title: Risk stratification of hospitalized COVID-19 patients through comparative studies of laboratory results with influenza

text: Background The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season. Methods We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020. We compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients based on these data. The clinical outcomes were compared among different clusters. Results Temporal analyses of laboratory results revealed that compared to influenza, patients with COVID-19 exhibited a continued increase in the white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen. Using these results, we sub-classified the COVID-19 patients into 5 clusters through a hierarchical clustering analysis. We then reviewed the medical record of these patients and risk stratified them based on the clinical outcomes. The cluster with the highest risk showed 27.8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin. Conclusions There are significant differences in the clinical and laboratory courses between COVID-19 and influenza. Risk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.


title: Molecular Insights Into SARS COV-2 Interaction With Cardiovascular Disease: Role of RAAS and MAPK Signaling

text: In December 2019, reports of viral pneumonia came out of Wuhan city in Hubei province in China. In early 2020, the causative agent was identified as a novel coronavirus (CoV) sharing some sequence similarity with SARS-CoV that caused the severe acute respiratory syndrome outbreak in 2002. The new virus, named SARS-CoV-2, is highly contagious and spread rapidly across the globe causing a pandemic of what became known as coronavirus infectious disease 2019 (COVID-19). Early observations indicated that cardiovascular disease (CVD) patients are at higher risk of progression to severe respiratory manifestations of COVID-19 including acute respiratory distress syndrome. Moreover, further observations demonstrated that SARS-CoV-2 infection can induce de novo cardiac and vascular damage in previously healthy individuals. Here, we offer an overview of the proposed molecular pathways shared by the pathogenesis of CVD and SARS-CoV infections in order to provide a mechanistic framework for the observed interrelation. We examine the crosstalk between the renin-angiotensin-aldosterone system and mitogen activated kinase pathways that potentially links cardiovascular predisposition and/or outcome to SARS-CoV-2 infection. Finally, we summarize the possible effect of currently available drugs with known cardiovascular benefit on these pathways and speculate on their potential utility in mitigating cardiovascular risk and morbidity in COVID-19 patients.


title: In silico Molecular Docking Analysis Targeting SARS-CoV-2 Spike Protein and Selected Herbal Constituents

text: In modern drug discovery, molecular docking analysis is routinely used to understand and predict the interaction between a drug molecule and a target protein from a microbe Drugs identified in this way may inhibit the entry and replication of pathogens in host cells The SARS-CoV-2 associated coronavirus disease, COVID-19, has become the most contagious and deadly pandemic disease in the world today In abeyance of any specific vaccine or therapeutic against SARS-CoV-2, the burgeoning situation urges a need for effective drugs to treat the virus-infected patients Herbal medicines have been used as natural remedies for treating various infectious diseases since ancient times The spike (S) protein of SARS-CoV-2 is important for the attachment and pathogenesis of the virus Therefore, this study focused on the search of useful ligands for S protein among active constituents present in common herbs that could serve as efficient remedies for COVID-19 We analysed the binding efficiency of twelve compounds present in common herbs with the S protein of SARS-CoV-2 through molecular docking analysis and also results are validated with two different docking tools The binding efficiency of ligands was scored based on their predicted pharmacological interactions coupled with binding energy estimates In docking analysis, compound "I" (Epigallocatechin gallate (EGCG)) was found to have the highest binding affinity with the viral S protein, followed by compounds, "F" (Curcumin),"D" (Apigenin) and "E" (Chrysophanol) The present study corroborates that compound "I" (EGCG) mostly present in the integrants of green tea, shows the highest potentiality for acting as an inhibitor of SARS-CoV-2 Further, characterization of the amino acid residues comprising the viral binding site and the nature of the hydrogen bonding involved in the ligand-receptor interaction revealed significant findings with herbal compound "I" (EGCG) binding to the S protein at eight amino acid residues The binding sites are situated near to the amino acids which are required for virus pathogenicity The findings of the present study need in vivo experiments to prove the utility of "I", "F","D" and "E" compounds and their further use in making herb-based anti-SARS-CoV-2 product in near future This analysis may help to create a new ethno-drug formulation for preventing or curing the COVID-19


title: Appendix B Laboratories Molecular Testing for Infectious Diseases

text: Unknown


title: Preliminary evaluation of COVID-19 disease outcomes, test capacities and management approaches among African countries.

