title: The COVID-19 Pandemic in Africa: Predictions using the SIR Model Indicate the Cases are Falling

text: Since the earliest reports of the Coronavirus disease - 2019 (COVID-19) in Wuhan, China in December 2019, the disease has rapidly spread worldwide, attaining pandemic levels in early March 2020. However, the spread of COVID-19 has differed in the African setting compared to countries on other continents. To predict the spread of COVID-19 in Africa and within each country on the continent, we applied a Susceptible-Infectious-Recovered mathematical model. Here, our results show that, overall, Africa is currently (May 29, 2020) at the peak of the COVID-19 pandemic, after which we predict the number of cases would begin to fall in June 2020. Furthermore, we predict that the ending phase of the pandemic would be in Mid-August 2020 and that decreasing cases of COVID-19 infections would be detected until around December 2020 and January 2021. Our results also reveal that of the 51 countries with reported COVID-19 cases, only nine, including South Africa, Egypt and Ethiopia, are likely to report higher monthly COVID-19 cases in June 2020 than those reported in the previous months. Overall, at the end of this pandemic, we predict that approximately 279,000 (about 154,000 future cases) individuals in Africa would have been infected with the COVID-19 virus. Here, our predictions are data-driven and based on the previously observed trends in the spread of the COVID-19 pandemic. Shifts in the population dynamics and/or changes in the infectiousness of the COVID-19 virus may require new forecasts of the disease spread.


First Person: No One is Ready for This


title: COVID-19 and smoking: A systematic review of the evidence

text: COVID-19 is a coronavirus outbreak that initially appeared in Wuhan, Hubei Province, China, in December 2019, but it has already evolved into a pandemic spreading rapidly worldwide(1,2). As of 18 March 2020, a total number of 194909 cases of COVID-19 have been reported, including 7876 deaths, the majority of which have been reported in China (3242) and Italy (2505)(3). However, as the pandemic is still unfortunately under progression, there are limited data with regard to the clinical characteristics of the patients as well as to their prognostic factors(4). Smoking, to date, has been assumed to be possibly associated with adverse disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases(5). Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases(6). Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak(7,8). Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients’ smoking status to evaluate the association between smoking and COVID-19 outcomes including the severity of the disease, the need for mechanical ventilation, the need for intensive care unit (ICU) hospitalization and death. The literature search was conducted on 17 March 2020, using two databases (PubMed, ScienceDirect), with the search terms: [‘smoking’ OR ‘tobacco’ OR ‘risk factors’ OR ‘smoker*’] AND [‘COVID-19’ OR ‘COVID 19’ OR ‘novel coronavirus’ OR ‘sars cov-2’ OR ‘sars cov 2’] and included studies published in 2019 and 2020. Further inclusion criteria were that the studies were in English and referred to humans. We also searched the reference lists of the studies included. A total of 71 studies were retrieved through the search, of which 66 were excluded after full-text screening, leaving five studies that were included. All of the studies were conducted in China, four in Wuhan and one across provinces in mainland China. The populations in all studies were patients with COVID-19, and the sample size ranged from 41 to 1099 patients. With regard to the study design, retrospective and prospective methods were used, and the timeframe of all five studies covered the first two months of the COVID-19 pandemic (December 2019, January 2020). Specifically, Zhou et al.(9) studied the epidemiological characteristics of 191 individuals infected with COVID-19, without, however, reporting in more detail the mortality risk factors and the clinical outcomes of the disease. Among the 191 patients, there were 54 deaths, while 137 survived. Among those that died, 9% were current smokers compared to 4% among those that survived, with no statistically significant difference between the smoking rates of survivors and non-survivors (p=0.21) with regard to mortality from COVID-19. Similarly, Zhang et al.(10) presented clinical characteristics of 140 patients with COVID-19. The results showed that among severe patients (n=58), 3.4% were current smokers and 6.9% were former smokers, in contrast to non-severe patients (n=82) among which 0% were current smokers and 3.7% were former smokers , leading to an OR of 2.23; (95% CI: 0.65–7.63; p=0.2). Huang et al.(11) studied the epidemiological characteristics of COVID-19 among 41 patients. In this study, none of those who needed to be admitted to an ICU (n=13) was a current smoker. In contrast, three patients from the non-ICU group were current smokers, with no statistically significant difference between the two groups of patients (p=0.31), albeit the small sample size of the study. The largest study population of 1099 patients with COVID-19 was provided by Guan et al.(12) from multiple regions of mainland China. Descriptive results on the smoking status of patients were provided for the 1099 patients, of which 173 had severe symptoms, and 926 had non-severe symptoms. Among the patients with severe symptoms, 16.9% were current smokers and 5.2% were former smokers, in contrast to patients with non-severe symptoms where 11.8% were current smokers and 1.3% were former smokers. Additionally, in the group of patients that either needed mechanical ventilation, admission to an ICU or died, 25.5% were current smokers and 7.6% were former smokers. In contrast, in the group of patients that did not have these adverse outcomes, only 11.8% were current smokers and 1.6% were former smokers. No statistical analysis for evaluating the association between the severity of the disease outcome and smoking status was conducted in that study. Finally, Liu et al.(13) found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of patients with a history of smoking (27.3%) than the group that showed improvement or stabilization (3.0%), with this difference statistically significant at the p=0.018 level. In their multivariate logistic regression analysis, the history of smoking was a risk factor of disease progression (OR=14.28; 95% CI: 1.58–25.00; p= 0.018). We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases(12). However, from their published data we can calculate that the smokers were 1.4 times more likely (RR=1.4, 95% CI: 0.98–2.00) to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers (RR=2.4, 95% CI: 1.43–4.04). In conclusion, although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19.


News: Life on a Rapid Response Team in NYC Quieter than Expected


title: Longitudinal symptom dynamics of COVID-19 infection in primary care

text: Importance: Data regarding the clinical characteristics of COVID-19 infection is rapidly accumulating. However, most studies thus far are based on hospitalized patients and lack longitudinal follow up. As the majority of COVID-19 cases are not hospitalized, prospective studies of symptoms in the population presenting to primary care are needed. Objective: To assess the longitudinal dynamic of clinical symptoms in non-hospitalized individuals prior to and throughout the diagnosis of SARS-CoV-2 infection. Design, Setting, and Participants: From 1/3/2020 to 07/06/2020, information on symptoms from either surveys or primary care visits was available for 206,377 individuals, including 2,471 who tested positive for COVID-19. Data were extracted from electronic health records (EHR) of the second largest Health Maintenance Organization in Israel, consisting of both results of PCR tests and symptoms recorded by primary care physicians, and linked longitudinal self reported symptoms. Exposures: Diagnosis of COVID-19 disease was made by PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Main Outcomes and Measures: Longitudinal prevalence of clinical symptoms Results: In adults, the most prevalent symptoms recorded in EHR were cough (11.6%), fever (10.3%), and myalgia (7.7%) and the most prevalent self-reported symptoms were cough (21%), fatigue (19%) and rhinorrhea and/or nasal congestion (17%). In children, the most prevalent symptoms recorded in the EHR were fever (7%), cough (5.5%) and abdominal pain (2.4%). Emotional disturbances were documented in 15.9% of the positive adults and 4.2% of the children. Loss of taste and smell, either self-reported or documented by a physician, 3 weeks prior to testing, were the most discriminative symptoms in adults (OR =11.18 and OR=5.47 respectively). Additional symptoms included self reported confusion (OR =4.02), and fatigue (OR = 1.73) and a documentation of syncope, rhinorrhea (OR = 2.09 for both ) and fever (OR= 1.62 ) by a physician. Mean time to recovery was 23.5 +- 9.9 days. Children had a significantly shorter disease duration (21.7 +- 8.8 days, p-value=0.01). Several symptoms, including fatigue, myalgia, runny nose and shortness of breath were reported weeks after recovery. Conclusions and Relevance: As the COVID-19 pandemic progresses rapidly worldwide, obtaining accurate information on symptoms and their progression is of essence. Our study shed light on the full clinical spectrum of symptoms experienced by infected individuals in primary care, and may alert physicians for the possibility of COVID-19 infection.


title: Loss of smell and taste in combination with other symptoms is a strong predictor of COVID-19 infection

text: Importance: A strategy for preventing further spread of the ongoing COVID-19 epidemic is to detect infections and isolate infected individuals without the need of extensive bio-specimen testing. Objectives: Here we investigate the prevalence of loss of smell and taste among COVID-19 diagnosed individuals and we identify the combination of symptoms, besides loss of smell and taste, most likely to correspond to a positive COVID-19 diagnosis in non-severe cases. Design: Community survey. Setting and Participants: Subscribers of RADAR COVID-19, an app that was launched for use among the UK general population asking about COVID-19 symptoms. Main Exposure: Loss of smell and taste. Main Outcome Measures: COVID-19. Results: Between 24 and 29 March 2020, 1,573,103 individuals reported their symptoms via the app; 26% reported suffering from one or more symptoms of COVID-19. Of those, n=1702 reported having had a RT-PCR COVID-19 test and gave full report on symptoms including loss of smell and taste; 579 were positive and 1123 negative. In this subset, we find that loss of smell and taste were present in 59% of COVID-19 positive individuals compared to 18% of those negative to the test, yielding an odds ratio (OR) of COVID-19 diagnosis of OR[95%CI]=6.59[5.25; 8.27], P= 1.90x10-59 . We also find that a combination of loss of smell and taste, fever, persistent cough, fatigue, diarrhoea, abdominal pain and loss of appetite is predictive of COVID-19 positive test with sensitivity 0.54[0.44; 0.63], specificity 0.86[0.80; 0.90], ROC-AUC 0.77[0.72; 0.82] in the test set, and cross-validation ROC-AUC 0.75[0.72; 0.77]. When applied to the 410,598 individuals reporting symptoms but not formally tested, our model predicted that 13.06%[12.97%;13.15] of these might have been already infected by the virus. Conclusions and Relevance: Our study suggests that loss of taste and smell is a strong predictor of having been infected by the COVID-19 virus. Also, the combination of symptoms that could be used to identify and isolate individuals includes anosmia, fever, persistent cough, diarrhoea, fatigue, abdominal pain and loss of appetite. This is particularly relevant to healthcare and other key workers in constant contact with the public who have not yet been tested for COVID-19.


