docid: lxjbabrj

title: A virtual care program for outpatients diagnosed with COVID-19: a feasibility study

text: BACKGROUND: In patients who are discharged home to self-isolate while coronavirus disease 2019 (COVID-19) test results are pending, there is no formal method for physician assessments or counselling to occur if the result returns positive Our aim was to develop and test the feasibility of a virtual care program for self-isolating outpatients diagnosed with COVID-19 METHODS: In preparation for this gap in health care, the COVID-19 Expansion to Outpatients (COVIDEO) program was developed at the Sunnybrook Health Sciences Centre, Toronto, Ontario, to provide ongoing care for outpatients diagnosed with COVID-19 As part of a feasibility study, we describe our experiences with the first 50 patients managed using this program from its inception (Mar 1, 2020) until Mar 27, 2020 RESULTS: All 50 people who tested positive for COVID-19 at the Sunnybrook Health Sciences Centre and were discharged home to self-isolation during the study period were assessed through the COVIDEO program Thirty-two patients (64%) were assessed via the Ontario Telemedicine Network virtual care platform, and the remainder by telephone The median time from viral swab collection to first COVIDEO program assessment was 2 (interquartile range [IQR] 1-2) days Among the 26 patients for whom further follow-up care through the COVIDEO program was discontinued by the end of March 2020, the median duration of virtual care was 12 5 (IQR 8 75-16) days During the study period, 6 patients required transfer to hospital for assessment, of whom 4 required admission INTERPRETATION: We have shown that a virtual care program can be used in the management of outpatients diagnosed with COVID-19 Further studies evaluating its sustainability and impact on health outcomes are underway


title: Teach, and teach and teach: does the average citizen use masks correctly during daily activities? Results from an observational study with more than 12,000 participants

text: COVID-19 is a new disease with no treatment and no vaccine so far. The pandemic is still growing in many areas. Among the core measures to prevent disease spread is the use of face masks. We observed 12,588 people in five Brazilian cities within the Baixada Santista metropolitan area. Even though this is densely populated region and heavily impacted by COVID-19 with a high risk population, only 45.1% of the observed population wore in face masks in a correct way, and another 15.5% simply did not use masks at all. The remainder used masks incorrectly, which is evidence of the worst scenario of people believing that they are protected when they are not. This is among the first studies, to the best of our knowledge, that measures real life compliance with face masks during this COVID-19 pandemic. It is our conclusion that it is paramount to first control the virus before allowing people back in the streets. We should not assume that people will wear masks properly. Equally important is to instruct and sensitize people on how to use face masks and why it is important.


title: Infectious pathways of SARS-cov-2 in renal tissue

text: Coronavirus disease in 2019 (COVID-19) has spread around the world and caused significantly pandemic mobility and mortality. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) usually infects lungs first and involves other organs including kidneys subsequently. Acute kidney injury and proteinuria in patients with COVID19 are resulted from the direct infection of the spikycrowned viruses to proximal tubules and podocytes, leading to acute tubular injury and collapsing focal segmental glomerulosclerosis. Therefore treatment strategy should target against the direct infection of SARS-CoV2 to the renal tissue.


title: Mathematical estimation of COVID-19 prevalence in Latin America

text: After the rapid spread with severe consequences in Europe and China, the SARS-CoV-2 virus is now manifesting itself in more vulnerable countries, including those in Latin America. In order to guide political decision-making via epidemiological criteria, it is crucial to assess the real impact of the epidemic. However, the use of large-scale population testing is unrealistic or not feasible in some countries. Based on a newly developed mathematical model, we estimated the seroprevalence of SARS-CoV-2 in Latin American countries. The results show that the virus spreads unevenly across countries. For example, Ecuador and Brazil are the most affected countries, with approximately 3% of the infected population. Currently, the number of new infections is increasing in all countries examined, with the exception of some Caribbean countries as Cuba. Moreover, in these countries, the peak of newly infected patients has not yet been reached.


title: COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

text: Background: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods: An IRB-approved prospective registry was set up at ICH for all breast cancer patients with COVID-19 symptoms or radiologic signs. Results: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (>70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe SARS-CoV-2 infection in breast cancer patients.


title: COVID-19 outbreak in Algeria: A mathematical Model to predict cumulative cases

text: Introduction: Since December 29, 2019 a pandemic of new novel coronavirus-infected pneumonia named COVID-19 has started from Wuhan, China, has led to 254 996 confirmed cases until midday March 20, 2020. Sporadic cases have been imported worldwide, in Algeria, the first case reported on February 25, 2020 was imported from Italy, and then the epidemic has spread to other parts of the country very quickly with 139 confirmed cases until March 21, 2020. Methods: It is crucial to estimate the cases number growth in the early stages of the outbreak, to this end, we have implemented the Alg-COVID-19 Model which allows to predict the incidence and the reproduction number R0 in the coming months in order to help decision makers. The Alg-COVIS-19 Model initial equation 1, estimates the cumulative cases at t prediction time using two parameters: the reproduction number R0 and the serial interval SI. Results: We found R0=2.55 based on actual incidence at the first 25 days, using the serial interval SI= 4,4 and the prediction time t=26. The herd immunity HI estimated is HI=61%. Also, The Covid-19 incidence predicted with the Alg-COVID-19 Model fits closely the actual incidence during the first 26 days of the epidemic in Algeria Fig. 1.A. which allows us to use it.


title: Global lessons and Potential strategies in combating COVID-19 pandemic in Ethiopia:Systematic Review

text: Background: Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease that has been classified a pandemic by the World Health Organization (WHO). In the absence of treatment for this virus, there is an urgent need to find alternative public health strategies to control the spread. Here, we have conducted an online search for all relevant public health interventions for COVID-19. We then characterize and summarize the global COVID-19 pandemic situation and recommend potential mitigation strategies in the context of Ethiopia. Methods: Initial search of Pub Med central and Google scholar was undertaken followed by analysis of the text words; COVID-19,SARS-CoV-2, Global lessons and Pandemic; A second search using all identified keywords including COVID-19, Epidemiology, Sociocultural, Ethiopia; thirdly, the reference list of all identified reports and articles were searched. Accordingly, of the 1,402 articles, 39 were included in the analysis for this review. Result: Countries COVID-19 mitigation strategies widely varied. The most common global COVID-19 mitigation strategies include; whole of government approach including individual, community and environmental measures, detecting and isolating cases, contact tracing and quarantine, social and physical distancing measures including for mass gatherings and international travel measures. Models revealed that, social and physical distancing alone could prevent the pandemic from 60-95%, if timely and effectively implemented. Moreover, detecting and isolation of cases were found to be crucial while access to testing was found to the global challenge. Individual measures including proper hand washing were also reported to be effective measures in preventing the pandemic. Asymptomatic cases of COVID-19 ranged from 25% to 80% and as a result, countries are revising the case definition for early detection of mild symptomatic cases of COVID-19 with inclusion of Chills, Muscle pain and new loss of taste or smell in addition to Cough, Shortness of breath, Fever and Sore throat. Global reports also revealed that the incubation period of COVID-19 could go to 24 days. Ethiopia is also unique in the aspects of sociocultural prospects while more than 99.3% of the population has a religion. Moreover, 69% of the population is under the age of 29 years old and the health policy in the country focused on prevention and primary health care. All these could be potential entries and opportunities to combat COVID-19 pandemic in the context of Ethiopia. Conclusion: While recommendations may change depending on the level of outbreak, we conclude that in Most countries have benefited from early interventions and in setups like Africa including Ethiopia where health system capability is limited, community engagement supported by local evidence with strict implementation of social and physical distancing measures is mandatory. Active involvement of religious Institutions and mobilizing youth could be entry to increase public awareness in mitigating COVID-19. Community level case detection could enhance early identification of cases which could be implemented through the health extension program. Isolation and quarantine beyond 14 days could help identify long term carriers of COVID-19. Validation and use of rapid test kits could be vital to increase access for testing. Revision of case definitions for COVID-19 could be important for early detection and identification of mild symptomatic cases.


title: Diabetes und Schwangerschaft – Update 2020

text: In this short review, the current findings on coronoavirus disease 2019 (COVID-19) in pregnant women are presented. Self-monitoring of capillary blood glucose levels is currently the gold standard in pregnant women. When using subcutaneous glucose sensors, the time in range (TIR) of 63–140 mg/dl (3.5–7.8 mmol/l) >70% should be reached as early as possible. In pregnant women with pre-existing diabetes, there is a high risk for stillbirth in a fetus with growth restriction. In the absence of evidence for improvement of relevant endpoints, pharmacological therapies in pregnant women with early gestational diabetes at <24 + 0 weeks of gestation should be considered critically. Women who are obese prior to conception should not gain more than 6 kg during pregnancy. In women who have undergone bariatric-metabolic surgery, there are advantages for the mothers and increased risks for newborns, e.g., an increased rate of newborns small for gestational age after Roux-en‑Y gastric bypass.