text: Background: Following the declaration of COVID-19 as a global pandemic and the report of index case in Africa, the number of countries in Africa with confirmed cases of the infection has grown tremendously with disease now being reported in almost all countries on the continent, with the exemption of Lesotho after 75 days. It is therefore necessary to evaluate the disease outcomes among the African countries as the situation unfolds for early identification of best practices for adoption. Methods: In this study, COVID-19 disease outcomes (confirmed cases, deaths and recoveries), testing capacities and disease management approaches among African countries were evaluated. The relationship between COVID-19 infections in African countries and their performance on global resilient indices including the Human Development Index (HDI), performance on Sustainable Development Goals (SDGs) and the Global Risk Index (GRI) were also examined. Data acquired from various standard databases were evaluated over a period of 75 days from the date of reporting the index case. Results: This study has revealed compelling spatial differences in the incidence, deaths and recoveries from COVID-19 among African countries. Egypt, South Africa, Morocco and Algeria were clustered as countries with highest values of COVID-19 disease outcomes on the continent during the 75-day period of observation. The cluster analysis and comparison of countries in terms of percentage recovered cases of confirmed infections revealed that Mauritius, Mauritania, Gambia, Burkina Faso, Madagascar, Togo and Uganda had the highest scores. Comparative analysis of COVID-19 across the world revealed that the parameters were relatively inconsequential in Oceania and Africa continents, while Europe, North America and Asia had significantly higher cases of disease outcomes. For COVID-19 testing capacities, South Africa, Ghana and Egypt are leading in total number of tests carried out. However when the number of tests carried out were related to population number of the countries, Djibouti, Mauritius, Ghana and South Africa are found to be the leading countries. With respect to management of the disease in Africa, all the countries adopted the WHO protocols, personal hygiene, economic palliatives and social distancing measures. Only three countries in Africa (Madagascar, Togo and Burkina Faso) had a state supported initiative to utilise traditional medicines or herbs as alternatives to control COVID-19. Additionally, most of the countries are providing prompt treatment of the patients with a range of drugs especially Hydroxychloroquine, Chloroquine and Chloroquine-Azithromycin combination. The study found that no strong relationship currently exists between the global resilient indicators (HDI, SDG and GRI) and COVID-19 cases across Africa. Conclusions: This study has revealed compelling spatial differences in disease outcomes among African countries and also found testing capacities for COVID-19 to be abysmally low in relation to the population. During the 75 days of observation, African countries have recorded significantly low number of deaths associated with COVID-19 and relatively high recovery rates. Countries in Africa with higher rate of recovery from the disease were found to have adopted strict adherence to some of WHO protocol to contain the disease, isolate all those who test positive to the disease and provide prompt treatment of the patients with a range of drugs especially Hydroxychloroquine, Chloroquine and Chloroquine-Azithromycin combination. The study recommends that the approaches adopted by the African countries which achieved high recovery rates from COVID-19 should be integrated into healthcare management plans for the disease across the continent even as the situation unfolds.


title: Lack of sufficient public space can limit the effectiveness of COVID-19's social distancing measures

text: One of the primary strategies of slowing down the COVID-19 pandemic has been the establishment of social distancing rules that recommend keeping a buffer distance between individuals, and this has proven effective in helping in reducing the basic reproduction number [R 0] . However, social distancing rules have put the use of public spaces in densely populated places under strain, and this is especially important as some of the most virulent outbreaks of the COVID-19 pandemic have been in compact cities. It is therefore fundamental to take into account each neighbourhood's morphological characteristics and the potential population densities each street, square or park can accommodate under such new regulations in order to effectively enforce social distancing rules. Otherwise, certain areas may be rapidly overwhelmed by crowds with citizens unable to maintain the minimum safe distance between individuals. In this paper, we develop a method to identify the potential public space accessibility if social distancing rules are followed and we apply it to three global and highly affected by COVID-19 cities. Our research finds that, at micro level there are important inequalities between neighbourhoods, so people will struggle to comply with social distancing rules and consequently it will make controlling infection rates more difficult.


title: Designed peptides as potential fusion inhibitors against SARA-CoV-2 coronavirus infection

text: Inspired by fusion-inhibitory peptides from heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains from human immuno-deficiency virus type 1 (HIV-1) envelope glycoprotein gp41 and severe acute respiratory syndrome-coronavirus (SARS-CoV) based on viral fusogenic mechanism in the present work, we provided a similar approach to design the synthesized peptides against the entry into host cells of SARA-CoV-2 virus that causes 2019 novel coronavirus disease (COVID-19). These peptides derived from HR1 and HR2 of SARA-CoV-2 spike protein were further tested for their interaction and potential fusion possibility through circular dichroism spectrum. Here we used the peptide COVID-2019-HR1P1 (40 amino acids) as the target, which was derived from HR1 of SARA-CoV-2 spike protein, while the designed peptides including COVID-2019-HR2P1 (37 amino acids), COVID-2019-HR2P2 (32 amino acids) and others derived from HR2 of SARA-CoV-2 were tested for their binding to COVID-2019-HR1P1. Interestingly, results showed that both COVID-2019-HR2P1 and COVID-2019-HR2P2 can form the complex with COVID-2019-HR1P1, respectively. This implied that these designed peptides could play an important role in blocking SARA-CoV-2 entry into mammalian host cells via viral fusogenic mechanism, and thus could be used for preventing SARA-CoV-2 infection.


title: Estimation of SARS-CoV-2 emissions from non-symptomatic cases

text: Importance: Cases of the coronavirus disease 2019 (COVID-19) with no or mild symptoms were reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome virus (SARS-COV-2) was found at very high concentrations in swab and sputum of such cases. Objective: We aimed to estimate virus release from such cases into different aerosol sizes by normal breathing and coughing, and what exposure can result from this in a room shared with such as case. Data Sources and Model: We combined the size-distribution of exhaled breath aerosols for coughing and normal breathing with viral sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50m3, the size of a small office or medical exam room. Results: The estimated viral load in aerosols emitted by patients while breathing normally was on average 0.34 copies/cm3 and could go up to 11.5 copies/cm3. The corresponding numbers for coughing patients were 10,900 copies/cm3 and 366,000 copies/cm3, respectively, per cough. The resulting concentrations in a room with a coughing emitter were always very high, up to 2.02*10^9 copies/m3. However, also regular breathing aerosol from high emitters was predicted to lead to several thousand copies/m3. Conclusions and Relevance: These very high predicted virus concentrations may provide an explanation why for COVID-19, frequent community transmissions from non-symptomatic cases and also high infection rates in medical staff in hospital settings were reported. Our findings suggest that strict respiratory protection is needed when there is a chance to be in the same room with a patient - whether symptomatic or not - especially if this was for a prolonged time.