title: Using Artificial Intelligence for COVID-19 Chest X-ray Diagnosis

text: Coronavirus disease-19 (COVID-19), caused by a novel member of the coronavirus family, is a respiratory disease that rapidly reached pandemic proportions with high morbidity and mortality. It has had a dramatic impact on society and world economies in only a few months. COVID-19 presents numerous challenges to all aspects of healthcare, including reliable methods for diagnosis, treatment, and prevention. Initial efforts to contain the spread of the virus were hampered by the time required to develop reliable diagnostic methods. Artificial intelligence (AI) is a rapidly growing field of computer science with many applications to healthcare. Machine learning is a subset of AI that employs deep learning with neural network algorithms. It can recognize patterns and achieve complex computational tasks often far quicker and with increased precision than humans. In this manuscript, we explore the potential for a simple and widely available test as a chest x-ray (CXR) to be utilized with AI to diagnose COVID-19 reliably. Microsoft CustomVision is an automated image classification and object detection system that is a part of Microsoft Azure Cognitive Services. We utilized publicly available CXR images for patients with COVID-19 pneumonia, pneumonia from other etiologies, and normal CXRs as a dataset to train Microsoft CustomVision. Our trained model overall demonstrated 92.9% sensitivity (recall) and positive predictive value (precision), with results for each label showing sensitivity and positive predictive value at 94.8% and 98.9% for COVID-19 pneumonia, 89% and 91.8% for non-COVID-19 pneumonia, 95% and 88.8% for normal lung. We then validated the program using CXRs of patients from our institution with confirmed COVID-19 diagnoses along with non-COVID-19 pneumonia and normal CXRs. Our model performed with 100% sensitivity, 95% specificity, 97% accuracy, 91% positive predictive value, and 100% negative predictive value. Finally, we developed and described a publicly available website to demonstrate how this technology can be made readily available in the future.


title: Phenomenological Modelling of COVID-19 epidemics in Sri Lanka, Italy and Hebei Province of China

text: The COVID-19 pandemic has resulted in increasing number of infections and deaths on a daily basis. There is no specific treatment or vaccine identified and the focus has been preventive measures based on statistical and mathematical models. These have relied on analyzing the behavior of populations and characteristics of the infection and applying modelling techniques. The analysis of epidemiological curve fitting on number of daily infections across affected countries could give useful insights on the characteristics of the epidemic. A variety of phenomenological models are available to capture dynamics of disease spread and growth. Data for this study used the number of daily new infections and cumulative number of infections in COVID-19 in three selected countries, Sri Lanka, Italy and Hebei province of China, from the first day of appearance of cases to 20th April 2020. In this study Gompertz, Logistic and Exponential growth curves were fitted on cumulative number of infections across countries. Akaikes information criteria (AIC) was used in determining the best fitting curve for each country. Results revealed that the most appropriate growth curves for Sri Lanka, Italy and China-Hebei are Exponential, Gompertz and Logistic curves respectively. The overall growth rate and final epidemic size evaluated from best models for the three countries and short-term forecasts were also generated. Log incidences over time in each country were regressed before and after the identified peak time of the respective outbreaks of countries. Hence, doubling time/halving time together with daily growth rates and predictions were estimated. Findings altogether demonstrate that outbreak seems extinct in Hebei-China whereas further transmissions are possible in Sri Lanka. In Italy, current outbreak transmits in a decreasing rate. Keywords: Novel Coronavirus (COVID-19), Phenomenological Models, Epidemiological Curve, Prediction


title: Genotypic and antigenic study of SARS-CoV-2 from an Indian isolate

text: Coronaviruses (CoVs) are one of the largest groups of positive-sense RNA virus families within the Nidovirales order, which are further classified into four genera: alpha, beta, gamma, and delta. Coronaviruses have an extensive range of natural hosts and are known to be responsible for a broad spectrum of diseases in multiple species. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) that has unleashed a global threat to public health and the economy. Coronaviruses are extensively present in birds and mammals, with horseshoe bats (Rhinolophus affinis), being the reservoir for the ongoing SARS-CoV-2 that seems to have resulted from a zoonotic spillover to the human host, causing respiratory infections, lung injury and Acute Respiratory Distress Syndrome(ARDS). About six coronavirus serotypes are linked with the disease in humans, namely HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, SARS-CoV-2, and MERS-CoV. SARS-CoV-2 is the seventh CoV to infect humans. We analyzed the genome sequence of CoV-2 from isolates derived from China as well from India and encountered minute variations in their sequence. A cladogram analysis revealed the predominant strain circulating in India belongs to the A2a clad. We took one such strain (MT012098) and performed a rigorous in-silico genotypic and antigenic analysis to identify its relatedness to other strains. Further, we also performed a detailed prediction for B and T cell epitopes using BepiPred 2.0 server and NetCTL 1.2 server (DTU Bioinformatics), respectively. We hope this information may assist in an effective vaccine designing program against SARS-CoV-2.


title: Efficacy of moist heat decontamination against various pathogens for the reuse of N95 respirators in the COVID-19 emergency

text: Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. The efficacy of inactivation or eradication against various pathogens should be evaluated thoroughly to understand the level of afforded disinfection. Methods commonly used in the sterilization of medical devices such as ionizing radiation, vaporized hydrogen peroxide, and ethylene oxide can provide a high level of disinfection, defined as a 6 log10 reduction, against bacterial spores, considered the most resistant microorganisms. CDC guidance on the decontamination and reuse of N95s also includes the use of moist heat (60{degrees}C, 80% relative humidity, 15-30 min) as a possible recommendation based on literature showing preservation of fit efficiency and inactivation of H1N1 on spiked masks. Here, we explored the efficacy of using moist heat under these conditions as a decontamination method for an N95 respirator (3M 1860S, St. Paul, MN) against various pathogens with different resistance; enveloped RNA viruses, Gram (+/-) bacteria, and non-enveloped viruses.


title: Risks to Children under-five in India from COVID-19

text: Objective: The novel coronavirus, COVID-19, has rapidly emerged to become a global pandemic and is known to cause a high risk to patients over the age of 70 and those with co-morbidities, such as hypertension and diabetes. Though children are at comparatively lower risk compared to adults, the Indian population has a large young demographic that is likely to be at higher risk due to exposure to pollution, malnutrition and poor access to medical care. We aimed to quantify the potential impact of COVID-19 on Indias child population. Methods: We combined district family household survey data with data from the COVID-19 outbreak in China to analyze the potential impact of COVID-19 on children under the age of 5, under three different scenarios; each of which assumed the prevalence of infection to be 0.5%, 1%, or 5%. Results: We find that in the lowest prevalence scenario, across the most populous 18 Indian states, asymptomatic, non-hospitalized symptomatic and hospitalized symptomatic cases could reach 87,200, 412,900 and 31,900, respectively. In a moderate prevalence scenario, these figures reach 174,500, 825,800, and 63,800, and in the worst case, high prevalence scenario these cases could climb as high as 872,200, 4,128,900 and 319,700. Conclusion: These estimates show COVID-19 has the potential to pose a substantial threat to Indias large population of children, particularly those suffering from malnutrition and exposure to indoor air pollution, who may have limited access to health services.


title: Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation

text: An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.


title: Neuroinflammation in the normal appearing white matter of multiple sclerosis brain causes abnormalities at the node of Ranvier

text: Changes to the structure of nodes of Ranvier in the normal-appearing white matter (NAWM) of MS brains are associated with chronic inflammation. We show that the paranodal domains in MS NAWM are longer on average than control, with Kv1.2 channels dislocated into the paranode. These pathological features are reproduced in a model of chronic meningeal inflammation generated by the injection of lentiviral vectors for the lymphotoxin-α (LTα) and interferon-γ (IFNγ) genes. We show that tumour necrosis factor (TNF), IFNγ and glutamate can provoke paranodal elongation in cerebellar slice cultures, which could be reversed by an NMDA blocker. When these changes were inserted into a computational model to simulate axonal conduction, a rapid decrease in velocity was observed, reaching conduction failure in small diameter axons. We suggest that glial cells activated by proinflammatory cytokines can produce high levels of glutamate, which triggers paranodal pathology, contributing to axonal damage and conduction deficits.


