title: Phase adjusted estimation of the number of 2019 novel coronavirus cases in Wuhan, China

text: An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV / SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R0 of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of Rt. In the first assumption, Rt was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with Rt = 1.9, 2.6 or 3.1. The number of infections would reach 11,044, 70,258 and 227,989, respectively, by 29 February 2020. In the second assumption, Rt was assumed to gradually decrease at different phases from high level of transmission (Rt = 3.1, 2.6 and 1.9) to below 1 (Rt = 0.9 or 0.5) owing to increasingly implemented public heath intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077-84,520 or 55,869-81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce Rt to an ideal level and control the infection.


title: Ethnic and regional variation in hospital mortality from COVID-19 in Brazil

text: Background: The COVID-19 pandemic is quickly spreading throughout Brazil, which is rapidly ascending the ranking of countries with the highest number of cases and deaths. A particularly unstable federal regime and fragile socioeconomic situation is likely to have contributed to the impact of the disease. Amid this crisis there is substantial concern in the possible socioeconomic, geopolitical and ethnic inequity of the impact of COVID-19 on the country's particularly diverse population. Methods: We performed a cross-sectional observational study of COVID-19 hospital mortality using observational data from the SIVEP-Gripe dataset. We present descriptive statistics to quantify the COVID-19 pandemic in Brazil. We assess the importance of regional factors such as education, income and health either on a state-by-state basis or by splitting Brazil into a North and a Central-South region. Mixed-effects survival analysis was used to estimate the effects of ethnicity and comorbidity at an individual level in the context of regional variation. Findings: Our results show that, compared to branco comparators, hospitalised pardo and preto Brazilians have significantly higher risk of mortality, with hazard ratios and 95% CI of 1.47 (1.33-1.58) and 1.32 (1.15-1.52), respectively. In particular, pardo ethnicity was the second most important risk factor (after age). We also found that hospitalised Brazilians in North regions tend to have more comorbidities than in the Central-South, with similar proportions between the various ethnic groups. Finally, we found that states in the North have a higher hazard ratio as compared to the Central-South, and that Rio de Janeiro obtained one of the highest hazard ratios, similar to the ones of the more underdeveloped Pernambuco and Amazonas. Interpretation: Our results can be interpreted according to the interplay of two independent, but correlated, effects: i) mortality by COVID-19 increases going North (vertical effect), ii) mortality increases for the pardo and preto population (horizontal effect). We speculate that the vertical effect is driven by increasing levels of comorbidity in Northern regions where levels of socioeconomic development are lower, whereas the horizontal effect may be related to lower levels of healthcare access or availability (including intensive care) for pardo and preto Brazilians. For most states the vertical and horizontal effects are correlated giving a larger cumulative mortality. However, Rio de Janeiro was found to be an outlier to this trend: It has an ethnicity composition (horizontal effect) similar to the states in the North region, despite high levels of socioeconomic development (vertical effect). Our analysis motivates an urgent effort on the part of Brazilian authorities to consider how the national response to COVID-19 can better protect pardo and preto Brazilians as well as the population of poorer states from their higher death risk from SARS-CoV-2 infection.


title: Extensive weight loss can reduce immune age by altering IgG N-glycosylation

text: Background Obesity represents a global health threat, and is associated not only with exponentially increased cardiometabolic morbidity and mortality, but with adverse clinical outcomes in patients infected with SARS-CoV-2 as well. Enzymatic attachment of complex oligosaccharides to proteins (glycosylation) is highly responsive to numerous (patho)physiological conditions and ageing, which is perhaps best exemplified on IgG. The prospect of immune age reduction, by reverting induced glycosylation changes through metabolic intervention, opens many possibilities. Herein, we have investigated whether weight loss interventions affect inflammation- and ageing-related glycosylation alterations, in a longitudinal cohort of bariatric-surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal TwinsUK cohort. Methods IgG and plasma N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet and then to bariatric surgery, across multiple timepoints. Similarly, plasma glycome was analysed in 1,680 TwinsUK participants and longitudinally monitored during a 20-year follow-up. Findings Low-calorie diet induced marked increase in low branched and significant decrease in highly branched, more complex plasma N-glycans - the change opposite to the one typically observed in inflammatory conditions. Bariatric surgery resulted in extensive, gradual alterations in IgG glycome, that accompanied progressive weight loss during one year follow-up. We observed significant increase in digalactosylated and sialylated, and substantial decrease in agalactosylated and core fucosylated IgG glycans. In general, such IgG glycan profile is associated with a younger biological age and reflects enhanced anti-inflammatory IgG potential. The TwinsUK cohort replicated weight loss-associated agalactosylation decrease and digalactosylation increase, estimated through BMI decrease over a 20-year period. Interpretation Altogether, these findings highlight that weight loss substantially affects both plasma and IgG N-glycosylation, resulting in improved biological and immune age.


Coronavirus Disease 2019 (COVID-19);Perspective of Pakistan COMMENT


title: Strategies for Controlling the Spread of COVID-19

text: We consider a deterministic epidemiological compartmental model that includes age and social contact structure for the COVID-19 crisis and explore the consequences of different strategies for easing current lockdown measures that are in place in many countries. We apply the model to the specific circumstances in the state of New Jersey, in the United States of America. As expected, only a rigorous program of testing, tracing and isolation of cases will allow the state to ease its lockdown with a reduced number of deaths. We also find that a slightly earlier date of lockdown, while reducing the number of deaths in the short term, will only reduce the total number of deaths in the long run if the ensuing strategies in easing the lockdown are carried out with the aforementioned test, trace and isolation program. Otherwise, a slightly earlier lockdown will result in increased deaths as the expected second wave of infection sweeps through the state in the coming months.


title: Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial

text: Aims: Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.


title: A discrete-time-evolution model to forecast progress of Covid-19 outbreak

text: Based on well-known infection models, we constructed a new model to forecast the propagation of the Covid-19 pandemic which yields a discrete-time evolution with one day interval. The proposed model can be easily implemented with daily updated data sets of the pandemic publicly available by many sources. It has only two adjustable parameters and is able to predict the evolution of the total number of infected people in a country for the next 14 days, if parameters do not change during this time. The model incorporates the main aspects of the disease such as the the fact that there are asymptomatic and symptomatic phases (both capable of propagating the virus), and that these phases take almost two weeks before the infected person status evolves to the next (asymptomatic becomes symptomatic or symptomatic becomes either recovered or dead). One advantage of the model is that it gives directly the number of total infected people in each day (in thousands, tens of thousands or hundred of thousands). The model was tested with data from Brazil, UK and South Korea, it predicts quite well the evolution of the disease and therefore may be an useful tool to estimate the propagation of the disease.


title: Private Health Sector in India: Ready and willing, yet underutilized in the Covid-19 pandemic.

text: Background: The private medical sector is a resource that must be estimated for efficient inclusion into public healthcare during pandemics. Methods: A survey was conducted among private healthcare workers to ascertain their views on the potential resources that can be accessed from the private sector and methods to do the same. Results: There were 213 respondents, 80% of them being doctors. Nearly half (47.4%) felt that the contribution from the private medical sector has been suboptimal. Areas suggested for improved contributions by the private sector related to patient care (71.8%) and provision of equipment (62.4%), with fewer expectations (39.9%) on the research front. Another area of deemed support was maintaining continuity of care for non-COVID patients using virtual consultation services (77.4%), tele-consultation being the preferred option (60%). 58.2% felt that the Government had not involved the private sector adequately; and 45.1% felt they should be part of policy-making. Conclusion: A streamlined pathway to facilitate the private sector to join hands with the public sector for a national cause is the need of the hour. Through our study, we have identified gaps in the current contribution by the private sector and identified areas in which they could contribute, by their own admission.


title: A Machine Vision Based Monitoring System for the LCD Panel Cutting Wheel Degradation

text: Abstract In Liquid Crystal Display (LCD) panel cutting, in-line monitoring of tool wear is important to maintain the dimension precision of finished products and to avoid possible damages to the workpiece. However, limited by the space for camera installation and the miniature structure of the tool itself, monitoring the wear of LCD panel cutting wheel is not a simple task. In this research, we proposed a machine-vision based instrumentation system and a systematic methodology for cutting wheel degradation monitoring. The proposed method describes the degradation of cutting wheel by estimating the tooth height of the cutting wheel blade based on the partially observed random samples. A series of methods are proposed to improve the reliability of the results. The effectiveness of the proposed method is validated based on the field data that is collected from three maintenance cycles. The validation results demonstrate consistent degradation trend of the cutting wheel over production cycles.