title: First SARS-CoV-2 detection in river water: implications in low sanitation countries

text: Since the beginning of SARS-CoV-2 pandemic studies on viral shedding have reported that this virus is excreted in feces in most patients. High viral loads are found at the sewage pipeline or at the entrance of wastewater treatment plants from cities where the number of COVID-19 cases are significant. In Quito (Ecuador) as in many other cities worldwide, wastewater is directly discharged into natural waters. The aim of this study was to evaluate SARS-CoV-2 presence in urban streams from a low sanitation context. Three river locations along the urban rivers of Quito were sampled on the 5th of June during a peak of COVID-19 cases. River samples were evaluated for water quality parameters and afterwards, concentrated for viral analysis using skimmed milk flocculation method. The viral concentrates were quantified for SARS-CoV-2 (N1 and N2 genes) and Human Adenovirus as a human viral indicator. The results showed that SARS-CoV-2 was detected for both target genes in all samples analyzed in a range of 2,91E+05 to 3,19E+06 GC/L for N1 and from 2,07E+05 to 2,22E+06 GC/L for N2. The high values detected in natural waters from a low sanitation region have several implications in health and ecology that should be further assessed.


title: Control with uncertain data of socially structured compartmental epidemic models

text: The adoption of containment measures to reduce the amplitude of the epidemic peak is a key aspect in tackling the rapid spread of an epidemic. Classical compartmental models must be modified and studied to correctly describe the effects of forced external actions to reduce the impact of the disease. In addition, data are often incomplete and heterogeneous, so a high degree of uncertainty must naturally be incorporated into the models. In this work we address both these aspects, through an optimal control formulation of the epidemiological model in presence of uncertain data. After the introduction of the optimal control problem, we formulate an instantaneous approximation of the control that allows us to derive new feedback controlled compartmental models capable of describing the epidemic peak reduction. The need for long-term interventions shows that alternative actions based on the social structure of the system can be as effective as the more expensive global strategy. The importance of the timing and intensity of interventions is particularly relevant in the case of uncertain parameters on the actual number of infected people. Simulations related to data from the recent COVID-19 outbreak in Italy are presented and discussed.


Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome


title: Human H-ferritin presenting RBM of spike glycoprotein as potential vaccine of SARS-CoV-2

text: The outbreak of COVID-19 has so far inflicted millions of people all around the world and will have a long lasting effect on every aspect of everyone’s life. Yet there is no effective approved treatment for the disease. In an effort of utilizing human ferritin as nanoplatform for drug delivery, we engineered a fusion protein by presenting receptor-binding motif (RBM) of SARS-CoV-2 virus spike glycoprotein on the N-terminus of ferritin subunits. The designed fusion protein with a cage-like structure, similar to that of corona virus, is a potential anti-SARS-CoV-2 vaccine. We hereby show the construction, preparation, and characterization of the fusion protein RBM-HFtn. Our initial affinity study confirmed its biological activity towards ACE2 receptor which suggests its mode of action against SARS-CoV-2 could be either through vaccine therapy or blocking the cellular entry of virus as antagonist of ACE2 receptor.


title: Remembering people with dementia during the COVID-19 crisis

text: This letter argues that we need to pay particular attention to people with dementia during this difficult time of the COVID-19 pandemic Social distancing rules and cocooning for people aged 70 years and over are now in place in Ireland to slow down the rate of infection and protect vulnerable older people This letter argues that we need, more than ever, to assert the personhood of people with dementia at this difficult time That means more person-centred care and practical support structures for family carers to allow them to continue to care at home in a safe and life-enhancing way New public broadcasting initiatives could create information and communication channels for people with dementia and their carers, as well as demonstrating empathy and solidarity with their predicament Government, the Department of Health, the HSE and the voluntary sector have risen to the challenge of COVID-19 in all sectors of society So too have ordinary citizens Now we need to unite even more to create an unyielding commitment and adherence to the principles of decency, justice and equity in the allocation of scarce health and social care resources By doing this, we will demonstrate our caring potential and capacity in a way that reflects our shared humanity, not only in the current crisis, but into the future


Special Coverage on COVID-19: EDs Should Hoard Every Gown and Surgical Mask and Lock Up N95s


title: Epidemiological and clinical characteristics of discharged patients infected with SARS-CoV-2 on the Qinghai plateau

text: Since the outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, a series of confirmed cases of COVID-19 were found on the Qinghai-Tibet plateau. We aimed to describe the epidemiological, clinical characteristics, and outcomes of all confirmed cases in Qinghai, a province at high altitude. With efficient measures to stop the spread of coronavirus, no new cases were found in Qinghai Province for 60 consecutive days between Feb 6 and April 6, 2020. Of all 18 patients with confirmed SARS-CoV-2 infection, 15 patients comprising 4 transmission clusters were identified. Three patients were infected by direct contact without travel history to Wuhan. Seven patients were asymptomatic on admission. Of 18 patients, 10 patients showed bilateral pneumonia and 2 patients showed no abnormalities. Three patients with comorbidities such as hypertension, liver diseases or diabetes developed severe illness. High C-reactive protein levels and elevations of both ALT and AST were observed in 3 severely ill patients on admission. All 18 patients were eventually discharged, including the 3 severe patients who recovered after treatment with non-invasive mechanical ventilation, convalescent plasma and other therapies. Our findings confirmed human-to-human transmission of SARS-CoV-2 in clusters. The strategies of early diagnosis, early isolation, and early treatment are important to prevent the spread of COVID-19 and improve the cure rate. Patients with comorbidities are more likely to develop severe illness and could benefit from convalescent plasma transfusion.


title: COVID-19: Are Africa’s diagnostic challenges blunting response effectiveness?