title: A simulation of a COVID-19 epidemic based on a deterministic SEIR model

text: An epidemic disease caused by a new coronavirus has spread in Northern Italy with a strong contagion rate. We implement an SEIR model to compute the infected population and number of casualties of this epidemic. The example may ideally regard the situation in the Italian Region of Lombardy, where the epidemic started on February 25, but by no means attempts to perform a rigorous case study in view of the lack of suitable data and uncertainty of the different parameters, namely, the variation of the degree of home isolation and social distancing as a function of time, the number of initially exposed individuals and infected people, the incubation and infection periods and the fatality rate. First, we perform an analysis of the results of the model, by varying the parameters and initial conditions (in order the epidemic to start, there should be at least one exposed or one infected human). Then, we consider the Lombardy case and calibrate the model with the number of dead individuals to date (April 19, 2020) and constraint the parameters on the basis of values reported in the literature. The peak occurs at day 37 (April 1) approximately, when there is a rapid decrease, with a reproduction ratio R0 = 3 initially, 1.38 at day 22 and 0.64 after day 35, indicating different degrees of lockdown. The predicted death toll is almost 14000 casualties, with 2.4 million infected individuals at the end of the epidemic. The incubation period providing a better fit of the dead individuals is 4.25 days and the infection period is 4 days, with a fatality rate of 0.00144/day [values based on the reported (official) number of casualties]. The infection fatality rate (IFR) is 0.57 %, and 2.36 % if twice the reported number of casualties is assumed. However, these rates depend on the initially exposed individuals. If approximately nine times more individuals are exposed, there are three times more infected people at the end of the epidemic and IFR = 0.47 %. If we relax these constraints and use a wider range of lower and upper bounds for the incubation and infection periods, we observe that a higher incubation period (13 versus 4.25 days) gives the same IFR (0.6 versus 0.57 %), but nine times more exposed individuals in the first case. Therefore, a precise determination of the fatality rate is subject to the knowledge of the characteristics of the epidemic. We plan to perform again these calculations and publish a short note when the epidemic is over and the complete and precise data is available. Besides the specific example, the analysis proposed in this work shows how isolation measures, social distancing and knowledge of the diffusion conditions help us to understand the dynamics of the epidemic. Hence, the importance to quantify the process to verify the effectiveness of the isolation.


title: Hypertension in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study

text: Objectives: It is unclear whether patients with hypertension are more likely to be infected with SARS-COV-2 than the general population and whether there is a difference in the severity of COVID-19 pneumonia in patients who have taken ACEI/ARB drugs to lower blood pressure compared to those who have not. Methods: This observational study included data from all patients with clinically confirmed COVID-19 who were admitted to the Hankou Hospital, Wuhan, China between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cutoff on March 8, 2020. Results: A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Patients with hypertension were older and were more likely to have pre-existing comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease than patients without hypertension. Moreover, patients with hypertension tended to have higher positive COVID-19 PCR detection rates. Patients with hypertension who had previously taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2 (P = 0.064). Conclusions: COVID-19 patients with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Patients with hypertension who had taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2. In future studies, a larger sample size and multi-center clinical data will be needed to support our conclusions.


title: Detection of Coronavirus Disease (COVID-19) using Radiological Examinations

text: An outbreak of Coronavirus disease 2019 (COVID-19) occurred in China The causative agent of COVID-19 is Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) The disease rapidly spreads from China to the world by trading and traveling Until April 24, 2020, approximately 2,544,792 cases were confirmed with 175,694 deaths throughout the world The highest number of cases were identified from the United States of America (USA) whereas the mortality rate is high in Portugal The diagnosis of COVID-19 is based on Computed Tomography Scanning (CT Scan) and Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) Assessing the extension of pathology, the exact location of the area involved, and assessment of the disease severity makes CT scan superior to other modalities This review shows that real-time polymerase chain reaction and imaging technology both play an important role in the diagnosis of COVID-19 However, imaging modalities have more importance in diagnosis and screening than qRT-PCR The qRT-PCR was positive in 81 3% whereas CT scan abnormality was observed in 89 8% Bilateral lobe (51 4%) abnormality was found more than a single lobe (21 5%) in COVID-19 infected patients The CT scan reports show a high-level abnormality in right lower lung lobe than others in COVID-19 infected patients The CT scan evaluates different manifestations such as the presence of ground-glass opacities, consolidations, crazy paying linear, cavitation, discrete nodules, pleural effusion, and lymphadenopathy It is concluded that imaging technology especially CT scan and X-rays play an important role in the screening and diagnosis of COVID-19 infected patients in limited access to qRT-PCR regions The common radiological manifestation was also determined, which will be helpful for the radiologist to diagnosed COVID-19 infected patients in the early stages Follow up studies required regarding the radiological examinations


title: Smart Pooled sample Testing for COVID-19: A Possible Solution for Sparsity of Test Kits

text: There is an exponential growth of COVID-19. The adaptation of preventive measures to limit the spread of infection among the people is the best solution to this health issue. The identification of infected cases and their isolation from healthy people is one of the most important preventive measures. In this regard, screening of the samples from a large number of people is needed which requires a lot of reagent kits for the detection of SARS-CoV-2. The use of smart pooled sample testing with the help of algorithms may be a quite useful strategy in the current prevailing scenario of the COVID-19 pandemic. With the help of this strategy, the optimum number of samples to be pooled for a single test may be determined based on the total positivity rate of the particular community.


title: Time Course of COVID-19 epidemic in Algeria: Retrospective estimate of the actual burden

text: Since December 2019, the five continents have been incrementally invaded by SARS-CoV-2. Africa is the last and least affected to date. However, Algeria is among the first countries affected since February 25, 2020. In order to benefit from its experience in the least affected countries, this study aims to describe the current situation of the epidemic and then retrospectively estimate its real burden. As a first part of the study, we described the indicators of the epidemic as; the cumulative and daily reported cases and deaths, and we computed the R0 evolution. Secondly, we used the New York City cases-fatality rate standardized by Algerian age structure, to retrospectively estimate the actual burden. We found that reported cases are in a clear diminution, but, the epidemic epicentre is moving from Blida to other cities. We noted a clear peak in daily cases-fatality from March 30, to April 17, 2020, Fig. 3, due to underestimating the actual infections of the first 25 days. Since May 8, 2020, the daily R0 is around one, Fig. 4. Moreover, we noticed 31% reduction of its mean value from 1,41 to 0,97 between the last two months. The Algerian Age-Standardized Infection Fatality Rate we found is 0,88%. Based on that, we demonstrated that only 1,5% of actual infections were detected and reported before March 30, and 20% after March 31, Fig. 5. Therefore, the actual infections burden is currently five times higher than reported. At the end, we found that at least 0,2 % of the population have been infected until May 27. Consequently, the acquired herd immunity to date is therefore not sufficient to avoid a second wave. We believe that, the under estimation of the actual burden of the epidemic is probably due to the lack of testing capacities, however, all the indicators show that the situation is currently controlled. This requires more vigilance for the next weeks during the gradual easing of the preventive measures.


title: A letter about the airborne transmission of sars-cov-2 based on the current evidence

text: World Health Organization has suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through person-to-person transmission and contact with contaminated surfaces. However, rapid spread of the coronavirus disease 2019 (COVID-19) suggests other routes such as airborne transmission may be involved. A few research studies have been conducted to evaluate the potential transmission of this virus through air. Although some studies have found no evidence of airborne transmission, other more recent work is proving the presence of SARS-CoV-2 even in public places. Also, the past experiences and knowledge about the mechanisms of similar viruses such as SARS-CoV support this hypothesis. It seems that the best decision at the moment is to follow a conservative approach, and accept the hypothesis that SARS-CoV-2 is able to be transmitted through air. By this, control measures could be employed to prevent further COVID-19 infection.


title: Aerosol-spread during chest compressions in a cadaver model

text: Objective: To evaluate aerosol-spread in cardiopulmonary resuscitation (CPR) using different methods of airway management. Knowledge about Aerosol spread is vital during the SARS-CoV-2-Pandemic. Methods: To evaluate feasibility we nebulized ultraviolet sensitive detergents into the artificial airway of a resuscitation dummy and performed CPR. The spread of the visualized aerosol was documented by a camera. In a second approach we applied nebulized detergents into human cadavers by an endotracheal tube and detected aerosol- spread during chest compressions the same way. We did recordings with undergoing compression- only-CPR, with a surgical mask and with an inserted laryngeal tube with and without a connected airway filter. Results: Most aerosol-spread at the direction of the provider was visualized during compression-only-CPR. The use of a surgical mask deflected the spread. Inserting a laryngeal tube connected to an airway filter lead to a remarkable reduction of aerosol-spread. Conclusion: The early insertion of a laryngeal tube connected to an airway filter before starting chest compression may be good for two Things: the treatment of hypoxemia as the likeliest cause of cardiac arrest and for staff protection during CPR.


title: Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor

text: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress.