title: Towards intervention development to increase the uptake of COVID-19 vaccination among those at high risk: outlining evidence-based and theoretically informed future intervention content

text: Objectives: Development of a vaccine against COVID-19 will be key to controlling the pandemic. We need to understand the barriers and facilitators to receiving a future COVID-19 vaccine so that we can provide recommendations for the design of interventions aimed at maximising vaccine uptake by the public. Design: Cross-sectional survey with high-risk individuals (older adults aged 65+ and patients with chronic respiratory disease). Methods: During the UK's early April 2020 lockdown period, participants (N=527; mean age = 59.5 years) completed an online questionnaire assessing willingness to receive a COVID-19 vaccine, perceptions of COVID-19, and intention to receive other vaccinations. The questionnaire included a free text response (n=502) to examine barriers and facilitators to uptake. The Behaviour Change Wheel informed the analysis of these responses, which were coded to the Theoretical Domains Framework (TDF). Behaviour change techniques (BCTs) were identified. Results: Eighty-six percent of respondents want to receive a COVID-19 vaccine. This was positively correlated with the perception that COVID-19 will continue for a long time, and negatively associated with the perception that the media has over-exaggerated the risk. The majority of barriers and facilitators could be mapped onto the beliefs about consequences TDF domain, with themes relating to personal health, health consequences to others, concerns of vaccine safety, and severity of COVID-19. Conclusions: Willingness to receive a COVID-19 vaccination is currently high among high-risk individuals. Mass media interventions aimed at maximising vaccine uptake should utilise the BCTs of information about health, emotional, social and environmental consequences, and salience of consequences.


title: Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission

text: Background: Influenza virus presents a significant challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid diagnosis of infection, rationalising antimicrobial therapy, and supporting interventions for infection control. This study aimed to evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings. Methods: We conducted Nanopore metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic testing. We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data. Results: Metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses compared with the diagnostic standard (Cepheid Xpress/BioFire FilmArray Respiratory Panel). We identified a H3N2 genome with the oseltamivir resistant S331R mutation in the NA protein, potentially associated with the emergence of a distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in the infectious diseases ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant strain circulating in the community. We also detected a range of other potentially pathogenic viruses and bacteria from the metagenome. Conclusion: Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Generation of full genomes can contribute to the investigation and management of nosocomial outbreaks.


title: Community Memory of COVID-19 Infections Post Lockdown as a Surrogate for Incubation Time

text: If the knowledge of the incubation time is helpful in designing non-pharmaceutical interventions such as quarantine measures, can one use the number of cases arising after a lockdown to check (a) if our assumptions of the incubation time were correct and (b) if the quarantine measures were as successful as they could theoretically be. These are the two questions we raise by studying the number of new cases arising after lockdowns in a few European countries. The analysis which purely relies on the publicly available data of the numbers of new infections, rather than extensive contact tracing of individual patients, suggests a memory of the infections in the community with a median of 13.3 days. This distribution of the memory of infections which may even be considered as a surrogate of the incubation time in a perfect lockdown, suggests that even a perfect quarantine of 30 days is only 90% complete.


title: Assessment of iranian nurses’ knowledge and anxiety toward covid-19 during the current outbreak in iran

text: Background: The world is affected by the Corona Virus Disease 2019 (COVID-19). Because of their direct contact with patients, health workers, especially nurses, play critical roles in the prevention of the COVID-19 outbreak through proper care and preventive procedures. Objectives: This study aimed to measure the awareness level of nurses in Shiraz, Iran, during the current COVID-19 outbreak. Methods: A self-administered questionnaire containing knowledge questions was distributed to 85 participants to complete. Results: More than half of the nurses (56.5%) had good knowledge about sources, transmission, symptoms, signs, prognosis, treatment, and mortality rate of COVID-19. The sources of information for the nurses were the World Health Organization and the Ministry of Health (55.29%), social applications (48.23%), and media (42.35%). Conclusions: Nurses had almost good knowledge of COVID-19. However, the WHO and the Ministry of Health still must provide more information for the medical staff for better control of the infectious disease.


title: Novel coronavirus (COVID-19) Outbreak in Iraq: The First Wave and Future Scenario

text: The first patient with COVID-19 was reported in Iraq on 24 February 2020 for the Iranian student came from Iran. As of 24 May 2020, the confirmed cases of COVID-19 infections reached 4469, with 160 deaths and 2738 patients were recovered from the infection. Significant public health strategies have been implemented by the authorities to contain the outbreak nationwide. Nevertheless however, the number of cases is still rising dramatically. Here, we aim to describe a comprehensive and epidemiological study of all cases diagnosed in Iraq by 24 May 2020. Most of the cases were recorded in Baghdad followed by Basra and Najaf. About 45% of the patients were female (with 31% deaths of the total cases) and 55% were male (with 68% deaths of the total cases). Most cases are between the ages of (20-59) years old, and (30-39) years are the most affected range (19%) Approximately (8%) of cases are children under 10 years old. Iraq has shown a cure rate lower than those reported by Iran, Turkey and Jordan; and higher than Saudi Arabia and Kuwait. Healthcare workers represented about (5%) of the total confirmed cases. These findings enable us to understand COVID-19 epidemiology and prevalence in Iraq that can alert the our community to the risk of this novel coronavirus and serve as a baseline for future studies.


title: Adhesive Contact Between Cylindrical (Ebola) and Spherical (SARS-CoV-2) Viral Particles and a Cell Membrane

text: A critical event during the process of cell infection by a viral particle is attachment, which is driven by adhesive interactions and resisted by bending and tension. The biophysics of this process has been studied extensively but the additional role of externally applied force or displacement has generally been neglected. In this work we study the adhesive force-displacement response of viral particles against a cell membrane. We have built two models: one in which the viral particle is cylindrical (say, representative of filamentous virus such as Ebola) and another in which it is spherical (such as SARS-CoV-2 and Zika). Our interest is in initial adhesion, in which case deformations are small and the mathematical model for the system can be simplified considerably. The parameters that characterize the process combine into two dimensionless groups that represent normalized membrane bending stiffness and tension. In the limit where bending dominates, for sufficiently large values of normalized bending stiffness, there is no adhesion between viral particles and the cell membrane without applied force. (The zero-external-force contact width and pull-off force are both zero.) For large values of normalized membrane tension, the adhesion between virus and cell membrane is weak but stable. (The contact width at zero external force has a small value.) Our results for pull-off force and zero force contact width help to quantify conditions that could aid the development of therapies based on denying the virus entry into the cell by blocking its initial adhesion.


title: Reconsidering global mobility–distancing from mass cruise tourism in the aftermath of COVID-19

text: The mass cruise tourism industry (MCTI) is inscribed in a neoliberal production of tourism space that promotes the economic, sociocultural and environmental marginalization of cruise destinations. With cruise tourism halted as a result of the COVID-19, but likely to resume in 2021, I question the relevance of this form of tourism and propose future development alternatives aligned with deglobalisation and degrowth of the industry. Power relations with destinations communities can be critiqued using the concepts of global mobility and local mobility to show that the former, imperative for the deployment of mass cruise tourism, is a weakness for the industry in a post-pandemic perspective of reduced mobility. Destinations must use the industry’s dependence on global mobility as leverage to transform the balance of power in their favor and promote local mobility. They must embrace radical solutions to take control of their territory to favor a transition from “Growth for development” to “Degrowth for liveability”. Host territories, relying on national and regional governance, should gradually ban or restrict the arrival of mega-cruise ships, implement policies that promote the development of a niche cruise tourism industry (NCTI) with small ships and develop a fleet controlled by local actors.


title: Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study

text: Aim: To evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID-19) infection and hospitalization. Methods: The study population included the 14,000 members of Leumit Health Services who were tested for COVID-19 infection from February 1st to April 30th, 2020, and who had at least one previous blood test for plasma 25(OH)D level. "Suboptimal" or "low" plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below 30 ng/mL. Results: Of 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval [CI] 18.41-19.59) vs. 20.55 (95% CI 20.32-20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01-4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI 1.08-1.95, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI 0.98-4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19.


title: Do latitude and ozone concentration predict Covid-2019 cases in 34 countries?