text: Since its emergence in Wuhan, China in December 2019, novel Coronavirus disease - 2019 (COVID-19) has rapidly spread worldwide, achieving pandemic status on 11 (th) March, 2020. As of 1 (st) April 2020, COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had infected over 800,000 people and caused over 40,000 deaths in 205 countries and territories. COVID-19 has had its heaviest toll on Europe, United States and China. As of 1 (st) of April 2020, the number of confirmed COVID-19 cases in Africa was relatively low, with the highest number registered by South Africa, which had reported 1,380 confirmed cases. On the same date (also the date of this review), Africa had reported 5,999 confirmed cases, of which 3,838 (almost 65%) occurred in South Africa, Algeria, Egypt, Morocco and Tunisia, with the remaining 2,071 cases distributed unevenly across the other African countries. We speculate that while African nations are currently experiencing much lower rates of COVID-19 relative to other continents, their significantly lower testing rates may grossly underestimate incidence rates. Failure to grasp the true picture may mean crucial windows of opportunity shut unutilized, while limited resources are not deployed to maximum effect. In the absence of extensive testing data, an overestimation of spread may lead to disproportionate measures being taken, causing avoidable strain on livelihoods and economies. Here, based on the African situation, we discuss COVID-19 diagnostic challenges and how they may blunt responses.


title: Organisms causing secondary pneumonias in COVID-19 patients at 5 UK ICUs as detected with the FilmArray test

text: ABSTRACT Introduction. Several viral respiratory infections - notably influenza - are associated with secondary bacterial infection and additional pathology. The extent to which this applies for COVID-19 is unknown. Accordingly, we aimed to define the bacteria causing secondary pneumonias in COVID-19 ICU patients using the FilmArray Pneumonia Panel, and to determine this tests potential in COVID-19 management. Methods. COVID-19 ICU patients with clinically-suspected secondary infection at 5 UK hospitals were tested with the FilmArray at point of care. We collected patient demographic data and compared FilmArray results with routine culture. Results. We report results of 110 FilmArray tests on 94 patients (16 had 2 tests): 69 patients (73%) were male, the median age was 59 yrs; 92 were ventilated. Median hospital stay before testing was 14 days (range 1-38). Fifty-nine (54%) tests were positive, with 141 bacteria detected. Most were Enterobacterales (n=55, including Klebsiella spp. [n= 35]) or Staphylococcus aureus (n=13), as is typical of hospital and ventilator pneumonia. Community pathogens, including Haemophilus influenzae (n=8) and Streptococcus pneumoniae (n=1), were rarer. FilmArray detected one additional virus (Rhinovirus/Enterovirus) and no atypical bacteria. Fewer samples (28 % vs. 54%) were positive by routine culture, and fewer species were reported per sample; Klebsiella species remained the most prevalent pathogens. Conclusion. FilmArray had a higher diagnostic yield than culture for ICU COVID-19 patients with suspected secondary pneumonias. The bacteria found mostly were Enterobacterales, S. aureus and P. aeruginosa, as in typical HAP/VAP, but with Klebsiella spp. more prominent. We found almost no viral co-infection. Turnaround from sample to results is around 1h 15 min compared with the usual 72h for culture, giving prescribers earlier data to inform antimicrobial decisions.


title: Glycomic analysis of host-response reveals high mannose as a key mediator of influenza severity

text: Influenza virus infections cause a wide variety of outcomes, from mild disease to 3-5 million cases of severe illness and ~290,000-645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity. SIGNIFICANCE Influenza virus infection causes a range of outcomes from mild illness to death. The molecular mechanisms leading to these differential host responses are currently unknown. Herein, we identify the induction of high mannose, a glycan epitope, as a key mediator of severe disease outcome. We propose a mechanism in which activation of the unfolded protein response (UPR) upon influenza virus infection turns on expression of high mannose, which is then recognized by the innate immune lectin MBL2, activating the complement cascade and leading to subsequent inflammation. This work is the first to systematically study host glycomic changes in response to influenza virus infection, identifying high mannose as a key feature of differential host response.


title: Reproductive number of COVID-19: A systematic review and meta-analysis based on global level evidence

text: Background The coronavirus (COVID-19) is now a global concern because of its higher transmission capacity and associated adverse consequences including death. The reproductive number of COVID-19 provides an estimate on the possible extent of the transmission. This study aims to provide the average reproductive number of COVID-19 based on available global level evidence. Methods We searched three databases (PubMed, Web of Science, and Science Direct) to find studies reported the reproductive number of COVID-19. The searches were conducted using a pre-specified search strategy that includes keywords of COVID-19 and its reproductive number related terms, which were combined using the Boolean operators. Narrative synthesis was used to explain the studies included and the meta-analysis was used to estimate the average reproduction number of COVID-19. Results Total of 30 studies included in this review whereas 24 of them were included in the meta-analysis. The average estimated reproductive number was 2.70 (95% CI, 2.21-3.30). We found evidence of very high heterogeneity (99.5%) of the reproductive numbers reported in the included studies. The highest reproductive number was reported for Diamond Princes Cruise Ship, Japan (14.8). In the country-level, the higher reproductive number was reported for France (R, 6.32, 95% CI, 5.72-6.98) following Germany (R, 6.07, 95% CI, 5.51-6.69) and Spain (R, 5.08, 95% CI, 4.50-5.73). We also found estimation models, methods, and the number of cases considered to estimate reproductive number were played a role in arising the heterogeneity of the estimated reproductive number. Conclusion The estimated reproductive number indicates an exponential increase of COVID-19 infection in the coming days. Comprehensive policies and programs are important to reduce new infections as well as the associated adverse consequences including death.


title: Computational analysis suggests putative intermediate animal hosts of the SARS-CoV-2

text: The authors have withdrawn their manuscript whilst they wish to perform additional experiments to validate their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author for more details.


