title: Effective repair of joint cartilage using human pluripotent stem cell-derived tissue

text: Adult articular cartilage lacks significant regenerative capacity, and damage to this tissue often leads to progressive joint degeneration (osteoarthritis). We developed strategies to generate articular cartilage from human pluripotent stem cells (hPSCs) as a source of clinically relevant tissues for joint repair1. Previously, we demonstrated that these chondrocytes retain cartilage forming potential following subcutaneous implantation in mice. In this report, we evaluated the potential of human embryonic stem cell (hESC)-derived articular cartilage tissue to repair osteochondral defects created in the rat knee. Following implantation, the hESCderived cartilage maintained a proteoglycan and type II collagen-rich matrix, and was well integrated with native rat tissue at the basal and lateral surfaces. The ability to generate cartilage tissue with integrative and reparative properties from an unlimited and robust cell source represents a significant clinical advance for cartilage repair that can be applied to large animal models and ultimately to patient care.


title: A first study on the impact of current and future control measures on the spread of COVID-19 in Germany

text: The novel coronavirus (SARS-CoV-2), identified in China at the end of December 2019 and causing the disease COVID-19, has meanwhile led to outbreaks all over the globe, with about 571,700 confirmed cases and about 26,500 deaths as of March 28th, 2020. We present here the preliminary results of a mathematical study directed at informing on the possible application or lifting of control measures in Germany. The developed mathematical models allow to study the spread of COVID-19 among the population in Germany and to asses the impact of non-pharmaceutical interventions. The overall goal is to suggest strategies for the mitigation of the current outbreak, slowing down the spread of the virus and thus reducing the peak in daily diagnosed cases, the demand for hospitalization or intensive care units admissions, and eventually fatalities.


title: The first 6 weeks: setting up a UK urgent dental care centre during the COVID-19 pandemic.

text: Introduction: The COVID-19 pandemic has posed many challenges, including provision of urgent dental care. This paper presents a prospective service evaluation during establishment of urgent dental care in the North-East of England over a six-week period. Aim: To monitor patient volumes, demographics and outcomes at the North-East urgent dental care service and confirm appropriate care pathways. Main Outcome Methods: Data were collected on key characteristics of patients accessing urgent care from 23rd March to 3rd May 2020. Analysis was with descriptive statistics. Results: There were 1746 patient triages, (1595 telephone and 151 face-to-face) resulting in 1322 clinical consultations. The most common diagnoses were: symptomatic irreversible pulpitis or apical periodontitis. 65% of clinical consultations resulted in extractions, 0.5% an aerosol generating procedure. Patients travelled 25km on average to access care, however this reduced as more urgent care centres were established. The majority of patients were asymptomatic of COVID-19 and to our knowledge no staff acquired infection due to occupational exposure. Conclusion: The urgent dental care centre effectively managed urgent and emergency dental care, with appropriate patient pathways established over the 6-week period. Dental preparedness for future pandemic crisis could be improved and informed by this data.


title: Predictive mathematical models for the number of individuals infected with COVID-19

text: We model the time-evolution of the number N(t) of individuals reported to be infected in a given country with a specific virus, in terms of a Riccati equation. Although this equation is nonlinear and it contains time-dependent coefficients, it can be solved in closed form, yielding an expression for N(t) that depends on a function (t). For the particular case that (t) is constant, this expression reduces to the well-known logistic formula, giving rise to a sigmoidal curve suitable for modelling usual epidemics. However, for the case of the COVID-19 pandemic, the long series of available data shows that the use of this simple formula for predictions underestimates N(t); thus, the logistic formula only provides a lower bound of N(t). After experimenting with more than 50 different forms of (t), we introduce two novel models that will be referred to as 'rational' and 'birational'. The parameters specifying these models (as well as those of the logistic model), are determined from the available data using an error-minimizing algorithm. The analysis of the applicability of the above models to the cases of China and South Korea suggest that they yield more accurate predictions, and importantly that they may provide an upper bound of the actual N(t). Results are presented for Italy, Spain, and France.


title: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery

text: We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.


title: Risk Assessment of nCOVID-19 Pandemic In India: A Mathematical Model And Simulation

text: The entire world is now eventually locked down due to the outbreak of nCOVID-19 corona virus outbreak. The fast and relentless spread nCOVID-19 has basically segmented the populace only into merely into three classes, such as susceptible, infected and recovered compartments. Adapting the classical SEIR- type epidemic modelling framework, the direct person-to-person contact transmission is taken as the direct route of transmission of nCOVID-19 pandemic. In this research, the authors have developed a model of the nation-wide trends of the outburst of the nCOVID-19 infection using an SEIR Model. The SEIR dynamics are expressed using ordinary differential equations. The creators initially determined the parameters of the model from the accessible day by day information for Indian States dependent on around 35 days history of diseases, recuperation and deaths. The determined parameters have been amassed to extend future patterns for the Indian subcontinent, which is right now at a beginning time in the contamination cycle. The novelty of the study lies in the prediction of both the pessimistic and optimistic mathematical model based comprehensive analysis of nCOVID-19 infection spreading, for two different conditions: (a) if lock down gets withdrawn and (b) if lock down continues as a whole. If the complete lock down in India is withdrawn on 14th April 2020, as a whole, then from the simulation, the authors have predicted that the infected population will flare-up to a large extent , suddenly, however, gradual or zone specific withdrawal would be more effective solution. This study also suggested some possible way-out to get rid of this situation by providing a trade-off between "flattening of the curve" as well as less economic turbulence. The projections are intended to provide a base/ action plan for the socio-economic counter measures to alleviate nCOVID-19.


title: Impact of the first COVID-19 shelter-in-place order in the United States on emergency department utilization, Marin County, California

text: Background: The first shelter-in-place (SIP) order in the United States was issued across six counties in the San Francisco Bay Area to reduce the impact of COVID-19 on critical care resources. We sought to assess the impact of this large-scale intervention on emergency departments (ED) in Marin County, California. Methods: We conducted a retrospective descriptive and trend analysis of all ED visits in Marin County, California from January 1, 2018 to May 4, 2020 to quantify the temporal dynamics of ED utilization before and after the March 17, 2020 SIP order. Results: The average number of ED visits per day decreased by 52.3% following the SIP order compared to corresponding time periods in 2018 and 2019. Both respiratory and non-respiratory visits declined, but this negative trend was most pronounced for non-respiratory admissions. Conclusions: The first SIP order to be issued in the United States in response to COVID-19 was associated with a significant reduction in ED utilization in Marin County.


title: B. Kaplan, L.H. Kahn, T.P. Monath (Eds.), ‘One Health-One Medicine’: Linking Human, Animal and Environmental Health, Veterinaria Italiana, vol. 45, January–March 2009, ISBN978-88-901726-0-1, 215 pp.

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title: Transmission of severe acute respiratory syndrome in dynamical small-world networks

text: The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.


title: When Can Elimination of SARS-CoV-2 Infection be Assumed? Simulation Modelling in a Case Study Island Nation

text: Aims: We aimed to determine the length of time from the last detected case of SARS-CoV-2 infection before elimination can be assumed at a country level in an island nation. Methods: A stochastic version of the SEIR model CovidSIM v1.1 designed specifically for COVID-19 was utilised. It was populated with data for the case study island nation of New Zealand (NZ) along with relevant parameters sourced from the NZ and international literature. This included a testing level for symptomatic cases of 7,800 tests per million people per week. Results: It was estimated to take between 27 and 33 days of no new detected cases for there to be a 95% probability of epidemic extinction. This was for effective reproduction numbers (Re) in the range of 0.50 to 1.0, which encompass such controls as case isolation (the shorter durations relate to low Re values). For a 99% probability of epidemic extinction, the equivalent time period was 37 to 44 days. In scenarios with lower levels of symptomatic cases seeking medical attention and lower levels of testing, the time period was up to 53 to 91 days (95% level). Conclusions: In the context of a high level of testing, a period of around one month of no new notified cases of COVID-19 would give 95% certainty that elimination of SARS-CoV-2 transmission had been achieved.