COVID-19: Prepare for Care Rationing—Know Your Hospital Policies


Shared voices of Filipino occupational therapists during the COVID-19 pandemic: reflections from an online forum


title: Balancing Service and Safety: Cardiovascular Medicine Divisional Response to the COVID-19 Pandemic

text: Abstract The COVID-19 pandemic highlights the critical need for preparation and innovation against a developing major healthcare challenge We review our cardiology division’s response at our tertiary hospital center below, paying special emphasis to a practical operational workflow achievable by most cardiac centers across the globe


Factors Associated with Mental Health Outcomes in Oman during COVID19: Frontline vs Non-frontline Healthcare Workers


title: Clinical, Radiological and Therapeutic Characteristics of Patients with COVID-19 in Saudi Arabia

text: BACKGROUND Coronavirus disease 2019 (COVID-19) is a rapidly spreading global pandemic. The clinical characteristics of COVID-19 has been reported; however, there are limited researches that investigated the clinical characteristics of COVID-19 in the Middle East. The aim of this study is to investigate the clinical, radiological and therapeutic characteristics of patients diagnosed with COVID19 in Saudi Arabia. METHODS This study is a retrospective single-centre case series study. We extracted data for patients who were admitted to the Al-Noor Specialist hospital with a PCR confirmed SARS-COV-2 between 12th and 31st of March 2020. Descriptive statistics were used to describe patients characteristics. Continuous data were reported as mean (SD). Chi-squared test/Fisher test were used as appropriate to compare proportions for categorical variables. RESULTS A total of 150 patients were hospitalised for COVID-19 during the study period. The mean age was 46.1 years (SD: 15.3 years). Around 61.0% (n= 90) were males and six patients (3.9%) reported working in the healthcare sector. The most common comorbidities were hypertension (28.8%, n= 42) and diabetes mellitus (26.0%, n= 38). The majority of the patients, 64.4% (n = 96) had a recent contact history with a COVID patient. Regarding the severity of the hospitalised patients, 105 patients (70.0%) were mild, 29 (19.3%) were moderate, and 16 patients (10.7%) were severe or required ICU care. From the 105 mild patients, around 31.3% (n= 47) were asymptomatic. CONCLUSION This case series provides clinical, radiological and therapeutic characteristics of hospitalised patients with confirmed COVID-19 in Saudi Arabia.


title: Estimation of Undetected Covid-19 Infections in India

text: Background and Objectives: While the number of detected COVID-19 infections are widely available, an understanding of the extent of undetected COVID- 19 cases is urgently needed for an effective tackling of the pandemic and as a guide to lifting the lockdown. The aim of this work is to estimate and predict the true number of COVID-19 (detected and undetected) infections in India for short to medium forecast horizons. In particular, using publicly available COVID-19 infection data upto 16th April 2020, we predict the true number of infections in India during and upto the end of the formal lockdown period (21st April 2020). Methods: The high death rate observed in most COVID-19 hit countries is suspected to be a function of the undetected infections existing in the population. An estimate of the age weighted infection fatality rate (IFR) of the disease of 0.41%, specifically calculated by taking into account the age structure of Indian population, is already available in the literature. In addition, the recorded case fatality rate (CFR= 0.70%) of Kerala, the only state in India to report single digit new infections over the second week of April, is used as a second estimate of the IFR. These estimates are used to formulate a relationship between deaths recorded and the true number of infections. The estimated undetected and detected cases time series based on these two IFR estimates are then used to fit a discrete time multivariate infection model to predict the total infections at the end of the formal lockdown period. Results: In two consecutive fortnights during the lockdown, it was noted that the rise in detected infections has decreased by 2.7 times. For an IFR of 0.41%, the rise in undetected infections decreased by 3.2 times and the predicted number of total infections in India is 3.14 lakhs. While for an IFR of 0.70%, the rise in undetected cases decreased by 3.3 times and the total number of infections predicted on 21st April is 1.75 lakhs. Interpretation and Conclusions: The behaviour of the undetected cases over time effectively illustrates the effects of lockdown and increased testing. From our estimates, it is found that the lockdown has brought down the undetected to detected cases ratio, and has consequently dampened the increase in the number of total cases. However, even though the rate of rise in total infections has fallen, the lifting of the lockdown should be done keeping in mind that 1.75 to 3 lakhs undetected cases will already exist in the population on 21st April.


title: Molecular Evolution of SARS-CoV-2 Structural Genes: Evidence of Positive Selection in Spike Glycoprotein

text: SARS-CoV-2 caused a global pandemic in early 2020 and has resulted in more than 8,000,000 infections as well as 430,000 deaths in the world so far. Four structural proteins, envelope (E), membrane (M), nucleocapsid (N) and spike (S) glycoprotein, play a key role in controlling the entry into human cells and virion assembly of SARS-CoV-2. However, how these genes evolve during its human to human transmission is largely unknown. In this study, we screened and analyzed roughly 3090 SARS-CoV-2 isolates from GenBank database. The distribution of the four gene alleles is determined:16 for E, 40 for M, 131 for N and 173 for S genes. Phylogenetic analysis shows that global SARS-CoV-2 isolates can be clustered into three to four major clades based on the protein sequences of these genes. Intragenic recombination event isn’t detected among different alleles. However, purifying selection has conducted on the evolution of these genes. By analyzing full genomic sequences of these alleles using codon-substitution models (M8, M3 and M2a) and likelihood ratio tests (LRTs) of codeML package, it reveals that codon 614 of S glycoprotein has subjected to strong positive selection pressure and a persistent D614G mutation is identified. The definitive positive selection of D614G mutation is further confirmed by internal fixed effects likelihood (IFEL) and Evolutionary Fingerprinting methods implemented in Hyphy package. In addition, another potential positive selection site at codon 5 in the signal sequence of the S protein is also identified. The allele containing D614G mutation has undergone significant expansion during SARS-CoV-2 global pandemic, implying a better adaptability of isolates with the mutation. However, L5F allele expansion is relatively restricted. The D614G mutation is located at the subdomain 2 (SD2) of C-terminal portion (CTP) of the S1 subunit. Protein structural modeling shows that the D614G mutation may cause the disruption of salt bridge among S protein monomers increase their flexibility, and in turn promote receptor binding domain (RBD) opening, virus attachment and entry into host cells. Located at the signal sequence of S protein as it is, L5F mutation may facilitate the protein folding, assembly, and secretion of the virus. This is the first evidence of positive Darwinian selection in the spike gene of SARS-CoV-2, which contributes to a better understanding of the adaptive mechanism of this virus and help to provide insights for developing novel therapeutic approaches as well as effective vaccines by targeting on mutation sites.


Coronavirus Disease 2019 and Influenza 2019-2020


title: Changes in Reproductive Rate of SARS-CoV-2 Due to Non-pharmaceutical Interventions in 1,417 U.S. Counties

text: In response to the rapid spread of the novel coronavirus, SARS-CoV-2, the U.S. has largely delegated implementation of non-pharmaceutical interventions (NPIs) to local governments on the state and county level. This staggered implementation combined with the heterogeneity of the U.S. complicates quantification the effect of NPIs on the reproductive rate of SARS-CoV-2. We describe a data-driven approach to quantify the effect of NPIs that relies on county-level similarities to specialize a Bayesian hierarchical inference model based on observed fatalities. Using this approach, we estimate change in reproductive rate, Rt, due to implementation of NPIs in 1,417 U.S. counties. We estimate that as of May 28th, 2020 1,177 out of the considered 1,417 U.S. counties have reduced the reproductive rate of SARS-CoV-2 to below 1.0. The estimated effect of any individual NPI, however, is different across counties. Stay-at-home orders were estimated as the only effective NPI in metropolitan and urban counties, while advisory NPIs were estimated to be effective in more rural counties. The expected level of infection predicted by the model ranges from 0 to 28.7% and is far from herd immunity even in counties with advanced spread. Our results suggest that county characteristics are pertinent to re-opening decisions.


title: Stroke increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs

text: Background The newly emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke are particularly susceptible to severe courses of SARS-CoV-2 infection, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke induce lymphocytopenia and systemic inflammation that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation following stroke can specifically modulate ACE2 expression in the lung has not been investigated. Methods Mice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1β were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry. Results Strikingly, 24 h after stroke, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1β in the lungs. Higher gene expression of cytokines IL-6 and IL-1β was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood and spleen as an indicator of sterile tissue injury-induced immunosuppression. Conclusions We demonstrate significantly augmented ACE2 levels and inflammation in murine lungs after experimental stroke. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke represent a high-risk group for the development of severe SARS-CoV-2 infections. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions. Highlights Brain tissue injury increases ACE2 levels in the lungs Brain injury induces pro-inflammatory cytokine expression in the lungs Brain injury causes parenchymal inflammation and systemic lymphopenia


title: A Tale of Three Fixatives: Detection of Middle East Respiratory Syndrome Coronavirus in Paraffin-Embedded Tissues Preserved in Three Fixatives