text: In this paper, I used multivariate linear regression analysis to determine if latitude and ozone concentration predict Covid-2019 cases in 34 countries worldwide. Data pertaining to Covid-2019 cases were extracted from Worldometer. Ozone concentration levels were taken from the open-access database of World Ozone and Ultraviolet Radiation Data Centre (WOUDC). Latitude of specific area where measurement took place was also provided in the database. Preliminary Kendall rank correlation test revealed that Covid-2019 incidence was positively and significantly related to ozone concentration; however, incidence was not significantly related to latitude. Using multivariate linear regression, a statistically significant link between ozone concentration and Covid-2019 incidence in 34 countries was established; however, I found no statistical association between latitude and Covid-2019 incidence refuting previous claims. Prompt health actions should be developed for areas with high ozone concentration in the present and possibly, future outbreaks; however, extensive laboratory analysis should be conducted to further confirm the findings of the study. Nevertheless, the results of this study could serve as a basis for further clinical and large-scale studies.


title: Applied Machine Learning in Agro-Manufacturing Occupational Incidents

text: Abstract Commercial grain elevators are hazardous agro-manufacturing work environments where workers are prone to serious and life-threatening injuries. The aim of this study is to give insight into safety risks in grain handling facilities through information processing of workers’ compensation data on agro-manufacturing occupational incidents within commercial grain elevators in the Midwest region of the United States between 2008 and 2016. The severity of occupational incidents is determined by total dollar amount incurred on medical, indemnity, and other expenses in workers’ compensation claims. The most important factors that affect the cost escalation of occupational incidents are extracted using bootstrap partitioning method, and are applied as input for constructing two machine learning models: random forests decision trees, and naïve Bayes. Both models show high accuracy (87.64% and 92.78% respectively) in predicting that a future claim is classified as either low or medium, severity. The models contribute to identifying high injury risk groups, and prevalent incident causes, allowing a more research-based focused intervention effort in grain handling workplaces. In addition, the results are applicable in forecasting cost severity of future claims, and identifying factors that contribute to the escalation of claims costs.


title: Knowledge, Attitude, and Practices of Healthcare Workers Regarding the Use of Face Mask to Limit the Spread of the New Coronavirus Disease (COVID-19)

text: Introduction Many countries including Pakistan are currently using face masks in their pandemic control plans. Being highly prevalent, the correct use of these masks is particularly important, as an incorrect use and disposal may actually increase the rate of transmission. The purpose of this study was to investigate the knowledge, attitude, and practices of healthcare workers (HCWs) in wearing a surgical face mask to limit the spread of the new coronavirus disease 2019 (COVID-19). Materials and Methods This survey was conducted by interviewing HCWs using a questionnaire consisting of the basic demographic characteristics, and the knowledge, attitude, and practices regarding the use of surgical face mask to limit the new COVID-19 exposure. Each correct answer was scored 1 and each incorrect answer scored 0. The total number of questions was 16, and the final score was calculated and then labeled according to the percentage (out of 16) of correct responses as good (>80%), moderate (60-80%), and poor (<60%). Results A total of 392 participants with a mean age of 42.37 ± 13.34 years (341 males and 51 females) were included in the study. The overall final results were good in 138 (35.2%), moderate in 178 (45.4%), and poor in 76 (19.3%). Around 43.6% of participants knew about the correct method of wearing the masks, 68.9% knew that there are three layers, 53% stated that the middle layer act as a filter media barrier, and 75.5% knew the recommended maximum duration of wearing it. The majority (88.2%) of participants knew that a cloth face mask is not much effective, around 79.8% knew that used face mask cannot be re-used, and 44.8% knew about the yellow-coded bag for disposal. Conclusions Knowledge, attitude, and practice of HCWs regarding the use of face masks were found to be inadequate. Studied HCWs had a positive attitude but moderate-to-poor level of knowledge and practice regarding the use of face mask. HCWs and general public awareness campaigns regarding the proper use of face mask by utilizing all social media available resources would be helpful during this pandemic.


title: Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation

text: Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins—receptor binding domain (RBD), S1 subunit and S ectodomain—in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 Å proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.


title: Mental Health and Its Influencing Factors among Self-Isolating Ordinary Citizens during the Beginning Epidemic of COVID-19

text: The study aims to investigate the current prevalence of anxiety, depression and PTSD among self-isolating general population, mainly college students, in the context of COVID-19 from January 26, 2020 to February 2, 2020, and to provide guidance for the general public. A total of 515 self-isolating people completed the online questionnaire including questions asking for demographic information and the impact of COVID-19 on their (mental and physical) health. The results showed that prevalence of anxiety, depression and PTSD was 14.4, 29.7, and 5.6%, respectively. Given the high prevalent but poorly recognized psychological disorders among self-isolating population under COVID-19, suggestions are provided in enhancing the media management in hope to improve self-isolating people’s understanding of the epidemic and themselves and, ultimately, the health and emotional well-being of the society.


Guidelines for Infection Prevention and Control in Sonography: Reprocessing the Ultrasound Transducer


Gastrointestinal cancer pathways may breakdown due to COVID-19


title: Model the transmission dynamics of COVID-19 propagation with public health intervention

text: In this work, a researcher develop $SHEIQRD$ (Susceptible-Stay at home-Exposed-Infected-Quarantine-Recovery-Death) coronavirus pandemic spread model. The disease-free and endemic equilibrium points are calculated and analyzed. The basic reproductive number $R_0$ is derived and its sensitivity analysis is done. COVID-19 pandemic spread is die out when $R_0\leq 1$ and its persist in the community whenever $R_0>1$. Efficient stay at home rate, high coverage of precise identification and isolation of expose and infected individuals, and redaction of transmission and stay at home return rate can be mitigate the pandemics. Finally, theoretical analysis and numerical results are consistent.


title: Continued and Serious Lockdown Could Minimize Many Newly Transmitted Cases of COVID-19 in the U.S.: Wavelets, Deterministic Models, and Data

text: All the newly reported COVID-19 cases of April in the U.S. have not acquired the virus in the same month. We estimate that there was an average of 29,000/day COVID-19 cases in the U.S. transmitted from infected to susceptible during April 1-24, 2020 after adjusting for under-reported and under-diagnosed. We have provided model-based predictions of COVID-19 for the low and high range of transmission rates and with varying degrees of preventive measures including the lockdowns. We predict that even if 10% of the susceptible and 20 % of the infected who were not identified as of April 23, 2020, do not adhere to proper care or do not obey lockdown, then by the end of May and by end of June 50,000 and 55,000 new cases will emerge, respectively. These values for the months of May and June with worse adherence rates of 50% by susceptible and infected (but not identified) will be 251,000 and 511,000, respectively. Continued and serious lockdown measures could bring this average daily new cases to a further low at 4,300/day to 8,000/day in May.


title: Prospects for detecting early warning signals in discrete event sequence data: application to epidemiological incidence data

text: Early warning signals (EWS) identify systems approaching a critical transition, where the system undergoes a sudden change in state. For example, monitoring changes in variance or autocorrelation offers a computationally inexpensive method which can be used in real-time to assess when an infectious disease transitions to elimination. EWS have a promising potential to not only be used to monitor infectious diseases, but also to inform control policies to aid disease elimination. Previously, potential EWS have been identified for prevalence data, however the prevalence of a disease is often not known directly. In this work we identify EWS for incidence data, the standard data type collected by the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO). We show, through several examples, that EWS calculated on simulated incidence time series data exhibit vastly different behaviours to those previously studied on prevalence data. In particular, the variance displays a decreasing trend on the approach to disease elimination, contrary to that expected from critical slowing down theory; this could lead to unreliable indicators of elimination when calculated on real-world data. We derive analytical predictions which can be generalised for many epidemiological systems, and we support our theory with simulated studies of disease incidence. Additionally, we explore EWS calculated on the rate of incidence over time, a property which can be extracted directly from incidence data. We find that although incidence might not exhibit typical critical slowing down properties before a critical transition, the rate of incidence does, presenting a promising new data type for the application of statistical indicators. Author summary The threat posed by infectious diseases has a huge impact on our global society. It is therefore critical to monitor infectious diseases as new data become available during control campaigns. One obstacle in observing disease emergence or elimination is understanding what influences noise in the data and how this fluctuates when near to zero cases. The standard data type collected is the number of new cases per day/month/year but mathematical modellers often focus on data such as the total number of infectious people, due to its analytical properties. We have developed a methodology to monitor the standard type of data to inform whether a disease is approaching emergence or disease elimination. We have shown computationally how fluctuations change as disease data get closer towards a tipping point and our insights highlight how these observed changes can be strikingly different when calculated on different types of data.