title: Development and validation of an early warning score (EWAS) for predicting clinical deterioration in patients with coronavirus disease 2019

text: Background: Since the pandemic outbreak of coronavirus disease 2019 (COVID-19), the health system capacity in highly endemic areas has been overwhelmed. Approaches to efficient management are urgently needed. We aimed to develop and validate a score for early prediction of clinical deterioration of COVID-19 patients. Methods: In this retrospective multicenter cohort study, we included 1138 mild to moderate COVID-19 patients admitted to 33 hospitals in Guangdong Province from December 27, 2019 to March 4, 2020 (N =818; training cohort), as well as two hospitals in Hubei Province from January 21 to February 22, 2020 (N =320; validation cohort) in the analysis. Results: The 14-day cumulative incidences of clinical deterioration were 7.9% and 12.1% in the training and validation cohorts, respectively. An Early WArning Score (EWAS) (ranging from 0 to 4.5), comprising of age, underlying chronic disease, neutrophil to lymphocyte ratio, C-reactive protein, and D-dimer levels, was developed (AUROC: 0.857). By applying the EWAS, patients were categorized into low-, medium-, and high risk groups (cut-off values: two and three). The 14-day cumulative incidence of clinical deterioration in the low-risk group was 1.8%, which was significantly lower than the incidence rates in the medium- (14.4%) and high-risk (40.9%) groups (P <.001). The predictability of EWAS was similar in the validation cohort (AUROC =0.781), patients in the low-, medium-, and high-risk groups had 14-day cumulative incidences of 2.6%, 10.0%, and 25.7%, respectively (P <.001). Conclusion: The EWAS, which is based on five common parameters, can predict COVID-19-related clinical deterioration and may be a useful tool for a rapid triage and establishing a COVID-19 hierarchical management system that will greatly focus clinical management and medical resources to reduce mortality in highly endemic areas.


title: Identification of SARS-CoV-2 RNA in Healthcare Heating, Ventilation, and Air Conditioning Units

text: Available information on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission by small particle aerosols continues to evolve rapidly. To assess the potential role of heating, ventilation, and air conditioning (HVAC) systems in airborne viral transmission, this study sought to determine the viral presence, if any, on air handling units in a healthcare setting where Coronavirus Disease 2019 (COVID-19) patients were being treated. The presence of SARS-CoV-2 RNA was detected in approximately 25% of samples taken from nine different locations in multiple air handlers. While samples were not evaluated for viral infectivity, the presence of viral RNA in air handlers raises the possibility that viral particles can enter and travel within the air handling system of a hospital, from room return air through high efficiency MERV-15 filters and into supply air ducts. Although no known transmission events were determined to be associated with these specimens, the findings suggest the potential for HVAC systems to facilitate transmission by environmental contamination via shared air volumes with locations remote from areas where infected persons reside. More work is needed to further evaluate the risk of SARS-CoV-2 transmission via HVAC systems and to verify effectiveness of building operations mitigation strategies for the protection of building occupants. These results are important within and outside of healthcare settings and may present a matter of some urgency for building operators of facilities that are not equipped with high-efficiency filtration.


title: No Excess Mortality of COVID-19 in Japan until April, 2020

text: Background: As of the end of June, 2020, the COVID-19 outbreak exhibited its highest peak on April 3. Nevertheless, no remarkable excess mortality attributable to COVID-19 has been observed. Object: We sought to quantify excess mortality in April using the National Institute of Infectious Diseases (NIID) model. Method: We applied the NIID model to deaths of all causes from 1987 up through April, 2020. Results: Results show no significant excess mortality in March or April, 2020, when the COVID-19 outbreak affected Japan most. Discussion and Conclusion: Because changes in application rule of the International Classification of Diseases in 2017 affected the number of pneumonia deaths drastically, we were unable to use pneumonia deaths to estimate excess mortality. it might be important to continue to monitor excess mortality of COVID-19 carefully after May 2020.


title: Extensive testing may reduce COVID-19 mortality: a lesson from northern Italy

text: We examined data on the progression of COVID-19 epidemics in four regions in northern Italy. Lombardy, Emilia-Romagna, and Piedmont had an extremely steeper increase in mortality with increasing number of tests performed than Veneto, which applied a policy of broader swab testing. This suggests that the strategy adopted in Veneto, similar to that in South Korea, is effective in containing COVID-19 epidemics and should be applied in other regions of Italy and countries in Europe.


title: Pandemics, professionalism and the duty of care: Concerns from the coalface

text: It is likely that the SARS-CoV-2 pandemic will affect a large part of the world's population and will last for several years Many critical ethical issues have arisen in the healthcare context While response from healthcare professionals to participating in the care of patients in the era of COVID-19 has generally been positive, there have also been disturbing experiences on the ground The practice of medicine is a social contract with humanity Challenges have arisen because the patient is both a victim and a vector of the coronavirus All humans should have a natural instinct to care for those in need Ethically and legally, healthcare professionals cannot be expected to assume a significant and unreasonable risk of harm While fear is understandable, altruism and interest in serving the sick exemplify the value of solidarity Social harms like stigmatisation and discrimination can occur Concerns have been raised regarding protection of privacy and respect for rights of infected individuals In the era of COVID-19, fear, misinformation and a detachment from one's calling put professionalism strongly to the test


title: Evaluation of remote monitoring device for monitoring vital parameters against reference standard: A diagnostic validation study for COVID-19 preparedness

text: Context: Vital parameters including blood oxygen level, respiratory rate, pulse rate, and body temperature are crucial for triaging patients to appropriate medical care. Advances in remote health monitoring system and wearable health devices have created a new horizon for delivery of efficient health care from a distance. Materials and Methods: This diagnostic validation study included patients attending the outpatient department of the institute. The accuracy of device under study was compared against the gold standard patient monitoring systems used in intensive care units. Statistical Analysis: The statistical analysis involved computation of intraclass correlation coefficient. Bland-Altman graphs with limits of agreement were plotted to assess agreement between methods. P <0.05 was considered statistically significant. Results: A total of 200 patients, including 152 males and 48 females in the age range of 2-80 years, formed the study group. A strong correlation (intraclass correlation coefficient; r > 0.9) was noted between the two devices for all the investigated parameters with significant P value (<0.01). Bland-Altman plot drawn for each vital parameter revealed observations in agreement from both the devices. Conclusion: The wearable device can be reliably used for remote health monitoring. Its regulated use can help mitigate the scarcity of hospital beds and reduce exposure to health-care workers and demand of personal protection equipment.


Responding to COVID-19 in Istanbul: Perspective from genomic laboratory


Breaking News: What Do We Know About COVID-19 Transmission?


title: Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2

text: The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Author summary In this study, we compared SARS-CoV-2 populations of 13 Chinese COVID-19 patients. Those viral populations contained a considerable proportion of viral sub-genomic messenger RNAs (sgmRNA), reflecting an active viral replication activity in the respiratory tract tissues. The comparison of 66 identified intra-host variants further showed a low viral genetic distance between intra-household patients and a narrow transmission bottleneck size. Despite the co-existence of genetically distinct viruses within the same host, most intra-host minor variants were not shared between transmission pairs, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Furthermore, the narrow bottleneck and active viral activity in the respiratory tract show that the passage of a small number of virions can cause infection. Our data have therefore delivered a key genomic resource for the SARS-CoV-2 transmission research and enhanced our understanding of the evolutionary dynamics of SARS-CoV-2.


title: Mathematical models as public troubles in COVID-19 infection control: following the numbers

text: Mathematical models are key actors in policy and public responses to the COVID-19 pandemic. The projections from COVID-19 models travel beyond science into policy decisions and social life. Treating models as ‘boundary objects’, and focusing on media and public communications, we ‘follow the numbers’ to trace the social life of key projections from prominent mathematical models of COVID-19. Public deliberations and controversies about models and their projections are illuminating. These help trace how projections are ‘made multiple’ in their enactments as ‘public troubles’. We need an approach to evidence-making for policy which is emergent and adaptive, and which treats science as an entangled effect of public concern made in social practices. We offer a rapid sociological response on the social life of science in the emerging COVID-19 pandemic to speculate on how evidence-making might be done differently going forwards.


title: A model for 2019-nCoV infection with treatment

text: The current emergence of coronavirus (2019-nCoV or COVID-19) puts the world in threat. 2019-nCoV remains the outbreak of SARS-CoV 2002-2003. The structural research on the receptor recognition by SARS-CoV has identified the key interactions between SARS-CoV spike protein and its host receptor, also known as angiotensin converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV. In this article, we have considered the infection dynamics of SARS-CoV-2 infection in the acute stage. Our aim is to propose and analyse a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a post-infection vaccine is administered at regular intervals. Dynamics of the system with and without impulses have been analysed using qualitative theory. Main findings are supported through numerical simulations.