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen endemic to dromedary camels known to cause a respiratory illness in humans that is fatal in 35% of cases As such, inactivated tissues provide a safer format when testing for this virus Neutral buffered formalin (NBF), pathology?s gold standard for tissue fixation, preserves histomorphology and inactivates many pathogens However, NBF causes the crosslinking and fragmentation of proteins and nucleic acids in tissues This results in a rapid decline in biomolecular quality after just 24 hours and damage increases thereafter NBF is also a volatile organic compound and carcinogen Two novel fixatives, phosphate-buffered 70% ethanol (BE70) and BE70 with added guanidium salts (BE70G), are alternative preservatives that cause less damage to biomolecules, even in tissues immersed for longer than 3 months These ethanol (EtOH)-based fixatives have equivalent histomorphology and inactivation profiles as well as better human safety profiles We hypothesized that existing anti-MERS-CoV immunohistochemistry (IHC) and in situ hybridization (ISH) protocols would work on tissues preserved with these EtOH-based fixatives Roughly equivalent tracheal and nasal turbinate samples from eight alpacas experimentally infected with MERS-CoV were fixed in 10% NBF, BE70, and BE70G, processed into paraffin and sectioned for hematoxylin and eosin staining or immunolabeling Anti-MERS-CoV nucleocapsid IHC using polymer-based detection and MERS-CoV specific ISH using RNAscope? 2 5 HD brown detection were conducted on all samples Because many EtOH-based fixatives do not require antigen retrieval (AR), ISH and IHC were run with and without AR on the EtOH-based fixed tissues Although MERS-CoV IHC and ISH appropriately labeled target molecules in all samples, signal strength varied across the fixatives The strongest labeling was seen in NBF, followed by BE70G, and finally BE70 This result was not unexpected as the protocols were optimized for use with NBF tissues Interestingly, both BE70 and BE70G required AR to successfully visualize the targets by both IHC and ISH, although BE70G did have weak ISH signal without AR Histomorphology for all three fixatives without AR was very similar However, AR blurred cell borders and reduced overall cellular definition in the EtOH-based fixed samples, particularly BE70G Taken together, these results support the use of these novel EtOH-based fixatives as alternatives to NBF, particularly when biomolecule preservation for downstream molecular biology assays is critical Finally, BE70 and BE70G increase human safety by inactivating pathogens with less harmful chemicals as well as provide a more flexible fixation time frame This is particularly useful for high containment work as it would allow safe transfer of inactivated tissues to lower biosafety level labs while better preserving the samples for downstream analysis Support or Funding Information This work was funded by the Department of Diagnostic Medicine, College of Veterinary Medicine, Kansas State University and the USDA APHIS NBAF Scientist Training Program Histomorphology, Immunohistochemistry (IHC), and In Situ Hybridization (ISH) of NBF-, BE70-, and BE70G-Fixed Tissues Column 1 is hematoxylin and eosin staining, Column 2 is anti-MERS-CoV nucleocapsid IHC, and Column 3 is MERS-CoV-specific ISH in fixed, paraffin-embedded nasal turbinates All immunolabeled tissues were counterstained with hematoxylin Row 1 is NBF-fixed tissue Row 2 is BE70-fixed tissue Row 3 is BE70G-fixed tissue The bar for all main images is 100 microns


title: Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP

text: Cancer cells initiate an innate immune response by synthesizing and exporting the small molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. An extracellular enzyme, ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), hydrolyzes cGAMP and negatively regulates this anti-cancer immune response. Small molecule ENPP1 inhibitors are much needed as tools to study basic biology of extracellular cGAMP and as investigational cancer immunotherapy drugs. Here, we surveyed structure-activity relationships around a series of cell-impermeable and thus extracellular-targeting phosphonate inhibitors of ENPP1. Additionally, we solved the crystal structure of an exemplary phosphonate inhibitor to elucidate the interactions that drive potency. This study yielded several best-in-class compounds with Ki < 2 nM and excellent physicochemical and pharmacokinetic properties. Finally, we demonstrate that an ENPP1 inhibitor delays tumor growth in a breast cancer mouse model. Together, we have developed ENPP1 inhibitors that are excellent tool compounds and potential therapeutics.


When the virus makes the timeline


title: Evolution of resistance to fluoroquinolones by dengue virus serotype 4 provides insight into mechanism of action and consequences for viral fitness

text: Drugs against flaviviruses such as dengue (DENV) and Zika (ZIKV) virus are urgently needed. We previously demonstrated that three fluoroquinolones, ciprofloxacin, enoxacin, and difloxacin, suppress replication of six flaviviruses. To investigate the barrier to resistance and mechanism(s) of action of these drugs, DENV-4 was passaged in triplicate in HEK-293 cells in the presence or absence of each drug. Resistance to ciprofloxacin was detected by the seventh passage and to difloxacin by the tenth, whereas resistance to enoxacin did not occur within ten passages. Two putative resistance-conferring mutations were detected in the envelope gene of ciprofloxacin and difloxacin-resistant DENV-4. In the absence of ciprofloxacin, ciprofloxacin-resistant viruses sustained a significantly higher viral titer than control viruses in HEK-293 and HuH-7 cells and resistant viruses were more stable than control viruses at 37°C. These results suggest that the mechanism of action of ciprofloxacin and difloxacin involves interference with virus binding or entry.


Possible factors associated with low case fatality rate of covid-19 in Kurdistan Region, Iraq


title: Who do not wash their hands during the Covid-19 pandemic? Social media use as a potential predictor

text: This study predicts handwashing behavior during the Covid-19 pandemic. An analysis of 674 adults in Malaysia identifies their time spent on social media per day as a key predictor of handwashing. The association between time spent on social media and handwashing also depends on gender and the number of children in the same household. Additional predictors include age and health condition. This study helps identify specific target groups for health communication on hand hygiene via individual use of social media, which can be a key channel for health communication campaigns during a pandemic.


title: Covid-19 health care demand and mortality in Sweden in response to non-pharmaceutical (NPIs) mitigation and suppression scenarios

text: While the outbreak in China is now contained, since mid March 2020, the epicentre of the COVID-19 pandemic is in Europe, with Italy reporting more deaths than China. Various European countries have seen an exponential growth in daily new cases, and unless strong reductions in transmission, the wave is expected to hit all of Europe by the end of March 2020. There is an urgent need to reduce transmission and thus reduce the growth rate of this epidemic, reduce the height of the epidemic peak and the peak demand on healthcare services, as well as reduce the total number of infected persons. Here we estimate the impact of COVID-19 on the Swedish population at the municipality level, considering demography and human mobility under scenarios of mitigation and suppression. We estimate the timelines of incidence, hospitalization rates, the intensive care (ICU) need, and the mortality in relation to the current Swedish ICU capacity, and costs of care. We further investigate the sensitivity to various degrees of potential underreporting on the estimates.


title: Estimating effectiveness of preventing measures for 2019 novel coronavirus diseases (COVID-19)

text: This paper implements the infection process of 2019 Novel Coronavirus Diseases (COVID-19) in an agent-based model and compares the effectiveness of multiple infection prevention measures. In the model, 1120 virtual residents agents live in two towns where they commute to office or school and visiting stores. The model simulates an infection process in which they were exposed to the risk of transmission of the novel coronavirus. The results of the experiments showed that individual infection prevention measures (commuting, teleworking, class closing, contact rate reduction, staying at home after fever) alone or partially combined them do not produce significant effects. On the other hand, if comprehensive measures were taken, it was confirmed that the number of deaths, the infection rate, and the number of severe hospitalised patients per day were decreased significantly at the median and maximum respectively.


title: Analysis and Applications of Adaptive Group Testing Methods for COVID-19

text: Abstract Testing strategies for Covid-19 to maximize number of people tested is urgently needed. Recently, it has been demonstrated that RT-PCR has the sensitivity to detect one positive case in a mixed sample 32 cases [9]. In this paper we propose non-adaptive and adaptive group testing strategies based on generalized binary splitting (GBS) [2] where we restrict the group test to the largest group that can be used. The method starts by choosing a group from the population to be tested, performing a test on the combined sample from the entire group and progressively splitting the group further into subgroups. Compared to individual testing at 4% prevalence we save 74% at 1% we save 91% and at 1% we save 97% of tests. We analyze the number of times each sample is used and show the method is still efficient if we resort to testing a case individually if the sample is running low. Abstract In addition we recommend clinical screening to filter out individuals with symptoms and show this leaves us with a population with lower prevalence. Our approach is particularly applicable to vulnerable confined populations such as nursing homes, prisons, military ships and cruise ships.