title: Transcriptional profiling of immune and inflammatory responses in the context of SARS-CoV-2 fungal superinfection in a human airway epithelial model

text: Superinfections of bacterial/fungal origin are known to affect the course and severity of respiratory viral infections. An increasing number of evidence indicate a relatively high prevalence of superinfections associated with COVID-19, including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection we sought to determine and compare the host transcriptional response to SARS-CoV-2 versus Aspergillus superinfection, using a model of reconstituted humain airway epithelium. Our analyses reveal that both simple infection and superinfection induce a strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyte- and neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and but also management of severe forms of aspergillosis in this specific context.


title: No Detectable Surge in SARS-CoV-2 Transmission due to the April 7, 2020 Wisconsin Election

text: We analyze confirmed cases and new hospitalizations in Wisconsin in the weeks surrounding the April 7, 2020 election, and find no evidence of a surge in SARS-CoV-2 transmission.


title: Impact of weather indicators on the COVID-19 outbreak: A multi-state study in India

text: The present study examines the impact of weather indicators on the COVID-19 outbreak in the majorly affected states of India. In this study, we hypothesize that the weather indicators could significantly influence the impact of the corona virus. The Kendall and Spearman rank correlation tests were chosen to conduct the statistical analysis. In this regard, we compiled a daily dataset including confirmed case counts, Recovered case counts, Deceased cases, Average Temperature, Maximum Relative Humidity, Maximum Wind Speed for six most affected states of India during the period of March 25, 2020 to April 24, 2020. We investigated that the average Humidity and Average Temperature seven days ago play a significant role in the recovery of coronavirus cases. The rise in average temperature will improve the recovery rate in the days to come. The cities with very high humidity levels or dry weather conditions have high probabilities of recovery from COVID-19. The findings of this research will help the policymakers to identify risky geographic areas and enforce timely preventive measures.


title: Risk factors for mortality of adult inpatients with Coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis of retrospective studies

text: Background: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection. Methods: Online databases including Web of Science, PubMed, Scopus and Google scholar were searched to detect relevant publications up to 22 March 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done. Results: In total, six retrospective studies with 22,350 COVID-19 infected patients and 741 cases of death were included in the current meta-analysis. A significant positive association was found between older age (≥65 years old) and COVID-19 mortality (combined effect size=2.39 (over twofold), 95% CIs=1.75-3.28, p<0.001). Such finding was also seen for hypertension (combined effect size=3.29 (over threefold), 95% CIs=1.54-7.05, p=0.002), diabetes (combined effect size=3.11 (over threefold), 95% CIs=1.10-8.80, p=0.032), chronic obstructive pulmonary disease (COPD) (combined effect size=7.69 (over sevenfold), 95% CIs=5.65-10.47, p<0.001) and cardiovascular diseases (CVDs) (combined effect size=7.39 (over sevenfold), 95% CIs=2.88-18.96, p<0.001). Conclusions: Older age, hypertension, diabetes, COPD and CVDs were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.


title: Role of the atmospheric pollution in the Covid-19 outbreak risk in Italy

text: Background: After the initial outbreak in China, the diffusion in Italy of SARS-CoV-2 is exhibiting a clear regional trend with Northern areas being the most affected in terms of both frequency and severity of cases. Among multiple factors possibly involved in such geographical differences, a role has been hypothesized for atmospheric pollution. Objectives: We provide additional evidence on the possible influence of air quality, particularly in terms of chronicity of exposure on the spread viral infection in Italian regions. Methods: Actual data on to COVID-19 outbreak in Italian provinces and corresponding long-term air quality evaluations, were obtained from Italian and European agencies, elaborated and tested for possible interactions. Discussion: Our elaborations reveal that, beside concentrations, the chronicity of exposure may influence the anomalous variability of SARS-CoV-2 in Italy. Data on distribution of atmospheric pollutants (NO2, O3, PM2.5 and PM10) in Italian regions during the last 4 years, days exceeding regulatory limits, and years of the last decade (2010-2019) in which the limits have been exceeded for at least 35 days, confirmed that Northern Italy has been constantly exposed to chronic air pollution. Long-term air-quality data significantly correlated with cases of Covid-19 in up to 71 Italian provinces (updated 6 April) providing further evidence that chronic exposure to atmospheric contamination may represent a favourable context for the spread of the virus. Pro-inflammatory responses and high incidence of respiratory and cardiac affections are well known, while the capability of this coronavirus to bind particulate matters remains to be established. Atmospheric and environmental pollution should be considered as part of an integrated approach for sustainable development, human health protection and prevention of epidemic spreads.


title: Variation in Covid-19 Cases Across New York City

text: The number of confirmed COVID -19 cases, relative to the population size, has varied greatly throughout the United States and, even, within the same city. In different zip codes in New York City, the epicenter of the epidemic, the number of cases per 100,000 residents has varied between 437 and 4227, i.e., in a 1:10 ratio. To guide policy decisions regarding containment and reopening of the economy, schools, and other institutions, it is vital to identify which factors drive this large variation. This paper reports on a statistical study of the incidence variation across New York City, conducted with data at zip code granularity. Among many socio-economical and demographic measures considered, the average household size emerges as the single most important explanatory variable: an increase of the average household size by one member accounts, in our final model specification, for at least 876 cases, a full 23% of the span of incidence numbers, at a 95% confidence level. The percentage of the population above the age of 65, as well as that below the poverty line, are additional indicators with a significant impact on the case incidence rate, along with their interaction term. Contrary to common belief, population density, per se, fails to have a significantly positive impact. Indeed, population densities and case incidence rates are negatively correlated, with a -33% correlation coefficient. Our model specification is anchored on a basic and established epidemiological model that explains the importance of household sizes on R0, the basic reproductive number of an epidemic. Our findings support implemented and proposed policies to quarantine pre-acute and post-acute patients, , as well as nursing home admission policies.


