronavirus live outside the body | ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection The COVID-19 pandemics is posing unprecedented challenges and threats to patients and healthcare systems worldwide. Acute respiratory complications that require intensive care unit (ICU) management are a major cause of morbidity and mortality in COVID-19 patients. Patients with worst outcomes and higher mortality are reported to include immunocompromised subjects, namely older adults and polymorbid individuals and malnourished people in general. ICU stay, polymorbidity and older age are all commonly associated with high risk for malnutrition, representing per se a relevant risk factor for higher morbidity and mortality in chronic and acute disease. Also importantly, prolonged ICU stays are reported to be required for COVID-19 patients stabilization, and longer ICU stay may per se directly worsen or cause malnutrition, with severe loss of skeletal muscle mass and function which may lead to disability, poor quality of life and additional morbidity. Prevention, diagnosis and treatment of malnutrition should therefore be routinely included in the management of COVID-19 patients. In the current document, the European Society for Clinical Nutrition and Metabolism (ESPEN) aims at providing concise guidance for nutritional management of COVID-19 patients by proposing 10 practical recommendations. The practical guidance is focused to those in the ICU setting or in the presence of older age and polymorbidity, which are independently associated with malnutrition and its negative impact on patient survival. |
12 | srbyxhxd | what are best practices in hospitals and at home in maintaining quarantine? | Delivering healthcare remotely to cardiovascular patients during COVID-19: A rapid review of the evidence. BACKGROUND Although attention is focused on addressing the acute situation created by the COVID-19 illness, it is imperative to continue our efforts to prevent cardiovascular morbidity and mortality, particularly during a period of prolonged social isolation which may limit physical activity, adversely affect mental health and reduce access to usual care. One option may be to deliver healthcare interventions remotely through digital healthcare solutions. Therefore, the aim of this paper is to bring together the evidence for remote healthcare during a quarantine situation period to support people living with cardiovascular disease during COVID-19 isolation. METHODS The PubMed, CINAHL and Google Scholar were searched using telehealth OR digital health OR mHealth OR eHealth OR mobile apps AND COVID-19 OR quarantine search terms. We also searched for literature relating to cardiovascular disease AND quarantine. RESULTS The literature search identified 45 potentially relevant publications, out of which nine articles were included. Three overarching themes emerged from this review: (1) preparing the workforce and ensuring reimbursement for remote healthcare, (2) supporting mental and physical health and (3) supporting usual care. CONCLUSION To support people living with cardiovascular disease during COVID-19 isolation and to mitigate the effects of quarantine and adverse effect on mental and physical well-being, we should offer remote healthcare and provide access to their usual care. |
24 | w84fqqqt | what kinds of complications related to COVID-19 are associated with diabetes | The COVID-19 Pandemic and its Impact on the Cardio-Oncology Population PURPOSE OF REVIEW: The novel Coronavirus (2019-nCoV, COVID-19) is historically one of the most severe acute respiratory syndromes and pandemics to affect the globe in the twenty-first century. Originating in Wuhan, the virus rapidly spread and impacted subsets of populations with initial unclear risk factors contributing to worsening morbidity and mortality. Patients with diagnosis of cancer and undergoing treatment further represent a population at risk for worsening cardiopulmonary outcomes. This review explores specific risk factors, diagnoses, and treatment options that impact cardio-oncologic patients with COVID-19. RECENT FINDINGS: Multiple studies globally, including Italy, China, and the USA, have documented severe outcomes. Cancer patients are at increased risk of cardiac injury which itself is a risk factor for mortality. Additionally, elderly cancer patients undergoing recent anti-cancer treatment may be at greater risk for sustaining worse outcomes, although data remains suboptimal in this population. Major gaps remain regarding risk associated with type of cancer and type of anti-cancer treatment, as well as the layered risk of cardiovascular disease and cancer. Immunomodulatory therapies used to treat cytokine release syndrome secondary to anti-cancer therapies, as well as other agents being traditionally used to treat cardiovascular and cancer disease states, are being investigated for treatment of COVID-19. SUMMARY: Hypertension, cardiovascular disease, diabetes, and cancer have been associated with more severe COVID-19 infection and worse outcomes. Patients undergoing anti-cancer therapy or those who have suffered from coronavirus infection may develop long-standing changes, not limited to pulmonary fibrosis, hyperlipidemia, and worsening atherosclerosis. Those undergoing anti-cancer therapy are at theoretically increased susceptibility for infection, with type of cancer not necessarily dictating outcome. A review of the literature of patients with cardiovascular and/or cancer disease is presented, as well as proposed strategies to attenuate risk regarding treatment, management, and surveillance in this vulnerable population. |
1 | blqzi69t | what is the origin of COVID-19 | Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis. According to the nucleotide C28144T variation, the SARS-CoV-2 can be divided into group A (117 strains) and group B (256 strains). The spike protein gene (S gene) coding region 1841 (total 23403) A1841G, formed a B1 subgroup (40 strains) in group B, of which 30 strains were from European and American countries in March (especially Washington, USA). These mutations are likely to be influenced by the environment or the immunization selection pressure of different populations. Although the mutation is not in the receptor binding region (RBD) and alkaline cleavage region, it may also affect the ability of transmission and pathogenicity; however, the significance is not yet clear. As the ratio of A / B strains in the epidemic months showed an increasing trend (0.35: 1 in January, 0.62: 1 in February and 0.76: 1 in March), it seems that the transmissibility of group A strains becomes stronger with time. Based on the variation of 11 nucleotide sites during the epidemic process, it is speculated that the Washington strain is more like an ancestor type, and the Wuhan strain is the offspring of the group A virus strain. By comparing the detection capabilities of primers in different countries, the SARS-CoV-2 nucleotide variation may only affect molecular detection of very few strains. The differences in the transmissibility, pathogenicity and clinical manifestations of different types of strains require further investigations. |
17 | y74jbnb2 | are there any clinical trials available for the coronavirus | COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities Abstract The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here we have provided a foundation for cardiovascular and cardio-oncology physicians who are on the frontline providing care to COVID-19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID-19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID-19 patients. |
9 | 35rwnedr | how has COVID-19 affected Canada | Time for an ecosystem approach to public health? Lessons from two infectious disease outbreaks in Canada. Ecosystem approaches recognize the complexity of many contemporary public health challenges and offer an alternative for dealing with problems that have proven intractable and unresponsive to conventional public health strategies. Infectious disease outbreaks are among the most dramatic aspects of systems failure, and the Canadian cases of SARS (Severe Acute Respiratory Syndrome) in Toronto, and the E. coli outbreak in Walkerton, serve as useful illustrative examples. This paper examines some of the limitations of current public health approaches, the fundamental tenets of an alternative, transdisciplinary ecosystem approach, and changes necessary for implementation, including those in philosophical approach, communications and education, and, finally, institutions and governance. |
12 | 0ea1r7gu | what are best practices in hospitals and at home in maintaining quarantine? | A Preliminary Evaluation of the Public Risk Perception Related to the COVID-19 Health Emergency in Italy Governments faced with the spread of COVID-19 pandemic are adopting strict and severe mitigation measures to influence people's behaviors. Public perception of health risk plays a key role in the adoption of these actions, in people's feelings, and in their daily habits. To support decision makers from international to local levels to face with future sanitary emergencies, this study aims at investigating Italian public perceptions of health risk. To this purpose, a questionnaire was designed and administered within the period of Italian COVID-19 lockdown and quarantine to almost 9000 citizens in Italy and abroad. The obtained results highlight a significative influence that mass media play on both the level of knowledge and the feelings of the respondents. The findings also point out future variations of some perceived behaviors consequent to the COVID-19 outbreak. |
24 | m5h19hy6 | what kinds of complications related to COVID-19 are associated with diabetes | Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O'Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors' affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus' origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term. |
48 | ilk9u1a8 | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | The scope of mental health research during the COVID-19 pandemic and its aftermath The effects of the COVID-19 pandemic on population mental health are unknown. We need to understand the scale of any such impact in different sections of the population, who is most affected and how best to mitigate, prevent and treat any excess morbidity. We propose a coordinated and interdisciplinary mental health science response. |
4 | kxd03q02 | what causes death from Covid-19? | Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan, China in December 2019 and has put the world on alert. To safeguard Chinese citizens and to strengthen global health security, China has made great efforts to control the epidemic. Many in the global community have joined China to limit the epidemic. However, discrimination and prejudice driven by fear or misinformation have been flowing globally, superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts. We analyze this phenomenon and its underlying causes and suggest practical solutions. |
26 | ajbypz7g | what are the initial symptoms of Covid-19? | First COVID-19 infections in the Philippines: a case report BACKGROUND: The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila. CASE PRESENTATION: Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient's condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China. CONCLUSIONS: This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases. |
43 | wi56kiki | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Online team‐based learning sessions as interactive methodologies during the pandemic The medical education system is currently facing robust challenges as a consequence of the COVID-19 pandemic. One of them is the maintenance of interactive learning techniques such as Team-Based Learning (TBL). TBL is an interactive teaching method that is learner-centered and instructor-directed. It sequentially involves self-work followed by teamwork. After providing the reading material, students are commonly asked to solve 10-20 multiple choice questions, known as the individual readiness assurance test (iRAT). Students are then assigned to answer the same questions while working together in teams, the team readiness assurance test (tRAT). |