title: Smoking and the risk of COVID-19 in a large observational population study

text: BACKGROUND Smokers are generally more susceptible to infectious respiratory diseases and are at higher risk of developing severe complications from these infections. Conflicting reports exist regarding the impact of smoking on the risk of Coronavirus disease 2019 (COVID-19) infection. METHODS We carried out a population-based study among over 3,000,000 adult members of Clalit Health Services, the largest health provider in Israel. Since the beginning of the disease outbreak, 114,545 individuals underwent RT-PCR testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and 4.0% had positive results. We performed a case-control study among patients who underwent SARS-CoV-2 testing, to assess the impact of smoking on infection incidence and severity. Individuals with positive tests were matched in a 1:5 ratio to individuals tested negative, of the same sex, age, and ethnicity/religion. Conditional logistic regressions were performed to evaluate odds ratios for current and previous smoking on the risk of testing positive. Multivariable logistic regressions were performed among patients infected with COVID-19 to estimate the association between smoking and fatal or severe disease requiring ventilation. Regressions were performed with and without adjustment for preexisting medical conditions. RESULTS In the matched cohort, current smokers (9.8%) were significantly less prevalent among members tested positive compared to the general population, and to matched members tested negative (19.4%, P<0.001). Current smoking was associated with significantly reduced odds ratio (OR) for testing positive OR=0.457 (95% confidence interval (CI) 0.407-0.514). Among patients tested positive, there was no evidence of significantly increased risk of developing severe or fatal disease. CONCLUSION The risk of infection by COVID-19 appears to be reduced by half among current smokers. This intriguing finding may reveal unique infection mechanisms present for COVID-19 which may be targeted to combat the disease and reduce its infection rate.


title: A model of COVID-19 propagation based on a gamma subordinated negative binomial branching process: A tool for decision making with small populations

text: We build a parsimonious Crump-Mode-Jagers continuous time branching process of COVID-19 propagation based on a negative binomial process subordinated by a gamma subordinator. By focusing on the stochastic nature of the process in small populations, our model provides decision making insight into mitigation strategies as an outbreak begins. Our model accommodates contact tracing and isolation, allowing for comparisons between different types of intervention. We emphasize a physical interpretation of the disease propagation throughout which affords analytical results for comparison to simulations. Our model provides a basis for decision makers to understand the likely trade-offs and consequences between alternative outbreak mitigation strategies particularly in office environments and confined work-spaces.


Aus Daten lernen?


Can We Utilize Existing Cancer-Related Therapies to Help COVID-19 Patients?


title: Clinical characteristics of 106 patients with neurological diseases and co-morbid coronavirus disease 2019: a retrospective study

text: Objectives:To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with co-morbid neurological symptoms. Design:Retrospective case series. Setting:Huoshenshan Hospital in Wuhan, China. Participants:From 4 February to 14 April 2020, 106 patients with neurological diseases were enrolled from all patients in the hospital with confirmed COVID-19 and divided into a severe group and a nonsevere group according to their COVID-19 diagnosis. Main outcome measures:Clinical characteristics, laboratory results, imaging findings, and treatment methods were all retrieved through an electronic medical records system and recorded in spreadsheets. Results:The mean (standard deviation, SD) age of patients was 72.7 (11.8) years, and 64 patients were male (60.4%). Among patients with co-morbid neurological diseases, 81 had a previous cerebral infarction (76.4%), 20 had dementia (18.9%), 10 had acute cerebral infarction (9.4%), 5 had sequelae of cerebral haemorrhage (4.7%), 4 had intracranial mass lesions (3.8%), 3 had epilepsy (2.8%), 2 had Parkinsons disease (1.9%), and 1 had myelopathy (0.9%). Fever (n = 62, 58.5%) was the most common symptom. The most common neurological symptoms were myalgia (n = 26, 24.5%), followed by extremity paralysis (n = 20, 18.9%), impaired consciousness (n = 17, 16%), and positive focal neurological signs (n = 42, 39.6%). Eight patients (7.5%) died. There were more patients with altered mental status in the severe group than in the non-severe group (6 [10.2%] vs. 0, P = 0.033). The inflammatory response in the severe group was more significant than that in the non-severe group. There were more patients taking anticoagulant drugs (25 [42.4%] vs. 4 [8.5%], P < 0.001) and sedative drugs (22 [37.3%] vs. 9 [19.1%], P = 0.041) in the severe group than in the non-severe group. Amid all 93 patients with cerebrovascular diseases, only 32 (34.4%) were taking aspirin, 13 (14%) taking clopidogrel, and 33 (35.5%) taking statins. Conclusions:Patients with COVID-19 with co-morbid neurological diseases had an advanced age, a high rate of severe illness, and a high mortality rate. Among the neurological symptoms, altered mental status was more common in patients with severe COVID-19 with co-morbid neurological diseases.


title: Feeling Positive About Reopening?New Normal Scenarios from COVID-19 ReopenSentiment Analytics

text: The Coronavirus pandemic has created complex challenges and adverse circumstances. This research identifies public sentiment amidst problematic socioeconomic consequences of the lockdown, and explores ensuing four potential sentiment associated scenarios. The severity and brutality of COVID-19 have led to the development of extreme feelings, and emotional and mental healthcare challenges. This research focuses on emotional consequences - the presence of extreme fear, confusion and volatile sentiments, mixed along with trust and anticipation. It is necessary to gauge dominant public sentiment trends for effective decisions and policies. This study analyzes public sentiment using Twitter Data, time-aligned to the COVID-19 reopening debate, to identify dominant sentiment trends associated with the push to 'reopen' the economy. Present research uses textual analytics methodologies to analyze public sentiment support for two potential divergent scenarios - an early opening and a delayed opening, and consequences of each. Present research concludes on the basis of exploratory textual analytics and textual data visualization, that Tweets data from American Twitter users shows more positive sentiment support, than negative, for reopening the US economy. This research develops a novel sentiment polarity based four scenarios framework, which will remain useful for future crisis analysis, well beyond COVID-19. With additional validation, this research stream could present valuable time sensitive opportunities for state governments, the federal government, corporations and societal leaders to guide local and regional communities, and the nation into a successful new normal future.


title: MODELING COVID19 IN INDIA (MAR 3 - MAY 7, 2020): HOW FLAT IS FLAT, AND OTHER HARD FACTS

text: A time-series model was developed for Number of Total Infected Cases in India, using data from Mar 3 to May 7, 2020. Two models developed in the early phases were discarded when they lost statistical validity, The third, current, model is a 3rd-degree polynomial that has remained stable over the last 30 days (since Apr 8), with R2 > 0.998 consistently. This model is used to forecast Total Covid cases, after cautionary discussion of triggers that would invalidate the model. The purpose of all forecasts in the study is to provide a comparator to evaluate policy initiatives to control the pandemic: the forecasts are not objectives by themselves. Actual observations less than forecasts mean successful policy interventions. Figures of Doubling Time, Fatality Rate and Recovery Rate used by authorities are questioned. Elongation of doubling rates is inherent in the model, and worthy of mention only when the time actually exceeds what the model predicts. The popular Fatality Rate and Recovery Rate metrics are shown to be illogical. The study defines two terms Ongoing Fatality Rate (OFR), and Ongoing Recovery Rate (ORR) and determines these currently to be ~9% and ~76% respectively in India. Over time, OFR will decline to the eventual Case Fatality Rate (CFR), while ORR will eventually climb to (1-CFR). There is no statistical basis to assume eventual Indian CFR, and 5.5% CFR at China is used as a proxy. Using these metrics, the current model forecasts by May-end, >150000 Total Infected, [~]5000 Deaths and >85000 Active Cases. There is no pull-back evident in the current model in the foreseeable future, and cases continue to rise at progressively slower rates. Subject to usual caveats, the model is used to forecast till Sep 15. The study argues that Indian hospital infrastructure is reasonably ready to handle Active Cases as predicted for Sept 15: in that sense, the curve is FLAT ENOUGH. However, the curve is NOT flat enough with respect to fatalities: nearly 100000 by Sept 15. Setting an arbitrary limit that Total Deaths must be within 50,000 by Sept 15, the study retrofits a model that shows what the desired growth of Covid19 cases should be. It is seen that overall doubling time of 38 days is required in period June 1 to Sep 15, if deaths are to remain below 50000.