title: The diagnostic evaluation of Convolutional Neural Network (CNN) for the assessment of chest X-ray of patients infected with COVID-19

text: Abstract Introduction : The main target of COVID-19 is the lungs where it may cause pneumonia in severely ill patients. Chest X- ray is an important diagnostic test to assess the lung for the damaging effects of COVID-19. Many other microbial pathogens can also cause damage to lungs leading to pneumonia but there are certain radiological features which can favor the diagnosis of pneumonia caused by COVID-19. With the rising number of cases of COVID-19, it would be imperative to develop computer programs which may assist the health professionals in the prevailing scenario. Materials & Methods : A total of two hundred and seventy eight (278) images of chest X-rays have been assessed by applying ResNet-50 convolutional neural network architectures in the present study. The digital images were acquired from the public repositories provided by University of Montreal and National Institutes of Health. These digital images of Chest X-rays were divided into three groups labeled as normal, pneumonia and COVID- 19. The third group contains digital images of chest X-rays of patients diagnosed with COVID-19 infection while the second group contains images of lung with pneumonia caused by other pathogens. Results : The radiological images included in the data set are 89 images of lungs with COVID-19 infection, 93 images of lungs without any radiological abnormality and 96 images of patient with pneumonia caused by other pathogens. In this data set, 80% of the images were employed for training, and 20% for testing. A pre-trained (on ImageNet data set) ResNet-50 architecture was used to diagnose the cases of COVID-19 infections on lung Xray images. The analysis of the data revealed that computer vision based program achieved diagnostic accuracy of 98.18 %, and F1-score of 98.19. Conclusion : The performance of convolutional neural network regarding the differentiation of pulmonary changes caused by COVID-19 from the other type of pneumonias on digital images of the chest X- rays is excellent and it may be an extremely useful adjunct tool for the health professionals. Keywords: COVID-19, Convolutional Neural Network, ResNet-50


title: Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders

text: Background: To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. Results: Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P=0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Conclusions: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys and for estimating the true infection prevalence in populations.


title: Association of SARS-CoV-2 Genomic Load with COVID-19 Patient Outcomes

text: Rationale: The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. Objectives: We explored the SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes. Methods: A retrospective cohort study among adult patients admitted to the hospital between March 31st to April 10th, 2020 with COVID-19 pneumonia was conducted. We segregated patients into 3 genomic load groups: low (Cycle threshold (Ct) [≥]35), intermediate (25 < Ct < 35), and high (Ct [≤] 25) using real-time polymerase chain reaction. Measurements: A composite outcome of death, intubation, and/or extracorporeal membrane oxygenation was used. Secondary outcomes included the severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Main Results: Of 457 patients with COVID-19 pneumonia from March 31st to April 10th, 2020, 316 met inclusion criteria. Included patients were followed for a median of 25 days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index (p=0.005), transplant recipient status (p<0.001), and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, a high genomic load remained an independent predictor of the primary outcome. Results remained significant in sensitivity analyses. Conclusions: Our findings suggest that a high genomic load of SARS-CoV-2 at the time of admission is an independent predictor of adverse outcomes, that above and beyond age, comorbidity, and severity of illness on presentation, may be used to risk-stratify patients, and call for a quantitative diagnostic assay to become available.


title: The Impact of Quarantine and Physical Distancing Following COVID-19 on Mental Health: Study Protocol of a Multicentric Italian Population Trial

text: The COVID-19 pandemic and its related containment measures—mainly physical distancing and isolation—are having detrimental consequences on the mental health of the general population worldwide. In particular, frustration, loneliness, and worries about the future are common reactions and represent well-known risk factors for several mental disorders, including anxiety, affective, and post-traumatic stress disorders. The vast majority of available studies have been conducted in China, where the pandemic started. Italy has been severely hit by the pandemic, and the socio-cultural context is completely different from Eastern countries. Therefore, there is the need for methodologically rigorous studies aiming to evaluate the impact of COVID-19 and quarantine measures on the mental health of the Italian population. In fact, our results will help us to develop appropriate interventions for managing the psychosocial consequences of pandemic. The “COVID-IT-mental health trial” is a no-profit, not-funded, national, multicentric, cross-sectional population-based trial which has the following aims: a) to evaluate the impact of COVID-19 pandemic and its containment measures on mental health of the Italian population; b) to identify the main areas to be targeted by supportive long-term interventions for the different categories of people exposed to the pandemic. Data will be collected through a web-platform using validated assessment tools. Participants will be subdivided into four groups: a) Group 1—COVID-19 quarantine group. This group includes the general population which are quarantined but not isolated, i.e., those not directly exposed to contagion nor in contact with COVID-19+ individuals; b) Group 2—COVID-19+ group, which includes isolated people directly/indirectly exposed to the virus; c) Group 3—COVID-19 healthcare staff group, which includes first- and second-line healthcare professionals; d) Group 4—COVID-19 mental health, which includes users of mental health services and all those who had already been diagnosed with a mental disorder. Mental health services worldwide are not prepared yet to manage the short- and long-term consequences of the pandemic. It is necessary to have a clear picture of the impact that this new stressor will have on mental health and well-being in order to develop and disseminate appropriate interventions for the general population and for the other at-risk groups.


title: Leveraging investments in Ebola preparedness for COVID-19 in Sub-Saharan Africa

text: The emergence of SARS-CoV-2 in China and transmission to more than 80 territories worldwide, including nine countries in Africa, presents a delicate situation for low-resource settings. Countries in Eastern and Central Africa have been on high alert since mid-2018 in anticipation of regional spread of the Ebola virus from the Democratic Republic of Congo. Significant investment has been made to support enhanced surveillance at point of entry and hospitals, infection control practices, clinical case management, and clinical research. With a new threat on the horizon, African countries have an opportunity to leverage the existing capacities for Ebola preparedness to brace for the imminent threat.


title: Decline in global COVID-19 transmission

text: We analyzed COVID-19 data through April 16, 2020 using a partially observed Markov process. Our method uses a hybrid deterministic and stochastic formalism that allows for time variable transmission rates and detection probabilities. The model was fit using iterated particle filtering to case count and death count time series from 51 countries. We found evidence for a declining transmission rate in 42 of the 51 examined countries. Of those 42 countries 34 have significant evidence for subcritical transmission rates, although the decline in new cases are relatively slow compared to the initial growth rates. This suggests that global scale social distancing efforts to slow the spread of COVID-19 are effective although they need to be strengthened in many regions and maintained in others to avoid further resurgence of COVID-19. The slow decline also suggests alternative strategies to control the virus are needed before social distancing efforts are partially relaxed.


title: Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine

text: SARS-CoV-2 rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus was able to infect millions of people. To date, close to half a million patients succumbed to the viral disease, COVID-19. The high need for treatment options, together with the lack of small animal models of infection has led to clinical trials with repurposed drugs before any preclinical in vivo evidence attesting their efficacy was available. We used Syrian hamsters to establish a model to evaluate antiviral activity of small molecules in both an infection and a transmission setting. Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan analysis of the lungs showed no improvement compared to non-treated animals, which was confirmed by histopathology. In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments. By modelling the PK profile of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster infection and transmission model to be a robust model for studying in vivo efficacy of antiviral compounds. The information acquired using hydroxychloroquine and favipiravir in this model is of critical value to those designing (current and) future clinical trials. At this point, the data here presented on hydroxychloroquine either alone or combined with azithromycin (together with previously reported in vivo data in macaques and ferrets) provide no scientific basis for further use of the drug in humans.


title: Impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists

text: Objectives: To evaluate the impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists during the month of April 2020. Materials and Methods: A 39-question, web-based survey was sent to all urologist members of the Brazilian Society of Urology. We assessed socio-demographic, professional, health and behavior parameters. The primary goal was to evaluate changes in urologists ' clinical practice and income after two months of COVID-19. We also looked at geographical differences based on the incidence rates of COVID-19 in different states. Results: Among 766 urologists who completed the survey, a reduction [≥] 50% of patient visits, elective and emergency surgeries was reported by 83.2%, 89.6% and 54.8%, respectively. An income reduction of [≥] 50% was reported by 54.3%. Measures to reduce costs were implemented by most. Video consultations were performed by 38.7%. Modifications in health and lifestyle included weight gain (32.9%), reduced physical activity (60.0%), increased alcoholic intake (39.9%) and reduced sexual activity (34.9%). Finally, 13.5% of Brazilian urologists were infected with SARS-CoV-2 and about one third required hospitalization. Urologists from the highest COVID-19 incidence states were at a higher risk to have a reduction of patient visits and non-essential surgeries (OR=2.95, 95% CI 1.86 - 4.75; p < 0.0001) and of being infected with SARS-CoV-2 (OR=4.36 95% CI 1.74 - 10.54, p = 0.012). Conclusions: COVID-19 produced massive disturbances in Brazilian urologists' practice, with major reductions in patient visits and surgical procedures. Distressing consequences were also observed on physicians' income, health and personal lives. These findings are probably applicable to other medical specialties.