14 | elho35ot | what evidence is there related to COVID-19 super spreaders | Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission. BACKGROUND Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmission. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader. METHODS The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time. RESULTS There were 66 women and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P < 0.05). No differences were found in maximum number of lung fields involved, duration from the onset of fever to the occurrence of pulmonary infiltrates and time from the initial pulmonary infiltrate to its peak among the multiple transmission generations (P > 0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P > 0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time from admission to starting these medication shortened (P < 0.05). CONCLUSIONS There is no evidence that SARS infection will evolve or transmit within a fashion that permits it to become less powerful throughout the successive transmission within a short time. |
6 | oye8zo44 | what types of rapid testing for Covid-19 have been developed? | Covid-19: BMA calls for rapid testing and appropriate protective equipment for doctors. |
40 | n69iewmx | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 3(10)-helix and helps to stabilize the active conformation. The coil-3(10)-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations. |
1 | ngietu0n | what is the origin of COVID-19 | Betacoronavirus Genomes: How Genomic Information has been Used to Deal with Past Outbreaks and the COVID-19 Pandemic. In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates. |
3 | ry9wpcxo | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Global transmission network of SARS-CoV-2: from outbreak to pandemic BACKGROUND. The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is straining health systems around the world. Although the Chinese government implemented a number of severe restrictions on people's movement in an attempt to contain its local and international spread, the virus had already reached many areas of the world in part due to its potent transmissibility and the fact that a substantial fraction of infected individuals develop little or no symptoms at all. Following its emergence, the virus started to generate sustained transmission in neighboring countries in Asia, Western Europe, Australia, Canada and the United States, and finally in South America and Africa. As the virus continues its global spread, a clear and evidence-based understanding of properties and dynamics of the global transmission network of SARS-CoV-2 is essential to design and put in place efficient and globally coordinated interventions. METHODS. We employ molecular surveillance data of SARS-CoV-2 epidemics for inference and comprehensive analysis of its global transmission network before the pandemic declaration. Our goal was to characterize the spatial-temporal transmission pathways that led to the establishment of the pandemic. We exploited a network-based approach specifically tailored to emerging outbreak settings. Specifically, it traces the accumulation of mutations in viral genomic variants via mutation trees, which are then used to infer transmission networks, revealing an up-to-date picture of the spread of SARS-CoV-2 between and within countries and geographic regions. RESULTS AND CONCLUSIONS. The analysis suggest multiple introductions of SARS-CoV-2 into the majority of world regions by means of heterogeneous transmission pathways. The transmission network is scale-free, with a few genomic variants responsible for the majority of possible transmissions. The network structure is in line with the available temporal information represented by sample collection times and suggest the expected sampling time difference of few days between potential transmission pairs. The inferred network structural properties, transmission clusters and pathways and virus introduction routes emphasize the extent of the global epidemiological linkage and demonstrate the importance of internationally coordinated public health measures. |
6 | r3nd2b5v | what types of rapid testing for Covid-19 have been developed? | Health service impact of testing for respiratory pathogens using cartridge-based multiplex array versus molecular batch testing Summary There is increasing demand for access to rapid microbiological testing, with a view to improving clinical outcomes. The possibility of rapid testing has been facilitated by development of cartridge-based random access molecular technologies that are now widely available. Whether the expense of cartridge-based assays is justified in terms of clinical or laboratory cost savings is controversial. This prospective study evaluated the impact of the Biofire FilmArray Respiratory Panel ('FilmArray'), a cartridge-based random access molecular test, compared with standard batched molecular testing using an 'in-house' respiratory polymerase chain reaction (PCR) on laboratory and health service outcomes for adult patients at a tertiary-level adult hospital in Melbourne, Australia. Laboratory result turnaround time was significantly reduced with the FilmArray (median 4.4 h) compared to a standard validated in-house respiratory PCR assay (median 21.6 h, p < 0.0001) and there was a significant increase in diagnostic yield with the Filmarray (71/124, 57.3%) compared to in-house PCR (79/200; 39.5%; p = 0.002). Despite improved result turnaround time and increased diagnostic yield from testing, there was no corresponding reduction in hospital length of stay or use of isolation beds. Although cartridge-based molecular testing reduced turnaround time to result for respiratory pathogen testing, it did not impact on health service outcomes such as hospital length of stay. Further work is warranted to determine whether cartridge-based tests at the point of care can improve clinical and health service impacts. |
10 | e4pr78n0 | has social distancing had an impact on slowing the spread of COVID-19? | Mathematical modeling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada Background: We evaluated how non-pharmaceutical interventions could be used to control the COVID-19 pandemic and reduce the burden on the healthcare system Methods: Using an age-structured compartmental model of COVID-19 transmission in the population of Ontario, Canada, we compared a base case with limited testing, isolation, and quarantine to scenarios with: enhanced case finding;restrictive social distancing measures;or a combination of enhanced case finding and less restrictive social distancing Interventions were either implemented for fixed durations or dynamically cycled on and off, based on projected ICU bed occupancy We present median and credible intervals (CrI) from 100 replicates per scenario using a two-year time horizon Results: We estimated that 56% (95% CrI: 42-63%) of the Ontario population would be infected over the course of the epidemic in the base case At the epidemic peak, we projected 107,000 (95% CrI: 60,760-149,000) cases in hospital and 55,500 (95% CrI: 32,700-75,200) cases in ICU For fixed duration scenarios, all interventions were projected to delay and reduce the height of the epidemic peak relative to the base case, with restrictive social distancing estimated to have the greatest effect Longer duration interventions were more effective Dynamic interventions were projected to reduce the proportion of the population infected at the end of the two-year period Dynamic social distancing interventions could reduce the median number of cases in ICU below current estimates of Ontario's ICU capacity Interpretation: Without significant social distancing or a combination of moderate social distancing with enhanced case finding, we project that ICU resources would be overwhelmed Dynamic social distancing could maintain health system capacity and also allow periodic psychological and economic respite for populations ### Competing Interest Statement The authors have declared no competing interest ### Funding Statement The research was supported by a grant to DNF from the Canadians Institutes for Health Research (2019 COVID-19 rapid researching funding OV4-170360) ### Author Declarations All relevant ethical guidelines have been followed;any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials gov I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance) Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable Yes Data are available from the corresponding author on request |
1 | d11cj86k | what is the origin of COVID-19 | Papa Giovanni XXIII Bergamo Hospital at the time of the COVID-19 outbreak: letter from the warfront. In early December 2019, the 2019 novel coronavirus (COVID-19) was identified as the agent responsible for the first pneumonia cases of unknown origin in Wuhan, the capital of the Hubei region in China. The virus has been identified as a novel enveloped RNA betacoronavirus2 , that has been promptly named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The World Health Organization (WHO), on January 12, 2020 declared the COVID-19 a public health emergency of international concern. On March 11, the WHO made the assessment that COVID-19 can be characterized as a pandemic. |
44 | ejskxpsu | How much impact do masks have on preventing the spread of the COVID-19? | COVID-19 pandemic: Lessons learned and future directions Emerging pandemics show that humans are not infallible and communities need to be prepared. Coronavirus outbreak was first reported towards the end of 2019 and has now been declared a pandemic by the World Health Organization. Worldwide countries are responding differently to the virus outbreak. A delay in detection and response has been recorded in China, as well as in other major countries, which led to an overburdening of the local health systems. On the other hand, some other nations have put in place effective strategies to contain the infection and have recorded a very low number of cases since the beginning of the pandemics. Restrictive measures like social distancing, lockdown, case detection, isolation, contact tracing, and quarantine of exposed had revealed the most efficient actions to control the disease spreading. This review will help the readers to understand the difference in response by different countries and their outcomes. Based on the experience of these countries, India responded to the pandemic accordingly. Only time will tell how well India has faced the outbreak. We also suggest the future directions that the global community should take to manage and mitigate the emergency. |
24 | 9lc9lckp | what kinds of complications related to COVID-19 are associated with diabetes | Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis Abstract It has been reported that frequent occurrence of COVID-19 infection in these patients is associated with low cytosolic pH. During virus infection, serum lactate dehydrogenase (LDH) level excessively rises. LDH is a cytosolic enzyme and the serum level increases as the cell break down. When anaerobic conditions develop, lactate formation increases from pyruvate. Cell pH is regulated by very complex mechanisms. When lactate increases in the extracellular area, this symporter carries lactate and H+ ion into the cell, and the intracellular pH quickly becomes acidic. Paradoxically, Na+/H+ exchanger activation takes place. While H+ ion is thrown out of the cell, Na+ and Ca+2 enter the cell. When Na+ and Ca+2 increase in the cell, the cells swell and die. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor. Dapagliflozin has been reported to reduce lactate levels by various mechanisms. Also, it reduces oxygen consumption in tissues and causes the use of glucose in the aerobic pathway, thereby reducing lactate production. A lactate decrease in the environment reduces the activation of lactate/H+ symporter. Thus, the H ion pumping into the cell by this symporter is reduced and the cytosolic pH is maintained. Dapagliflozin also directly inhibits NHE. Thus, Na+ and Ca+2 flow to the cell are inhibited. Dapagliflozin provides the continuation of the structure and functions of the cells. Dapagliflozin can prevent the severe course of COVID-19 infection by preventing the lowering of cytosolic pH and reducing the viral load. |
38 | u7zxlgxz | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | The epidemiology, diagnosis and treatment of COVID-19 Abstract In December 2019, the outbreak of the novel coronavirus disease (COVID-19) in China spread worldwide, becoming an emergency of major international concern. SARS-CoV-2 infection causes clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus. Human-to-human transmission via droplets, contaminated hands or surfaces has been described, with incubation times of 2-14 days. Early diagnosis, quarantine, and supportive treatments are essential to cure patients. This paper reviews the literature on all available information about the epidemiology, diagnosis, isolation and treatments of COVID-19. Treatments, including antiviral agents, chloroquine and hydroxychloroquine, corticosteroids, antibodies, convalescent plasma transfusion and vaccines, are discussed in this article. In addition, registered trials investigating treatment options for COVID-19 infection are listed. |