title: Ozone Treatment for Elimination of Bacteria and SARS-CoV-2 for Medical Environments

text: Pathogenic bacteria and viruses in medical environments can lead to treatment complications and hospital-acquired infections (HAIs), and current cleaning protocols do not address hard-to-access areas or that may be beyond line-of-sight treatment such as with ultraviolet radiation. At the time of writing, the ongoing pandemic of the novel coronavirus known as novel coronavirus (2019-nCoV) has claimed over 4 million cases worldwide and is expected to have multiple peaks, with possible resurgences throughout 2020. It is therefore imperative that disinfection methods in the meantime be employed to keep up with the supply of personal protective equipment (PPE) and sterilize a wide array of surfaces as quarantine lockdowns begin to be lifted. Here, we tested the efficacy of Sani Sport ozone devices as a means to treat hospital equipment and surfaces for killing bacteria, degrading synthetic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and RNA from non-replicative capsid enclosed SARS-CoV-2. We observed a rapid killing of medically-relevant and environmental bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtlis, and Deinococcus radiodurans) across four surfaces (blankets, catheter, remotes, and syringes) within 30 minutes, and up to a 99% reduction in viable bacteria at the end of 2-hour treatment cycles. Significant RNA degradation of synthetic SARS-CoV-2 RNA was seen an hour into the ozone treatment as compared to non-treated controls and a non-replicative form of the virus was shown to have significant RNA degradation at 30 minutes compared to a no treatment control and RNA degradation could be reliably detected at 10,000 and 1,000 copies of virus per sample. These results show the strong promise of ozone treatment for reducing risk of infection and HAIs.


title: Interim Analysis of Risk Factors for Severe Outcomes among a Cohort of Hospitalized Adults Identified through the U.S. Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET)

text: Background: As of May 15, 2020, the United States has reported the greatest number of coronavirus disease 2019 (COVID-19) cases and deaths globally. Objective: To describe risk factors for severe outcomes among adults hospitalized with COVID-19. Design: Cohort study of patients identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network. Setting: 154 acute care hospitals in 74 counties in 13 states. Patients: 2491 patients hospitalized with laboratory-confirmed COVID-19 during March 1-May 2, 2020. Measurements: Age, sex, race/ethnicity, and underlying medical conditions. Results: Ninety-two percent of patients had at least 1 underlying condition; 32% required intensive care unit (ICU) admission; 19% invasive mechanical ventilation; 15% vasopressors; and 17% died during hospitalization. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84 and 85+ years versus 18-39 years (adjusted risk ratio (aRR) 1.53, 1.65, 1.84 and 1.43, respectively); male sex (aRR 1.34); obesity (aRR 1.31); immunosuppression (aRR 1.29); and diabetes (aRR 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84 and 85+ years versus 18-39 years (aRR 3.11, 5.77, 7.67 and 10.98, respectively); male sex (aRR 1.30); immunosuppression (aRR 1.39); renal disease (aRR 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR 1.28); neurologic disorders (aRR 1.25); and diabetes (aRR 1.19). Race/ethnicity was not associated with either ICU admission or death. Limitation: Data were limited to patients who were discharged or died in-hospital and had complete chart abstractions; patients who were still hospitalized or did not have accessible medical records were excluded. Conclusion: In-hospital mortality for COVID-19 increased markedly with increasing age. These data help to characterize persons at highest risk for severe COVID-19-associated outcomes and define target groups for prevention and treatment strategies.


title: Reduced mortality and shorten ICU stay in SARS-COV-2 pneumonia: a low PEEP strategy

text: Background Intensive Care Unit (ICU) management of COVID-19 patients with severe hypoxemia is associated with high mortality. We implemented a "care map", as a standardized multidisciplinary approach to improve patients monitoring using: uniform patient selection for ICU admission, a low-PEEP strategy and a pharmacologic strategic thromboembolism management. Methods A standardized protocol for managing COVID-19 patients and ICU admissions was implemented through accurate Early Warning Score (EWS) monitoring and thromboembolism prophylaxis at hospital admission. Dyspnea, mental confusion or SpO2 less than 85% were criteria for ICU admission. Ventilation approach employed low PEEP values (about 10 cmH2O in presence of lung compliance > 40 mL/cmH2O) and FiO2 as needed. In presence of lower lung compliance (< 40 mL/cmH2O) PEEP value was increased to about 14 cmH2O. Results From March 16th to April 12nd 2020, 41 COVID-19 patients were admitted to our ICU from a total of 310 patients. 83% (34) of them needed mechanical ventilation. The ventilation approach chosen employed low PEEP value based on BMI (PEEP 11+/- 3.8 (10-12) cmH2O if BMI < 30 Kg/m2; PEEP 15+/- 3.26 (12-18) cmH2O if BMI >30 Kg/m2). To date, ten patients (24%) died, four (9.7%) received mechanical ventilation, two were transferred to another hospital and 25 (60.9%) were discharged from ICU after a median of nine days. Discussion A multimodal approach for COVID-19 patients is mandatory. The knowledge of this multi-organ disease is growing rapidly, requiring improvements in the standard of care. Our approach implements an accurate pre-ICU monitoring and strict selection for ICU admission, and allows to reduce mechanical ventilation, ICU stay and mortality. Funding No funding has been required.


title: Casting In-Situ Cu/CrBx Composites via Aluminum-Assisted Reduction

text: Abstract Chromium borides (CrBx) have been considered as promising strengthening phases for copper (Cu). However, traditional manufacturing methods such as powder metallurgy greatly restrict the sample size and part complexity. Here, we report that bulk Cu containing high volume percentages of uniformly distributed CrBx were fabricated by casting via in-situ reduction assisted by aluminum (Al). Two sets of precursors, i.e., borax-CuCr and KBF4-CrF3, were used and the respective reaction mechanisms were illustrated. In addition, the resultant in-situ particle morphologies and sizes from the precursors were studied. The use of KBF4-CrF3 generated smaller in-situ particles due to the less severe coalescence of particles. The microhardness of in-situ Cu/CrBx was significantly enhanced over pure Cu.


title: Role of meteorological temperature and relative humidity in the January-February 2020 propagation of 2019-nCoV in Wuhan, China

text: Identified in December 2019, the 2019-nCoV emerged in Wuhan, China, and its spread increased rapidly, with cases arising across Mainland China and several other countries. By January 2020, the potential risks imposed by 2019-nCoV in human health and economical activity were promptly highlighted. Considerable efforts have been devoted for understanding the transmission mechanisms aimed to pursue public policies oriented to mitigate the number of infected and deaths. An important question requiring some attention is the role of meteorological variables (e.g., temperature and humidity) in the 2019-nCoV transmission. Correlations between meteorological temperature and relative humidity with the number of daily confirmed cases were explored in this work for the epicenter city of Wuhan, China for the period from 29 January to March 6, 2020. Long-term trend of temperature and relative humidity was obtained with a 14-days adjacent-averaging filter, and lagged correlations of the number of daily confirmed cases were explored. The analysis showed negative correlations between temperatures with the number of daily confirmed cases. Maximum correlations were found for 6-day lagged temperatures, which is likely reflecting the incubation period of the virus. It was postulated that the indoor crowding effect is responsible of the high incidence of 2019-nCoV cases, where low absolute humidity and close human contact facilitate the transport of aerosol droplets.


title: Calreticulin co-expression supports high level production of a recombinant SARS-CoV-2 spike mimetic in Nicotiana benthamiana

text: An effective prophylactic vaccine is urgently needed to protect against SARS-CoV-2 infection. The viral spike, which mediates entry into cells by interacting with the host angiotensin-converting enzyme 2, is the primary target of most vaccines in development. These vaccines aim to elicit protective immunity against the glycoprotein by use of inactivated virus, vector-mediated delivery of the antigen in vivo, or by direct immunization with the purified antigen following expression in a heterologous system. These approaches are mostly dependent on the growth of mammalian or insect cells, which requires a sophisticated infrastructure that is not generally available in developing countries due to the incumbent costs which are prohibitive. Plant-based subunit vaccine production has long been considered as a cheaper alternative, although low expression yields and differences along the secretory pathway to mammalian cells have posed a challenge to producing certain viral glycoproteins. Recent advances that have enabled many of these constraints to be addressed include expressing the requisite human proteins in plants to support the maturation of the protein of interest. In this study we investigated these approaches to support the production of a soluble and putatively trimeric SARS-CoV-2 spike mimetic in Nicotiana benthamiana via transient Agrobacterium-mediated expression. The co-expression of human calreticulin dramatically improved the accumulation of the viral spike, which was barely detectable in the absence of the co-expressed accessory protein. The viral antigen was efficiently processed even in the absence of co-expressed furin, suggesting that processing may have occurred at the secondary cleavage site and was mediated by an endogenous plant protease. In contrast, the spike was not efficiently processed when expressed in mammalian cells as a control, although the co-expression of furin improved processing considerably. This study demonstrates the feasibility of molecular engineering to improve the production of viral glycoproteins in plants, and supports plant-based production of SARS-CoV-2 spike-based vaccines and reagents for serological assays.


title: They stumble that run fast: the economic and COVID-19 transmission impacts of reopening industries in the US

text: COVID-19 has laid bare the United States economically and epidemiologically. Decisions must be made as how and when to reopen industries. Here we quantify economic and health risk tradeoffs of reopening by industry for each state in the US. To estimate total economic impact, we summed income loss due to unemployment and profit loss. We assess transmission risk by: (1) workplace size, (2) human interactions, (3) inability to work from home, and (4) industry size. We found that the industry with the highest estimated economic impact from COVID-19 was manufacturing in 40 states; the industry with the largest transmission risk index was accommodation and food services in 41 states, and the industry with the highest economic impact per unit of transmission risk, interpreted as the value of reopening, was manufacturing in 37 states. Researchers and decision makers must work together to consider both health and economics when making tough decisions.