title: A graph-based approach identifies dynamic H-bond communication networks in spike protein S of SARS-CoV-2

text: Corona virus spike protein S is a large homo-trimeric protein embedded in the membrane of the virion particle. Protein S binds to angiotensin-converting-enzyme 2, ACE2, of the host cell, followed by proteolysis of the spike protein, drastic protein conformational change with exposure of the fusion peptide of the virus, and entry of the virion into the host cell. The structural elements that govern conformational plasticity of the spike protein are largely unknown. Here, we present a methodology that relies upon graph and centrality analyses, augmented by bioinformatics, to identify and characterize large H-bond clusters in protein structures. We apply this methodology to protein S ectodomain and find that, in the closed conformation, the three protomers of protein S bring the same contribution to an extensive central network of H-bonds, has a relatively large H-bond cluster at the receptor binding domain, and a cluster near a protease cleavage site. Markedly different H-bonding at these three clusters in open and pre-fusion conformations suggest dynamic H-bond clusters could facilitate structural plasticity and selection of a protein S protomer for binding to the host receptor, and proteolytic cleavage. From analyses of spike protein sequences we identify patches of histidine and carboxylate groups that could be involved in transient proton binding.


title: A Logistic Model for Age-Specific COVID-19 Case-Fatality Rates

text: Objectives To develop a mathematical model to characterize age-specific case-fatality rates (CFR) of COVID-19. Materials and Method Based on two large-scale Chinese and Italian CFR data, a logistic model was derived to provide quantitative insight on the dynamics between CFR and age. Results and Discussion We inferred that CFR increased faster in Italy than in China, as well as in females over males. In addition, while CFR increased with age, the rate of growth eventually slowed down, with a predicted theoretical upper limit for males (32%), females (21%), and the general population (23%). Conclusion Our logistic model provided quantitative insight on the dynamics of CFR.


title: Coronavirus genomes carry the signatures of their habitats

text: Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of COVID-19. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 protein (APOBEC3). The former binds to CpG dinucleotides to facilitate the degradation of viral transcripts while the latter deaminates C into U residues leading to dysfunctional transcripts. We tested the hypothesis that both APOBEC3 and ZAP may act as primary selective pressures that shape the genome of an infecting coronavirus by considering a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, MERS, Bovine CoV, Murine MHV, Porcine HEV, and Canine CoV). We show that coronaviruses that regularly infect tissues with abundant AVPs have CpG-deficient and U-rich genomes; whereas viruses that do not infect tissues with abundant AVPs do not share these sequence hallmarks. In SARS-CoV-2, CpG is most deficient in the S protein region to evaded ZAP-mediated antiviral defense during cell entry. Furthermore, over four months of SARS-CoV-2 evolutionary history, we observed a marked increase in C to U substitutions in the 5’ UTR and ORF1ab regions. This suggests that the two regions could be under constant C to U deamination by APOBEC3. The evolutionary pressures exerted by host immune systems onto viral genomes may motivate novel strategies for SARS-CoV-2 vaccine development.


title: Feasibility of Controlling COVID-19 Outbreaks in the UK by Rolling Interventions

text: Background: Recent outbreak of a novel coronavirus disease 2019 (COVID-19) in China has led a rapid global spread around the world. For controlling COVID-19 outbreaks, many countries have implemented two non-pharmaceutical interventions: suppression like immediate lockdowns in cities at epicentre of outbreak; or mitigation that slows down but not stopping epidemic for reducing peak healthcare demand. Both interventions have apparent pros and cons; the effectiveness of any one intervention in isolation is limited. We aimed to conduct a feasibility study for robustly estimating the number and distribution of infections, growth of deaths, peaks and lengths of COVID-19 breakouts by taking multiple pharmaceutical interventions in London and the UK, accounting for reduction of healthcare demand. Methods: We developed a model to attempt to infer the impact of mitigation, suppression and multiple rolling interventions for controlling COVID-19 outbreaks in London and the UK. Our model assumed that each intervention has equivalent effect on the reproduction number R across countries and over time; where its intensity was presented by average-number contacts with susceptible individuals as infectious individuals; early immediate intensive intervention led to increased health need and social anxiety. We considered two important features: direct link between Exposed and Recovered population, and practical healthcare demand by separation of infections into mild and critical cases. Our model was fitted and calibrated with data on cases of COVID-19 in Wuhan and Hubei to estimate how suppression intervention impacted on the number and distribution of infections, growth of deaths over time during January 2020, and April 2020. We combined the calibrated model with data on the cases of COVID-19 in London, the UK (non-London) and the UK during February 2020 and March 2020 to estimate the number and distribution of infections, growth of deaths, and healthcare demand by using multiple interventions. Findings: We estimated given that multiple interventions with an intensity range from 3 to 15, one optimal strategy was to take suppression with intensity 3 in London from 23rd March for 100 days, and 3 weeks rolling intervention with intensity between 3 and 5 in non-London regions. In this scenario, the total infections and deaths in the UK were limited to 2.43 million and 33.8 thousand; the peak time of healthcare demand was due to the 65th day (April 11th), where it needs hospital beds for 25.3 thousand severe and critical cases. If we took a simultaneous 3 weeks rolling intervention with intensity between 3 and 5 in all regions of the UK, the total infections and deaths increased slightly to 2.69 million and 37 thousand; the peak time of healthcare kept the same at the 65th day, where it needs equivalent hospital beds for severe and critical cases of 25.3 thousand. But if we released high band of rolling intervention intensity to 6 or 8 and simultaneously implemented them in all regions of the UK, the COVID-19 outbreak would not end in 1 year and distribute a multi-modal mode, where the total infections and deaths in the UK possibly reached to 16.2 million and 257 thousand.


title: Quantifying hospital flows and occupancy due to COVID-19 outbreak in France. Was French lockdown effective?

text: Context. The spread of SARS-CoV-2 led to a rapid and deadly pandemic which reached almost all countries in the world in a few months. In most countries, rigorous measures of mitigation, including national or subnational lockdowns were established. The present work aimed at quantifying the effect of national lockdown in France on hospital occupancy. Methods. A compartmental model describing patient hospital flows was developed, where the effect of lockdown was quantified on the hospitalization rate. Model parameters were estimated using nonlinear mixed-effects (NLME) modelling. Results. French lockdown led to a hospitalization rate decreased by thrice from 12 days after its beginning. However, lockdown may not to have decreased either hospital occupancy or deaths in hospital, which would have been both decreased by 30% and 85% in average if lockdown was started 20 and 30 days before this date, respectively. Conclusion. The present work showed an intrinsic effect of lockdown to decrease hospital burden, but its efficacy on hospital burden may have been increased if established sooner.


title: The political economy of Taiwan’s regional relations

text: In a world of globalized markets, sizeable core states gain greater benefits from economic integration. Small peripheral states generally increase in trade incomes yet at cost of sovereignty and agenda decisions. Recent studies in the field of political economy have demonstrated that concerted economic integration efforts actually lead to disproportional gains for bigger powers at the expense of smaller neighboring states. This differential in integration benefits results in political disintegration for the latter.1In the case of Asia Pacific, Taiwan is situated at the forefront of regional superpower China’s unification campaign. We examine the history of Taiwan’s cross-Straits relations highlighting its experience with China’s various forms of power. For other smaller states in the region, what lessons can be learnt from Taiwan’s experience in the last few decades characterized by China’s “peaceful ascendance” and regional bloc initiative? We suggest that Taiwan serves as a reference for other states in the region. We discuss on the implications of China’s economic integration projects, such as the Belt and Road Initiative (BRI) and the role of Taiwan in the political economy of regional relations. Not only can its experience provide reference data for other small states like canary in the mines,2but it can also be a facilitator of synergetic strategies among smaller state to broker new possibilities under China’s expansive influence.


title: An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2

text: COVID-19 is a new viral emergent human disease caused by a novel strain of Coronavirus. This virus has caused a huge problem in the world as millions of the people are affected with this disease in the entire world. We aimed to design a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system and can be used later to create a new peptide vaccine that could replace conventional vaccines. A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. Then we docked the best predicted CTL epitopes with HLA alleles. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. Potentially continuous B cell epitopes were predicted using tools from IEDB. The Allergenicity of predicted epitopes was analyzed by AllerTOP tool and the coverage was determined throughout the worlds. We found these CTL epitopes to be T helper epitopes also. The B cell epitope, SRVKNL and T cell epitope, FLAFVVFLL were suggested to become a universal candidate for peptide-based vaccine against COVID-19. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate.


title: Can routine laboratory tests discriminate 2019 novel coronavirus infected pneumonia from other community-acquired pneumonia?

text: Background. The clinical presentation of 2019 Novel Coronavirus (2019-nCov) infected pneumonia (NCIP) resembles that of other etiologies of community-acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish NCIP from CAP. Methods. We compared the ability of the hematological and biochemical features of 84 patients with NCIP at hospital admission and 316 patients with CAP. Parameters independently predictive of NCIP were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. Results. Most hematological and biochemical indexes of patients with NCIP were significantly different from patients with CAP. Nine laboratory parameters were identified to be highly predictive of a diagnosis of NCIP by multivariate analysis. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.88 and Hemoglobin (HGB) with an AUC of 0.82. Red blood cell (RBC), albumin (ALB), eosinophil (EO), hematocrit (HCT), alkaline phosphatase (ALP), and white blood cell (WBC) had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone. Conclusions. Routine laboratory examinations may be helpful for the diagnosis of NCIP. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.