8 | 9mzs5dl4 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | The Application of the Haddon Matrix to Public Health Readiness and Response Planning State and local health departments continue to face unprecedented challenges in preparing for, recognizing, and responding to threats to the public's health. The attacks of 11 September 2001 and the ensuing anthrax mailings of 2001 highlighted the public health readiness and response hurdles posed by intentionally caused injury and illness. At the same time, recent natural disasters have highlighted the need for comparable public health readiness and response capabilities. Public health readiness and response activities can be conceptualized similarly for intentional attacks, natural disasters, and human-caused accidents. Consistent with this view, the federal government has adopted the all-hazards response model as its fundamental paradigm. Adoption of this paradigm provides powerful improvements in efficiency and efficacy, because it reduces the need to create a complex family of situation-specific preparedness and response activities. However, in practice, public health preparedness requires additional models and tools to provide a framework to better understand and prioritize emergency readiness and response needs, as well as to facilitate solutions; this is particularly true at the local health department level. Here, we propose to extend the use of the Haddon matrix—a conceptual model used for more than two decades in injury prevention and response strategies—for this purpose. |
21 | ess006ni | what are the mortality rates overall and in specific populations | Pneumonia severity index in viral community acquired pneumonia in adults Pneumonia severity index (PSI) is an important scoring system that can assess the severity of community acquired pneumonia and determine admission status. However, there is a lack of research on whether this scoring system can be applied to viral community acquired pneumonia. The purpose of this study was to evaluate the usefulness of PSI in viral community acquired pneumonia. This retrospective cohort study included 1,434 adult patients (aged ≥18 years) who were admitted to the emergency department of a university hospital during 2013–2015 because of community-acquired pneumonia. Viral infections were diagnosed by multiplex PCR. Patients diagnosed with non-viral community-acquired pneumonia were included in the control group (N = 1,173). The main outcome was 30-day all-cause mortality. multivariate Cox regression analyses were performed to calculate the risk of death. Respiratory viruses were detected in 261 (18.2%) patients with community-acquired pneumonia. Two types of respiratory viruses were detected in 7 cases. Of the 254 cases detected with only one virus, 62 were influenza A, 18 were influenza B, 65 were rhinovirus, 35 were respiratory syncytial virus, 25 were metapneumovirus, 20 were parainfluenza, 17 were coronavirus, 7 were bocavirus, and 5 were adenovirus. Mortality was not significantly different between patients with respiratory virus and those without respiratory virus; the 30-day all-cause mortality rates were 20.3% and 22.4%, respectively (P = 0.45). Mortality rate increased with an increasing PSI score with or without respiratory viral infection. Pulmonary severity index was significantly associated with mortality adjusted for respiratory virus detection (hazard ratio = 1.024, 95% confidence interval = 1.020–1.028). Pneumonia severity index score is an important factor for assessing the prognosis of patients with community-acquired pneumonia, regardless of respiratory virus detection. |
38 | kl431ev6 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue. |
10 | lgqseo8t | has social distancing had an impact on slowing the spread of COVID-19? | COVID-19 in Colombia endpoints. Are we different, like Europe? Abstract The infection by the new coronavirus (SARS-CoV-2) has taken the dimension of a pandemic, affecting more than 160 countries in a few weeks. In Colombia, despite the implementation of the rules established by the national government, exists an elevate concern both for mortality and for the limited capacity of the health system to respond effectively to the needs of patients infected. For Colombia, assuming a case fatality rate among people infected with SARS-CoV-2 of 0.6% (average data from the information reported for Latin American countries for March 18) (Table 1), the number of deaths, in one or two weeks, could be 16 and 243, respectively. These estimates differ markedly from those documented in countries such as Spain and Italy, in which COVID-19 case fatality rates exceed 8% (case of Italy) and from the percentage of patients who have required intensive care, which has ranged from 9% to 11% of patients in Mediterranean European countries. These differences could be explained due to: a) the percentage of the population at risk (individuals older than 60 years); b) a higher epidemiological exposure to viral respiratory infections associated with more frequent exposure to them, due to geographic and climatic conditions; c) less spread of the virus by location in the tropical zone; and d) earlier preventive measures to contain the spread of SARS-CoV-2 infection. Therefore, it is possible to establish that the situation in this country will be different from in European Mediterranean and that Colombia could have different endpoints from Spain and Italy. |
25 | ljc7ojzt | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Prognosis of COVID-19: Changes in laboratory parameters. INTRODUCTION Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity. |
2 | 8uctsgh1 | how does the coronavirus respond to changes in the weather | Achievements and highlights for Infection, Disease and Health |
33 | sp87qdkr | What vaccine candidates are being tested for Covid-19? | Chikungunya Virus Vaccines: Viral Vector–Based Approaches In 2013, a major chikungunya virus (CHIKV) epidemic reached the Americas. In the past 2 years, >1.7 million people have been infected. In light of the current epidemic, with millions of people in North and South America at risk, efforts to rapidly develop effective vaccines have increased. Here, we focus on CHIKV vaccines that use viral-vector technologies. This group of vaccine candidates shares an ability to potently induce humoral and cellular immune responses by use of highly attenuated and safe vaccine backbones. So far, well-described vectors such as modified vaccinia virus Ankara, complex adenovirus, vesicular stomatitis virus, alphavirus-based chimeras, and measles vaccine Schwarz strain (MV/Schw) have been described as potential vaccines. We summarize here the recent data on these experimental vaccines, with a focus on the preclinical and clinical activities on the MV/Schw-based candidate, which is the first CHIKV-vectored vaccine that has completed a clinical trial. |
19 | oat1kqt7 | what type of hand sanitizer is needed to destroy Covid-19? | Taraxacum officinale and Urtica dioica extracts inhibit dengue virus serotype 2 replication in vitro BACKGROUND: Urtica dioica, Taraxacum officinale, Calea integrifolia and Caesalpinia pulcherrima are widely used all over the world for treatment of different illnesses. In Mexico, these plants are traditionally used to alleviate or counteract rheumatism and inflammatory muscle diseases. In the present study we evaluated the activity of aqueous and methanolic extracts of these four plants, on the replication of dengue virus serotype 2 (DENV2). METHODS: Extraction process was carried out in a Soxtherm® system at 60, 85 and 120 °C; a chemical fractionation in silica gel chromatography was performed and compounds present in the active fractions were identified by HPLC-DAD-ESI/MSn. The cytotoxic concentration and the inhibitory effect of extracts or fractions on the DENV2 replication were analyzed in the BHK-21 cell line (plaque forming assay). The half maximal inhibitory concentration (IC(50)) and the selectivity index (SI) were calculated for the extracts and fractions. RESULTS: The methanolic extracts at 60 °C of T. officinale and U. dioica showed the higher inhibitory effects on DENV2 replication. After the chemical fractionation, the higher activity fraction was found for U. dioica and T. officinale, presenting IC(50) values of 165.7 ± 3.85 and 126.1 ± 2.80 μg/ml, respectively; SI values were 5.59 and 6.01 for each fraction. The compounds present in T. officinale, were luteolin and caffeoylquinic acids derivatives and quercertin diclycosides. The compounds in the active fraction of U. dioica, were, chlorogenic acid, quercertin derivatives and flavonol glycosides (quercetin and kaempferol). CONCLUSIONS: Two fractions from U. dioica and T. officinale methanolic extracts with anti-dengue activity were found. The compounds present in both fractions were identified, several recognized molecules have demonstrated activity against other viral species. Subsequent biological analysis of the molecules, alone or in combination, contained in the extracts will be carried out to develop therapeutics against DENV2. |
2 | 39mfts0g | how does the coronavirus respond to changes in the weather | Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study BACKGROUND: A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19. METHODS: We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (R(t)) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20–23, Feb 11–14, and March 10–13, 2020. FINDINGS: COVID-19 transmissibility measured by R(t) has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% CI 34–53%) reduction in transmissibility in the community, from an estimated R(t) of 1·28 (95% CI 1·26–1·30) before the start of the school closures to 0·72 (0·70–0·74) during the closure weeks. Similarly, a 33% (24–43%) reduction in transmissibility was seen based on paediatric hospitalisation rates, from an R(t) of 1·10 (1·06–1·12) before the start of the school closures to 0·73 (0·68–0·77) after school closures. Among respondents to the surveys, 74·5%, 97·5%, and 98·8% reported wearing masks when going out, and 61·3%, 90·2%, and 85·1% reported avoiding crowded places in surveys 1 (n=1008), 2 (n=1000), and 3 (n=1005), respectively. INTERPRETATION: Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February, 2020. FUNDING: Health and Medical Research Fund, Hong Kong. |
31 | 4i0gici7 | How does the coronavirus differ from seasonal flu? | Estimating the Early Outbreak Cumulative Incidence of COVID-19 in the United States: Three Complementary Approaches Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the weekly incidence of COVID-19. Unfortunately, a lack of systematic testing across the United States (US) due to equipment shortages and varying testing strategies has hindered the usefulness of the reported positive COVID-19 case counts. We introduce three complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 during the early outbreak in each state in the US as well as in New York City, using a combination of excess influenza-like illness reports, COVID-19 test statistics, and COVID-19 mortality reports. Instead of relying on an estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our three approaches, there is a consistent conclusion that estimated state-level COVID-19 symptomatic case counts from March 1 to April 4, 2020 varied from 5 to 50 times greater than the official positive test counts. Nationally, our estimates of COVID-19 symptomatic cases in the US as of April 4 have a likely range of 2.2 to 5.1 million cases, with possibly as high as 8.1 million cases, up to 26 times greater than the cumulative confirmed cases of about 311,000. Extending our method to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 6.0 to 12.2 million, which compares with 1.5 million positive test counts. Our approaches demonstrate the value of leveraging existing influenza-like-illness surveillance systems during the flu season for measuring the burden of new diseases that share symptoms with influenza-like-illnesses. Our methods may prove useful in assessing the burden of COVID-19 during upcoming flu seasons in the US and other countries with comparable influenza surveillance systems. |