title: ‘We are doing better’: Biopolitical nationalism and the COVID-19 virus in East Asia

text: The COVID-19 pandemic stirs up strong nationalist and localist sentiments; places pride themselves on containing the virus more effectively: We are doing better. We call this ‘biopolitical nationalism’, understood by us as the dynamics between body, geopolitics and affect. When looking at mainland China, Taiwan and Hong Kong, we analyse how the biopolitical efforts of these places are being compared, applauded and supported. Under a discourse of life and survival, this celebration of biopolitical control does not fall into the classic reproduction of capital, but speaks to geopolitical identification. Biopolitics has morphed into a field of competition, of rivalry, of nationalistic – or, perhaps more generally, localist – power games. What can we do as Cultural Studies scholars?


title: The production of antibodies for SARS-CoV-2 and its clinical implication

text: Background: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge. Methods: Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method. Findings: The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%34.48%) for IgG and 23.05% (IQR, -27.96%46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets. Interpretation: The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated.


title: SARS-CoV-2 serological testing using electrochemiluminescence reveals arapid onset of seroconversion in severe COVID-19 patients

text: Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. We report the development of a rapid, highly specific and sensitive electrochemiluminescent assay for detecting IgM, IgA, and IgG antibodies toward two distinct SARS-CoV-2 antigens namely, the receptor binding domain (RBD) and the nuclear protein (NP). Whereas IgM antibodies toward RBD were detected at early stages of the disease, IgM antibodies against NP did not develop. Analysis of the antibody response in mild versus moderate/severe patients revealed a rapid onset of IgG and IgA antibodies, specifically in moderate/severe patients. Finally, we observed a marked reduction in IgM/IgA antibodies and to lesser extent, IgG, over time. We provide a comprehensive analysis of the human antibody response, and has major implications on our understanding and monitoring of SARS-CoV-2 infections, as well as finding effective vaccines.


title: CAS curates data set of antiviral compounds

text: To help accelerate the development of antiviral therapies against COVID-19, CAS, a division of the American Chemical Society, has curated a data set of nearly 50,000 chemical substances with known or potential antiviral activity that could serve as potential leads The data set, which CAS has made publicly available through open access, was curated from the CAS Registry of more than 160 million chemical substances “We have this wealth of knowledge that we’re sitting on—these databases in science that we’ve built for the last 113 years—and we want to open up key parts of it to help accelerate treatments and/or vaccines to COVID-19,” says Michael Dennis, vice president for innovation at CAS Dennis says the idea for this data set came out of two tables in a recent publication by CAS in ACS Central Science that included antiviral and small molecules with potential therapeutic applications against COVID-19 (DOI: 10 1021/acscentsci 0c00272) The article has already received more than 200,000 views, and CAS wanted to expand this resource


docid: dwyqrdzx

title: COVID-19 and cancer: The bad and the ugly

text: Patients with cancer are more vulnerable to COVID-19 infection with higher risk of severe symptoms and death


title: Empirical non-linear modeling & forecast of global daily deaths of COVID-19 pandemic & evidence that a third wave is beginning to decay

text: Objectives: The present COVID-19 pandemic (C19P) is challenging our socities all over the world. In this work, based on massive health information daily updated, the C19P daily death numbers at a global level, are modelled, analyzed and forecasted. Methods: Two empirical models are proposed to explain daily death (DD) records: a) self-similar (SS) recurrences of the global responses, and b) geometric averaging of two independent SS models for global DD records. Findings: The detected self-similar recurrences in the global response suggest three global self-similar waves that support multi-month forecasts of the DD numbers. However, there are upper and lower-limit SS forecast DD scenarios that were jointly integrated with a geometrical average (GA) model, that support the existence of a moderated third wave, with a decaying stage for the next months (July-September 2020). It appears that the third world (South America [SAM]+Asia [ASI] +Africa [AFR]), is the actual big player, (following China, and Europe [EUR]+North America [NAM]) with its biggest contribution to a global third wave (W3) of C19P. Conclusion: The empirical global modeling of the C19P has suggested us a possible moderated W3 scenario, with contributions mainly coming from the third world people. This moderated W3 scenario, after to be calibrated with the last weeks, has provided to stakeholders of significant data and criteria to define, sustain and support plans for the next months, based on data and self-similarities. These scenarios provide a well-based perspective on non-linear dynamics of C19P, that will complement the standard health and economic models.


docid: jtszdioh

title: ACE2 Homo-dimerization, Human Genomic variants and Interaction of Host Proteins Explain High Population Specific Differences in Outcomes of COVID19

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive single-stranded RNA virus that causes a highly contagious Corona Virus Disease (COVID19). Entry of SARS-CoV-2 in human cells depends on binding of the viral spike (S) proteins to cellular receptor Angiotensin-converting enzyme 2 (ACE2) and on S-protein priming by host cell serine protease TMPRSS2. Recently, COVID19 has been declared pandemic by World Health Organization (WHO) yet high differences in disease outcomes across countries have been seen. We provide evidences to explain these population-level differences. One of the key factors of entry of the virus in host cells presumably is because of differential interaction of viral proteins with host cell proteins due to different genetic backgrounds. Based on our findings, we conclude that a higher expression of ACE2 is facilitated by natural variations, acting as Expression quantitative trait loci (eQTLs), with different frequencies in different populations. We suggest that high expression of ACE2 results in homo-dimerization, proving disadvantageous for TMPRSS2 mediated cleavage of ACE2; whereas, the monomeric ACE2 has higher preferential binding with SARS-CoV-2 S-Protein vis-a-vis its dimerized counterpart. Further, eQTLs in TMPRSS2 and natural structural variations in the gene may also result in differential outcomes towards priming of viral S-protein, a critical step for entry of the Virus in host cells. In addition, we suggest that several key host genes, like SLC6A19, ADAM17, RPS6, HNRNPA1, SUMO1, NACA, BTF3 and some other proteases as Cathepsins, might have a critical role. To conclude, understanding population specific differences in these genes may help in developing appropriate management strategies for COVID19 with better therapeutic interventions.


docid: tiixwaqi

title: What Has the COVID-19 Pandemic Taught Us so Far? Addressing the Problem from a Hepatologist’s Perspective


title: The inhibitory effect of a Corona virus spike protein fragment with ACE2

text: In this paper, we investigate the molecular assembly processes of a Coronavirus Spike protein fragment, the hexapeptide YKYRYL on the ACE2 receptor and its inhibitory effect on the aggregation and activation of the CoV-2 spike receptor protein at the same receptor protein. In agreement with an experimental study, we find a high affinity of the hexapeptide to the binding interface between the spike receptor protein and ACE2, which we investigate using 20 independent equilibrium MD simulations over a total of 1 μs and a 200 ns enhanced MD simulation. We then evaluate the effect of the hexapeptide on the aggregation process of the spike receptor protein to ACE2 in long-time enhanced MD simulations. In that set of simulations, we find that the spike receptor protein does not bind to ACE2 with the binding motif shown in experiments, but it rotates due to an electrostatic repulsion and forms a hydrophobic interface with ACE2. Surprisingly, we observe that the hexapeptide binds to the spike receptor domain, which has the effect that this protein only weakly attaches to ACE2, so that the activation of the spike protein receptor might be inhibited in this case. Our results indicate that the hexapeptide might be a possible treatment option which prevents the viral activation through the inhibition of the interaction between ACE2 and the spike receptor protein. SIGNIFICANCE A novel coronavirus, CoV-19 and a later phenotype CoV-2 were identified as primary cause for a severe acute respiratory syndrome (SARS CoV-2). The spike (S) protein of CoV-2 is one target for the development of a vaccine to prevent the viral entry into human cells. The inhibition of the direct interaction between ACE2 and the S-protein could provides a suitable strategy to prevent the membrane fusion of CoV-2 and the viral entry into human cells. Using MD simulations, we investigate the assembly process of a Coronavirus Spike protein fragment, the hexapeptide YKYRYL on the ACE2 receptor and its inhibitzory effect on the aggregation and activation of the CoV-2 spike receptor protein at the same receptor protein.


title: Recommendations for sample pooling on the Cepheid GeneXpert® system using the Cepheid Xpert® Xpress SARS-CoV-2 assay

text: The coronavirus disease 2019 (Covid-19) pandemic, caused by SARS-CoV-2, has resulted in a global testing supply shortage. In response, pooled testing has emerged as a promising strategy that can immediately increase testing capacity. Here, we provide support for the adoption of sample pooling with the point-of-care Cepheid Xpert® Xpress SARS-CoV-2 molecular assay. Corroborating previous findings, the Xpert® Xpress SARS-CoV-2 assay limit of detection was comparable to central laboratory reverse-transcription quantitative PCR tests with observed SARS-CoV-2 detection below 100 copies/mL. The Xpert® Xpress assay detected SARS-CoV-2 after samples with minimum viral loads of 461 copies/mL were diluted into six sample pools. Based on these data, we recommend the adoption of pooled testing with the Xpert® Xpress SARS-CoV-2 assay where warranted by population public health needs. The suggested number of samples per pool, or pooling depth, is unique for each point-of-care test site and should be determined by assessing positive test rates. To statistically determine appropriate pooling depth, we have calculated the pooling efficiency for numerous combinations of pool sizes and test rates. This information is included as a supplemental dataset that we encourage public health authorities to use as a guide to make recommendations that will maximize testing capacity and resource conservation.