title: A Robust, Safe and Scalable Magnetic Nanoparticle Workflow for RNA Extraction of Pathogens from Clinical and Environmental Samples

text: Diagnosis and surveillance of emerging pathogens such as SARS-CoV-2 depend on nucleic acid isolation from clinical and environmental samples. Under normal circumstances, samples would be processed using commercial proprietary reagents in Biosafety 2 (BSL-2) or higher facilities. A pandemic at the scale of COVID-19 has caused a global shortage of proprietary reagents and BSL-2 laboratories to safely perform testing. Therefore, alternative solutions are urgently needed to address these challenges. We developed an open-source method called Magnetic- nanoparticle-Aided Viral RNA Isolation of Contagious Samples (MAVRICS) that is built upon reagents that are either readily available or can be synthesized in any molecular biology laboratory with basic equipment. Unlike conventional methods, MAVRICS works directly in samples inactivated in acid guanidinium thiocyanate-phenol-chloroform (e.g., TRIzol), thus allowing infectious samples to be handled safely without biocontainment facilities. Using 36 COVID-19 patient samples, 2 wastewater samples and 1 human pathogens control sample, we showed that MAVRICS rivals commercial kits in validated diagnostic tests of SARS-CoV-2, influenza viruses, and respiratory syncytial virus. MAVRICS is scalable and thus could become an enabling technology for widespread community testing and wastewater monitoring in the current and future pandemics.


title: Obesity and COVID-19: The role of visceral adipose tissue

text: INTRODUCTION: During the unprecedented health crisis of the COVID-19 pandemic it was suggested that obesity might aggravate severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). Therefore, this study aims to investigate the association between Compute Tomography (CT)-based measurements of visceral and subcutaneous fat as measures of obesity and COVID-19 severity. METHODS: 30 patients with laboratory-confirmed COVID-19 and a mean age of 65.59 plus/minus 13.06 years from a level one medical center in Berlin, Germany, were retrospectively analyzed and included in the present analysis. SARS-CoV-2 was confirmed by polymerase chain reaction from throat swaps or deep nasal swabs on the day of admission. Severe clinical courses of COVID-19 were defined by hospitalization in intensive care unit (ICU) and invasive mechanical ventilation. All patients received low-dose chest CT-based fat measurements at the level of the first lumbar vertebra. RESULTS: An increase in visceral fat area (VFA) by one square decimeter was associated with a 22.53-fold increased risk for ICU treatment and a 16.11-fold increased risk for mechanical ventilation (adjusted for age and sex). For upper abdominal circumference, each additional centimeter of circumference showed a 1.13-fold increased risk for ICU treatment and a 1.25-fold increased risk for mechanical ventilation. There was no significant correlation of subcutaneous fat area (SFA) or body mass index (BMI) with severe clinical courses of COVID-19. CONCLUSIONS: Our results suggest that visceral adipose tissue and upper abdominal circumference specifically increasing the risk of COVID-19 severity. CT-based quantification of visceral adipose tissue and upper abdominal circumference in routinely acquired chest CTs may therefore be a simple tool for risk assessment in SARS-CoV-2-patients.


title: A resampling-based test to detect person-to-person transmission of infectious disease

text: Early detection of person-to-person transmission of emerging infectious diseases such as avian influenza is crucial for containing pandemics. We developed a simple permutation test and its refined version for this purpose. A simulation study shows that the refined permutation test is as powerful as or outcompetes the conventional test built on asymptotic theory, especially when the sample size is small. In addition, our resampling methods can be applied to a broad range of problems where an asymptotic test is not available or fails. We also found that decent statistical power could be attained with just a small number of cases, if the disease is moderately transmissible between humans.


title: Rapid Molecular Detection of SARS-CoV-2 (COVID-19) Virus RNA Using Colorimetric LAMP

text: The ability to detect an infectious agent in a widespread epidemic is crucial to the success of quarantine efforts in addition to sensitive and accurate screening of potential cases of infection from patients in a clinical setting. Enabling testing outside of sophisticated laboratories broadens the scope of control and surveillance efforts, but also requires robust and simple methods that can be used without expensive instrumentation. Here we report a method to identify SARS-CoV-2 (COVID-19) virus RNA from purified RNA or cell lysis using loop-mediated isothermal amplification (LAMP) using a visual, colorimetric detection. This test was additionally verified using RNA samples purified from respiratory swabs collected from COVID-19 patients in Wuhan, China with equivalent performance to a commercial RT-qPCR test while requiring only heating and visual inspection. This simple and sensitive method provides an opportunity to facilitate virus detection in the field without a requirement for complex diagnostic infrastructure.


title: Epistemic Responsibility in the Face of a Pandemic

text: The COVID-19 pandemic currently wracking the world represents a crucial test for our ethical toolkit Governments, institutions and individuals are suddenly called upon to make life and death decisions for which they typically ill-prepared Vocabulary which has suddenly become so familiar—“flatten the curve”;“social distancing”;“R0”—was unknown to most of us a bare few weeks ago Even for experts, every option continues to have huge uncertainties associated with it When experts are divided and unsure, how are the rest of us responsibly to decide how to act and who to trust?


title: COVID-19: Comparison between 8-days and extended 4-weeks outbreak periods through socioeconomic and natural factors

text: Since mid-March 2020, global COVID-19 pandemic has experienced an exponential growth in process from sporadic to sudden outbreaks. This paper selects the 8-day surge data of daily cases, death and recovery rates (March 19-26, 2020) from 18 countries with severe pandemic situation to discuss the impact of 9 factors of both socioeconomic and natural on the pathogen outbreak. Moreover, the paper also elaborates analysis and comparison of relatively slow 4-week (February 1-29, 2020) data of China's surge cases to determine the relationship between social and natural factors and on the spread of pandemic, which provides an effective reference for delaying and controlling the pandemic development.


title: COVID-19: A NYC Department Chair’s Perspective

text: When I was interviewing for chair positions 3 years ago, a few chair colleagues across the country warned me this job was a lonely one. I understood as a chair you cannot maintain work friendships like those I once cherished, that people see and treat you differently because you are their boss, that due to the importance of privacy conversations are sometimes limited to maintain confidentiality, and that you are ultimately responsible for factors that may be beyond your control. My first two years as chair in a new organization, in a new city, were filled with extensive listening, learning, challenges, and accomplishments: starting a new academic department at a renowned institution, hiring 47 new faculty members and 37 administrative staff, adding a fourth clinical site, expanding the educational and research missions. Then, just a few weeks after what then felt like a monumental change, the implementation of a new electronic health record, COVID-19 emerged.


title: COVID-19 mathematical model reopening scenarios for Sao Paulo - Brazil

text: The objective of the current investigation was to produce a generalized computational model to predict consequences of various reopening scenarios on COVID-19 infections rates and available hospital resources in Sao Paulo - Brazil. We were able to use the Susceptible-Exposed-Infected-Recovered (SEIR) model to fit both accumulated death data and corrected accumulated cases data associated with COVID-19 for both Brazil and the state of Sao Paulo. In addition, we were able to simulate the consequences of reopening under different possible scenarios in Brazil, in special for the state of Sao Paulo. The model was able to provide a predicted scenario in which reopening could occur with minimal impact on human life considering people careful behavior in combination with continued social distancing measures.


title: Intra-genome variability in the dinucleotide composition of SARS-CoV-2

text: CpG dinucleotides are under-represented in the genomes of single stranded RNA viruses, and coronaviruses, including SARS-CoV-2, are no exception to this. Artificial modification of CpG frequency is a valid approach for live attenuated vaccine development, and if this is to be applied to SARS-CoV-2, we must first understand the role CpG motifs play in regulating SARS-CoV-2 replication. Accordingly, the CpG composition of the newly emerged SARS-CoV-2 genome was characterised in the context of other coronaviruses. CpG suppression amongst coronaviruses does not significantly differ according to genera of virus, but does vary according to host species and primary replication site (a proxy for tissue tropism), supporting the hypothesis that viral CpG content may influence cross-species transmission. Although SARS-CoV-2 exhibits overall strong CpG suppression, this varies considerably across the genome, and the Envelope (E) open reading frame (ORF) and ORF10 demonstrate an absence of CpG suppression. While ORF10 is only present in the genomes of a subset of coronaviruses, E is essential for virus replication. Across the Coronaviridae, E genes display remarkably high variation in CpG composition, with those of SARS and SARS-CoV-2 having much higher CpG content than other coronaviruses isolated from humans. Phylogeny indicates that this is an ancestrally-derived trait reflecting their origin in bats, rather than something selected for after zoonotic transfer. Conservation of CpG motifs in these regions suggests that they have a functionality which over-rides the need to suppress CpG; an observation relevant to future strategies towards a rationally attenuated SARS-CoV-2 vaccine.


title: Seroprevalence of antibodies against SARS-CoV-2 among public community and health-care workers in Alzintan City of Libya

text: Abstract A study was conducted to determine the seroprevalence of antibodies against SARS-CoV-2 among public community and health care workers in Alzintan City, Libya. During the period from 2/4/2020 to 18/5/2020, a total of 219 blood samples were collected and analyzed for the presence of antibodies against SARS-CoV-2. Collection of samples were divided in two categories; random samples from public community and samples from health care workers belong to two Governmental hospitals and one private clinic. One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test was used. Out of the 219 samples tested, 6 (2.74%) samples were seropositive for SARS-CoV-2. All health-care workers were tested negative. All positive cases were females and 5 of them aged between 44 to 75 years and one aged 32 years. The prevalence in young females ([≤]40 years) was 1.4% in total young females tested in the study and 1.75% in young females taken from public community. The prevalence in older females aged ( 40 years), was 11.1% in total females tested and 13.9% in females taken from public community. In conclusion, the preliminary investigation of SARS-CoV-2 revealed considerable prevalence in Alzintan City although the disease seems to be in its mild form. Active surveillance studies with high number of samples using both virological and serological tests are in urgent need.