Challenges to be considered to evaluate the COVID-19 preparedness and outcome in Bangladesh


title: Displacement ventilation: available ventilation strategy for makeshift hospitals and public buildings to contain Covid-19and other airborne diseases

text: The SARS-CoV-2 virus has so far infected more than2.4 million people around the world, and its impact is being felt by all. Patients with airborne diseases such as Covid-19 should ideally be treated in negative pressure isolation rooms. However, due to the overwhelming demand for hospital beds, patients treated in general wards, hospital corridors, and makeshift hospitals. Adequate building ventilationin hospitals and public spaces is a crucial factor to contain the disease [1,2], to exit the current lockdown situation, and reduce the chance of subsequent waves of outbreaks. Lu et al. [3] reported an air-conditioner induced Covid-19 outbreak, by an asymptomatic patient, in a restaurant in Guangzhou, China, which exposes our vulnerability to future outbreaks linked to ventilation in public spaces. We demonstrate that displacement ventilation(either mechanical or naturalventilation), where air intakes are at low level and extracts are at high level, is a viable alternative to negative pressure isolation rooms, which are often not available on site in hospital wards and makeshift hospitals. Displacement ventilation produces negative pressure at the occupant level, which draws fresh air from outdoor, and positive pressure near the ceiling, which expels the hot and contaminated air out. We acknowledge that, in both developed and developing countries, many modern large structures lack the openings required for natural ventilation. This lack of openings can be supplemented by installing extract fans. We provide guidelines for such mechanically assisted-naturally ventilated makeshift hospitals, and public spaces such as supermarkets and essential public buildings


title: The specificity of Japanese PCR assays for SARS-CoV-2 exceeds 99.7%

text: The Japanese government arranged a total of three charter flights to evacuate Japanese residents out of Wuhan Jan 29, 30, and 31, 2020. The project to rescue Japanese residents can be recognized as a randomized sampling study for the COVID-19 epidemic in Wuhan at that time. Jan 23, Jonathan MR et al stated in the medRxiv, in 14 days time (Feb 4, 2020), the number of infected people in Wuhan is estimated to be greater than 190 thousand (prediction interval, 132,751 to 273,649). In our study, the estimation of the COVID-19 cases in Wuhan around Jan 29, 30 and 31, 2020 exceeds the lower prediction 132,751 in the prior probability: 0.0134. Our statistical analysis is consistent with Jonathan MR et al, if the specificity of SARS-CoV-2 PCR assays in Japan exceeds 99.7%.


title: On the relationships between COVID-19 and extended urbanization

text: This commentary focuses on the relationship between extensive forms of urbanization and emerging infectious disease, using empirical examples from the COVID-19 pandemic. Specifically, it examines the role of shifting urban-ecological relationships, infrastructures, and governance dynamics in both giving rise to, and mitigating, the impact of infectious disease outbreaks.


title: Extension of a SIR model for modelling the propagation of Covid-19 in several countries.

text: Background Several epidemiologic models have been published to forecast the spread of the COVID-19 pandemic yet there are still uncertainties regarding their accuracy. We report the main features of the development of a novel freely accessible model intended to urgently help researchers and decision makers to predict the evolution of the pandemic in their country. Methods and findings We built a SIR-type compartmental model with additional compartments and features. We made the hypothesis that the number of contagious individuals in the population was negligible as compared to the population size. We introduced a compartment D corresponding to the deceased patients and a compartment L representing the group of individuals who will die but who will not infect anybody (due to social or medical isolation). Our model integrated a time-dependent transmission rate, whose variations can be thought to be related to the public measures taken by each country and a cosine function to incorporate a periodic weekly component linked to the way in which numbers of cases and deaths are counted and reported, which can change from day to day. The model was able to accurately capture the different changes in the dynamics of the pandemic for nine different countries whatever the type of pandemic spread or containment measures. The model provided very accurate forecasts in the relatively short term (10 days). Conclusions In early evaluation of the performance of our model, we found a high level of accuracy between prediction and observed data, regardless of the country. The model should be used by the community to help public health decisions as we will refine it over time and further investigate its performance.


title: MATHEMATICAL PREDICTIONS FOR COVID-19 AS A GLOBAL PANDEMIC

text: This study shows that the disease free equilibrium (E_0 ) for COVID-19 coronavirus does not satisfy the criteria for a locally or globally asymptotic stability. This implies that as a pandemic as declared by WHO (2020) the COVID-19 coronavirus does not have a curative vaccine yet and precautionary measures are advised through quarantine and observatory procedures. Also, the Basic Reproductive number (R_0<1) by Equation (33) shows that there is a chance of decline of secondary infections when the ratio between the incidence rate in the population and the total number of infected population quarantined with observatory procedure. The effort to evaluate the disease equilibrium shows that unless there is a dedicated effort from government, decision makers and stakeholders, the world would hardly be reed of the COVID-19 coronavirus and further spread is eminent and the rate of infection will continue to increase despite the increased rate of recovery because of the absence of vaccine at the moment.


title: Impact of population mask wearing on Covid-19 post lockdown

text: COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.


title: Tiger team: a panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes

text: The novel highly transmissible human coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Thus far, there is no approved therapeutic drug, specifically targeting this emerging virus. Here we report the isolation and characterization of a panel of human neutralizing monoclonal antibodies targeting the SARS-CoV-2 receptor binding domain (RBD). These antibodies were selected from a phage display library constructed using peripheral circulatory lymphocytes collected from patients at the acute phase of the disease. These neutralizing antibodies are shown to recognize distinct epitopes on the viral spike RBD, therefore they represent a promising basis for the design of efficient combined post-exposure therapy for SARS-CoV-2 infection.


Environmental Justice Roundtable on COVID-19


title: Differential Expression Analysis of ZIKV Infected Human RNA Sequence Reveals Potential Biomarkers

text: Zika virus (ZIKV) is considered to be an emerging viral outbreak due to its link to diseases like microcephaly, Guillain-Barre Syndrome in human. In this paper, we identify differentially expressed genes (DEGs) using RNA-seq data. In this study, we adopted the RNA-seq analysis pipeline to quantify RNA-seq data into read counts. Our analysis uncovers the significant DEGs which may be involved in the altered biological process somehow. Here, we report the list of significant DEGs, out of which three genes are found to be highly differentially expressed. In addition, our analysis also predicts other moderate DEGs, low DEGs whose differential expression was induced due to ZIKV infections.


title: Suppressive myeloid cells are a hallmark of severe COVID-19

text: 'Severe Acute Respiratory Syndrome - Coronavirus-2' (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46 + n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DR high CD11c high inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DR low monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.


title: Sicken thy neighbour: The initial trade policy response to COVID-19

text: Since the onset of the COVID-19 pandemic, many governments have limited exports of medical supplies and medicines. Pre-pandemic barriers to imports of medical supplies and soap remain largely in place. Having characterised trade policy stance towards COVID-19-related goods, this study critically assesses the resort to export curbs and import taxes. Elements of an alternative, positive trade policy contribution to surmount this pandemic are presented.


title: A comparison of health care worker-collected foam and polyester nasal swabs in convalescent COVID-19 patients

text: Background: The exponential growth of COVID-19 cases and testing has created supply shortages at various points in the testing workflow. As of April 15, 2020 FDA recommendations only allowed for the use of nasopharyngeal, flocked mid turbinate, or foam nasal swabs, all of which are in very low supply. Polyester swabs are more readily available and mass producible. We compare the performance of polyester and foam swabs stored in different transport media. Methods: Both polyester and foam nasal swabs were collected from convalescent COVID-19 patients at a single visit. Using the foam nasal swabs as the comparator, sensitivity of the polyester swabs in each media were calculated, three by three tables were constructed to measure concordance, and cycle threshold (Ct) values were compared. Findings: 126 visits had polyester and foam swabs stored in viral transport media (VTM), 51 had polyester and foam swabs stored in saline, and 63 had a foam swab in VTM and a polyester swab stored in a dry tube. Using nasal foam swabs as a comparator, polyester nasal swabs had a sensitivity of 86*5% when both samples were stored in VTM, 86*7% when both samples were stored in saline, and 72*4% when the polyester swab was stored dry and the foam swab was stored in VTM. Polyester and foam Ct values from the same visit were correlated, but polyester swabs showed decreased performance for cases with a viral load near the detection threshold and higher Ct values on average. Interpretation: Polyester nasal swabs showed a reduction in performance from foam nasal swabs, but may still provide a viable sample collection method given the current supply shortages and public health emergency.