title: Case Report: Walking Pneumonia in Novel Coronavirus Disease (COVID-19): Mild Symptoms with Marked Abnormalities on Chest Imaging

text: This case report underlines the appearance of a “walking pneumonia” in a novel coronavirus disease (COVID-19) patient, with evidence of progressive lung involvement on chest imaging studies. The patient traveled from Wuhan, Hubei, China, to Thailand in January 2020. One of her family members was diagnosed with COVID-19. She presented to the hospital because of her concern, but she was without fever or any respiratory symptoms. Three days earlier, her nasopharyngeal and throat swabs revealed a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Her initial chest radiography was abnormal, and her first sputum SARS-CoV-2 test yielded inconclusive results. A subsequent sputum test was positive for SARS-CoV-2. Diagnosis in this patient was facilitated by chest imaging and repeat viral testing. Thus, chest imaging studies might enhance capabilities for early diagnosis of COVID-19 pneumonia.


Special Coverage on COVID-19: Get Rid of Your Stethoscope!


title: Standardization and Age-Distribution of COVID-19: Implications for Variability in Case Fatality and Outbreak Identification

text: Background: Epidemiological data from the COVID-19 pandemic has demonstrated variability in attack rates by age, and country-to-country variability in case fatality ratio (CFR). Objective: To use direct and indirect standardization for insights into the impact of age-specific under-reporting on between-country variability in CFR, and apparent size of COVID-19 epidemics. Design: Post-hoc secondary data analysis (case studies), and mathematical modeling. Setting: China, global. Interventions: None. Measurements: Data were extracted from a sentinel epidemiological study by the Chinese Center for Disease Control (CCDC) that describes attack rates and CFR for COVID-19 in China prior to February 12, 2020. Standardized morbidity ratios (SMR) were used to impute missing cases and adjust CFR. Age-specific attack rates and CFR were applied to different countries with differing age structures (Italy, Japan, Indonesia, and Egypt), in order to generate estimates for CFR, apparent epidemic size, and time to outbreak recognition for identical age-specific attack rates. Results: SMR demonstrated that 50-70% of cases were likely missed during the Chinese epidemic. Adjustment for under-recognition of younger cases decreased CFR from 2.4% to 0.8% (assuming 50% case ascertainment in older individuals). Standardizing the Chinese epidemic to countries with older populations (Italy, and Japan) resulted in larger apparent epidemic sizes, higher CFR and earlier outbreak recognition. The opposite effect was demonstrated for countries with younger populations (Indonesia, and Egypt). Limitations: Secondary data analysis based on a single country at an early stage of the COVID-19 pandemic, with no attempt to incorporate second order effects (ICU saturation) on CFR. Conclusion: Direct and indirect standardization are simple tools that provide key insights into between-country variation in the apparent size and severity of COVID-19 epidemics.


title: SARS-CoV-2 RNA titers in wastewater anticipated COVID-19 occurrence in a low prevalence area

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 200,000 reported COVID-19 cases in Spain resulting in more than 20,800 deaths as of April 21, 2020. Faecal shedding of SARS-CoV-2 RNA from COVID-19 patients has extensively been reported. Therefore, we investigated the occurrence of SARS-CoV-2 RNA in six wastewater treatments plants (WWTPs) serving the major municipalities within the Region of Murcia (Spain), a low prevalence area. Firstly, an aluminum hydroxide adsorption-precipitation concentration method was tested using a porcine coronavirus (Porcine Epidemic Diarrhea Virus, PEDV) and mengovirus (MgV). The procedure resulted in average recoveries of 10.90% and 10.85% in influent water and 3.29% and 6.19% in effluent water samples for PEDV and MgV, respectively. Then, the method was used to monitor the occurrence of SARS-CoV-2 from March 12 to April 14, 2020 in influent, secondary and tertiary effluent water samples. By using the real-time RT-PCR (RT-qPCR) Diagnostic Panel validated by US CDC that targets three regions of the virus nucleocapsid (N) gene, we estimated quantification of SARS-CoV-2 RNA titers in untreated wastewater waters of 5.29 log genomic copies/L on average. Moreover, we tested as negative all secondary and tertiary treated water samples, highlighting that current water disinfection treatments applied in the analyzed WWTP are able to remove SARS-CoV-2 RNA. This environmental surveillance data were compared to declared COVID-19 cases at municipality level, revealing that SARS-CoV-2 was circulating among the population even before the first cases were reported by local or national authorities in many of the cities where wastewaters have been sampled. The detection of SARS-CoV-2 in wastewater in early stages of the spread of COVID-19 highlights the relevance of this strategy as an early indicator of the infection within a specific population. At this point, this environmental surveillance could be implemented by municipalities right away as a tool, designed to help authorities to coordinate the exit strategy to gradually lift its coronavirus lockdown.


title: Ethnic variation in outcome of people hospitalised with Covid-19 in Wales (UK): A rapid analysis of surveillance data using Onomap, a name-based ethnicity classification tool

text: There is growing evidence that ethnic minorities in Europe are disproportionately affected by Covid-19. Using a name-based ethnicity classifier, we found that hospitalised Black, Asian and minority ethnic cases were younger and more likely to be admitted to intensive care (ICU). Pakistani, Bangladeshi and White - other than British or Irish, ethnic groups were most at risk. In this study, older age and male gender, but not ethnicity, were associated with death in hospitalised patients.


title: Diagnosing COVID-19

text: hina continues to fight the outbreak of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected tens of thousands and killed more than 2,100 people since the end of 2019 The outbreak’s hot spot is in the central province of Hubei, in particular, its capital city Wuhan, where there have been more than 62,000 infections and 2,029 deaths as of last week, according to the World Health Organization (WHO) There, doctors and scientists are desperately struggling to find reliable ways to diagnose infected patients to help treat them and control the spread of the virus The struggle has involved two diagnostic options—computed tomography (CT) scans of patients’ lungs and a nucleic acid lab test—each with advantages and disadvantages With “a suddenly rampant new virus, it is normal to have multiple test approaches,” says a virologist at the Chinese Center for Disease Control and Prevention


title: Comparing dynamics and determinants of SARS-CoV-2 transmissions among health care workers of adult and pediatric settings in central Paris

text: Background: From the start of the pandemic, health-care workers (HCW) have paid a heavy toll to the coronavirus disease-19 (COVID-19) outbreak. Objectives: To describe the dynamics and determinants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in HCW. Design: Prospective observational study conducted from February 24th until April 10th, 2020. Setting: Comparison of a 1,500-bed adult and a 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. Participants: All symptomatic HCW screened for SARS-CoV-2 on a nasopharyngeal swab. Measurements: HCW screened positive were prospectively questioned on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2. Results: Among 1344 symptomatic HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death were reported. Most HCW (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on March 23rd, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric setting, respectively (p=0.0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0.046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period. Limitations: Lack of COVID-19 negative controls and recall bias. Conclusion: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.