title: Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis

text: Rationale: Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare to those observed in critically ill patients with ARDS or sepsis due to other causes. Objectives: To directly compare plasma levels of inflammatory cytokines, with a focus on 6 cytokines associated with cytokine storm (IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNF), between hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients from prior to the COVID-19 pandemic. Findings: 15 hospitalized COVID-19 patients, 9 of whom were critically ill, were compared to 28 critically ill patients with ARDS or sepsis. There were no statistically significant differences in baseline levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNF between patients with severe COVID-19 and critically ill controls with ARDS or sepsis. Conclusions: Levels of inflammatory cytokines IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNF were not higher in critically ill COVID-19 patients than in critically ill patients admitted with ARDS or sepsis due to other causes in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 is likely unwarranted.


title: N-glycosylation network construction and analysis to modify glycans on the spike S glycoprotein of SARS-CoV-2

text: Background The spike S-protein of SARS-CoV-2 is N-glycosylated. The N-glycan structure and composition of this glycoprotein influence how the virus interacts with host cells. Objective To identify a putative N-glycan biosynthesis pathway of SARS-CoV-2 (HEK293 cell recombinant) from previously published mass spectrometric studies, and to identify what effect blocking some enzymes has on the overall glycoprotein profile. Finally, our goal was to provide the biosynthesis network, and glycans in easy-to-use format for further glycoinformatics work. Methods We reconstructed the glycosylation network based on previously published empirical data using GNAT, a glycosylation network analysis tool. Our compilation of the network tool had 23 glycosyltransferase and glucosidase enzymes, and could infer the pathway of glycosylation machinery based on glycans identified in the virus spike protein. Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes - Mannosidase-II and alpha-1,6-fucosyltransferase to see how they would affect the biosynthesis network. Results Of the 23 enzymes, a total of 12 were involved in glycosylation of SARS-CoV-2 - Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B4GalT, B4GalT, Man II, SiaT, ST3GalI, ST3GalVI and FucT8. Blocking enzymes resulted in a substantially modified glycan profile of the protein. Conclusions A network analysis of N-glycan biosynthesis of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies. Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, could be a factor in the host response to the infection and response to antibodies. Here we provide all the resources generated - the glycans derived from mass spectrometry and intermediate glycans in glycoCT xml format, and the biosynthesis network for future drug and vaccine development work.


title: Racial and Ethnic Disparities in SARS-CoV-2 Pandemic: Analysis of a COVID-19 Observational Registry for a Diverse U.S. Metropolitan Population

text: Importance: Despite emerging reports of poor COVID-19 outcomes among African Americans, data on race and ethnic susceptibility to SARS-CoV-2 infection are limited. Objective: To determine socio-demographic factors associated with higher likelihood of SARS-CoV-2 infection. To explore mediating pathways for race disparities in the SARS-CoV-2 pandemic. Design: Cross sectional analysis of COVID-19 Surveillance and Outcomes Registry (CURATOR). Multivariable logistic regression models were fitted to provide likelihood estimates (adjusted Odds Ratios: aOR, 95% confidence intervals: CI) of positive SARS-CoV-2 test. Structural Equation Modeling (SEM) framework was utilized to explore three mediation pathways (low income, high population density, high comorbidity burden) for association between African American race and SARS-CoV-2 infection. Setting: A large healthcare system comprising of one central tertiary care, seven large community hospitals and an expansive ambulatory and emergency care network in the Greater Houston area. Participants: Individuals of all ages, races, ethnicities and sex tested for SARS-CoV-2. Exposure: Socio-demographic (age, sex, race, ethnicity, household income, residence population density) and comorbidity (hypertension, diabetes, obesity, cardiac disease) factors. Main Outcome: Positive reverse transcriptase polymerized chain reaction test for SARS-CoV-2. Results: Among 4,513 tested individuals, 754 (16.7%) tested positive. Overall mean (SD) age was 50.6 (18.9) years, 62% females and 26% were African American. African American race was associated with higher comorbidity burden, lower socio-economic status, and higher population density residence. In the fully adjusted model, African American race (vs. White; aOR, CI: 1.84, 1.49-2.27) and Hispanic ethnicity (vs. non-Hispanic; aOR, CI: 1.70, 1.35-2.14) had a higher likelihood of infection. Older individuals and males were also at a higher risk of SARS-CoV-2 infection. The SEM framework demonstrated a statistically significant (p = 0.008) indirect effect of African American race on SARS-CoV-2 infection mediated via a pathway that included residence in densely populated zip code. Conclusions and Relevance: There is strong evidence of race and ethnic disparities in the SARS-CoV-2 pandemic potentially mediated through unique social determinants of health.


title: Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission

text: The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has a capability of gaining rapid mutations as the virus spreads. Whole genome sequencing data offers a wide range of opportunities to study the mutation dynamics. The advantage of increasing amount of whole genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity and to investigate the implications of those mutations in protein stability and viral transmission. Four proteins, surface glycoprotein, nucleocapsid, ORF1ab and ORF8 showed frequent mutations, while envelop, membrane, ORF6 and ORF7a proteins showed conservation in terms of amino acid substitutions. Some of the mutations across different proteins showed co-occurrence, suggesting their functional cooperation in stability, transmission and adaptability. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Analysis of protein structure stability of surface glycoprotein mutants indicated viability of specific variants and are more prone to be temporally and spatially distributed across the globe. Similar empirical analysis of other proteins indicated existence of important functional implications of several variants. Analysis of co-occurred mutants indicated their structural and/or functional interaction among different SARS-COV-2 proteins. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing and containment of the disease.


title: Anesthesia management of ophthalmic surgery for patient with suspected/confirmed COVID-19 -Saudi Anesthesia Society guidelines-

text: The outbreak of the novel coronavirus (COVID-19) has been declared a global pandemic. With a mortality rate reaching up to 5%, healthcare professionals treating patients with COVID-19 are at a significantly higher risk for exposure themselves. Given the rapidly progressing rate of COVID-19, there is an urgent need for developing guidelines within each specialty. This article discusses guidelines specifically for anesthesiologists dealing with ophthalmic surgeries with suspected or confirmed COVID-19 patients. Anesthesiologists always work in the proximity of the patient's face while performing either ocular regional anesthesia or while managing the airway in the process of intubation/extubation. Within these guidelines, the emphasis is provided on thorough preoperative screening to identify COVID-19 patients and to prevent the exposure of healthcare staff by following standard personal protective equipment (PPE) precautions.


title: SARS-CoV-2 mutations and where to find them: An in silico perspective of structural changes and antigenicity of the Spike protein

text: The recent emergence of a novel coronavirus (SARS-CoV-2) is causing a severe global health threat characterized by severe acute respiratory syndrome (Covid-19). At the moment, there is no specific treatment for this disease, and vaccines are still under development. The structural protein Spike is essential for virus infection and has been used as the main target for vaccine and serological diagnosis test development. We analysed 2363 sequences of the Spike protein from SARS-CoV-2 isolates and identified variability in 44 amino acid residues and their worldwide distribution in all continents. We used the three-dimensional structure of the homo-trimer model to predict conformational epitopes of B-cell, and sequence of Spike protein Wuhan-Hu-1 to predict linear epitopes of T-Cytotoxic and T-Helper cells. We identified 45 epitopes with amino acid variations. Finally, we showed the distribution of mutations within the epitopes. Our findings can help researches to identify more efficient strategies for the development of vaccines, therapies, and serological diagnostic tests based on the Spike protein of Sars-Cov-2.


title: KNOWLEDGE AND BEHAVIORS RELATED TO THE COVID-19 PANDEMIC IN MALAWI

text: Background: There are limited data on knowledge and behaviors related to COVID-19, and on the adoption of preventive behaviors, in sub-Saharan countries. Methods: Between April 25th and May 23rd, we contacted 793 individuals aged 18 and older, who previously participated in studies conducted in the Karonga Health and Demographic Surveillance Site in Karonga District, Malawi. During an interview by mobile phone, we ascertained sources of information about COVID-19 and we evaluated knowledge of respondents about the transmission and course of SARS-CoV-2/COVID-19. We also asked them to evaluate their own risk of infection and severe illness. Finally, we inquired about the preventive measures they had adopted in response to the pandemic. We describe patterns of knowledge and behaviors among survey respondents, by area of residence (rural vs. urban). Results: We interviewed 630 respondents (79.5% response rate) which included 260 men and 370 women. Four hundred and eighty-nine respondents resided in rural areas (77.6%) and 141 resided in urban areas (22.4%). Only one respondent had never heard of COVID-19. Respondents reported on average 4 distinct sources of information about COVID-19. Misconceptions about the modes of transmission of SARS-CoV-2, and about the course and severity of COVID-19, were common. For example, two thirds of respondents believed that everyone with COVID-19 would eventually become severely ill. Increased hand washing and avoiding crowds were the most reported strategies to prevent the spread of SARS-CoV-2. Use of face masks was more common among urban residents (22.5%) than among rural residents (5.0%). Conclusion: Despite widespread access to information about the COVID-19 pandemic, gaps in knowledge about COVID-19 persist in this population. The adoption of preventive strategies remains limited, possibly due to limited perceived risk of infection among a large fraction of the population.