title: Potent synthetic nanobodies against SARS-CoV-2 and molecular basis for neutralization

text: SARS-CoV-2, the Covid-19 causative virus, adheres to human cells through binding of its envelope Spike protein to the receptor ACE2. The Spike receptor-binding domain (S-RBD) mediates this key event and thus is a primary target for therapeutic neutralizing antibodies to mask the ACE2-interacting interface. Here, we generated 99 synthetic nanobodies (sybodies) using ribosome and phage display. The best sybody MR3 binds the RBD with KD of 1.0 nM and neutralizes SARS-CoV-2 pseudovirus with IC50 of 0.40 μg mL-1. Crystal structures of two sybody-RBD complexes reveal a common neutralizing mechanism through which the RBD-ACE2 interaction is competitively inhibited by sybodies. The structures allowed the rational design of a mutant with higher affinity and improved neutralization efficiency by ∼24-folds, lowering the IC50 from 12.32 to 0.50 μg mL-1. Further, the structures explain the selectivity of sybodies between SARS-CoV strains. Our work presents an alternative approach to generate neutralizers against newly emerged viruses. One sentence summary Structural and biochemical studies revealed the molecular basis for the neutralization mechanism of in vitro-selected and rationally designed nanobody neutralizers for SARS-CoV-2 pseudovirus.


title: Application of COVID-19 pneumonia diffusion data to predict epidemic situation

text: Objective: To evaluate novel coronavirus pneumonia cases by establishing the mathematical model of the number of confirmed cases daily, and to assess the current situation and development of the epidemic situation, so as to provide a digital basis for decision-making. Methods: The number of newly confirmed covid-19 cases per day was taken as the research object, and the seven-day average value (M)) and the sequential value (R) of M were calculated to study the occurrence and development of covid-19 epidemic through the analysis of charts and data. Results: M reflected the current situation of epidemic development; R reflected the current level of infection and the trend of epidemic development. Conclusion: The current data can be used to evaluate the number of people who have been infected, and when R < 1, the peak of epidemic can be predicted.


title: Survival in adult inpatients with COVID-19

text: We conducted a nationwide and retrospective cohort study to assess the survival experience and determining factors in adult inpatients with laboratory-confirmed COVID-19. Data from 5,393 individuals were analyzed using the Kaplan-Meier method and a multivariate Cox proportional hazard regression model was fitted. The 7-day survival was 0.822 and went to 0.482, 0.280, and 0.145 on days 15, 21, and 30 of hospital stay, respectively. In the multiple analysis, factors associated with an increased risk of dying were: male gender, age, longer disease evolution before hospital entry, exposure to mechanical ventilator support, and personal history of chronic noncommunicable diseases (namely obesity, type-2 diabetes mellitus, and chronic kidney disease). To the best of our knowledge, this is the first study analyzing the survival probability in a large subset of Latin-American adults with COVID-19 and our results contribute to achieving a better understanding of disease evolution.


title: Biased and unbiased estimation of the average lengths of stay in intensive care units in the COVID-19 pandemic

text: Background: The average length of stay (LOS) in the intensive care unit (ICU_ALOS) is a helpful parameter summarizing critical bed occupancy. During the outbreak of a novel virus, estimating early a reliable ICU_ALOS estimate of infected patients is critical to accurately parameterize models examining mitigation and preparedness scenarios. Methods: Two estimation methods of ICU ALOS were compared: the average LOS of already discharged patients at the date of estimation (DPE), and a standard parametric method used for analyzing time-to-event data which fits a given distribution to observed data and includes the censored stays of patients still treated in the ICU at the date of estimation (CPE). Methods were compared on a series of all COVID-19 consecutive cases (n=59) admitted in an ICU devoted to such patients. At the last follow-up date, 99 days after the first admission, all patients but one had been discharged. A simulation study investigated the generalizability of the methods' patterns. CPE and DPE estimates were also compared to COVID-19 estimates reported to date. Findings: LOS [≥] 30 days concerned 14 out of the 59 patients (24%), including 8 of the 21 deaths observed. Two months after the first admission, 38 (64%) patients had been discharged, with corresponding DPE and CPE estimates of ICU_ALOS (95%CI) at 13.0 days (10.4, 15.6) and 23.1 days (18.1, 29.7), respectively. Series' true ICU_ALOS was greater than 21 days, well above reported estimates to date. Interpretation: Discharges of short stays are more likely observed earlier during the course of an outbreak. Cautious unbiased ICU_ALOS estimates suggest parameterizing a higher burden of ICU bed occupancy than that adopted to date in COVID-19 forecasting models. Funding: Support by the National Natural Science Foundation of China (81900097 to Dr. Zhou) and the Emergency Response Project of Hubei Science and Technology Department (2020FCA023 to Pr. Zhao).


title: An in-silico based clinical insight on the effect of noticeable CD4 conserved residues of SARS-CoV-2 on the CD4-MHC-II interactions

text: The study is aimed to unveil the conserved residues of CD4 in the context of its purposeful interaction with MHC-II at the receptor-binding domain (RBD) of SARS-CoV-2 compared with the envelope (Env) glycoprotein (gp) 120 of HIV-1. The paired CD4 conserved residues, including the matched CD4 interacting MHC-II epitopes of the structural viral protein domains, were chosen for the protein modelling using the SWISS-MODEL online server. Energy minimization and structural validation of the modelled viral protein domains, including the CD4 and MHC-II protein were achieved by CHIMERA and PROCHECK-Ramachandran Plot respectively. Protein-protein docking was performed by the HADDOCK online tool. The binding affinity score was measured using the PRODIGY online server. As per our docking report, the Env gp120 of HIV-1 with three identical and three conserved residues of CD4 exhibited the highest binding affinity (−13.9 kcal/mol) with MHC-II than the second-highest RBD-S1-SARS-CoV-2 (−12.5 kcal/mol) with three identical and a single conserved residue of CD4. With a noticeable single salt bridge formation identified at the interacting residues Lys305 (of Env gp120-HIV-1) and Glu139 (of MHC-II); the Env gp120 interaction with MHC-II occupied the crucial His144 and Glu194 (salt-bridge) interacting residues of CD4 with the measured buried surface area 2554.8±40.8 Å2. Similarly, the RBD-S1-SARS-CoV-2-MHC-II complex showed two salt bridge formations at the residue sites: 1) Arg567 (of SARS-CoV-2)-Glu194 (of MHC-II) 2) 2) Asp568(of SARS-CoV-2)-Arg165 (of MHC-II) with the increased buried surface area of 1910.9±97.1 Å2 over the SARS-CoV score 1708.2±50.8 Å2; that camouflaged all crucial CD4 interacting residues of MHC-II. In conclusion, the noticeable conserved residues of CD4 at the RBD-S1 sites of SARS-CoV-2 could interrupt the aspired CD4-MHC-II interactions of adaptive immune activation.


title: Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: a systematic review

text: Background The recently established association between higher levels of DNA-incorporated thioguanine nucleotides and lower relapse risk in childhood acute lymphoblastic leukaemia (ALL) calls for reassessment of prolonged 6-thioguanine (6TG) treatment, while avoiding the risk of hepatotoxicity. Objectives To assess the incidence of hepatotoxicity in patients treated with 6TG, and to explore if a safe dose of continuous 6TG can be established. Data sources Databases, conference proceedings, and reference lists of included studies were systematically searched for 6TG and synonyms from 1998–2018. Methods We included studies of patients with ALL or inflammatory bowel disorder (IBD) treated with 6TG, excluding studies with 6TG as part of an intensive chemotherapy regimen. We uploaded a protocol to PROSPERO (registration number CRD42018089424). Database and manual searches yielded 1823 unique records. Of these, 395 full-texts were screened for eligibility. Finally, 134 reports representing 42 studies were included. Results and conclusions We included data from 42 studies of ALL and IBD patients; four randomised controlled trials (RCTs) including 3,993 patients, 20 observational studies including 796 patients, and 18 case reports including 60 patients. Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9–25% of the ALL patients in two of the four included RCTs using 6TG doses of 40–60 mg/m2/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. In IBD patients treated with 6TG doses of approximately 23 mg/m2/day, NRH occurred in 14% of patients; SOS has not been reported. At a 6TG dose of approximately 12 mg/m2/day, NRH was reported in 6% of IBD patients, which is similar to the background incidence. According to this review, doses at or below 12 mg/m2/day are rarely associated with notable hepatotoxicity and can probably be considered safe.