title: A practical approach to the management of breast cancer in the COVID-19 era and beyond

text: The COVID-19 pandemic has resulted in a major shift in how breast services are being utilised and managed. The guidelines relating to this have been published by recognised medical associations from the UK, Europe and the USA, addressing many aspects of breast cancer care. There is an awareness that there may be limitations in resources during this time, and therefore, prioritisation strategies have been identified to ensure that breast cancer patients are appropriately treated, whilst reducing the risk of infection from COVID-19 to both patients and staff. Equally important is the consideration of how breast cancer services can be safely re-introduced, as infection rates from COVID-19 decline. However, until there is a definite management strategy for COVID-19, such as a vaccine being developed, it is likely that there will still be a significant impact from COVID-19 on breast cancer care. This paper, therefore, aims to highlight the current guidance and evidence regarding breast cancer management in the era of COVID-19, and also aims to look at future management strategies in this period of uncertainty.


title: COVIEdb: A database for potential immune epitopes of coronaviruses

text: 2019 novel coronavirus (2019-nCoV) has caused large-scale pandemic COVID-19 all over the world. It’s essential to find out which parts of the 2019-nCoV sequence are recognized by human immune system for vaccine development. And for the prevention of the potential outbreak of similar coronaviruses in the future, vaccines against immunogenic epitopes shared by different human coronaviruses are essential. Here we predict all the potential B/T-cell epitopes for SARS-CoV, MERS-CoV, 2019-nCoV and RaTG13-CoV based on the protein sequences. We found YFKYWDQTY in ORF1ab protein, VYDPLQPEL and TVYDPLQPEL in spike (S) protein might be pan-coronavirus targets for vaccine development. All the predicted results are stored in a database COVIEdb (http://biopharm.zju.edu.cn/coviedb/).


title: Pericardial Fluid in a COVID-19 Patient: Is It Exudate or Transudate?

text: BACKGROUND: Very limited information is available on pericardial effusion as a complication of COVID-19 infection. There are no reports regarding pericardial fluid findings in COVID-19 patients. CASE DESCRIPTION: We describe a 41-year-old woman, with confirmed COVID-19, who presented with a large pericardial effusion. The pericardial fluid was drained. We present the laboratory findings to improve knowledge of this virus. DISCUSSION: We believe this is the first such reported case. Findings suggested the fluid was exudative, with remarkably high lactate dehydrogenase and albumin levels. We hope our data provide additional insight into the diagnosis and therapeutic options for managing this infection. LEARNING POINTS: Laboratory findings of drained pericardial fluid in a patient with COVID-19 are presented. The clinical presentation of pericardial involvement in COVID-19 infection and the role of echocardiography in diagnosis and management are described.


title: Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach

text: The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.


title: COVID-19 and Inflammatory Bowel Diseases: risk assessment, shared molecular pathways and therapeutic challenges

text: Background. The novel coronavirus SARS-CoV-2 causing COVID-19 disease is yielding a global outbreak with serious threats to public health. In this paper, we aimed to review the current knowledge about COVID-19 infectious risk status in inflammatory bowel disease (IBD) patients requiring immunosuppressive medication. Also, we focused on several molecular insights that could explain why IBD patients appear to not have higher risks of infection and worse outcome in COVID-19 than the general population, in attempt to provide scientific support for safer decisions in IBD patient care. Methods. PubMed electronic database was interogated for relevant articles involving data about common molecular pathways and shared treatment strategies between SARS-CoV-2, SARS-CoV-1, MERS-CoV and inflammatory bowel diseases. In addition, Neural Covidex, an artificial intelligence tool, was used to answer queries about pathogenic coronaviruses and possible IBD interactions using the COVID-19 Open Research Dataset (CORD-19). Discussions. Few molecular and therapeutic interactions between IBD and pathogenic coronaviruses were explored. First, we showed how the activity of soluble angiotensin-converting enzyme 2, CD209L alternate receptor and phosphorylated subunit of eukaryotic translation initiation factor 2 might exert protective impact in IBD in case of coronavirus infection. Second, IBD medication was discussed in the context of possible beneficial effects on COVID-19 pathogeny including "cytokine storm" prevention and treatment, immunomodulation, interferon signaling blocking, viral endocytosis inhibition. Conclusions. Using current understanding of SARS-CoV-2 as well as other pathogenic coronaviruses immunopathology, we showed why IBD patients should not be considered at an increased risk of infection or more severe outcomes. Whether our findings are entirely applicable to the pathogenesis, disease susceptibility and treatment management of SARS-CoV-2 infection in IBD must be further explored.


title: Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2

text: SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A, MYO5B & MYO5C had maximum interaction with viral hub proteins (Nucleocapsid, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 and N proteins which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.


title: The role of age distribution, time lag between reporting and death and healthcare system capacity on case fatality estimates of COVID-19

text: European countries report large differences in coronavirus disease (COVID-19) case fatality risk (CFR). CFR estimates depend on demographic characteristics of the cases, time lags between reporting of infections and deaths and infrastructural characteristics, such as healthcare and surveillance capacities. We discuss the impact of these factors on the CFR estimates for Germany, Italy, France, and Spain for the COVID-19 pandemic from early March to mid-April, 2020. We found that, first, a large proportion of the difference in CFRs can be attributed to different age structures of the cases. Second, lags of 5-10 days between day of case report and death should be used, since these provide the most constant estimates. Third, for France, Italy, and Spain, intensive care beds occupied by COVID-19 patients were positively associated with fatality risks of hospitalized cases. Our results highlight that cross-country comparisons of crude CFR estimates can be misleading and should be avoided.