title: Scientific solidarity in the face of the COVID-19 pandemic: researchers, publishers, and medical associations

text: In the face of COVID-19, the scientific community has rapidly come together to address this outbreak in an open and collaborative manner to support the global response to this outbreak by rapidly sharing and highlighting research data and relevant findings COVID-19 research is being published at a furious pace Over 6,000 articles have been published as of 20 April 2020, and at least 15 online resource centers/websites for COVID-19 have been created by publishers to enable fast and free access to the latest research, evidence, and data available Moreover, many evidence-based guidelines for COVID-19 have been issued based on academic articles and summaries of the experiences of frontline medical personnel Various academic medical associations are also actively sharing information and providing technical support As an example, 93 guides/proposals/responses to COVID-19 have been issued so far by 50 medical associations in Japan However, few publications and national situation reports have provided information on the number of infected healthcare workers (HCWs) More publications and national situation reports are urgently needed to provide scientific information to devise specific infection prevention and control measures in order to protect HCWs from infection


title: Epidemiological Identification of A Novel Pathogen in Real Time: Analysis of the Atypical Pneumonia Outbreak in Wuhan, China, 2019–2020

text: Virological tests have now shown conclusively that a novel coronavirus is causing the 2019–2020 atypical pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing. Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of eleven pathogens that have previously caused cases of atypical pneumonia. The probability that the current outbreak is due to “Disease X” (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued. The probability (expressed as a percentage) that Disease X is driving the outbreak was assessed as over 29% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 January 2020, the inferred probability of Disease X was over 49%. We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, which uses only routinely observed non-virological data, can aid ongoing risk assessments in advance of virological test results becoming available.


Offline: 2019-nCoV outbreak—early lessons


title: Product design and manufacturing system operations: An integrated approach for product customization

text: Abstract To stay competitive in the marketplace, manufacturing firms that rely on high product variety should involve the customer in the product design process. However, customer interaction with the product at the design level could compromise the product functionality and the operational arrangement of the manufacturing system. To address these challenges, we aim to align the preferences of the design and manufacturing teams within a manufacturing firm in the context of mass customization. The preference of the design team is in terms of product modularity, associated with product upgradeability and flexibility. In the manufacturing team, complexity is a preference associated with cost and quality. In our research, the motivation for selecting these attributes is that product modularity is used to deal with product variety, and complexity is related to the uncertainty of product manufacturing. These two perspectives could support the manufacturing firm decision of selecting which product architecture is more convenient for a given operational arrangement and vice versa. We use a Multi-Attribute Utility function to assess the preferences of the design and manufacturing teams in terms of modularity and manufacturing complexity. We analyze the functional requirements of the product and then their mapping into the product architecture. Finally, we study the relationship of the product components to the operational arrangement of the manufacturing system. In addition, we include a case study in which we analyze two products and their relationship to a single manufacturing system, where the highest utility produces the best relationship between product design and manufacturing configuration complexity. By using this integrated approach, a manufacturer can decide to update the product design, the related operational configuration, or both.


title: Estimation and monitoring of COVID-19 transmissibility from publicly available data

text: The COVID-19 pandemic began in the city of Wuhan, China, at the end of 2019 and quickly spread worldwide. The disease is caused by contact with the SARS-CoV-2 virus, which probably jumped from an animal host to humans. SARS-CoV-2 infects various tissues in the body, notably the lungs, and patients usually die from respiratory complications. Mathematical models of the disease have been instrumental to guide the implementation of mitigation strategies aimed at slowing the spread of the disease. One of the key parameters of mathematical models is the basic reproduction ratio R0, which measures the degree of infectivity of affected individuals. The goal of mitigation is to reduce R0 as close or below 1 as possible, as it means that new infections are in decline. In the present work, we use the recursive least-squares algorithm to establish the stochastic variability of a time-varying R0(t) from eight different countries: Argentina, Belgium, Brazil, Germany, Italy, New Zealand, Spain, and the United States of America. The proposed system can be implemented as an online tracking application providing information about the dynamics of the pandemic to health officials and the public at large.


title: The disproportionate rise in COVID-19 cases among Hispanic/Latinx in disadvantaged communities of Orange County, California: A socioeconomic case-series

text: Background: Recent epidemiological evidence has demonstrated a higher rate of COVID-19 hospitalizations and deaths among minorities. This pattern of race-ethnic disparities emerging throughout the United States raises the question of what social factors may influence spread of a highly transmissible novel coronavirus. The purpose of this study is to describe race-ethnic and socioeconomic disparities associated with COVID-19 in patients in our community in Orange County, California and understand the role of individual-level factors, neighborhood-level factors, and access to care on outcomes. Methods: This is a case-series of COVID-19 patients from the University of California, Irvine (UCI) across six-weeks between 3/12/2020 and 4/22/2020. Note, California's shelter-in-place order began on 3/19/2020. Individual-level factors included race-ethnicity status were recorded. Neighborhood-level factors from census tracts included median household income, mean household size, proportion without a college degree, proportion working from home, and proportion without health insurance were also recorded. Results: A total of 210-patients tested were COVID-19 positive, of which 73.3% (154/210) resided in Orange County. Hispanic/Latinx patients residing in census tracts below the median income demonstrated exponential growth (rate = 55.9%, R2 = 0.9742) during the study period. In addition, there was a significant difference for both race-ethnic (p < 0.001) and income bracket (p = 0.001) distributions prior to and after California's shelter-in-place. In addition, the percentage of individuals residing in neighborhoods with denser households (p = 0.046), lower levels of college graduation (p < 0.001), health insurance coverage (p = 0.01), and ability to work from home (p < 0.001) significantly increased over the same timeframe. Conclusions and Relevance: Our study examines the race-ethnic disparities in Orange County, CA, and highlights vulnerable populations that are at increased risk for contracting COVID-19. Our descriptive case series illustrates that we also need to consider socioeconomic factors, which ultimately set the stage for biological and social disparities.


title: COVID-19 Epidemic Forecast in Different States of India using SIR Model

text: The epidemiological data up to 12th May 2020 for India and its 24 states has been used to predict COVID-19 outbreak within classical SIR (Susceptible-Infected-Recovered) model. The basic reproduction number R0 of India is calculated to be 1.15, whereas for various states it ranges from 1.03 in Uttarakhand to 7.92 in Bihar. The statistical parameters for most of the states indicates the high significance of the predicted results. It is estimated that the epidemic curve flattening in India will start from the first week of July and epidemic may end in the third week of October with final epidemic size ~1,75,000. The epidemic in Kerala is in final phase and is expected to end by first week of June. Among Indian states, Maharashtra is severely affected where the ending phase of epidemic may occur in the second week of September with epidemic size of ~55,000. The model indicates that the fast growth of infection in Punjab is from 27th April 2020 to 2nd June 2020, thereafter, curve flattening will start and the epidemic is expected to finished by the first week of July with the estimated number of ~3300 infected people. The epidemic size of COVID-19 outbreak in Delhi, West Bengal, Gujrat, Tamil Nadu and Odisha can reach as large as 24,000, 18,000, 16,000, 13,000 and 11,000, respectively, however, these estimations may be invalid if large fluctuation of data occurs in coming days.


title: Test Agreement Between Roche Cobas 6800 and Cepheid GeneXpert Xpress SARS-CoV-2 Assays at High Cycle Threshold Ranges

text: The SARS-CoV-2 pandemic has changed the face of the globe and upended the daily lives of billions. In an effort to bring mass-testing to as many as possible, multiple diagnostic tests including molecular, antigen detection and serological assays have been rapidly developed. However, there is very little information on positive test agreement across modalities, especially for lower viral loads. Thirty-five nasopharyngeal samples that had cycle threshold (Ct) values greater than 30.0 from the Roche cobas 6800 assay were run on the Cepheid GeneXpert Xpress SARS-CoV-2 assay. Ct values ranged from 30.1 to 37.9 (mean 36.7 ± 1.9) on the Roche cobas 6800 assay and 24.6 to 42.4 (mean 32.8±4.1) on the Cepheid assay. There was a bias of 0.33 ± 3.21, (mean difference −1.59, 95% limits of agreement −5.97, 6.63) signifying close agreement between the 2 instruments with a high standard deviation. The close test agreement between the cobas 6800 and GeneXpert at high Ct values allows for utilization of both assays interchangeable in accordance with testing algorithms.


COVID-19 Provides An Opportunity to Reassess How Frequent and How Extensive Elective Spine Surgery Should Be


title: Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results

text: Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/.