41 | fwint7w7 | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | AI4COVID-19: AI Enabled Preliminary Diagnosis for COVID-19 from Cough Samples via an App Inability to test at scale has become Achille's heel in humanity's ongoing war against COVID-19 pandemic. An agile, scalable and cost-effective testing, deployable at a global scale, can act as a game changer in this war. To address this challenge, building on the promising results of our prior work on cough-based diagnosis of a motley of respiratory diseases, we develop an Artificial Intelligence (AI)-based test for COVID-19 preliminary diagnosis. The test is deployable at scale through a mobile app named AI4COVID-19. The AI4COVID-19 app requires 2-second cough recordings of the subject. By analyzing the cough samples through an AI engine running in the cloud, the app returns a preliminary diagnosis within a minute. Unfortunately, cough is common symptom of over two dozen non-COVID-19 related medical conditions. This makes the COVID-19 diagnosis from cough alone an extremely challenging problem. We solve this problem by developing a novel multi-pronged mediator centered risk-averse AI architecture that minimizes misdiagnosis. At the time of writing, our AI engine can distinguish between COVID-19 patient coughs and several types of non-COVID-19 coughs with over 90% accuracy. AI4COVID-19's performance is likely to improve as more and better data becomes available. This paper presents a proof of concept to encourage controlled clinical trials and serves as a call for labeled cough data. AI4COVID-19 is not designed to compete with clinical testing. Instead, it offers a complementing tele-testing tool deployable anytime, anywhere, by anyone, so clinical-testing and treatment can be channeled to those who need it the most, thereby saving more lives. |
31 | u8nk63i5 | How does the coronavirus differ from seasonal flu? | Influenza A☆ Abstract The influenza viruses, which contain single-stranded RNA, are classified into 3 types, A, B, and C and belong to the Orthomyxoviridae family of viruses. Types A and B cause annual epidemics and often pandemics of influenza illness, while type C is a less common disease with fewer symptoms. |
27 | 2wshgzjk | what is known about those infected with Covid-19 but are asymptomatic? | Effectiveness of airport screening at detecting travellers infected with 2019-nCoV As the number of novel coronavirus cases grows both inside and outside of China, public health authorities require evidence on the effectiveness of control measures such as thermal screening of arrivals at airports. We evaluated the effectiveness of exit and entry screening for 2019-nCoV infection. In our baseline scenario, we estimated that 46.5% (95%CI: 35.9 to 57.7) of infected travellers would not be detected, depending on the incubation period, sensitivity of exit and entry screening, and the proportion of cases which are asymptomatic. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers. We developed an online tool so that results can be updated as new information becomes available. |
28 | fnb0ywka | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Is GSK3β a molecular target of chloroquine treatment against COVID-19? The recent clinical trial reports pertaining to the efficacy of chloroquine and hydroxychloroquine against COVID-19 albeit yet to be validated with larger clinical trials, have sparked much interest globally to evaluate whether this anti-malarial drug can be repurposed for the treatment of COVID-19. In addition to its anti-viral activity, the anti-inflammatory activity of chloroquine may also contribute to its efficacy. Based on our data obtained from an animal infection model of melioidosis (a disease caused by the bacteria Burkholderia pseudomallei), treatment with chloroquine can result in the phosphorylation and consequent inhibition of glycogen synthase kinase-3β (GSK3β). This serine/threonine protein kinase is now recognised as a point of convergence for host inflammatory response. In view of this, it is plausible that the mechanism for the anti-inflammatory effect of chloroquine against COVID-19 involves inhibition of host GSK3β. |
6 | mpa0kdse | what types of rapid testing for Covid-19 have been developed? | The laboratory's role in combating COVID-19 Since Coronavirus Disease 2019 (COVID-19) first emerged in December 2019, the disease has rapidly evolved into a pandemic that threatens societies around the world. As soon as the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified and its genome sequence determined, a laboratory diagnosis based on nucleic acid amplification technologies was quickly established and has played essential roles in the confirmation of a clinical diagnosis. Serological testing for antibodies against SARS-CoV-2 is becoming available for complementary diagnosis, identification of convalescent plasma, and epidemiologic studies. Additional laboratory biochemical tests, including monitoring the change in blood cells, blood gas, coagulation, liver function, cardiac markers, and inflammatory responses such as cytokine levels in plasma, are also critical in combating COVID-19. Nevertheless, with overwhelming numbers of patients and potentially large numbers of asymptomatic cases, clinical laboratories encounter enormous challenges in diagnostic approaches that can rapidly and accurately identify infected persons. Strategies that can effectively detect disease progression in order to stratify patients for appropriate care, and that can thereby prevent exacerbation of the disease, are urgently needed. This review discusses the laboratory's role and challenges in combating COVID-19. |
43 | 8ywevius | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | The Impact of Green Space on Violent Crime in Urban Environments: An Evidence Synthesis. Can the presence of green space in urban environments reduce the frequency of violent crime? To ascertain the evidence on this topic, we conducted an in-depth literature review using the PRISMA checklist. The search parameters included US articles written in English and published since 2000. More than 30,000 potential paper titles were identified and ultimately, 45 papers were selected for inclusion. Green spaces typically comprised tree cover, parks and ground cover. Criminal behaviors typically included murder, assault, and theft. The majority of the research reviewed involved quantitative methods (e.g., comparison of green space area to crime data). We extracted multiple mechanisms from the literature that may account for the impact of green space on crime including social interaction and recreation, community perception, biophilic stress reduction, climate modulation, and spaces expressing territorial definition. Recommendations are made for future research, such as meta-analysis of existing data and the development of grounded theory through qualitative data-gathering methods. By providing evidence that access to nature has a mitigating impact on violence in urban settings, city governments and communities are empowered to support these interventions. |
29 | 8y4j510s | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11ß-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets. |
9 | 2ytec133 | how has COVID-19 affected Canada | The first three months of the COVID-19 epidemic: Epidemiological evidence for two separate strains of SARS-CoV-2 viruses spreading and implications for prevention strategies About one month after the COVID-19 epidemic peaked in Mainland China and SARS-CoV-2 migrated from China westward to Europe and then the U.S., the epidemiological data begin to provide important insights into the risks associated with the disease and the effectiveness of intervention strategies. Like other respiratory diseases, including the 2003 SARS epidemic, the virus remains only about two months in any given population, yet the peak incidence and the lethality can vary. The data suggest that at least two strains of the 2020 SARS-CoV-2 virus have evolved during its migration from Mainland China to Europe. South Korea, Iran, and Italy were hit by the more dangerous "SKII" variant. While the epidemic in China is about to end, and in Europe about to level off, the course of the epidemic in the younger US population is still increasing and the peak level will likely depend on which of the strains has entered the US first. The same models that help us to understand the epidemic also help us to choose prevention strategies. While containment merely prolongs the time the disease circulates until the proportion of immune people is high enough for "herd immunity", reducing disease severity, either by vaccination or by early treatment of complications, is the best strategy against a respiratory virus disease. |
2 | b9fjmaec | how does the coronavirus respond to changes in the weather | Catastrophe évolutive, quelle pourrait-être l'influence des conditions météorologiques sur l'évolution de la pandémie CoViD-19? Résumé Une des préoccupations classiques de la gestion des catastrophes est d'en connaître l'évolutivité. Quelle est celle de la CoViD-19? Un questionnaire a été adressé à des confrères de 14 pays situés dans la zone chaude intertropicale pour établir une comparaison avec deux pays tempérés. Nous avons pu disposer des cas relevés et des conditions météorologiques de six îles françaises et de six pays africains francophones pour lesquels les mesures barrières gouvernementales ont été identiques à celles prises en Italie et en France. Le rôle positif de la température qui diminue la diffusion de la CoViD-19 et sa létalité a pu être mis en évidence. Dans les îles tropicales françaises, les cas importés (avions, bateaux) ont représenté en moyenne 33% de la totalité des cas sans influence sur la propagation virale, restée faible. La saisonnalité de la CoViD-19 doit faire craindre son retour à l'entrée de l'hiver et inciter à mieux préparer personnels et moyens. Summary One of the classic factors in disaster management is knowing its scalability. What is it in the case of CoViD-19? A questionnaire was sent to our colleagues from 14 countries located in the intertropical hot zone to establish a comparison with two temperate countries. We were able to collect the recorded cases and weather conditions from six French islands and six French-speaking African countries for which the government barrier measures were identical to those taken in Italy and France. We highlighted the positive role of temperature, which decreases the diffusion and the lethality of CoViD-19. In the French tropical islands, imported cases (by air, ships) represented a large percentage of cases (33% on average) which had no influence on the viral spread, which remained low. The seasonality of CoViD-19 should raise concern for its return at the start of winter and encourage better preparation of personnel and resources. |
9 | 0kss5r7u | how has COVID-19 affected Canada | Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China Abstract Background A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. Methods We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. Results 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. Conclusions The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients. |
5 | mg7k1pt8 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Chapter 5 Respiratory infections of the human bocavirus Abstract The human bocavirus is one of the most common respiratory viruses and occurs in all age groups. It is associated with upper and lower respiratory tract infections, and causes clinical symptoms from the mild common cold to life threatening respiratory diseases. Besides its ability to persist the virus appears to trigger chronic lung disease and increase the clinical symptoms, while being a putative trigger for fibrotic lung diseases. Laboratory diagnostics should include serological diagnostics in order to rule out a viremia because due to prolonged viral shedding acute and chronic infections cannot be differentiated on the detection of viral nucleic acids in respiratory specimen alone. Although Koch's postulates cannot be formally fulfilled due to the lack of an animal model and the chance for clinical trials with volunteers are limited due to the long term effects of HBoV infections, there is no doubt that the virus is a serious pathogen and requires attention. The aim of the chapter is to present an overview of our current knowledge on respiratory infections with the human bocavirus, and to provide basic and essential information on clinical features, molecular diagnostics, and epidemiologic challenges arising with this pathogen. |
40 | beguhous | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | The proximal origin of SARS-CoV-2 |
31 | 2bw8nbyb | How does the coronavirus differ from seasonal flu? | COVID-19 Pandemic and Impending Global Mental Health Implications The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases. |