title: Prioritisation of potential anti-SARS-CoV-2 drug repurposing opportunities based on ability to achieve adequate target site concentrations derived from their established human pharmacokinetics

text: Many papers are emerging that describe the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS-CoV-2. However, no comprehensive evaluation of these molecules in the context of the achievable plasma pharmacokinetics after administration of approved doses and schedules to humans has been conducted. Moreover, most publications have focussed on 50% maximum effective concentrations (EC50), which may be an insufficiently robust indicator of antiviral activity because of marked differences in the slope of the concentration-response curve between drugs. Accordingly, in vitro anti-SARS-CoV-2 activity data was digitised from all available publications up to 13th April 2020 and used to recalculate an EC90 value for each drug. EC90 values were then expressed as a ratio to the achievable maximum plasma concentrations (Cmax) reported for each drug after administration of the approved dose to humans (Cmax/EC90 ratio). Only 14 of the analysed drugs achieved a Cmax/EC90 ratio above 1 meaning that plasma Cmax concentrations exceeded those necessary to inhibit 90% of SARS-CoV-2 replication. A more in-depth assessment of these drugs demonstrated that only nitazoxanide, nelfinavir, tipranavir (boosted with ritonavir) and sulfadoxine achieved plasma concentrations above their anti-SARS-CoV-2 activity across their entire approved dosing interval at their approved human dose. For all drugs reported, the unbound lung to plasma tissue partition coefficient (KpUlung) was also simulated and used along with reported Cmax and fraction unbound in plasma to derive a lung Cmax/EC50 as a better indicator of potential human efficacy (lung Cmax/EC90 ratio was also calculable for a limited number of drugs). Using this parameter hydroxychloroquine, chloroquine, mefloquine, atazanavir (boosted with ritonavir), tipranavir (boosted with ritonavir), ivermectin, azithromycin and lopinavir (boosted with ritonavir) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50. This analysis was not possible for nelfinavir because insufficient data were available to calculate KpUlung but nitozoxanide and sulfadoxine were also predicted to exceed their reported EC50 by 3.1- and 1.5-fold in lung, respectively. The antiviral activity data reported to date is of variable quality and conducted under different conditions by different investigators. However, this analysis has prioritised candidates with the best chance for success in therapy or chemoprevention of Covid-19 based upon the currently available in vitro activity and human plasma pharmacokinetic data. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials.


title: Mechanistic Cutting Force Model and Specific Cutting Energy Prediction for Modulation Assisted Machining

text: Abstract This paper presents a mechanistic model for analytical cutting force and specific energy prediction for modulation assisted turning. Kinematics of the process is used to analyze the cut surface topography and derive the uncut chip thickness variation for various modulation parameters. It is found that uncut chip thickness is governed by successive spindle rotations and can be represented in the form of trigonometric functions. The cut and no-cut phase durations are controlled by the modulation frequency and amplitude. Cutting (machining) forces are predicted based on the orthogonal cutting mechanics. The thin shear plane angle is predicted considering oscillations in the cutting velocity, resultant effective rake angle and by employing the well-known Minimum Energy Principle (MEP). In order to accurately predict the shear forces, length of the shear plane is estimated directly from the uncut and cut part surface geometries, which incorporates waviness of the surface. Analytical chip thickness predictions and proposed cutting force models are combined used to predict the specific cutting energy in MAM. Experimental results verify accuracy of developed force models in estimating cutting forces and energy in orthogonal modulated assisted turning of Al6061 T6511.


title: Amplifying RNA Vaccine Development

text: There are several strategies to elicit immunity with an RNA vaccine;they all involve coaxing the host cell to replicate and translate an exogenous RNA encoding the vaccine antigen A recent study describes a new, versatile approach


title: Importance of homo-dimerization of Fanconi-associated nuclease 1 in DNA flap cleavage

text: Fanconi-associated nuclease 1 (FAN1) removes interstrand DNA crosslinks (ICLs) through its DNA flap endonuclease and exonuclease activities. Crystal structures of human and bacterial FAN1 bound to a DNA flap have been solved. The Pseudomonas aeruginosa bacterial FAN1 and human FAN1 (hFAN1) missing a flexible loop are monomeric, while intact hFAN1 is homo-dimeric in structure. Importantly, the monomeric and dimeric forms of FAN1 exhibit very different DNA binding modes. Here, we interrogate the functional differences between monomeric and dimeric forms of FAN1 and provide an explanation for the discrepancy in oligomeric state between the two hFAN1 structures. Specifically, we show that the flexible loop in question is needed for hFAN1 dimerization. While monomeric and dimeric bacterial or human FAN1 proteins cleave a short 5’ flap strand with similar efficiency, optimal cleavage of a long 5’ flap strand is contingent upon protein dimerization. Our study therefore furnishes biochemical evidence for a role of hFAN1 homodimerization in biological processes that involve 5’ DNA Flap cleavage.


title: SARS-CoV-2 infection in the lungs of human ACE2 transgenic mice causes severe inflammation, immune cell infiltration, and compromised respiratory function

text: Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) emerged in late 2019 and has spread worldwide resulting in the Coronavirus Disease 2019 (COVID-19) pandemic. Although animal models have been evaluated for SARS-CoV-2 infection, none have recapitulated the severe lung disease phenotypes seen in hospitalized human cases. Here, we evaluate heterozygous transgenic mice expressing the human ACE2 receptor driven by the epithelial cell cytokeratin-18 gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lung tissues with additional spread to other organs. Remarkably, a decline in pulmonary function, as measured by static and dynamic tests of respiratory capacity, occurs 4 days after peak viral titer and correlates with an inflammatory response marked by infiltration into the lung of monocytes, neutrophils, and activated T cells resulting in pneumonia. Cytokine profiling and RNA sequencing analysis of SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with prominent signatures of NF-kB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection recapitulates many features of severe COVID-19 infection in humans and can be used to define the mechanistic basis of lung disease and test immune and antiviral-based countermeasures.


title: Erratum: Correction to: Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial (Trials (2020) 21 1 (499))

text: An amendment to this paper has been published and can be accessed via the original article


title: Decoding herbal materials of representative TCM preparations with the multi-barcoding approach

text: With the rapid development of high-throughput sequencing (HTS) technology, the techniques for the assessment of biological ingredients in Traditional Chinese Medicine (TCM) preparations have also advanced. By using HTS together with the multi-barcoding approach, all biological ingredients could be identified from TCM preparations in theory, as long as their DNA is present. The biological ingredients of a handful of classical TCM preparations were analyzed successfully based on this approach in previous studies. However, the universality, sensitivity and reliability of this approach used on TCM preparations remain unclear. Here, four representative TCM preparations, namely Bazhen Yimu Wan, Da Huoluo Wan, Niuhuang Jiangya Wan and You Gui Wan, were selected for concrete assessment of this approach. We have successfully detected from 77.8% to 100% prescribed herbal materials based on both ITS2 and trnL biomarkers. The results based on ITS2 have also shown a higher level of reliability than those of trnL at species level, and the integration of both biomarkers could provide higher sensitivity and reliability. In the omics big-data era, this study has undoubtedly made one step forward for the multi-barcoding approach for prescribed herbal materials analysis of TCM preparation, towards better digitization and modernization of drug quality control.


title: Loneliness during lockdown: trajectories and predictors during the COVID-19 pandemic in 35,712 adults in the UK

text: There are increasing worries that lockdowns and stay-at-home orders due to the COVID-19 pandemic could lead to a rise in loneliness, which is recognised as a major public health concern. But profiles of loneliness during the pandemic and risk factors remain unclear. Data from 35,712 UK adults in the UCL COVID -19 Social Study (a panel study collecting data weekly during the pandemic) were analysed from 21/03/2020-03/05/2020. The sample was well-stratified and weighted to population proportions of gender, age, ethnicity, education and geographical location. Growth mixture modelling was used to identify the latent classes of loneliness growth trajectories and their predictors. Analyses revealed four classes, with the baseline loneliness level ranging from low to high. In the first six weeks of lockdown, loneliness levels increased in the highest loneliness group, decreased in the lowest loneliness group, and stayed relatively constant in the middle two groups. Younger adults (OR=2.17-6.81), women (OR=1.59), people with low income (OR=1.3), the economically inactive (OR=1.3-2.04) and people with mental health conditions (OR=5.32) were more likely to be in highest loneliness class relative to the lowest. Further, living with others or in a rural area, and having more close friends or greater social support were protective. Perceived levels of loneliness in the first few weeks of lockdown during COVID-19 were relatively stable in the UK, but for many people these levels were high with no signs of improvement. Results suggest that more efforts are needed to address loneliness, especially amongst young people.


title: Estimating the time-varying reproduction number of COVID-19 with a state-space method

text: After slowing down the spread of the novel coronavirus COVID-19, many countries have started to relax their severe confinement measures in the face of critical damage to socioeconomic structures. At this point, it is desirable to monitor the degree to which political measures or social affairs have exerted influence on the spread of disease; however, tracing back individual transmission of infections whose incubation periods are long and highly variable seems to be difficult. Nevertheless, it may be possible to estimate the changes that may have occurred in the past, if we can suitably fit a proper model to daily event-occurrences. We have devised a state-space method for fitting the Hawkes process to a given dataset of daily confirmed cases. This method detects changes occurring in the spread of the contagion in each country. Furthermore, this method can assess the impact of social events in terms of the temporally varying reproduction number representing the average number of cases directly caused by a single infected case. This information might serve as a reference for the behavioral guidelines that should be adopted according to the varying risk of infection.