title: Evidence for systematic autopsies in COVID-19 positive deceased: Case report of the first German investigated COVID-19 death

text: Forensic medicine and pathology involve specific health risks, whereby health workers are dealing with microorganisms, cells or parasites, which are referred to as biological agents. Biological agents are divided into four categories according to § 3 of the Biological Agents Ordinance. The newly identified coronavirus, severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) that has spread rapidly around the world is placed into category 3 of the Biological Agents Ordinance, meaning pathogens that can cause serious illnesses in humans and may pose a risk to workers. The Robert Koch Institute, the German government’s central scientific institution in the field of biomedicine issued the announcement, that aerosol-producing measures (including autopsies) of SARS-CoV‑2 infected bodies should be avoided, despite the fact that autopsies are an important source of understanding the pathomorphological course of new diseases. The first German case of death due to a proven SARS-CoV‑2 infection is presented with global multifocal reticular consolidation in the post-mortem computed tomography (CT) scan, a macroscopic and microscopic viral pneumonia and viral RNA of SARS-CoV‑2 in pharyngeal mucosa and lung tissue.


title: Dynamics of psychological responses to Covid-19 in India: A longitudinal study

text: To curb the spread of the novel coronavirus, India announced a nationwide lockdown on 24th March 2020 for 21 days, later extended for a longer time. This long period of lockdown greatly disrupted routine life and likely affecting citizens psychological well-being. The psychological toll of the pandemic on Indians is documented. However, no study has assessed whether the psychological toll changed over time due to repeated extensions of the lockdown. We followed up 159 Indian adults during the first two months of the lockdown to assess any change in their anxiety, stress, and depressive symptoms. Multilevel linear regression models of repeated observations nested within individuals, adjusted for socio-demographic covariates, showed that anxiety ({beta}=0.81, CI: 0.03, 1.60), stress ({beta}=0.51, CI: 0.32, 0.70), and depressive symptoms ({beta}=0.37, CI: 0.13, 0.60) increased over time during the lockdown. This increase was higher among women than men independent of covariates. Individual resilience was negatively associated with the psychological outcomes. This suggests that the state needs to address the current mental health impacts of a long-drawn out lockdown and its long-term sequelae. Disproportionate burden on women needs immediate attention. Sustainable change requires addressing the root causes driving the gender inequalities in psychological distress during such crises.


title: Specific cutting energy reduction of granite using plasma treatment: A feasibility study for future geothermal drilling

text: Abstract Geothermal Energy is one of the most consistent and viable sources of renewable energy. However, harnessing this energy has proved to be a challenge mainly due to the difficulty in drilling hard igneous rock formations that occur in and around geothermal wells. Therefore, an energy efficient method that can drill hard rocks needs to be developed. In this paper, the effect of micro-scale energy delivery, in the form of plasma, to weaken rock by inducing micro-cracks is studied. Two different types of granite (igneous rock) were sampled and used in this study, out of which the one control group was treated with five, 40kV, 80J pulses of plasma while the other was left uncracked. The effect of the cracks is quantified by conducting facing tests on the plasma cracked and uncracked samples and measuring a reduction in the specific cutting energy. Two different methods were used to estimate the specific cutting energy, where the first method considered the entire cutting process and the second method considered only the stable cutting region. The plasma treatment showed a maximum of 65% and a minimum of 15% reduction in specific cutting energy and was regarded as being dependent on mainly the hardness and size of the samples. All results in this study are validated using statistical analysis.


title: Effectiveness of quarantine measure on transmission dynamics of COVID-19 in Hong Kong

text: The rapid expansion of COVID-19 has caused a global pandemic. Although quarantine measures have been used widely, the critical steps among them to suppress the outbreak without a huge social-economic loss remain unknown. Hong Kong, unlike other regions in the world, had a massive number of travellers from Mainland China during the early expansion period, and yet the spread of virus has been relatively limited. Understanding the effect of control measures to reduce the transmission in Hong Kong can improve the control of the virus spreading. We have developed a susceptible-exposed-infectious-quarantined-recovered (SEIQR) meta-population model that can stratify the infections into imported and subsequent local infections, and therefore to obtain the control effects on transmissibility in a region with many imported cases. We fitted the model to both imported and local confirmed cases with symptom onset from 18 January to 29 February 2020 in Hong Kong with daily transportation data and the transmission dynamics from Wuhan and Mainland China. The model estimated that the reproductive number was dropped from 2.32 to 0.76 (95% CI, 0.66 to 0.86) after an infected case was estimated to be quarantined half day before the symptom onset, corresponding to the incubation time of 5.43 days (95% CI, 1.30-9.47). If the quarantine happened about one day after the onset, community spread would be likely to occur, indicated by the reproductive number larger than one. The results suggest that the early quarantine for a suspected case before the symptom onset is a key factor to suppress COVID-19.


title: Financing Vaccines for Global Health Security

text: Recent outbreaks of infectious pathogens such as Zika, Ebola, and COVID-19 have underscored the need for the dependable availability of vaccines against emerging infectious diseases (EIDs). The cost and risk of R&D programs and uniquely unpredictable demand for EID vaccines have discouraged vaccine developers, and government and nonprofit agencies have been unable to provide timely or sufficient incentives for their development and sustained supply. We analyze the economic returns of a portfolio of EID vaccine assets, and find that under realistic financing assumptions, the expected returns are significantly negative, implying that the private sector is unlikely to address this need without public-sector intervention. We have sized the financing deficit for this portfolio and propose several potential solutions, including price increases, enhanced public-private partnerships, and subscription models through which individuals would pay annual fees to obtain access to a portfolio of vaccines in the event of an outbreak.


title: Blood and Bone: The Quarantine Chronicles

text: In the midst of the chaos of the global pandemic, the online daily webinar series Blood and Bone was created. The series started with a blank schedule on a google doc and, with enthusiasm and participation from the hematopoiesis and hemostasis/thrombosis communities, was quickly filled through September 2020. In the absence of any editing of the speaker list, a diverse, well-balanced, and scientifically exciting program emerged. The seminar is hosted on Zoom and live-streamed on YouTube daily, and can accommodate up to 1000 attendees. Attendance has topped over 600 and averages 200-300 people daily; this has been sustained for 7 weeks. In addition, there is a weekly Thursday trainee series that hosts 3, 20-minute seminars. In this forum, we reflect on a series that allowed global scientists to come together to help shape chaos into an opportunity for community and growth.


title: CO2 emissions drop by 17% during the pandemic

text: Policies requiring people to stay home during the COVID-19 pandemic have resulted in dramatic reductions in global carbon dioxide emissions At their lowest point, CO2 emissions dropped by 17% in early April, as China was ramping its economy back up and the US and other countries slowed theirs Researchers expect that these extreme decreases won’t last the entire year and estimate that daily CO2 emissions will be down by at least 4% overall for 2020 (Nat Clim Change 2020, DOI: 10 1038/s41558-020-0797-x) The 17% decline is the biggest change in CO2 emissions since World War II, and may turn out to be the most precipitous drop ever observed, says Robert Jackson, an earth system scientist at Stanford University To estimate changes in CO2 emissions, Jackson and a team of researchers led by University of East Anglia climate scientist Corinne Le Quéré used data on traffic, flights, steel production, electricity usage, and[truncated]


title: 30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study

text: Background: Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. Methods: This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Results: Forty-eight (20.6%) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1%) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7% (95% CI 14.6-24.9%) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95% CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95% CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95% CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95% CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95% CI 1.37-4.87) upon admission. Conclusions: Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20%. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.


Virtual Members: Parliaments During the Pandemic


title: Assessment of COVID-19 exposure risk in the blood transfusion laboratory

text: Abstract Healthcare workers run the risk of contracting COVID-19 during the course of their work if required precautions and usage of appropriate personal protective equipment is not adhered to In the transfusion testing laboratory, indirect exposure to COVID-19 may result from environmental contamination that may occur through surface contact or be airborne Handling of potentially contaminated surfaces such as sample tubes and sample packaging, and subsequent self-inoculation through the mucous membranes of mouth, nose and eyes may occur Information on the risk of indirect contact transmission of COVID-19 from such surfaces is limited When risk assessments are conducted in the laboratory, assumptions often need to be based on studies derived from other coronaviruses and respiratory viruses such as HCoV-229E, SARS-CoV, MERS-CoV and Influenza The other mode of potential indirect transmission is through aerosols generated from certain laboratory processes The risk of inhaling aerosolized blood containing COVID-19 viral RNA is unresolved Laboratories need to perform risk assessment of their activities before appropriate decisions can be made with regards to COVID-19 exposure risk reduction or elimination