The Case for Cannabis: Advising: Cannabis: Users about COVID-19


title: SARS-CoV-2 On-the-Spot Virus Detection Directly From Patients

text: Many countries are currently in a lockdown state due to the SARS-CoV-2 pandemic. One key aspect to transition safely out of lockdown is to continuously test the population for infected subjects. Currently, detection is performed at points of care using quantitative reverse-transcription PCR (RT-qPCR) and requires dedicated professionals and equipment. Here, we developed a protocol based on Reverse Transcribed Loop-Mediated Isothermal Amplification (RT-LAMP) for detection of SARS-CoV-2, directly from crude nose and throat swabs. We applied this protocol to over 180 suspected patients, and determined its specificity and sensitivity by comparison to their RT-qPCR results. In addition, we further succeeded to apply the protocol on self-sampled saliva from confirmed cases. Since the proposed protocol provides results on-the-spot, and can detect SARS-CoV-2 from saliva, it can allow simple and continuous surveillance of the community.


title: Loss of pH switch unique to SARS-CoV2 supports unfamiliar virus pathology

text: Cell surface receptor engagement is a critical aspect of viral infection. This paper compares the dynamics of virus-receptor interactions for SARS-CoV (CoV1) and CoV2. At low (endosomal) pH, the binding free energy landscape of CoV1 and CoV2 interactions with the angiotensin-converting enzyme 2 (ACE2) receptor is almost the same. However, at neutral pH the landscape is different due to the loss of a pH-switch (His445Lys) in the receptor binding domain (RBD) of CoV2 relative to CoV1. Namely, CoV1 stabilizes a transition state above the bound state. In situations where small external strains are applied by, say, shear flow in the respiratory system, the off rate of the viral particle is enhanced. As a result, CoV1 virions are expected to detach from cell surfaces in time scales that are much faster than the time needed for other receptors to reach out and stabilize virus attachment. On the other hand, the loss of this pH-switch, which sequence alignments show is unique to CoV2, eliminates the transition state and allows the virus to stay bound to the ACE2 receptor for time scales compatible with the recruitment of additional ACE2 receptors diffusing in the cell membrane. This has important implications for viral infection and its pathology. CoV1 does not trigger high infectivity in the nasal area because it either rapidly drifts down the respiratory tract or is exhaled. By contrast, this novel mutation in CoV2 should not only retain the infection in the nasal cavity until ACE2-rich cells are sufficiently depleted, but also require fewer particles for infection. This mechanism explains observed longer incubation times, extended period of viral shedding, and higher rate of transmission. These considerations governing viral entry suggest that number of ACE2-rich cells in human nasal mucosa, which should be significantly smaller for children (and females relative to males), should also correlate with onset of viral load that could be a determinant of higher virus susceptibility. Critical implications for the development of new vaccines to combat current and future pandemics that, like SARS-CoV2, export evolutionarily successful strains via higher transmission rates by viral retention in nasal epithelium are also discussed.


title: COVID-19 Healthcare Demand Projections: Arizona

text: Beginning in March 2020, the United States emerged as the global epicenter for COVID-19 cases. In the ensuing weeks, American jurisdictions attempted to manage disease spread on a regional basis using non-pharmaceutical interventions (i.e. social distancing), as uneven disease burden across the expansive geography of the United States exerted different implications for policy management in different regions. While Arizona policymakers relied initially on state-by-state national modeling projections from different groups outside of the state, we sought to create a state-specific model using a mathematical framework that ties disease surveillance with the future burden on Arizona's healthcare system. Our framework uses a compartmental system dynamics model using an SEIRD framework that accounts for multiple types of disease manifestations for the COVID-19 infection, as well as the observed time delay in epidemiological findings following public policy enactments. We use a bin initialization logic coupled with a fitting technique to construct projections for key metrics to guide public health policy.


title: Digital force prediction for milling

text: Abstract This paper presents a fully digital, integrated approach for milling force prediction with arbitrary end mill-work material combinations. The approach includes: 1) structured light scanning to identify the end mill’s cutting edge macro-geometry along the tool axis; 2) structured light scanning to measure the cutting edge cross-sectional rake and relief profiles; 3) finite element analysis of orthogonal cutting to determine the force model coefficients that relate the force to chip area using the work material’s constitutive model and tool’s rake and relief profiles; and 4) time domain simulation with inputs that include the measured cutting edge macro-geometry, finite element-based force model, and measured structural dynamics. Milling force predictions are compared to in-process measurements to validate the method.


title: Association of BMI and Obesity with Composite poor outcome in COVID-19 adult patients: A Systematic Review and Meta-Analysis

text: Aim: This study aimed to evaluate the association between obesity and composite poor outcome in coronavirus disease 2019 (COVID-19) patients. Methods: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles in COVID-19 adult patients and obesity based on classification of Body Mass Index (BMI) and composite poor outcome which consist of mortality, morbidity, admission of Intensive Care Unit (ICU), mechanical ventilation, Acute Respiratory Distress Syndrome (ARDS), and severe COVID-19. Results: Nine studies were included in meta-analysis with 6 studies presented BMI as continuous outcome and 3 studies presented BMI as dichotomous outcome (obese and non-obese). Most studies were conducted in China (55.5%) with remaining studies from French, Germany, and United States (US). COVID-19 patients with composite poor outcome had higher BMI with mean difference 0.55 kg/m2 (95% CI 0.07-1.03, P=0.02). BMI [≥]30 (obese) was associated with composite poor outcome with odds ratio 1.89 (95% CI 1.06-3.34, P=0.03). Multivariate meta-regression analysis by including three moderators: age, hypertension, and Diabetes Mellitus type 2 (DM type 2) showed the association between obesity and composite poor outcome was affected by age with regression coefficient =-0.06 and P=0.02. Subgroup analysis was not performed due to the limited number of studies for several outcomes. Conclusion: Obesity is a risk factor of composite poor outcome of COVID-19. On the other hand, COVID-19 patients with composite poor outcome have higher BMI. BMI is an important routine procedure that should be assessed in the management of COVID-19 patients and special attention should be given to patients with obesity. Keywords: Covid-19, Obesity, Body Mass Index


title: The effect of ambient temperature on worldwide COVID-19 cases and deaths - an epidemiological study

text: Background The role of ambient temperature in the spread of SARS-CoV-2 infections and subsequent deaths due to COVID-19 remains contentious. Coronaviruses such as the 2003 SARS-CoV showed an increased risk of transmission during cooler days. We sought to analyse the effects of ambient temperature on SARS-COV-2 transmission and deaths related to the virus. Methods The world population of COVID-19 cases and attributable deaths from the 23rd January 2020 to 11th April 2020 were analysed. Temperature 5 days before cases and 23 days prior to deaths (to account for the time lag of incubation period and time from symptoms to death) was compared to the average temperature experienced by the world population. Results The total number of cases during this period was 1,605,788 and total number of deaths was 103,471. The median temperature at the time of COVID-19 infection was 9.12C (10-90th percentile 4.29-17.97C) whilst the median temperature of the world population for the same period was 9.61C warmer at 18.73C (10-90th percentile 4.09-28.49C) with a notional p-value = 5.1 x10-11. The median temperature at the time of a COVID-19 death was 9.72C (10-90th percentile 5.39-14.11C) whilst the median temperature of the world population was 7.55C warmer at 17.27C (10-90th percentile 2.57C-27.76C) with a notional p-value = 1.1 x10-10. 80% of all COVID-19 related cases and deaths occurred between 4.29C and 17.97C. Conclusion A definitive association between infection rate and death from COVID-19 and ambient temperature exists, with the highest risk occurring around 9C. Governments should maintain vigilance with containment strategies when the ambient temperatures correspond to this highest risk.


title: 1 vol. (15,5×23,5 cm), 429+xvi pages. Prix: $54.00; B.—RNA viruses. 1 vol (15,5×23,5 cm), 694+xxii pages. Prix: $79.00 Kurstak E.

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FORSCHUNG, LICHT UND COVID-19


title: Continuous Electroencephalography (cEEG) Characteristics and Acute Symptomatic Seizures in COVID-19 Patients

text: Background: Neurological manifestations of COVID-19 have only recently been described, with a paucity of literature reporting the potential relationship between COVID-19 and acute symptomatic seizures. Two prior studies found no clinical or electrographic seizures in their cohorts of COVID-19 patients with altered mental status (AMS) and clinical seizure-like events (SLEs). Methods: In this retrospective cohort study, 22 critically-ill COVID-19 patients above the age of 18 years who underwent EEG (electroencephalography) monitoring between April 20th, 2020 and May 20th, 2020 were studied. 19 patients underwent continuous EEG (cEEG) for at least 24 hours, and 3 patients underwent routine EEGs (<1 hour). Demographics including age, gender, comorbid medical, and neurological conditions were collected. Clinical variables included EEG findings, anti-seizure medications, discharge disposition, and survival. Findings: 17 patients underwent EEG monitoring for unexplained altered mental status changes and 5 patients underwent monitoring for a seizure-like event. 5 patients had epileptiform abnormalities on EEG (4 patients on cEEG, 1 on routine EEG); and only 2 of 5 epileptic EEG patients had a prior history of epilepsy. 2 patients in our cohort had electrographic seizures in the absence of prior epilepsy history. No patients with epileptiform abnormalities or electrographic seizures had acutely abnormal neuroimaging on CT or MRI. Interpretation: Encephalopathic COVID-19 positive patients had a range of EEG abnormalities, and a higher proportion of patients in this series had electrographic seizures than previous literature suggests. This may be influenced by the duration of monitoring with cEEG and the use of a 21 channel electrode system. cEEG findings may help to guide antiseizure medical therapy, as well as the workup of altered mental status in the setting of unremarkable neuroimaging. Funding: No funding was used for this study.