title: COVID-19 and Food Safety: Risk Management and Future Considerations

text: COVID-19, also known as the “novel coronavirus disease 2019,” is a respiratory illness, and the causative pathogen is officially named as “SARS-CoV-2 ” Infections with SARS-CoV-2 have now been amplified to a global pandemic—as of April 3, 2020, nearly 1 018 000 cases have been confirmed in more than 195 countries, including more than 300 000 cases within the United States Public safety guidelines are followed worldwide to stop the spread of COVID-19 and stay healthy Despite COVID-19 is a respiratory illness with mode of invasion through the respiratory tract, not the gastrointestinal tract, an average food consumer is anxious and concerned about the food safety Could an individual catch the deadly contagious COVID-19 from groceries brought home from the supermarket—or from the next restaurant takeout order? This brief review elucidates the epidemiology and pathobiological mechanism(s) of SARS-CoV-2 and its implications in food-borne infections, transmission via food surfaces, food processing, and food handling


title: Disparate temperature-dependent virus – host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium

text: The human conductive respiratory tract spans a long anatomical distance and represents an important barrier to constrain invading respiratory pathogens. The disparate ambient temperatures found in the upper and lower respiratory tract have been demonstrated to influence the replication kinetics of common cold viruses as well as the associated host responses. Here, we employed the human airway epithelial cell (hAEC) culture model to investigate the impact of ambient temperatures found in the upper and lower respiratory tract, 33°C and 37°C, respectively, on the viral replication kinetics and host innate immune response dynamics during SARS-CoV-2 and SARS-CoV infections. Strikingly, SARS-CoV-2, in contrast to SARS-CoV, replicated more efficiently at temperatures encountered in the upper respiratory tract, and displayed higher sensitivity to type I and type III IFNs than SARS-CoV. Time-resolved transcriptome analysis highlighted a temperature-dependent induction of IFN-mediated antiviral response, whose amplitude inversely correlated with the replication kinetic efficiencies of both SARS-CoV-2 and SARS-CoV at temperatures found in the upper and lower respiratory tract. Altogether, these data reflect clinical features of SARS-CoV-2 and SARS-CoV and subsequently, their associated human-to-human transmission efficiencies. They provide crucial insights of the profound impact of ambient temperatures on viral replication and associated pivotal virus - host interaction dynamics. This knowledge can be exploited for the development of novel intervention strategies against SARS-CoV-2.


title: Virtual Classrooms for Hearing-impaired Students during the COVID-19 Pandemic

text: Distance learning has become an essential educational option during the COVID-19 pandemic However, students with varied needs require diverse learning experiences For example, deaf and hard-of-hearing students need specific accommodations to aid their learning This study aimed to identify the obstacles that instructors face when conducting virtual classroom sessions for these students Data were collected from 11 lecturers who taught deaf or hard-of-hearing students using distance learning tools during the COVID-19 pandemic Time, technical problems, and lack of simultaneous translation are among the barriers that must be overcome to address the learning needs of this group of students Recommended improvements to the virtual classroom experience for deaf or hard-of-hearing students were provided


title: Surgery in a Time of Uncertainty: A Need for Universal Respiratory Precautions in the Operating Room

text: This Viewpoint proposes that universal respiratory precautions in the operating room—use of respirators with face masks and eye protection—could protect staff from possible coronavirus disease 2019 (COVID-19) infection and facilitate resumption of elective surgeries canceled during the first wave of the pandemic [ABSTRACT FROM AUTHOR] Copyright of JAMA: Journal of the American Medical Association is the property of American Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )


The role of medical imaging in the diagnosis and treatment of COVID-19/ 医学影像在新型冠状病毒肺炎诊治中的作用及思考


title: Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study

text: Objective: Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented. Design: Retrospective population-based study. Setting: Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018. Participants: 5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020). Measurements: Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid19 patients and the corresponding mortality in the 2018 general population. Results: A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05). Limitations: Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified. Conclusions: Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.


title: Prevalence of IgG and IgM antibodies to SARS-CoV-2 among clinic staff and patients

text: The coronavirus disease 2019 (COVID-19) is now a pandemic with devastating social and economic consequences. The extent of the spread of COVID-19 within populations is uncertain since diagnostic tests have not been carried out on all eligible persons and doing such diagnostic tests on everyone is much less feasible in developing countries such as Nigeria. Tests for antibodies to SARS-CoV-2, the virus that causes COVID-19, are more affordable, readily available, and require minimal training than current diagnostic tests. Employing a seroepidemiological strategy, serological tests were conducted on 66 volunteering staff and patients at the University of Calabar Teaching Hospital (UCTH), a Federal Government owned tertiary healthcare facility, to determine the extent of exposure to SARS-CoV-2, from 17th to 25th June 2020. Using a COVID-19 IgG/IgM Rapid Test Cassette with emergency use authorization (EUA) from the Food and Drug Administration (FDA) of the United States, it was observed that of the 66 samples tested, 5 (7.6%) were both IgG and IgM positive and 17 (26%) were IgG positive. Moreover, for 44 of the 66 participants, simultaneous tests were carried out using a rapid test kit from a different manufacturer but without FDA-EUA and all the results completely matched with the FDA-EUA kit, except one case where the FDA-EUA kit showed positive for both IgG and IgM while the other kit was positive only for IgM. The 26% positive IgG indicates a high exposure rate for the hospital staff and patients and points to community transmission where the facility is situated. Hence, immediate activation of WHO guidelines for controlling community transmission is called for. These results can further serve as a pilot study to guide public health policies in response to COVID-19 pandemic in both the general population and in healthcare settings.


title: Low-cost measurement of facemask efficacy for filtering expelled droplets during speech

text: Mandates for mask use in public during the recent COVID-19 pandemic, worsened by global shortage of commercial supplies, have led to widespread use of homemade masks and mask alternatives. It is assumed that wearing such masks reduces the likelihood for an infected person to spread the disease, but many of these mask designs have not been tested in practice. We have applied a simple optical measurement method to evaluate the efficacy of masks to reduce the transmission of respiratory droplets during regular speech. We compare a variety of commonly available mask types and observe that some mask types approach the performance of standard surgical masks, while some mask alternatives, such as neck fleece or bandanas, offer very little protection. Our measurement setup is inexpensive and can be built and operated by non-experts, allowing for rapid evaluation of mask performance during speech, sneezing, or coughing.


title: Risk of Depression in Family Caregivers: Unintended Consequence of COVID-19

text: Background: COVID-19 is likely to exacerbate the symptoms of poor mental health family caregivers. To investigate whether rates of depression increased in caregivers during COVID-19 and whether the unintended consequences of health protective measures, i.e., social isolation, exacerbated this risk. Another aim was to see if caregivers accessed any online/phone psychological support during COVID. Method: Data (1349 caregivers; 7527 non-caregivers) was extracted from Understanding Society, UK population level dataset. The General Health Questionnaire cut-off scores identifying those with and without depression were our primary outcome. Results: After adjustment for confounding caregivers had a higher risk of having depression compared with non-caregivers, Odds ratio (OR) = 1.22 (95% confidence interval (95% CI), 1.05-1.40)), p=.008 evidenced by higher levels of depression pre-COVID-19 (16.7% vs 12.1%) and during COVID-19 (21.6% vs 17.9%), respectively. Further, higher levels of loneliness increased the risk of depression almost 4-fold risk in caregivers, OR = 3.85 (95% confidence interval (95% CI), 3.08-4.85)), p<.001), while access to therapy attenuated the risk (47%. While 60% of caregivers with depression reported not accessing any therapeutic support (e.g., online or face to face) during COVID-19. Conclusion: COVID-19 has had a negative impact on family caregivers mental health with loneliness a significant contributor to caregivers depression. However, despite these detriments in mental health, the majority of caregivers do not access any online or phone psychiatric support. Reducing feelings of isolation therefore provides an opportunity for psychiatric services and health care professionals to support at-risk caregivers.