title: Sense of community responsibility at the forefront of crisis management

text: The COVID-19 pandemic has made it clear that a sense of community responsibility is crucial to mitigate the effects of viral spread. Many citizens across the world have heeded the call to isolate and self-distance, yet large numbers of individuals do not seem to understand their responsibility for others. This article explores how a sense of community responsibility is born in community contexts, how various features of a crisis impact community responsibility, and how public administration plays a crucial role in facilitating mitigation and solutions to crisis. The article also explores the utility of the Community Experience Model in crisis management contexts, and sets the stage for further exploration of community experiences in disaster and crisis scholarship and practice.


title: Clinical and pathological characteristics of 2019 novel coronavirus disease (COVID-19): a systematic review

text: Importance: In 2002-2003, a severe pulmonary infectious disease occurred in Guangdong, China. The disease was caused by SARS-CoV, 17 years apart, also happen in China, and SARS-CoV-2, this epidemic has posed a significant hazard to people health both China and the whole world. Objective: Summarized the latest epidemiological changes, clinical manifestations, auxiliary examination and pathological characteristics of COVID-19. Evidence Review: PubMed database were searched from 2019 to 2020 using the index terms novel coronavirus or COVID-19 or 2019-nCoV or SARS-CoV-2 and synonyms. Articles that reported clinical characteristics, laboratory results, imageological diagnosis and pathologic condition were included and were retrospectively reviewed for these cases. This paper adopts the method of descriptive statistics. Results: 34 COVID-19-related articles were eligible for this systematic review;Four of the articles were related to pathology. We found that Fever (86.0%), cough (63.9%) and Malaise/Fatigue (34.7%) were the most common symptoms in COVID-19. But in general, the clinical symptoms and signs of COVID-19 were not obvious. Compared with SARS, COVID-19 was transmitted in a more diverse way. The mortality rates of COVID-19 were 2.5%, and the overall infection rate of healthcare worker of COVID-19 was 3.9%. We also found that the pathological features of COVID-19 have greatly similar with SARS, which manifested as ARDS. But the latest pathological examination of COVID-19 revealed the obvious mucinous secretions in the lungs. Interpretation: The clinical and pathological characteristics of SARS and COVID-19 in China are very similar, but also difference. The latest finds of pathological examination on COVID-19 may upend existing treatment schemes, so the early recognition of disease by healthcare worker is very important.


title: Meaningful life in the time of Corona-economics

text: The COVID-19 pandemic offers an opportunity to think more deeply about who and what we value in society, with value determined not on conditions set by capital but instead on achieving meaning in life. In this commentary, we pose a series of interconnected questions to geography: What does it mean to live a meaningful life? Furthermore, is such a life possible under capitalism? And what does a society that prioritizes meaningful life look like?


title: AutoTriage - An Open Source Edge Computing Raspberry Pi-based Clinical Screening System

text: With the recent COVID-19 pandemic, healthcare systems all over the world are struggling to manage the massive increase in emergency department (ED) visits. This has put an enormous demand on medical professionals. Increased wait times in the ED increases the risk of infection transmission. In this work we present an open-source, low cost, off-body system to assist in the automatic triage of patients in the ED based on widely available hardware. The system initially focuses on two symptoms of the infection - fever and cyanosis. The use of visible and far-infrared cameras allows for rapid assessment at a 1m distance, thus reducing the load on medical staff and lowering the risk of spreading the infection within hospitals. Its utility can be extended to a general clinical setting in non-emergency times as well to reduce wait time, channel the time and effort of healthcare professionals to more critical tasks and also prioritize severe cases. Our system consists of a Raspberry Pi 4, a Google Coral USB accelerator, a Raspberry Pi Camera v2 and a FLIR Lepton 3.5 Radiometry Long-Wave Infrared Camera with an associated IO module. Algorithms running in real-time detect the presence and body parts of individual(s) in view, and segments out the forehead and lip regions using PoseNet. The temperature of the forehead-eye area is estimated from the infrared camera image and cyanosis is assessed from the image of the lips in the visible spectrum. In our preliminary experiments, an accuracy of 97% was achieved for detecting fever and 77% for the detection of cyanosis, with a sensitivity of 91% and area under the receiver operating characteristic curve of 0.91. Although preliminary results are promising, we note that the entire system needs to be optimized before use and assessed for efficacy. The use of low-cost instrumentation will not produce temperature readings and identification of cyanosis that is acceptable in many situations. For this reason, we are releasing the full code stack and system design to allow others to rapidly iterate and improve the system. This may be of particular benefit in low-resource settings, and low-to-middle income countries in particular, which are just beginning to be affected by COVID-19.


title: COVID-19, indigenous peoples and tourism: a view from New Zealand

text: The COVID-19 pandemic’s impact is predicted to be long-lasting with intergenerational impacts for both Indigenous and non-Indigenous peoples. Indigenous peoples offer untapped potential for understanding how we are shaping resilient solutions to COVID-19 and similar threats in the future. In New Zealand, the Māori people occupy diverse leadership and occupational roles throughout society. As a result of the 1840 Treaty of Waitangi (Te Tiriti o Waitangi) they are recognised, through Acts of Parliament, as government partners who work in governance and planning processes, including the COVID-19 response. Such recognition can result in the inclusion of Māori values such as whanaungatanga (kinship and belonging), kaitiakitanga (environmental guardianship and responsibility) and manaakitanga (respect, care, and hospitality) within policy and Acts of Parliament. Māori leaders and spokespeople are stressing that environmental and social welfare needs of all communities should be prioritised as part of the COVID-19 solution and that tourism responses cannot be separated from social needs. Government responses and planning efforts that incorporate diverse cultural values ensure more equitable futures and positive experiences for tourism providers, travellers and the hosts. In this way Indigenous-informed approaches would positively contribute to transforming business, health and education for a more positive global society.


title: Modelling the impact of COVID-19 on elective waiting times

text: In an early stage of the COVID-19 outbreak, hospitals in England were asked to postpone elective treatments in order to accommodate the expected demand for COVID-19 related admissions. This study aims to forecast the extent to which waiting times could increase as a result of these measures, and estimate the level of effort required to restore performance to pre COVID-19 levels. A time-driven simulation is configured and calibrated based upon conditions in England as of February 2020. As a worst case scenario, where restrictions on elective care extend to twelve months and elective treatment rates are halved, results suggest performance could drop to levels not seen since 2007 and the size of the waiting list could double. Restoring performance would take two years assuming additional capacity injections of 12.5%, costing an estimated £14.7b. The modelling presented here offers clinicians and managers an insight into the outcomes that could result under a range of scenarios considered plausible at the early stage of the outbreak. Freely available as open source code, the model may be locally-calibrated for regional healthcare systems and used more widely in countries where similar elective performance measures exist.


title: Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of SARS-CoV-2 entry

text: Background Leading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of SARS-CoV-2. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited. Methods In order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level. Results The bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results. Conclusions Based on these findings, we speculated that SARS-CoV-2 could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.