title: Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

text: BACKGROUND The outbreak of a novel coronavirus (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) since December 2019 in Wuhan, China, has become an emergency of major international concern. Apart from the respiratory system, it is unclear whether SARS-CoV-2 can also directly infect other tissues such as the kidney or induce acute renal failure. METHODS We conducted a retrospective analysis of estimated glomerular filtration rate (eGFR) along with other clinical parameters from 85 patients with laboratory-confirmed COVID-19 admitted to a hospital in Wuhan from January 17, 2020 to March 3, 2020. Kidney tissues from six patients with postmortem examinations were analyzed by Hematoxylin and Eosin (H&E) and in situ expression of viral nucleocaspid protein (NP) antigen, immune cell markers (CD8, CD68 and CD56) and the complement C5b-9 was detected by immunohistochemistry. Moreover, the viral particles in kidneys were also investigated by transmission electronic microscope (EM). RESULTS 27.06% (23/85) patients exhibited acute renal failure (ARF). The eldery patients and cases with comorbidities such as hypertension and heart failure more easily developed ARF (65.22% vs 24.19%, p< 0.001; 69.57% vs 11.29%, p< 0.001, respectively). H&E staining demonstrated kidney tissues from postmortems have severe acute tubular necrosis and lymphocyte infiltration. Immunohistochemistry showed that SARS-CoV-2 NP antigen was accumulated in kidney tubules. EM observation also demonstrated that viruses- like particles are visible in the kidneys. Viral infection not only induces CD68+ macrophages infiltrated into tubulointerstitium, but also enhances complement C5b-9 deposition on tubules. CONCLUSIONS SARS-CoV-2 induces ARF in COVID-19 patients. Viruses directly infect human kidney tubules to induce acute tubular damage. The viruses not only have direct cytotoxicity, but also initiate CD68+ macrophage together with complement C5b-9 deposition to mediate tubular pathogenesis.


title: A shred of evidence that BCG vaccine may protect against COVID-19: Comparing cohorts in Spain and Italy

text: Introduction: There is evidence that the BCG vaccine against tuberculosis also helps prevent other diseases- perhaps including COVD-19. Spain had a program for universal BCG vaccination until 1981. Objective: To see whether cohorts born when Spain had a program of universal BCG vaccination had lower rates of confirmed cases of COVID-19 and mortality (relative to similar cohorts in Italy). Methods: We compare COVID-19 mortality and confirmed cases for those born roughly a decade before and after 1981. We compare the outcomes to the same age cohorts in Italy, which never had universal BCG vaccination. Results: The Spanish cohort that received BCG had a relative risk of 0.962 of having a confirmed case of COVID-19. This risk is statistically significantly below unity (95% CI 0.952 to 0.972, P< 0.001). There is also suggestive evidence the BCG cohort in Spain had lower mortality (relative risk 0.929, CI 0.850 to 1.01, P = 0.11). The small sample size makes this test underpowered. Conclusion: These suggestive results provide a shred of evidence that BCG vaccinations help protect against COVID. I outline many limitations to this study and point how better data can help be more convincing.


title: ISG15 drives immune pathology and respiratory failure during viral infection

text: Cytokine storm during respiratory viral infection is an indicator of disease severity and poor prognosis. Type 1 interferon (IFN-I) production and signaling has been reported to be causal in cytokine storm-associated pathology in several respiratory viral infections, however, the mechanisms by which IFN-I promotes disease pathogenesis remain poorly understood. Here, using Usp18-deficient, USP18 enzymatic-inactive and Isg15-deficient mouse models, we report that lack of deISGylation during persistent viral infection leads to severe immune pathology characterized by hematological disruptions, cytokine amplification, lung vascular leakage and death. This pathology requires T cells but not T cell-intrinsic deletion of Usp18. However, lack of Usp18 in myeloid cells mimicked the pathological manifestations observed in Usp18-/- or Usp18C61A mice which were dependent on Isg15. We further mechanistically demonstrate that interrupting the ISGylation/deISGylation circuit increases extracellular levels of ISG15 which is accompanied by inflammatory neutrophil accumulation to the lung. Importantly, neutrophil depletion reversed morbidity and mortality in Usp18C61A mice. In summary, we reveal that the enzymatic function of Usp18 is crucial for regulating extracellular release of ISG15. This is accompanied by altered neutrophil differentiation, cytokine amplification and mortality following persistent viral infection. Moreover, our results suggest that extracellular ISG15 may drive the inflammatory pathology observed and could be both a prospective predictor of disease outcome and a therapeutic target during severe respiratory viral infections.


title: Multi-task Deep Learning Based CT Imaging Analysis For COVID-19: Classification and Segmentation

text: The fast spreading of the novel coronavirus COVID-19 has aroused worldwide interest and concern, and caused more than one million and a half confirmed cases to date. To combat this spread, medical imaging such as computed tomography (CT) images can be used for diagnostic. An automatic detection tools is necessary for helping screening COVID-19 pneumonia using chest CT imaging. In this work, we propose a multitask deep learning model to jointly identify COVID-19 patient and segment COVID-19 lesion from chest CT images. Our motivation is to leverage useful information contained in multiple related tasks to help improve both segmentation and classification performances. Our architecture is composed by an encoder and two decoders for reconstruction and segmentation, and a multi-layer perceptron for classification. The proposed model is evaluated and compared with other image segmentation and classification techniques using a dataset of 1044 patients including 449 patients with COVID-19, 100 normal ones, 98 with lung cancer and 397 of different kinds of pathology. The obtained results show very encouraging performance of our method with a dice coefficient higher than 0.78 for the segmentation and an area under the ROC curve higher than 93% for the classification.


title: Measuring Italian Citizens' Engagement in the First Wave of the COVID-19 Pandemic Containment Measures A Cross-sectional Study

text: Background: In January 2020, the coronavirus disease 2019 (COVID-19) started to spread in Italy. The Italian government adopted urgent measures to hold its spread. Enforcing compliance to such measures is crucial in order to enhance their effectiveness. Engaging citizens' in the COVID-19 preventive process is today urgent in Italy and around the world. However, to the best of our knowledge, no previous studies have investigated the role of health engagement in predicting citizens compliance to health emergency containment measures. Method: An online survey was administered between February 28th and March 4th 2020 on a representative sample of 1000 Italians. The questionnaire included a measure of Health Engagement (PHE-S) and a series of ad hoc items intended to measure both affective and behavioral responses of the citizens to the emergency in terms of perceived susceptibility to and severity of the disease, orientation towards health management, change in habits and in purchases. To investigate the relationship between Health Engagement and these variables, a series of ANOVAs, Logistic regressions and crosstabs have been carried out. Results: Less engaged people show higher levels of perceived susceptibility to the virus and of severity of the disease; they trust less scientific and healthcare authorities, they feel less self-effective in managing their own health - both in normal conditions and under stress - and are less prone to cooperate with healthcare professionals. Low levels of Health Engagement are also associated with a change in the usual purchase behavior. Conclusions: The Patient Health Engagement Model (PHE) provides a useful framework for understanding how people will respond to health threats such as pandemics. Therefore, intervention studies should focus on particular groups and on raising their levels of engagement to increase the effectiveness of educational initiatives devoted to promote preventive behaviors.


title: The Association Between Biomarkers and Clinical Outcomes in Novel Coronavirus (COVID-19) Pneumonia in a U.S. Cohort

text: Background: The global pandemic caused by COVID-19 remains poorly understood by clinicians. Identifying biologic markers associated with prognosis can help clinicians recognize disease severity. Objective: To describe the association between D-dimer, CRP, IL-6, ferritin, LDH, and clinical outcomes in a cohort of COVID-19 patients treated on the inpatient medical service at a university hospital in Washington, DC. Design: In this retrospective study, we included all adults admitted to the inpatient medicine service at George Washington University Hospital between March 12, 2020 and May 9, 2020 with laboratory confirmed COVID-19. Clinical and laboratory data were extracted from electronic medical records and compared between survivors not requiring ICU transfer, survivors requiring ICU transfer, survivors requiring intubation, and non-survivors. Key Results: 299 patients were included in our study, of whom 69 required transfer to the ICU, 39 required intubation, and 71 died. Threshold values for IL-6 (>50 pg/mL), D-dimer (>3 mcg/mL), ferritin (>450 ng/mL), CRP (>100 mg/L), and LDH (1,200 u/L) were found to be statistically significant and independently associated with higher odd of clinical deterioration and death. Hypertension, CVA and heart disease independently had an increased risk of all three outcomes, while CKD had only an increased risk of death. Patient co-morbidities had no effect on the different biomarkers' significant association with poor patient clinical outcomes, except cancer. Conclusion: Laboratory markers of inflammation and coagulopathy can help clinicians identify patients who are at high risk for clinical deterioration, independent of clinically significant medical comorbidities


title: Dominant and rare SARS-Cov2 variants responsible for the COVID-19 pandemic in Athens, Greece.