11 | grx4gx95 | what are the guidelines for triaging patients infected with coronavirus? | Coronavirus disease-19: The First 7,755 Cases in the Republic of Korea We report the first 7,755 patients with confirmed COVID19 in Korea as of March 13, 2020. A total of 66 deaths were identified, resulting case fatality proportion of 0.9%. Older people, and those with coexisting medical conditions were at risk for fatal outcomes. The highest number of cases were from Daegu, followed by Gyeongbuk, with elevated age-stratified case fatality. This summary may help to understand the disease dynamics in the early phase of COVID19 outbreak, therefore, to guide future public health measures. |
5 | r49ox9x9 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Molecular dynamic simulations analysis of ritronavir and lopinavir as SARS-CoV 3CLpro inhibitors Abstract Since the emergence of the severe acute respiratory syndrome (SARS) to date, neither an effective antiviral drug nor a vaccine against SARS is available. However, it was found that a mixture of two HIV-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the SARS virus. To understand the fine details of the molecular interactions between these proteinase inhibitors and the SARS virus via complexation, molecular dynamics simulations were carried out for the SARS-CoV 3CLpro free enzyme (free SARS) and its complexes with lopinavir (SARS–LPV) and ritonavir (SARS–RTV). The results show that flap closing was clearly observed when the inhibitors bind to the active site of SARS-CoV 3CLpro. The binding affinities of LPV and RTV to SARS-CoV 3CLpro do not show any significant difference. In addition, six hydrogen bonds were detected in the SARS–LPV system, while seven hydrogen bonds were found in SARS–RTV complex. |
13 | oiat9mq9 | what are the transmission routes of coronavirus? | A scoping review on bio-aerosols in healthcare and the dental environment BACKGROUND: Bio-aerosols originate from different sources and their potentially pathogenic nature may form a hazard to healthcare workers and patients. So far no extensive review on existing evidence regarding bio-aerosols is available. OBJECTIVES: This study aimed to review evidence on bio-aerosols in healthcare and the dental setting. The objectives were 1) What are the sources that generate bio-aerosols?; 2) What is the microbial load and composition of bio-aerosols and how were they measured?; and 3) What is the hazard posed by pathogenic micro-organisms transported via the aerosol route of transmission? METHODS: Systematic scoping review design. Searched in PubMed and EMBASE from inception to 09-03-2016. References were screened and selected based on abstract and full text according to eligibility criteria. Full text articles were assessed for inclusion and summarized. The results are presented in three separate objectives and summarized for an overview of evidence. RESULTS: The search yielded 5,823 studies, of which 62 were included. Dental hand pieces were found to generate aerosols in the dental settings. Another 30 sources from human activities, interventions and daily cleaning performances in the hospital also generate aerosols. Fifty-five bacterial species, 45 fungi genera and ten viruses were identified in a hospital setting and 16 bacterial and 23 fungal species in the dental environment. Patients with certain risk factors had a higher chance to acquire Legionella in hospitals. Such infections can lead to irreversible septic shock and death. Only a few studies found that bio-aerosol generating procedures resulted in transmission of infectious diseases or allergic reactions. CONCLUSION: Bio-aerosols are generated via multiple sources such as different interventions, instruments and human activity. Bio-aerosols compositions reported are heterogeneous in their microbiological composition dependent on the setting and methodology. Legionella species were found to be a bio-aerosol dependent hazard to elderly and patients with respiratory complaints. But all aerosols can be can be hazardous to both patients and healthcare workers. |
30 | slapc5xt | is remdesivir an effective treatment for COVID-19 | A Chinese Case of Coronavirus Disease 2019 (COVID-19) Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey Controversy remains over whether the coronavirus disease 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period. |
20 | 96v185b2 | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection Abstract SARS-CoV-2 causes the recent global COVID-19 public health emergency. ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV. To predict the potential host range of SARS-CoV-2, we analyzed the key residues of ACE2 for recognizing S protein. We found that most of the selected mammals including pets (dog and cat), pangolin and Circetidae mammals remained the most of key residues for association with S protein from SARS-CoV and SARS-CoV-2. The interaction interface between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2. Our finding will provide important insights into the host range of SARS-CoV-2 and a new strategy to design an optimized ACE2 for SARS-CoV-2 infection. |
14 | 5qupha9z | what evidence is there related to COVID-19 super spreaders | Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020 Abstract The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 death in Italy by 5 March 2020. We modeled the transmission process in Republic of Korea and Italy with a stochastic model and estimated the basic reproduction number R 0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020. |
4 | ao93c31w | what causes death from Covid-19? | Estimating cases of COVID-19 from Daily Death Data in Italy COVID-19 is an emerging infectious disease which has been declared a pan- demic by the World Health Organisation. Due to limited testing capacity for this new virus, variable symptomatology the majority of infected showing non-specific mild or no symptoms it is likely current prevalence data is an underestimate. Methods: We present an estimate of the number of cases of COVID-19 com- pared to the number of confirmed case in Italy based on the daily reported deaths and information about the incubation period, time from symptom on- set to death and reported case fatality rate. Results: Our model predicts that on the 31st of January 2020 when the first 3 infected cases had been identified by Italian authorise there were already nearly 30 cases in Italy, and by the 24th of February 2020 only 0.5% cases had been detected and confirmed by Italian authorities. While official statistics had 132 confirmed case we believe a more accurate estimate would be closer to 26000. With a case-doubling period of about 2.5 days. |
9 | jjjk4z9a | how has COVID-19 affected Canada | Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations Abstract This document outlines recommendations for physiotherapy management for COVID-19 in the acute hospital setting. It includes: recommendations for physiotherapy workforce planning and preparation; a screening tool for determining requirement for physiotherapy; and recommendations for the selection of physiotherapy treatments and personal protective equipment. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with confirmed or suspected COVID-19. |
2 | yzffm05r | how does the coronavirus respond to changes in the weather | A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research. |
19 | txcy91w7 | what type of hand sanitizer is needed to destroy Covid-19? | Active surveillance for suspected COVID-19 cases in inpatients with information technology |
39 | qvpjci4y | What is the mechanism of cytokine storm syndrome on the COVID-19? | COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term "hyperferritinemic syndromes" and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and "hyperferritinemic syndromes" are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and "hyperferritinemic syndromes" which would allow considering severe COVID-19 as a fifth member of this spectrum of inflammatory conditions. |
36 | 33i6lzjd | What is the protein structure of the SARS-CoV-2 spike? | Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity BACKGROUND: Following the recent outbreak of the new coronavirus pandemic (Covid-19), the rapid determination of the structure of the homo-trimeric spike glycoprotein has prompted the study reported here. The aims were to identify potential "druggable" binding pockets in the protein and, if located, to virtual screen pharmaceutical agents currently in use for predicted affinity to these pockets which might be useful to restrict, reduce, or inhibit the infectivity of the virion. RESULTS: Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. This pocket is found at the inter-chain interface that exists between two domains prior to the virion binding to human Angiotensin Converting Enzyme 2 (ACE2) protein. One of these domains is the highly mobile receptor binding domain, which must move into position to interact with ACE2, which is an essential feature for viral entry to the host cell. Virtual screening with a library of purchasable drug molecules has identified pharmaceuticals currently in use as prescription and over the counter medications that, in silico, readily bind into this pocket. CONCLUSIONS: This study highlights possible drugs already in use as pharmaceuticals that may act as agents to interfere with the movements of the domains within this protein essential for the infectivity processes and hence might slow, or even halt, the infection of host cells by this new coronavirus. As these are existing pharmaceuticals already approved for use in humans, this knowledge could accelerate their roll-out, through repurposing, for affected individuals and help guide the efforts of other researchers in finding effective treatments for the disease. |
28 | ondv8c78 | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Evidence of Protective Effect of Hydroxychloroquine on COVID-19 We would like to share ideas on the report "Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials"1 Balevic noted that "well-designed clinical trials that include patients with rheumatic disease are urgently needed to characterize the efficacy, safety, and target exposures for hydroxychloroquine1". |
1 | fby616ap | what is the origin of COVID-19 | Comment on "Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade" |
40 | uqykia6i | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus. To understand how Middle East respiratory syndrome coronavirus (MERS-CoV) transmitted from bats to humans, we compared the virus surface spikes of MERS-CoV and a related bat coronavirus, HKU4. Although HKU4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. These mutations are present in MERS-CoV spike, explaining why MERS-CoV infects human cells. These mutations therefore played critical roles in the bat-to-human transmission of MERS-CoV, either directly or through intermediate hosts. |
50 | pa5i13fj | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic As the world is witnessing the epidemic of COVID-19, a disease caused by a novel coronavirus, SARS-CoV-2, emerging genetics and clinical evidences suggest a similar path to those of SARS and MERS. The rapid genomic sequencing and open access data, together with advanced vaccine technology, are expected to give us more knowledge on the pathogen itself, including the host immune response as well as the plan for therapeutic vaccines in the near future. This review aims to provide a comparative view among SARS-CoV, MERS-CoV and the newly epidemic SARS-CoV-2, in the hope to gain a better understanding of the host-pathogen interaction, host immune responses, and the pathogen immune evasion strategies. This predictive view may help in designing an immune intervention or preventive vaccine for COVID-19 in the near future. |
3 | 6gj02k04 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain BACKGROUND: Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. RESULTS: Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8(+) T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. CONCLUSION: Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV. |
13 | 3n05cb49 | what are the transmission routes of coronavirus? | Insights into the Evolution and Emergence of a Novel Infectious Disease Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1). Adaptation is often a key factor for successfully establishing sustained human-to-human transmission. Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population. We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event. Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes. We compare our analytical results with a stochastic model, which has previously been studied computationally. Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction. For example, if [Image: see text] or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution. We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected. For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation. We conclude by discussing implications for surveillance and control of emerging infections. |