title: Comparative performance of four nucleic acid amplification tests for SARS-CoV-2 virus

text: Coronavirus disease 2019 (COVID-19) can be screened and diagnosed through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction. SARS-CoV-2 nucleic acid amplification tests (NAATs) have been rapidly developed and quickly applied to clinical testing during the pandemic. However, studies evaluating the performance of these NAAT assays are limited. We evaluated the performance of four NAATs, which were marked by the Conformité Européenne and widely used in China during the pandemic. Results showed that the analytical sensitivity of the four assays was significantly lower than that claimed by the NAAT manufacturers. The limit of detection (LOD) of Daan, Sansure, and Hybribio NAATs was 3000 copies/mL, whereas the LOD of Bioperfectus NAATs was 4000 copies/mL. The results of the consistency test using 46 samples showed that Daan, Sansure, and Hybribio NAATs could detect the samples with a specificity of 100% (30/30) and a sensitivity of 100% (16 /16), whereas Bioperfectus NAAT detected the samples with a specificity of 100% (30/30) and a sensitivity 81.25% (13/16). The sensitivity of Bioperfectus NAAT was lower than that of the three other NAATs; this finding was consistent with the result that Bioperfectus NAAT had a higher LOD than the three other kinds of NAATs. The four above mentioned reagents presented high specificity; however, for the detection of the samples with low virus concentration, Bioperfectus reagent had the risk of missing detection. Therefore, the LOD should be considered in the selection of SARS-CoV-2 NAATs.


title: Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England

text: The NHS Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.


title: Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis

text: Purpose: Coronaviruses may activate dysregulated host immune responses. As exploratory studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of complicated COVID-19 and that the anti-IL-6 biologic tocilizumab may be beneficial, we undertook a systematic review and meta-analysis to assess the evidence in this field. Methods: We systematically searched MEDLINE and EMBASE for studies investigating the immunological response in COVID-19 or its treatment with tocilizumab; additional grey literature searches were undertaken. Meta-analysis was undertaken using random effects models. Results: Eight published studies, three pre-prints, and five registered trials were eligible. Meta-analysis of mean IL-6 concentrations demonstrated 2.9-fold higher levels in patients with complicated COVID-19 compared with patients with non-complicated disease (six studies; n=1302; 95%CI, 1.17-7.19; I2=100%). A single non-randomized, single-arm study assessed tocilizumab in patients with severe COVID-19, demonstrating decreased oxygen requirements, resolution of radiographic abnormalities, and clinical improvement. No adverse events or deaths were observed. Conclusions: In patients with COVID-19, IL-6 levels are significantly elevated and associated with adverse clinical outcomes. While inhibition of IL-6 with tocilizumab appears to be efficacious and safe in preliminary investigation, the results of several ongoing clinical trials should be awaited to better define the role of tocilizumab in COVID-19 prior to routine clinical application.


title: Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity

text: The spike protein of SARS-CoV-2 binds to respiratory epithelium through the ACE2 receptor, an endogenous receptor for Angiotensin II (AngII). The mechanisms by which this viral infection leads to hypoxia and respiratory failure have not yet been elucidated. Interactions between the sulfated glycosaminoglycans heparin and heparan sulfate and the SARS-CoV-2 spike glycoprotein have been identified as participating in viral adherence and infectivity. In this brief report, we present data indicating that stimulation of vascular smooth muscle cells by AngII leads to increased expression of two chondroitin sulfotransferases (CHST11 and CHST15), which are required for the synthesis of the sulfated glycosaminoglycans chondroitin 4-sulfate (C4S) and chondroitin 4,6-disulfate (CSE). We suggest that increased expression of these chondroitin sulfotransferases and the ensuing production of chondroitin sulfates may contribute to viral adherence to bronchioalveolar cells and to the progression of respiratory disease in Covid-19. The enzyme Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase), which removes 4-sulfate groups from the non-reducing end of chondroitin 4-sulfate residues, is required for degradation of C4S and CSE. In hypoxic conditions or following treatment with chloroquine, ARSB activity is reduced. Decline in ARSB can contribute to ongoing accumulation and airway obstruction by C4S and CSE. Decline in ARSB leads to increased expression of Interleukin(IL)-6 in human bronchial epithelial cells, and IL-6 is associated with cytokine storm in Covid-19. These findings indicate how chondroitin sulfates, chondroitin sulfotransferases, and chondroitin sulfatases may participate in the progression of hypoxic respiratory insufficiency in Covid-19 disease and suggest new therapeutic targets.


title: Effect of tourism FDI and international tourism to the economic growth in Morocco: Evidence from ARDL bound testing approach

text: This study examined the influence of international tourism and foreign direct investment on economic growth in Morocco during the period 1983–2018. Using autoregressive distributed lag (ARDL) approach and causality tests, the study analyzed the relationship between real GDP, tourist arrivals, foreign direct investment (FDI) flowing into the tourism sector and FDI in the others sectors. The results obtained indicate that there is a positive relationship between tourist arrivals and economic growth in the long-run. The results also show that non-tourism FDI has a positive and significant impact on economic growth, while tourism FDI has a negative effect on economic growth. In addition, long-run causality results show that the hypothesis of economic growth driven by tourist arrivals and foreign direct investment is significant at the 1% level. Similarly, our results show that in the long-run, the hypothesis of tourism demand driven by economic growth and FDI is significant at the 1% level. The Granger causality test reveals a one-way causal relationship from economic growth to tourist arrivals, FDI flows in the tourism sectors and FDI flows in the non-tourism sectors in Morocco. This study suggests that decisions-makers should align the tourism strategy with other sectoral plans in a global, coherent and integrated strategic vision to take full advantage of FDI and international tourism. Policy implications of this study and future research suggestions are also mentionned.


title: BRAZIL IS PROJECTED TO BE THE NEXT GLOBAL COVID-19 PANDEMIC EPICENTER

text: Coronavirus disease 2019 (COVID-19) is a disease triggered by SARS-CoV-2 infection, which is related in the most recent pandemic situation, significantly affecting health and economic systems. In this study we assessed the death rate associated to COVID-19 in Brazil and the United States of America (USA) to estimate the probability of Brazil becoming the next pandemic epicenter. We equated data between Brazil and USA obtained through the Worldometer website (www.worldometer.info). Epidemic curves from Brazil and USA were associated and regression analysis was undertaken to predict the Brazilian death rate regarding COVID-19 in June. In view of data from April 9th 2020, death rates in Brazil follow a similar exponential increase to USA (r=0.999; p<0.001), estimating 64,310 deaths by June 9th 2020. In brief, our results demonstrated that Brazil follows an analogous progression of COVID-19 deaths cases when compared to USA, signifying that Brazil could be the next global epicenter of COVID-19. We highlight public strategies to decrease the COVID-19 outbreak.


Neurologists on the Front Lines: The Burden of COVID-19 on Native American Communities


title: A considerable proportion of individuals with asymptomatic SARS-CoV-2 infection in Tibetan population

text: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) quickly became a major epidemic threat in the whole China. We analysed SARS-Cov-2 infected cases from Tibetan Autonomous Prefecture, and noted divergent characteristics of these Tibetans infected cases compared to Han Chinese, characterizing by a considerable proportion of asymptomatic carriers (21.7%), and few symptomatic patients with initial symptom of fever (7.7%). Here, we did a descriptive study on clinical characteristics of 18 asymptomatic individuals with SARS-CoV-2 infection. The median age of these asymptomatic carriers was 31 years and one third of them were students, aged under 20 years. Notably, some of asymptomatic carriers had recognizable changes in radiological and laboratory indexes. Our finding indicates a potentially big number of SARS-CoV-2 asymptomatic carriers in prevalent area, highlighting a necessity of screening individuals with close contact of infected patients, for a better control on the spread of SARS-CoV-2 infection.


title: Pandemic Politics: Timing State-Level Social Distancing Responses to COVID-19

text: Social distancing policies are critical but economically painful measures to flatten the curve against emergent infectious diseases. As the novel coronavirus that causes COVID-19 spread throughout the United States in early 2020, the federal government issued social distancing recommendations but left to the states the most difficult and consequential decisions restricting behavior, such as canceling events, closing schools and businesses, and issuing stay-at-home orders. We present an original dataset of state-level social distancing policy responses to the epidemic and explore how political partisanship, COVID-19 caseload, and policy diffusion explain the timing of governors' decisions to mandate social distancing. An event history analysis of five social distancing policies across all fifty states reveals the most important predictors are political: all else equal, Republican governors and governors from states with more Trump supporters were slower to adopt social distancing policies. These delays are likely to produce significant, on-going harm to public health.


Unmatched clinical presentation and chest CT manifestation in a patient with severe coronavirus disease 2019 (COVID-19)