title: AN EPIDEMIOLOGICAL MODEL TO AID DECISION-MAKING FOR COVID-19 CONTROL IN SRI LANKA

text: Background: Sri Lanka diagnosed its first local case of COVID-19 on 11 March 2020. The government acted swiftly to contain transmission, with extensive public health measures. At the end of 30 days, Sri Lanka had 197 cases, 54 recovered and 7 deaths; a staged relaxing of the lockdown is now underway. This paper proposes a theoretical basis for estimating the limits within which transmission should be constrained in order to ensure that the case load remains within the capacity of the health system. Methods: We used the Susceptible, Infected, Recovered (SIR) model to explore the number of new infections and estimate ICU bed requirement at different levels of R0 values after lockout. We developed a web-based application that enables visualization of cases and ICU bed requirements with time, with adjustable parameters that include: population exposed; proportion asymptomatic; number of active and recovered cases; infectious period; R0 or doubling time; proportion critically ill; available ICU beds; duration of ICU stay; and uncertainty of projection. Results: The three-day moving average of the caseload suggested two waves of transmission from Day 0 to 17 (R0=3.32, 95% CI 1.85 - 5.41) and from Day 18 - 30 (R=1.25, 95%CI: 0.93 - 1.63). We estimate that if there are 156 active cases with 91 recovered at the time of lockout, and R increases to 1.5 (doubling time 19 days), under the standard parameters for Sri Lanka, the ICU bed capacity of 300 is likely to be saturated by about 100 days days, signalled by 18 new infections (95% CI 15 - 22) on Day 14 after lockout. Conclusion: Our model suggests that to ensure that the case load remains within the available capacity of the health system after lockout, transmission should not exceed R=1.5. This model and the web-based application may be useful in other low and middle income countries which have similar constraints on health resources.


title: Rolling Circle Amplification is a high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones

text: Alphaviruses (genus Alphavirus; family Togaviridae) are a medically relevant family of viruses that include chikungunya virus, Eastern equine encephalitis virus, and the emerging Mayaro virus. Infectious cDNA clones of these viruses are necessary molecular tools to understand viral biology and to create effective vaccines. The traditional approach to rescuing virus from an infectious cDNA clone requires propagating large amounts of plasmids in bacteria, which can result in unwanted mutations in the viral genome due to bacterial toxicity or recombination and requires specialized equipment and knowledge to propagate the bacteria. Here, we present an alternative to the bacterial-based plasmid platform that uses rolling circle amplification (RCA), an in vitro technology that amplifies plasmid DNA using only basic equipment. We demonstrate that the use of RCA to amplify plasmid DNA is comparable to the use of a midiprepped plasmid in terms of viral yield, albeit with a slight delay in virus recovery kinetics. RCA, however, has lower cost and time requirements and amplifies DNA with high fidelity and with no chance of unwanted mutations due to toxicity. We show that sequential RCA reactions do not introduce mutations into the viral genome and, thus, can replace the need for glycerol stocks or bacteria entirely. These results indicate that RCA is a viable alternative to traditional plasmid-based approaches to viral rescue. Importance The development of infectious cDNA clones is critical to studying viral pathogenesis and for developing vaccines. The current method for propagating clones in bacteria is limited by the toxicity of the viral genome within the bacterial host, resulting in deleterious mutations in the viral genome, which can only be detected through whole-genome sequencing. These mutations can attenuate the virus, leading to lost time and resources and potentially confounding results. We have developed an alternative method of preparing large quantities of DNA that can be directly transfected to recover infectious virus without the need for bacteria by amplifying the infectious cDNA clone plasmid using rolling circle amplification (RCA). Our results indicate that viral rescue from an RCA product produces a viral yield equal to bacterial-derived plasmid DNA, albeit with a slight delay in replication kinetics. The RCA platform, however, is significantly more cost and time-efficient compared to traditional approaches. When the simplicity and costs of RCA are combined, we propose that a shift to an RCA platform will benefit the field of molecular virology and could have significant advantages for recombinant vaccine production.


title: Quantifying the Impact of COVID-19 on Cancer Patients: A Technical Report of Patient Experience During the COVID-19 Pandemic at a High-volume Radiation Oncology Proton Center in New York City

text: The COVID-19 pandemic has rapidly spread across the world and now affects more people within the United States than any other country. New York City has emerged as the epicenter of the outbreak in the United States. Both locally and across the country, there is great concern in our ability to deliver appropriate medical care during this time. Radiation therapy is another essential clinical service that cannot afford to suffer prolonged delays without compromising patient outcomes. Early action and guidance are therefore critical to minimize transmission events and ensure safe and timely delivery of radiation therapy. The New York Proton Center (NYPC) is a high-volume free-standing multi-institutional proton center located in Manhattan. The purpose of this report is to describe the institutional patient experience and quantify the impact of treatment delays and interruptions over the first month of the COVID-19 outbreak. We also quantify the incidence of COVID-19 positive patients on census and provide guidance on proactive institutional policies to mitigate patient risk.