12 | 7ofa04l1 | what are best practices in hospitals and at home in maintaining quarantine? | The 5% of the Population at High Risk for Severe COVID-19 Infection Is Identifiable and Needs to Be Taken Into Account When Reopening the Economy. The goal of this column is to help mental health care professionals understand coronavirus disease 2019 (COVID-19) so that they can better explain the complexities of the current crisis to their patients. The bottom-line of this column is that, while COVID-19 can infect virtually everyone in the human population, only about 5% are susceptible to severe infection requiring admission to an intensive care unit and/or causing a fatal outcome and this population can be identified on the basis of comorbid medical illness and/or age. These numbers are based on experience in China, the United States, and Europe. Table 1 presents an analysis conducted by the US Centers for Disease Control and Prevention (CDC), which is further supported by several other sources reviewed in the article. The population at risk for severe infection are individuals with comorbid medical illness and those 85 years of age and older. The comorbid medical illnesses identified as risk factors are preexisting respiratory and cardiovascular disease, immunocompromised status, morbid obesity (ie, body mass index ≥40), diabetes mellitus, and possibly significant kidney or liver impairment. Parenthetically, news reports and the literature sometimes cite age 60 years and older as a risk factor but age between 60 and 85 years is likely a surrogate for having 1 or more of these comorbid medical conditions. While 5% may initially seem like a small number, it nevertheless potentially represents 16.5 million people, given the United States population of 330 million. That is a tremendous number of people requiring intensive care unit admission and/or potentially dying, and individuals in this population have overwhelmed the US health care system in some hotspots. For this reason, this column suggests taking this at-risk population into account in mitigation strategies when attempting to open the US economy. The column addresses the following questions: (1) What are the 3 aspects of the race to minimize the damage caused by COVID-19? (2) What data are currently available to help guide decisions to be made? (3) What strategies have been employed to date and how successful have they been? and (4) Might risk stratification of exposure be a viable strategy to minimize the damage caused by the virus? The race to minimize the damage caused by COVID-19 requires that we obtain knowledge about the disease and its treatment or prevention, how to best safeguard public health and avoid overwhelming the health care system, and how to minimize the societal damage caused by substantial disruption of the economy. Data gathered over the past 4 months since the COVID-19 virus emerged as a human pathogen have provided guidance for our decisions going forward. The most widely adopted strategies for dealing with the COVID-19 pandemic to date have involved the epidemiological approach of encouraging good hygiene practices and social distancing, including orders to "shelter in place," quarantine of high-risk individuals, and isolation of infected individuals. The goal of this epidemiological approach has been to "flatten the curve" by reducing the height of the peak of the infection to avoid overwhelming the health care system and society in general, while buying time to learn more about the disease and find more effective ways to deal with it. However, now that more is known about COVID-19 and the portion of the population that is most at risk for serious adverse outcomes including death, it may be possible to move from a shelter-in-place approach for the entire population to focus on those at most risk and thus facilitate a gradual and rational phased reduction of social restrictions to reopen the economy. Such a graduated opening would be based on regions of countries meeting specific criteria in terms of being able to contain the virus, coupled with vigorous monitoring to look for outbreaks, followed by case monitoring, isolation of infected individuals and quarantine of exposed individuals, and increased use of testing for active disease as well as for immunity. Taking the data on high-risk individuals into account would allow for a gradual lifting of restrictions on the majority of the population while maintaining more stringent safeguards to protect the vulnerable portion of the population. Nevertheless, the entire population would need to continue to practice good hygiene and social distancing while simultaneously-and perhaps even more vigorously-focusing on sheltering the vulnerable population until adequate community immunity has been achieved to prevent the spread of the virus, whether that is accomplished through natural exposure alone or with the addition of safe and effective vaccine(s) which may not be available for a year. Continued widespread testing for antibodies will help determine how far or close this country is-and other countries are-from developing effective community immunity. |
15 | l9rh8xz7 | how long can the coronavirus live outside the body | Further studies on human enteric coronaviruses Comparisons were made between human enteric coronaviruses and the enteric coronaviruses of pigs and calves by negative staining. Examination of human intestinal organ culture fluids at various time intervals after inoculation with the human enteric coronavirus showed increasing numbers of particles in the fluids. Thin sections of the columnar epithelial cells of these explants showed a number of features consistent with the replication of known human and animal coronaviruses. Virus particles found in thin sections had a mean diameter of 68 nm. In addition, a structure was found in thin sections which has not been described previously. This structure may represent the viral nucleocapsid. |
44 | b4znk2wr | How much impact do masks have on preventing the spread of the COVID-19? | Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak. |
12 | 5blojnvc | what are best practices in hospitals and at home in maintaining quarantine? | Weight Stigma and the "Quarantine‐15" The coronavirus SARS‐CoV‐2 (i.e., COVID‐19) has caused significant disruption in everyday life on a global scale. Due to stay‐at‐home orders and sudden unemployment, millions have found themselves isolated at home without their usual routines. This rise in unstructured time, combined with the enormous stress of the pandemic and its far‐reaching consequences, have led to widespread concerns among the general public about vulnerability to overeating, sedentary behavior, and weight gain. These concerns are reflected in the explosion of social media posts referencing the "quarantine‐15." |
13 | tmbv6xxv | what are the transmission routes of coronavirus? | Prisoners in a pandemic: We should think about detainees during Covid-19 outbreak In Italy, where the Covid-19 emergency developed immediately after China, the spread of the pandemic has highlighted some unsolved problems inherent to the prison system. This theme is already, unfortunately, of distressing topicality. Among these, the complex balance between the security needs and the protection of the prisoner's right to health deserves particular attention. The detainees, in fact, constitute a group particularly vulnerable to the spread of an infectious disease, both because they have an average level of health lower than that of the general population, and because they live forced in cramped, overcrowded, poorly ventilated environments, in which it is not always possible to observe the general hygiene rules. For these reasons, during the ongoing pandemic emergency, it could be even more difficult to concretely protect the right to health of this portion of the population. |
43 | h8s1c5my | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents' individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated. |
13 | c0ihtj5k | what are the transmission routes of coronavirus? | The comparison of trends in Spain and the Nederland: a Dynamical compartment model of the transmission of Coronavirus The recent spreading of coronavirus made many countries impose restrictions in order to control its dangerous effect on the citizens. We developed a theoretical dynamical model based on compartmental SIR system with additional adjustment taken from Flow network and Markov chain frameworks to illustrate developments and trends based on publicly available data. Based on this Model, code in R was written and fed by stamped publicly available data from authorized governmental websites in Spain and in the Nederlands, to compare trends. Our results show that the 'peak' of infection is already behind us in both countries, but also demonstrate that there is a danger of rebound of a spread. It is obvious that measures imposed are giving the results, but we should be precarious of near future practices and developments since the majority of population will still be without immunity. |
27 | jntrjg8u | what is known about those infected with Covid-19 but are asymptomatic? | Radiotherapy Workflow and Protection Procedures During the Coronavirus Disease 2019 (COVID-19) Outbreak: Experience of the Hubei Cancer Hospital in Wuhan, China Abstract The epidemic of Coronavirus Disease 2019 (COVID-19) first broke out in Wuhan in December 2019, and reached its peak in Wuhan in February 2020. It became a major public health challenge for China, and evolved into a global pandemic in March 2020. For radiation oncology departments, the COVID-19 pandemic presents a unique challenge for disease protection and prevention for both patients and staff, owing to the weakened immune systems of cancer patients and the need to deliver timely and uninterrupted radiotherapy. At the Hubei Cancer Hospital, the only hospital in Wuhan that specializes in oncology, we organized an emergency infection control team to lead special efforts to combat COVID-19 during this challenging time. Under its lead, the following measures were implemented in the radiation oncology department: the radiotherapy clinic was divided into different infection control zones with varying levels of protection; special staff and patient infection control training sessions were conducted and appropriate measures deployed; daily symptom testing criteria were implemented for patients undergoing treatment; special rotating schedules and infection control methods were implemented for various staff members such as medical physicists/dosimetrists and radiation therapists; modified radiotherapy workflow and specialized treatment area cleaning and disinfection policies and procedures were designed and executed; and special medical waste disposal methods were implemented. We began treating patients using this new COVID-19 radiotherapy treatment workflow and infection control measures on January 30, 2020. During more than one and a half months of uninterrupted radiation oncology clinical operation through the worst of the Wuhan outbreak, no known COVID-19 infection occurred at our radiotherapy center to our patients or employees. This report may provide valuable information for other radiation oncology departments during this unprecedented public health crisis. |
23 | 5sbkd7cj | what kinds of complications related to COVID-19 are associated with hypertension? | Implications of COVID-19 for patients with pre-existing digestive diseases |
9 | v7hmc9sj | how has COVID-19 affected Canada | Predicting turning point, duration and attack rate of COVID-19 outbreaks in major Western countries Abstract In this paper, we employed a segmented Poisson model to analyze the available daily new cases data of the COVID-19 outbreaks in the six Western countries of the Group of Seven, namely, Canada, France, Germany, Italy, UK and USA. We incorporated the governments' interventions (stay-at-home advises/orders, lockdowns, quarantines and social distancing) against COVID-19 into consideration. Our analysis allowed us to make a statistical prediction on the turning point (the time that the daily new cases peak), the duration (the period that the outbreak lasts) and the attack rate (the percentage of the total population that will be infected over the course of the outbreak) for these countries. |