text: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel Coronavirus responsible for the Coronavirus Disease-2019 (COVID-19) pandemic. Since the beginning of the pandemic, the virus has spread in almost the entire world. Tracing and tracking virus international and local transmission has been an enormous challenge. Chains of infections starting from various countries worldwide seeded the outbreak of COVID-19 in Athens, capital city of Greece. Full-genome analysis of isolates from Athens' Hospitals and other healthcare providers revealed the variety of SARS-CoV-2 that initiated the pandemic before lock-down and passenger flight restrictions. The present work may serve as reference for resolving future lines of infection in the area and Europe especially after resumption of passenger flight connections to Athens and Greece during summer of 2020.


title: Low testosterone and high cytokine levels correlate with lethal H7N9 infections in men: a retrospective cohort study from 98 H7N9 patients

text: Background. Human infections with avian influenza A (H7N9) virus emerged in East China in March 2013. In contrast to seasonal influenza A viruses, H7N9 infections showed a strong sex bias. Over the five epidemic waves in China, ~70% of all H7N9 cases were observed in men. Thus, in this human cohort, we retrospectively analyzed sex hormones as well as inflammatory cytokine and chemokine levels in men and women infected with avian H7N9 influenza. Methods. We systematically analyzed the underlying correlation based on established human cohorts of two age groups (18-49 years and [≥]50 years) including laboratory-confirmed H7N9 cases as well as seasonal influenza cases, H7N9 close contacts and poultry workers as controls in dependency on sex. The level of testosterone, estradiol and cytokines/chemokines were measured in all study participants. We compared the levels of sex hormones, cytokines/chemokines by sex and disease outcome. Findings. We included H7N9 cases (n=98), close contacts (n=71), poultry workers (n=108) and mild seasonal influenza cases (n=53) in this study. Samples were collected between 2014 and 2017. All control groups showed similar median age within H7N9 cases except for the seasonal influenza group with a younger median age. In H7N9 infected men, testosterone levels were strongly reduced compared to male H7N9 virus-negative close contacts or males with seasonal influenza. Low testosterone levels in H7N9 infected men correlated with high inflammatory cytokine levels, e.g. IL-6, and lethal outcome in those 18-49 years of age. No significant differences were detected in estradiol levels in H7N9 infected men. In H7N9 infected women ([≥] 50 years), estradiol levels were significantly elevated compared to H7N9 virus-negative close contacts. However, increased estradiol levels did not significantly correlate with lethal outcome in women albeit a slight tendency towards poor outcome could be detected. Interpretation. This study provides evidence that low testosterone levels in H7N9 influenza infected men correlate with inflammatory cytokine/chemokine responses and lethal outcome. Thus, treatment of H7N9 influenza virus infected patients should consider sex-specific mitigation strategies.


title: The Estimated Time-Varying Reproduction Numbers during the Ongoing Epidemic of the Coronavirus Disease 2019 (COVID-19) in China

text: Background: How could we anticipate the progression of the ongoing epidemic of the coronavirus disease 2019 (COVID-19) in China? As a measure of transmissibility, the value of basic reproduction number varies over time during an epidemic of infectious disease. Hence, this study aimed to estimate concurrently the time-varying reproduction number over time during the COVID-19 epidemic in China. Methods: We extracted the epidemic data from the "Tracking the Epidemic" website of the Chinese Center for Disease Control and Prevention for the duration of January 19, 2020 and March 14, 2020. Then, we applied the novel method implemented in the incidence and EpiEstim packages to the data of daily new confirmed cases for robustly estimating the time-varying reproduction number in the R software. Results: The epidemic curve of daily new confirmed cases in China peaked around February 4-6, 2020, and then declined gradually, except the very high peak on February 12, 2020 owing to the added clinically diagnosed cases (Hubei Province only). Under two specified plausible scenarios for the distribution of serial interval, both curves of the estimated time-varying reproduction numbers fell below 1.0 around February 17-18, 2020. Finally, the COVID-19 epidemic in China abated around March 7-8, 2020, indicating that the prompt and aggressive control measures of China were effective. Conclusion: Seeing the estimated time-varying reproduction number going downhill was more informative than looking for the drops in the daily number of new confirmed cases during an ongoing epidemic of infectious disease. We urged public health authorities and scientists to estimate time-varying reproduction numbers routinely during epidemics of infectious diseases and to report them daily to the public until the end of the COVID-19 epidemic.


title: Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: Study Protocol for a Pragmatic Randomized Controlled Trial

text: Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease 2019 (COVID-19) pandemic. Currently, there are a lack of evidence-based therapies to prevent COVID-19 following exposure, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis and pre-emptive therapy for COVID-19. Methods: We will conduct two nested multicenter international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) post-exposure prophylaxis (PEP) of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) pre-emptive therapy (PET) for symptomatic outpatients with COVID-19 with a total symptom duration of less than 4 days. We will recruit 1500 patients for each the PEP and PET trials. Participants will be randomized 1:1 to receive 5 days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19 disease. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized; hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. Discussion: These complementary randomized control trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted in order to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. Trials Registration: clinicaltrials.gov (NCT04308668); 16 March 2020.


title: Changes in the Tertiary Education System in Pandemic Times: Comparison of Ukrainian and Polish Universities

text: The article discusses the challenges faced by universities during forced quarantine because of COVID-19 The article provides examples of successful online learning practices of Polish and Ukrainian universities, as well as the problematic aspects faced by HEIs The focus of the article is on the forms of online learning, the specifics of their combination and the particularities of use in leading universities in Poland and Ukraine The situation of the need for self-isolation has forced universities not only to shift the vector of providing educational services Approaches to accounting of working hours and forms of direct communication between students and teachers were modernized Vectors of changing approaches to university education, requirements for teachers and students are given in connection with the possible prolonged period of self-isolation because of coronavirus


title: Association of country-wide coronavirus mortality with demographics, testing, lockdowns, and public wearing of masks.

text: Background. Wide variation between countries has been noted in per-capita mortality from the disease (COVID-19) caused by the SARS-CoV-2 virus. Determinants of this variation are not fully understood. Methods. Potential predictors of country-wide per-capita coronavirus-related mortality were studied, including age, sex ratio, temperature, urbanization, viral testing, smoking, duration of infection, lockdowns, and public mask-wearing norms and policies. Multivariable linear regression analysis was performed. Results. In univariate (but not multivariable) analyses, prevalence of smoking, per-capita gross domestic product, and colder average country temperature were positively associated with coronavirus-related mortality. In a multivariable analysis of 183 countries, urbanization, the duration of the infection in the country, and percent of the population at least 60 years of age were all positively associated with per-capita mortality, while duration of mask-wearing by the public was negatively associated with mortality (all p<0.001). In countries with cultural norms or government policies supporting public mask-wearing, per-capita coronavirus mortality increased on average by just 5.4% each week, as compared with 48% each week in remaining countries. In the multivariable analysis, lockdowns tended to be associated with less mortality (p=0.31), and per-capita testing with higher reported mortality (p=0.26), though neither association was statistically significant. Conclusions. Societal norms and government policies supporting the wearing of masks by the public are independently associated with less mortality from COVID-19.


title: Intestinal Flora as a Potential Strategy to Fight SARS-CoV-2 Infection

text: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide, seriously endangering human health. In addition to the typical symptoms of pulmonary infection, patients with COVID-19 have been reported to have gastrointestinal symptoms and/or intestinal flora dysbiosis. It is known that a healthy intestinal flora is closely related to the maintenance of pulmonary and systemic health by regulating the host immune homeostasis. Role of the “gut-lung axis” has also been well-articulated. This review provides a novel suggestion that intestinal flora may be one of the mediators of the gastrointestinal responses and abnormal immune responses in hosts caused by SARS-CoV-2; improving the composition of intestinal flora and the proportion of its metabolites through probiotics, and personalized diet could be a potential strategy to prevent and treat COVID-19. More clinical and evidence-based medical trials may be initiated to determine the strategy.


title: Document addressed to cardiovascular echography operators at the time of COVID-19: A Document by the 'Società Italiana di Ecocardiografia e CardioVascular Imaging' Board 2019-2021

text: The epidemic of COVID-19 has grown to pandemic proportions and the preventive and mitigation measures have been widely spread through the media. The cardiologists are called as consultants for the cardiovascular pathologies and echocardiography is a fundamental examination in many clinical situations, but not without risks for health staff. Società Italiana di Ecocardiografia e CardioVascular Imaging Council has decided to formulate a document aimed to highlight the importance of a correct indication and execution procedure of the echocardiogram during a COVID-19 pandemic.


On the possibility of interrupting the coronavirus (COVID-19) epidemic based on the best available scientific evidence.