title: Mortality Analysis of COVID-19 Confirmed cases in Pakistan

text: Introduction: COVID-19, a novel disease, appeared in December 2019 in China and rapidly spread across the world. Till the second week of April 2020, high incidence (2.9/100,000) and cases fatality rates (1.7%) were observed in Pakistan. This study was conducted to determine the temporal and spatial distribution of the first 100 deaths attributed to COVID-19 in Pakistan and their associated demographic factors. Method: We conducted a descriptive epidemiological analysis of the first 100 deaths reported among RT-PCR confirmed COVID-19 cases. Demographic, epidemiological, and risk factors information was obtained associated comorbidities and clinical signs and symptoms were recorded and frequencies were determined. Results: A total of 100 mortalities with overall Case Fatality Rate 1.67% (CFR) were analysed. Median age of patients was 64.5 years (IQR: 54-70) with 75% (n=75) Males. Among all deaths reported, 71 (71%) cases had one or more documented comorbidities at the time of diagnosis. Most frequently reported co-morbidities were; hypertension (67 %), followed by Diabetes Mellitus 945%) and Ischemic Heart Diseases (27%). First death was reported on 18 March 2020 and the most frequent presenting symptoms were shortness of breath (87%) and fever (79%). Median duration of illness was eight days (IQR: 4-11 days), the median delay reaching hospital to seek health care was three days (IQR: 0-6 days) while median duration of hospital stay was also three days (IQR: 1-7 days). Among all reported deaths, 62% were attributed to local transmission as these cases had no history of international travel. The most affected age group was 60-69 years while no death reported in age group below 20 years. Conclusion: High CFR among old age group and its association with co-morbidities (chronic disease) suggests targeted interventions such as social distancing and strict quarantine measure for elderly and morbid people. Comparative studies among deaths and recovered patients are recommended to explore further disease dynamics. Key words: COVID-19, Cases Fatality Rates, Co-morbidities, Epidemiology, Pakistan, Co-morbidities


title: Spreading of COVID-19 in Brazil: Impacts and uncertainties in social distancing strategies

text: Brazil's continental dimension poses a challenge to the control of the spread of COVID-19. Due to the country specific scenario of high social and demographic heterogeneity, combined with limited testing capacity, lack of reliable data, under-reporting of cases, and restricted testing policy, the focus of this study is twofold: (i) to develop a generalized SEIRD model that implicitly takes into account the quarantine measures, and (ii) to estimate the response of the COVID-19 spread dynamics to perturbations/uncertainties. By investigating the projections of cumulative numbers of confirmed and death cases, as well as the effective reproduction number, we show that the model parameter related to social distancing measures is one of the most influential along all stages of the disease spread and the most influential after the infection peak. Due to such importance in the outcomes, different relaxation strategies of social distancing measures are investigated in order to determine which strategies are viable and less hazardous to the population. The results highlight the need of keeping social distancing policies to control the disease spread. Specifically, the considered scenario of abrupt social distancing relaxation implemented after the occurrence of the peak of positively diagnosed cases can prolong the epidemic, with a significant increase of the projected numbers of confirmed and death cases. An even worse scenario could occur if the quarantine relaxation policy is implemented before evidence of the epidemiological control, indicating the importance of the proper choice of when to start relaxing social distancing measures.


title: COVID-19: An Emeritus Faculty’s Perspective

text: Life in academics often seems like an endless series of transitions: from medical student to intern, from junior resident to senior, from fellow to faculty, from junior faculty to senior, and sometimes from local leader to national figure. Looking back now on my own career and those of others, the most important lesson I’ve learned is that we are ultimately defined more by how we manage those transitions, and how we treat the people we meet along the way, than we are by the professional accomplishments that bring us recognition and awards.


title: Inexpensive multi-patient respiratory monitoring system for helmet ventilation during COVID-19 pandemic

text: Helmet non-invasive ventilation (NIV) is a form of continuous positive applied pressure that has emerged as a useful therapy for COVID-19 patients who require respiratory support but may not require invasive ventilation. Helmet NIV has seen an increase in use during the COVID-19 pandemic because it is low-cost, readily available, and provides viral filters between the patient and clinician. Helmet NIV may also provide better patient outcomes by delaying or eliminating the need for invasive ventilation. Its widespread adoption has been limited, however, by the lack of a respiratory monitoring system that is needed to address known safety vulnerabilities and to provide clinicians with a respiratory profile of the patient. To address this safety need, we have developed an inexpensive respiratory monitoring system that is based on readily available commercial components and is suitable for rapid local manufacture. The system is designed for use in conjunction with the COVID-19 Helmet developed by Sea-Long Medical Systems, but is modular and can be used with other ventilation systems. The monitoring system comprises one or more flow and pressure sensors and a central remote station that can be used to remotely monitor up to 20 patients simultaneously. The system reports flow, pressure, and clinically relevant metrics including respiratory rate, tidal volume equivalent, peak inspiratory pressure (PIP), positive end-expiratory pressure (PEEP) and the ratio of inspiratory time to expiratory time (I:E). The device will sound alarms based on clinician-set thresholds. In bench tests using a commercial ventilator and artificial lung system, our device performs comparably to a commercial single-patient respiratory monitor. Results are presented from human-subject tests on a healthy volunteer undergoing helmet non-invasive ventilation. Detailed design and manufacturing documents are provided.


title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum

text: In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2.


title: Private Antibody Repertoires Are Public

text: When faced with a given pathogen, the antibody response generally functions similarly across different people,1–4 but the source of this similarity has been unclear. One hypothesis was that people share a high proportion of the same VDJ-recombined antibody genes, but this has been disproven.5,6 An alternative is that people share a high proportion of functionally similar antibodies,7,8 but testing this hypothesis requires a method for measuring functional similarity that scales to the millions of antibodies per repertoire and across multiple repertoires, which is impossible experimentally. We recently described a framework for doing so computationally,9 which revealed that repertoires consist of loose overlapping functional classes of antibodies with similar antigen-binding capacities;10–12 this framework allowed us to estimate a repertoire’s antigen-binding capacity, τ, for the ideal target of any given antibody. Here, we show that this framework supports the second hypothesis, and provide the first comprehensive demonstration of overwhelming functional overlap between repertoires from 20 different individuals directly from sequence, without need of binding studies. Overlap is highest among the young and falls with age, due to the selective loss of antibodies that represent a core set of shared or “public” antigen-binding capacities. We reveal considerable heterogeneity in antigen-binding capacities for antibodies against influenza, HIV, and SARS-CoV-2, and show that while some of these classes shrink with age, others persist across individuals. These discoveries change our understanding of repertoire diversity and have implications for vaccine and therapeutic-antibody development, especially for the aged.


title: ‘Quit During COVID-19’—staying smokefree in mental health in-patient settings

text: Cigarette smoking is one of the main preventable causes of cancers globally. At this time of global emergency, mental health professionals all over the world are joining hands with the public health and other healthcare communities to focus on acute measures to save lives from COVID-19. This has been particularly challenging in mental health hospital settings where numerous additional factors need to be considered, including difficulties of implementing social distancing, potential impacts of social isolation, increased stress levels and implications of all this on smoking. In this article, we will briefly discuss the prevalence of smoking in mental health patients, especially in those in mental health hospital settings and also what is the possible impact of COVID-19 pandemic in these people. Then we will go through the main reasons as to why encouraging smoking cessation in mental health patients is so important and measures we can take for supporting mental health patients quit smoking even during COVID-19 times. The smoking cessation interventions have a direct bearing on preventing future cancers and achieving smoking cessation among cancer patients in this already disadvantaged group.


title: Hospital practice in COVID-19 times: Perceptions of the midwifery interns in Peru

text: Objective: To evaluate the perception of midwifery interns regarding hospital practices during COVID-19. Material and methods: Study of qualitative approach, of phenomenological design, where 80 obstetric interns from the different regions of Peru participated, who are also representatives of their hospital headquarters. An in-depth interview was applied where the perception of hospital practices was addressed according to: i) current problems and ii) solution proposals. Results: Midwifery interns have been removed from hospital practices, mainly due to the absence of personal protective equipment and health insurance, financially affecting those who must continue to make rent and food payments; Likewise, a large part of the universities have not offered proposals for solutions to the delay in internships, raising concerns about delays in administrative procedures, even more so for students from non-licensed universities. Among the proposals, those who are close to graduating suggest being exempted from the months when there were no activities, so as not to delay future processes such as tuition and rural service; likewise, suspend payment for these months and strengthen knowledge through the discussion of clinical cases, which could be virtual. Conclusions: The cessation of hospital practice responds to a lack of guarantees in the health care of the student, generating economic repercussions and a negative perception regarding university management. Finally, solutions that could be considered for the next decisions made by the institutions are reported.