13 | tesje8gl | what are the transmission routes of coronavirus? | COVID-19, Australia: Epidemiology Report 2 (Reporting week ending 19:00 AEDT 8 February 2020) This is the second epidemiological report for coronavirus disease (COVID-19), previously known as novel coronavirus (2019-nCoV), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 8 February 2020. It includes data on Australian cases notified during the week ending 19:00 AEDT 8 February 2020, the international situation and current information on the severity, transmission and spread of the COVID-19 infection. |
11 | cgcf7mgj | what are the guidelines for triaging patients infected with coronavirus? | Evaluation of potential anti-toxoplasmosis efficiency of combined traditional herbs in a mouse model Toxoplasma gondii is a worldwide spread protozoan and is able to infect almost all warm-blood animals. No effective drugs are available clinically on toxoplasmosis. Chinese traditional herbal medicines have provided remedies for many health problems. There exists a possibility that Chinese herbs may provide protection against T. gondii. This work aims to assess the protective efficacy of combined Chinese herbs against T. gondii. We screened five herbal medicines that have different pharmacological effects and combined them into a prescription according to the traditional Chinese medicine compatibility principle. The drug potential and protective efficacy were evaluated through a mouse model by determining the survival time, the parasite load in blood and tissues, the change of cell proportions in blood and histological detection. The results showed that the survival time of mice in the 500 mg Chinese herbs group and sulfadiazine group was significantly longer than that of the PBS control group. Also the parasite load in blood and tissues of 500 mg Chinese herbs and sulfadiazine groups was significantly lower than that of PBS group at 7 days post infection (dpi), which was in accordance with the result of histological detection. Monocyte and neutrophil of infected mice were remarkably increased while lymphocyte was dramatically decreased compared to that of blank group at 7 dpi. The results demonstrated that the 500 mg dosage of our Chinese herbs could slow down the replication of T. gondii and prolong the survival time of mice and could be considered as possible candidate drug against toxoplasmosis. |
1 | mwj2qby4 | what is the origin of COVID-19 | MERS coronavirus: diagnostics, epidemiology and transmission The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users. |
8 | zav5gksq | how has lack of testing availability led to underreporting of true incidence of Covid-19? | The timing of one-shot interventions for epidemic control The apparent early success in China's large-scale intervention to control the COVID-19 epidemic has led to interest in whether other countries can replicate it as well as concerns about a resurgence of the epidemic if or when China relaxes the interventions. In this paper we look at the impact of a single short-term intervention on an epidemic. We see that if an intervention cannot be sustained long-term, it has the greatest impact if it is imposed once infection levels have become large enough that there is an appreciable number of infections present. For minimising the total number infected it should start close to the peak so that there is no rebound once the intervention is stopped, while to minimise the peak prevalence, it should start earlier, allowing two peaks of comparable size rather than one very large peak. In populations with distinct subgroups, synchronized interventions are less effective than targeting the interventions in each sub-population separately. We do not attempt to clearly determine what makes an intervention sustainable or not. We believe that is a policy question. If an intervention is sustainable, it should be kept in place. Our intent is to offer insight into how best to time an intervention whose impact on society is too great to maintain. |
5 | kn1lcsia | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | SARS-CoV-2, COVID-19 and inherited arrhythmia syndromes Abstract Ever since the first case was reported at the end of 2019, the SARS-COV-2 virus and associated lung disease COVID-19 has spread throughout the world and has become a pandemic. In particular, the high transmission rate of the virus has made it a threat to public health globally. Currently, there is no proven effective therapy against the virus, and the impact on other diseases is also uncertain, especially inherited arrhythmia syndrome. Arrhythmogenic effect of COVID-19 can be expected, potentially contributing to disease outcome. This may be of importance for patients with an increased risk for cardiac arrhythmias, either secondary to acquired conditions or co-morbidities or consequent to inherited syndromes. Management of patients with inherited arrhythmia syndromes such as Long QT syndrome, Brugada syndrome, Short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia in the setting of the COVID-19 pandemic may prove particularly challenging. Depending on the inherited defect involved, these patients may be susceptible to pro-arrhythmic effects of COVID-19-related issues such as fever, stress, electrolyte disturbances and use of antiviral drugs. We here describe the potential COVID-19 associated risks and therapeutic considerations for patients with distinct inherited arrhythmia syndromes and provide recommendations, pending local possibilities, for their monitoring and management during this pandemic. |
24 | o56j4qio | what kinds of complications related to COVID-19 are associated with diabetes | Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis Abstract Background An outbreak of Novel Coronavirus (COVID -19) in Wuhan, China, the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries. Aims The aim of the meta-analysis was to assess the prevalence of comorbidities in the COVID-19 infection patients and the risk of underlying diseases in severe patients compared to non-severe patients. Methods A literature search was conducted using the databases PubMed, EMBASE, and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using random-effects models. Results Eight studies were included in the meta- analysis, including 46248 infected patients. The result showed the most prevalent clinical symptom was fever ( 91 ± 3, 95% CI 86-97% ), followed by cough (67 ± 7, 95% CI 59-76%), fatigue ( 51 ± 0, 95% CI 34-68% ) and dyspnea ( 30 ± 4, 95% CI 21-40%). The most prevalent comorbidity were hypertension (17 ± 7, 95% CI 14-22%) and diabetes ( 8 ± 6, 95% CI 6-11% ), followed by cardiovascular diseases ( 5 ± 4, 95% CI 4-7% ) and respiratory system disease( 2 ± 0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds ratio of hypertension, respiratory system disease, cardiovascular disease in severe patients were (OR 2.36, 95% CI: 1.46-3.83), (OR 2.46, 95% CI: 1.76-3.44) and (OR 3.42, 95% CI: 1.88-6.22)respectively. Conclusion We assessed the prevalence of comorbidities in the COVID-19 infection patients and found underlying disease, including hypertension, respiratory system disease and cardiovascular, may be a risk factor for severe patients compared with Non-severe patients. |
19 | ayunmlpk | what type of hand sanitizer is needed to destroy Covid-19? | Coronavirus (COVID-19) outbreak: what the department of endoscopy should know Italy recorded its first case of confirmed acute respiratory illness because of coronavirus on February 18, 2020, soon after the initial reports in China. Since that time, Italy and nations throughout the world have adopted very stringent and severe measures to protect populations from spread of infection. Despite these measures, the number of infected people is growing exponentially, with a significant number of patients developing acute respiratory insufficiency. Endoscopy departments face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the measures, with specific focus on personal protection equipment and dress code modalities, implemented in our hospital to prevent further dissemination of COVID-19 infection. |
20 | lqdgvsaq | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective Coronaviruses (CoVs) possess an enveloped, single, positive-stranded RNA genome which encodes for four membrane proteins, namely spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins 3-5 [1]. With regard to pathogenicity, S proteins are essential for viral entry into host cells [2, 3]. SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. Of note, CD209L or liver/lymph node special intercellular adhesion molecule-3-grabbing non-integrin (SIGN) and dendritic cell (DC)-SIGN are alternative receptors for SARS-CoV but with lower affinity [7]. In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. Then, viruses replicate in target cells with release of mature virions, which, in turn, invade new target cells [9]. Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. Moreover, by means of two residues at positions 479 and 487 RBD allows virus progression and tropism [10, 11]. In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13]. In a very recent paper, Wan and associates [14] have investigated the receptor recognition by COVID-19 (a new term to indicate the 2019-nCoV in Wuhan) on the bases of structural studies. In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. These predictive findings by Wan and associates [14] are confirmed by two contemporary studies by Letko and Muster [15] and Peng and associates [16]. In particular, the report by Peng and associates [16], points out the possible origin of COVID-19 from bats [16]. From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. In fact, in the course of SARS-CoV infection, a number of immune disorders have been detected. Three reports have demonstrated the ability of CoV to inhibit interferon (IFN)- production in the course of SARS acting as IFN antagonist [20-22]. In senescent Balb/c mice, depletion of T lymphocytes is associated to more severe interstitial pneumonitis and delayed clearance of SARS-CoV, thus, suggesting a protective role played by these cells [23]. In this connection, both SARS-CoV and MERS-CoV have been shown to induce T cell apoptosis, thus, aggravating the clinical course of disease [24, 25]. Quite interestingly, memory CD8+ T cells specific for SARS-CoV M and N proteins have been detected up to 11 years post-infection [26]. As far as humoral immune responsiveness is concerned, evidence has been provided that S1 subunit from MERS-CoV is highly immunogenic in mice [27]. Moreover, monoclonal antibodies have been shown to be highly neutralizing against MERS-CoV replication and endowed with post exposure effectiveness in susceptible mice [28, 29]. Human neutralizing antibodies have also been isolated from a recovered patient, thus, suggesting the role of humoral immunity in the control of the persistence of CoV in the host [30]. In particular, IgG response occurs early in infection and its prolonged production may serve for virus clearance during recovery also in view of the absence of viremia in convalescent sera from SARS patients [31]. According to current literature, severity of COVID-19 infection correlates with lymphopenia and patients who died from COVID-19 had lower lymphocyte counts when compared to survivors [32, 33]. These data suggest that lymphocyte-mediated anti-viral activity is poorly effective against COVID-19. Despite lymphopenia, evidence for an exaggerate release of proinflammatory cytokines [interleukin (IL)-1 and IL-6] has been reported in the course acute respiratory syndrome in COVID19 infected patients, thus, aggravating the clinical course of disease [34]. As recently reported, during COVID-19 pandemic in both Italy and China higher frequency of fatalities have been observed in the frail elderly population with previous comorbidities [35]. It is well known that decline of immunity occurs in ageing and, therefore, COVID-19 may gain easier access to the respiratory tract in frail elderly patients [36]. There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37]. It is well known that ANG II via activation of the AT1R promotes detrimental effects on the host, such as, vasoconstriction, reactive oxygen species generation, inflammation and matrix remodelling [38]. ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39]. In this framework, Gurwitz [40] proposed to use AT1R blockers, such as losartan, as a potential treatment of COVID-19 infection. In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41]. Then, Gurwitz suggests to evaluate severity of symptoms in COVID-19 infected patients under previous chronic treatment with AT1R blockers in comparison to COVID-19 infected patients who did not take AT1R blockers [40]. Quite interestingly, 75% of aged COVID-19 infected patients admitted to Italian hospitals had hypertension [unpublished data]. However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies. Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44]. In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively. As far as the mechanism of action of RES is concerned, this polyphenol is able to activate sirtuin (Sirt)1 [45-47]. In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48]. Of importance, Lin and associates [48] have demonstrated the ability of RES to in vitro inhibit MERS-CoV infection of Vero E6 cells, thus, prolonging cell survival in virtue of an anti-apoptotic mechanism. These findings suggest a direct antiviral effect exerted by RES. It would be very interestingly to evaluate the direct effects of RES on COVID-19, in vitro. The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49]. Then, successful animal studies may pave the way for RES-based human trials in COVID-infected patients. Note added in proof During the reviewing process of this perspective other related papers have been published. Hanff and associates [50] have discussed the possible association between COVID-19-associated cardiovascular mortality and dysregulation of the Renin Angiotensin System (RAS). From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients. Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture. Such a dilemma would be solved byclinical trials based on RAS blockade or initiation and monitoring related effects. Contemporarily, Danser and associates [51] claim that there is no evidence to stop RAS blockers in the course of COVID-19 infection. In fact, there are no available data which support that ACE inhibitors or ANG II type I receptor blockers increase COVID-19 infection via its binding to ACE2. Finally, Kuster and associates [52] write that there are no data on the strict relationship between ACE2 activity and SARS-CoV2 mortality. Moreover, in the SARSCoV2, cells expressing ACE2 were not attacked by the virus, while cells lacking ACE2 were bound by the SARS-CoV2 virus [53]. These findings suggest that also in the case of RES effects on COVID-19 infection, the dual role of ACE2 should be taken into serious consideration. |
8 | 3dzv20b7 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | A model to predict SARS-CoV-2 infection based on the first three-month surveillance data in Brazil. Background: COVID-19 diagnosis is a critical problem, mainly due to the lack or delay in the test results. We aimed to obtain a model to predict SARS-CoV-2 infection in suspected patients reported to the Brazilian surveillance system. Methods: We analyzed suspected patients reported to the National Surveillance System that corresponded to the following case definition: patients with respiratory symptoms and fever, who traveled to regions with local or community transmission or who had close contact with a suspected or confirmed case. Based on variables routinely collected, we obtained a multiple model using logistic regression. The area under the receiver operating characteristic curve (AUC) and accuracy indicators were used for validation. Results: We described 1468 COVID-19 cases (confirmed by RT-PCR) and 4271 patients with other illnesses. With a data subset, including 80% of patients from Sao Paulo (SP) and Rio Janeiro (RJ), we obtained a function which reached an AUC of 95.54% (95% CI: 94.41% - 96.67%) for the diagnosis of COVID-19 and accuracy of 90.1% (sensitivity 87.62% and specificity 92.02%). In a validation dataset including the other 20% of patients from SP and RJ, this model exhibited an AUC of 95.01% (92.51% - 97.5%) and accuracy of 89.47% (sensitivity 87.32% and specificity 91.36%). Conclusion: We obtained a model suitable for the clinical diagnosis of COVID-19 based on routinely collected surveillance data. Applications of this tool include early identification for specific treatment and isolation, rational use of laboratory tests, and input for modeling epidemiological trends. |
27 | ajlpb9li | what is known about those infected with Covid-19 but are asymptomatic? | The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients Following the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), another highly pathogenic coronavirus named SARS‐CoV‐2 (previously known as 2019‐nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS‐CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID‐19) with clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV. The most characteristic symptom of patients with COVID‐19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID‐19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse‐connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS‐CoV and SARS‐CoV2, it remains to make clear whether the potential invasion of SARS‐CoV2 is partially responsible for the acute respiratory failure of patients with COVID‐19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS‐CoV‐2‐induced respiratory failure. |
1 | ec8lpgl3 | what is the origin of COVID-19 | Scientists 'strongly condemn' rumors and conspiracy theories about origin of coronavirus outbreak ;Science ;AAAS A group of 27 prominent public health scientists from outside China is pushing back against a steady stream of stories and even a scientific paper suggesting a laboratory in Wuhan, China, may be the origin of the outbreak of COVID-19 "The rapid, open, and transparent sharing of data on this outbreak is now being threatened by rumours and misinformation around its origins," the scientists, from nine countries, write in a statement published online by The Lancet yesterday |
20 | m9tn3qu0 | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Angiotensin-converting enzyme 2 and new insights into the renin–angiotensin system Abstract Components of the renin–angiotensin system are well established targets for pharmacological intervention in a variety of disorders. Many such therapies abrogate the effects of the hypertensive and mitogenic peptide, angiotensin II, by antagonising its interaction with its receptor, or by inhibiting its formative enzyme, angiotensin-converting enzyme (ACE). At the turn of the millennium, a homologous enzyme, termed ACE2, was identified which increasingly shares the limelight with its better-known homologue. In common with ACE, ACE2 is a type I transmembrane metallopeptidase; however, unlike ACE, ACE2 functions as a carboxypeptidase, cleaving a single C-terminal residue from a distinct range of substrates. One such substrate is angiotensin II, which is hydrolysed by ACE2 to the vasodilatory peptide angiotensin 1–7. In this commentary we discuss the latest developments in the rapidly progressing study of the physiological and patho-physiological roles of ACE2 allied with an overview of the current understanding of its molecular and cell biology. We also discuss parallel developments in the study of collectrin, a catalytically inactive homologue of ACE2 with critical functions in the pancreas and kidney. |
25 | gtywvr2e | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Community-acquired Pseudomonas aeruginosa-pneumonia in a previously healthy man occupationally exposed to metalworking fluids Although the Pseudomonas aeruginosa infection is well known and frequently found in hospitals and nursing care facilities, many cases are also reported outside these boundaries. In general, this pathogen infects debilitated patients either by comorbidities or by any form of immunodeficiency. In cases of respiratory infection, tobacco abuse seems to play an important role as a risk factor. In previously healthy patients, community-acquired pneumonia (CAP) with P. aeruginosa as the etiological agent is extremely rare, and unlike the cases involving immunocompromised or hospitalized patients, the outcome is severe, and is fatal in up to 61.1% of cases. Aerosolized contaminated water or solutions are closely linked to the development of respiratory tract infection. In this setting, metalworking fluids used in factories may be implicated in CAP involving previously healthy people. The authors report the case of a middle-aged man who worked in a metalworking factory and presented a right upper lobar pneumonia with a rapid fatal outcome. P. aeruginosa was cultured from blood and tracheal aspirates. The autopsy findings confirmed a hemorrhagic necrotizing pneumonia with bacteria-invading vasculitis and thrombosis. A culture of the metalworking fluid of the factory was also positive for P. aeruginosa. The pulsed-field gel electrophoresis showed that both strains (blood culture and metalworking fluid) were genetically indistinguishable. The authors highlight the occupational risk for the development of this P. aeruginosa-infection in healthy people. |
38 | gj2bnruy | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Network Analysis and Transcriptome Profiling Identify Autophagic and Mitochondrial Dysfunctions in SARS-CoV-2 Infection Lack of effective treatment strategy and vaccine makes SARS-CoV-2 infection a big threat to mankind. Analyzing the host transcriptional changes in response to virus infection will help delineate the biological processes impacted by the virus and will potentially facilitate drug development. Using RNA seq datasets of virus infected lung cell lines A549 (infected with either SARS-CoV-2 or Influenza A virus (IAV)) and Calu3 (infected with either SARS-CoV-2 or MERS-CoV), we present a detailed analysis of genes expression changes in response to each of these viral infections. Upregulation of the antiviral interferon signaling was observed with all three viral infections. However, upregulation of the cytokine/inflammatory processes, downregulation of mitochondrial organization and respiration processes, and perturbation in the autophagic processes were specifically observed in SARS-CoV-2 infected cells, which were absent in IAV infected cells. Upregulation of the inflammatory processes was concordant with the gene expression signature of COVID-19 lungs and with inflammatory symptoms observed in severe cases of COVID-19 patients. Coexpression networks analysis also facilitated the identification of protein-protein interaction (PPI) subnetworks of genes in the inflammation and mitochondrial processes that were either coordinately up or downregulated in SARS-CoV-2 infected cells, respectively. Comparing the expression of marker genes of lung cell types from single cell RNA seq data with expression profile of A549 cells revealed that they likely represent the lung epithelial lineage cells. The cellular processes uniquely perturbed in infected cells that were identified in this analysis likely delineates lung epithelial cells response to the SARS-CoV-2 infection. |
33 | 1qniriu0 | What vaccine candidates are being tested for Covid-19? | Machine intelligence design of 2019-nCoV drugs Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed. |
20 | wyw5992m | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Cerebrovascular Accident in a Pediatric Patient Presenting With Influenza Abstract Background Acute ischemic stroke (AIS) in pediatric populations accounts for more than half of pediatric strokes and is associated with significant morbidity and mortality. Pediatric AIS can present with nonspecific symptoms or symptoms that mimic alternate pathology. Case Report A 4-month-old female presented to the emergency department for fever, decreased oral intake, and "limp" appearance after antibiotic administration. She was febrile, tachypneic, and hypoxic. Her skin was mottled with 3-s capillary refill, her anterior fontanelle was tense, and she had mute Babinski reflex bilaterally but was moving all extremities. The patient was hyponatremic, thrombocytopenic, and tested positive for influenza A. A computed tomography scan of the brain revealed an acute infarction involving the right frontal, parietal, temporal, and occipital lobes in addition to hyperdensities concerning for thrombosed cortical veins. The patient was transferred for specialty evaluation and was discharged 2 weeks later on levetiracetam. Why Should an Emergency Physician be Aware of This? Pediatric AIS can present with nonspecific symptoms that mimic alternate pathology. A high level of suspicion is needed so as not to miss the diagnosis of pediatric AIS in the emergency department. A thorough neurologic assessment is warranted, and subtle abnormalities should be investigated further. |
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