title: Recommendations for standardized management of CML patients in the core epidemic area of COVID-19(Multi-center survey results in Hubei Province, China)

text: Background Since late December 2019, the outbreak of the novel coronavirus disease, COVID-19, that began in Wuhan, has become endemic in China and more than 100 countries and regions in the world. There is no report about the prevalence of COVID-19 in CML patients untill now. We aimed to describe the clinical course, outcomes of CML patients with COVID-19 and prevalence of COVID-19 in CML patients. Methods In this multi-center survey, cross-sectional survey, observational study, the clinical data of CML patients with COVID-19 in each center were collected. Simultaneously, an online survey was conducted for information about the CML patients under the management at each center by asking the CML patients to complete a questionnaire,from February 15, 2020 to February 21, 2020. The questionnaire includes demographic data, place of residence, smoking status, CML diagnosis and treatment, comorbidities, combined medications, epidemiological history, symptoms(fever, cough, shortness of breath, etc) during the epidemic. Additional clinical data was collected on respondents suspected or confirmed to have COVID-19. We described and analyzed the prevalence of COVID-19 in CML patients, and focus on the clinical characteristics and outcomes of COVID-19 patients. Data were compared between the CML patients with optimal response and those with non-optimal response. The primary outcome was prevalence of COVID-19 in CML patients, as of Feb 21, 2020. Secondary outcomes included the history of epidemiology of CML patients, the clinical characteristics and outcomes of CML patients with COVID-19 . Findings Of 392 respondents, 223( 56.9%) were males, and 240( 61.2%) were 50 years or younger. Only 10 patients took drugs irregularly due to the influence of the epidemic because of traffic control, pharmacies unable to operate normally, etc. In the history of epidemiology, there were 4 patients with definite contact with COVID-19, of which 3 were remote contact and 1 was close contact. 12 respondents had fever, cough or shortness of breath during the epidemic, 1 case (common type) was confirmed with COVID-19 and cured after treatment. 1 patient was clinically diagnosed and succumbed. 1 of 299 (0.3%) patients with an optimal response was diagnosed with COVID-19. Of the 50 patients who failed to respond to CML treatment or had a poor response, 1 patient (2%) had a clinical diagnosis of COVID-19. Interpretation While the 392 CML respondents required regular referrals to hospitals, they did not have much contact with COVID-19 patients during the outbreak. Patients who failed to achieved an optimal response to CML therapy appear more likely to have a symptomatic infection with SARS-CoV-2. Older patients with comorbidities are at increased risk of death.


title: Next weeks of SARS-CoV-2: Projection model to predict time evolution scenarios of accumulated cases in Spain

text: Background and objectives: SARS-CoV-2 is a new type of coronavirus that can affect people and causes respiratory disease, COVID-19. It is affecting the entire planet and we focus in Spain, where the first case was detected at the end of January 2020 and in recent weeks it has increased in many cases. We need predictive models in order to be efficient and take actions. The general goal of this work is present a new model of SARS-CoV-2 to predict different scenarios of accumulated cases in Spain. Material and methods: In this short report is used a model proposed previously, based on a parametric model Weibull and in a the library BDSbiost3 developed in R to infer and predict different scenarios of the evolution of SARS-CoV-2 for the accumulated cases in Spain after the spread that affects Spain detected at the end of January of this year. Results: In the analyses presented, projective curves have been generated for the evolution of accumulated cases in which they reach about 4,000 cases or about 15,000 cases, for which the lines of the day in which the value for 90 will be reached can be seen vertically 90, 95 and 99% of the asymptote (maximum number of cases, from that day they will begin to descend or remain the same), that is why the vertical lines would indicate the brake of the disease. For the worst-case scenario, it takes 118, 126 or 142 days to reach the maximum number of cases (n = 15,000) to reach 90, 95 and 99% of the asymptote (maximum number of cases), respectively. This means translated in a time scale that in the worst case the virus will not stop its progress, in Spain, until summer 2020, hopefully before. Comments and conclusions: This model could be used to plan the resources and see if the policies or means dedicated to the virus are slowing the progress of the virus or it is necessary to implement others that are more effective, and can also validate a method for future outbreaks of diseases such as these.


title: Crippled community governance and suppressed scientific/professional communities: a critical assessment of failed early warning for the COVID-19 outbreak in China

text: The public governance of epidemic outbreaks faces great uncertainty. Successful governance is only possible with a competent early warning system, which hinges upon efficient production, sharing, and use of relevant knowledge and information. In this process, functional scientific/professional communities are critical gatekeepers. Analyzing China’s failed early warning for the COVID-19 outbreak, we show that an epidemic governance system dominated by bureaucratic forces is doomed to failure. In particular, we identify the lack of autonomy of scientific/professional communities—in this case, virologists, physicians, and epidemiologists—as one of the major contributing factors to the malfunction of the early warning system. Drawing upon the idea of community governance, we argue that only by empowering scientific/professional groups to exert efficient community governance can a state modernize its early warning system and perform better in combatting epidemics.


title: Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cruise ship outbreak

text: The Diamond Princess (DP) cruise ship was put under quarantine offshore Yokohama, Japan, after a passenger who disembarked in Hong Kong was confirmed as a COVID-19 case. We performed whole genome sequencing of SARS-CoV-2 directly from PCR-positive clinical specimens and conducted a haplotype network analysis of the outbreak. All tested isolates exhibited a transversion at G11083T, suggesting that SARS-CoV-2 dissemination on the DP originated from a single introduction event before the quarantine started. Although further spreading might have been prevented by quarantine, some progeny clusters were linked to transmission through mass-gathering events in the recreational areas and direct transmission among passengers who shared cabins during the quarantine. This study demonstrates the usefulness of haplotype network analysis in identifying potential infection routes.


title: Determination of Johnson-Cook material model parameters for AISI 1045 from orthogonal cutting tests using the Downhill-Simplex algorithm

text: Abstract Despite the increasing digitalization of manufacturing processes in the context of Industry 4.0, the process design and development of machining processes poses major challenges for today’s manufacturing technology. Compared to the conventional process design, which is influenced by an empirical "trial-and-error" principle, the simulative process design offers the possibility of reducing development time and costs while at the same time improving the process understanding. A possible simulation technique to achieve these goals is the Finite Element Method (FEM). The FEM enables the calculation of the thermo-mechanical load spectrum underlying the machining process. Therefore, different input models are required. One of the most critical input models is the material model, which describes the constitutive material behavior. To determine the material model parameters, either (conventional) material tests, which require an extrapolation into the regime of metal cutting, or inverse techniques are used, where the process itself is used as a material test. Using the inverse technique, the model parameters are modified iteratively until a predefined agreement between simulations and experiments is achieved. The evaluation of the agreement bases on integral process variables, such as the cutting force, and their simulative counterparts. However, the procedure of the inverse determination requires high computational efforts and is not robust. This paper presents a novel approach to enhance the robustness of the inverse material model parameter determination from the cutting process. Orthogonal cutting tests on AISI 1045 steel have been conducted on a broaching machine tool over a range of different cutting speeds and undeformed chip thicknesses to set an experimental database. Thereby, the workpiece material was investigated in the two different heat treatments: normalized and coarse-grain annealed. The machining experiments showed differences in terms of the integral process results when comparing the two heat treatments. These results motivated for the development of a methodology capable to determine material model parameters robust and inversely from the machining process, which can be used with lower computational effort. To simulate the machining process, a Coupled-Eulerian-Lagrangian (CEL) model of the orthogonal cutting process has been set up. The material model parameters have been inversely determined using the Downhill-Simplex-Algorithm, which has been modified for this case. By using the Downhill-Simplex-Algorithm, it was possible to determine material model parameters within 17 iterations and achieving an average deviation between the experiment and the simulations below 10 %. Thereby, different process observables such as temperature, forces, and chip form have been used for the evaluation. Through this method, it is possible to determine material model parameters, which enable a good match between experiments and simulations with a low computational effort.


title: Mathematical modeling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada

text: 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


title: COVID-19 genomic susceptibility: Definition of ACE2 variants relevant to human infection with SARS-CoV-2 in the context of ACMG/AMP Guidance

text: BACKGROUND: Mortality remains very high and unpredictable in COVID-19, with intense public protection strategies tailored to preceived risk. Genomic studies are in process to identify differences in host susceptibility to infection by the SARS-CoV-2 virus. Open source research publications are accessible to pre-genotyped individuals. Males are more at risk from severe COVID-19. METHODS: To facilitate development of Clinical Genetics support to the public and healthcare professionals, genomic structure and variants in 213,158 exomes/genomes were integrated for ACE2 encoding the SARS-CoV-2 receptor. ACMG/AMP-based pathogenicity criteria were applied. RESULTS: Across the 19 ACE2 exons on the X chromosome, 9 of 3596 (0.25%) nucleotides were homozygous variant in females compared to 262/3596 (7.3%) hemizygous variant in males (p< 0.0001). 90% of variants were very rare, although K26R affecting a SARS-CoV-2-interacting amino acid is present in ~1/239 people. Modelling the ''COVID-resistant '' state where pathogenic alleles would be beneficial, nine null alleles met PVS1. Thirty-seven variants met PM1 based on critical location +/-PP3 based on computational modelling. Modelling a ''COVID-susceptible '' state, 31 variants in four upstream open reading frames and 5' untranslated regions could meet PM1, and may have differential effects if aminoglycoside antibiotics were prescribed for pneumonia and sepsis. CONCLUSIONS: Males are more likely to exhibit consequences from a single variant ACE2 allele. Differential allele frequencies in COVID-19 susceptible and resistant individuals are likely to emerge before variants meet ACMG/AMP criteria for actionable results in patients. Prioritising genomic regions for functional study and ACMG/AMP-structured approaches to research-based presentation of COVID-19 susceptibility variant results are encouraged.