title: Modeling projections for COVID-19 pandemic by combining epidemiological, statistical, and neural network approaches

text: As the number of people affected by COVID-19 disease caused by the novel coronavirus SARS-CoV-2 ebbs and flows in different national and sub-national regions across the world, it is evident that our lifestyle and socio-economic trajectories will have to be adapted and adjusted to the changing scenarios. Novel forecasting tools and frameworks provide an arguable advantage to facilitate this adapting and adjusting process, by promoting efficient resource management at individual and institutional levels. Based on deterministic compartment models we propose an empirical top-down modeling approach to provide epidemic forecasts and risk calculations for (local) outbreaks. We use neural networks to develop leading indicators based on available data for different regions. These indicators are not only used to assess the risk of a (new) outbreak or to determine the effectiveness of a measure at an early stage, but also in parametric models to determine an effective forecast, along with the associated uncertainty. Based on initial results, we show the performance of such an approach and its robustness against inherent disturbances in epidemiological surveillance data. We foresee such a statistical framework to drive web-based automatic platforms to democratize the dissemination of prognosis results.


title: Shedding of infectious SARS-CoV-2 in symptomatic neonates, children and adolescents

text: Children are underrepresented in COVID-19 case numbers, with most pediatric cases exhibiting limited severity, and do not seem to be major drivers of transmission, unlike for other respiratory viruses. That said, SARS-CoV-2 infects children across all age groups, and despite the high proportion of mild or asymptomatic infections, it would be naive not to consider them as transmitters. To address this point we used cell culture to systematically assess the presence of cultivable SARS-CoV-2 in the upper respiratory tract in a cohort of our institution first 23 symptomatic neonates, children and teenagers with COVID-19 diagnosed by RT-PCR (See Appendix). Median age was 12.0 years (interquartile range [IQR 3.8-14.5], range 7 days-15.9 yrs). Most patients had an upper respiratory tract infection (n=13), followed by fever without source and pneumonia (each, n=2). Samples were collected at a median of 2 days (IQR 1-3) after symptom onset. Median viral load (VL) at time of diagnosis was 3.0x106 copies/ml (mean 4,4x108, IQR 6.9x103-4.4x108) from a nasopharyngeal swab (NPS). SARS-CoV-2 virus isolation was successful in 12/23 (52%) children after inoculating VeroE6 cells with a NPS specimen. SARS-CoV-2 isolation was determined by the presence of a typical cytopathic effect (CPE) and increased viral RNA in the supernatant. SARS-CoV-2 replication in all positive isolates (12/12) was confirmed by a second passage using new VeroE6 cells. Virus isolation was successful from NPS from all age groups, with a median initial VL of 1.7x108 copies/ml (mean 7.9x108, IQR 4.7x106-1.0x109) (Figure 1). The youngest patient that SARS-CoV-2 was isolated from was a 7-day old neonate. No correlation between disease presentation and success of virus isolation was observed. Our data show that initial VLs at diagnosis in symptomatic children is comparable to those in adults, and that symptomatic children of all ages shed infectious virus in early acute illness. Infectious virus isolation success was largely comparable to that of adults, although two specimens yielded an isolate at a lower VL (1.2x104 and 1.4x105 copies/ml) than what was observed in adults. SARS-CoV-2 shedding patterns of culture competent virus in symptomatic children resemble those observed in adults. Therefore, transmission of SARS-CoV-2 from children is plausible. Considering the relatively low frequency of infected children at this time, biological or other unknown factors could reduce transmission in this population. Both large serological investigations and systematic surveillance of acute respiratory diseases are needed to understand the role of children in this new pandemic.


title: Serological diagnostic kit of SARS-CoV-2 antibodies using CHO-expressed full-length SARS-CoV-2 S1 proteins

text: WHO has declared COVID-19 a pandemic with more than 300,000 confirmed cases and more than 14,000 deaths. There is urgent need for accurate and rapid diagnostic kits. Here we report the development and validation of a COVID-19/SARS-CoV-2 S1 serology ELISA kit for the detection of total anti-virus antibody (IgG+IgM) titers in sera from either the general population or patients suspected to be infected. For indirect ELISA, CHO-expressed recombinant full length SARS-CoV-2-S1 protein with 6*His tag was used as the coating antigen to capture the SARS-CoV-2-S1 antibodies specifically. The specificity of the ELISA kit was determined to be 97.5%, as examined against total 412 normal human sera including 257 samples collected prior to the outbreak and 155 collected during the outbreak. The sensitivity of the ELISA kit was determined to be 97.5% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. Most importantly, in one case study, the ELISA test kit was able to identify an infected person who had previously been quarantined for 14 days after coming into contact with a confirmed COVID-19 patient, and discharged after testing negative twice by nucleic acid test. With the assays developed here, we can screen millions of medical staffs in the hospitals and people in residential complex, schools, public transportations, and business parks in the epidemic centers of the outbreaks to fish out the "innocent viral spreaders", and help to stop the further spreading of the virus.


Merits and demerits of the web


Oncologist Urges COVID-19 “Castrated” Live Vaccine Initiative


title: Potential spreading risks and disinfection challenges of medical wastewater by the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA in septic tanks of fangcang hospital

text: The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia raises the concerns of effective deactivation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in medical wastewater by disinfectants. In this study, we evaluated the presence of SARS-CoV-2 viral RNA in septic tanks of Wuchang Fangcang Hospital and found their unexpected occurrence after disinfection with sodium hypochlorite. Embedded viruses in faeces particles might be released in septic tanks, behaving as a source of SARS-CoV-2 and potentially contributing to its spread through drainage pipelines. Current recommended disinfection strategy (free chlorine above 6.5 mg/L after 1.5-hour contact) needs to be reevaluated to completely remove SARS-CoV-2 viral RNA in non-centralized disinfection system and effectively deactivate SARS-CoV-2. The effluents showed negative results for SARS-CoV-2 viral RNA when overdosed with sodium hypochlorite but had high a level of disinfection by-product residuals, possessing significant ecological risks.


title: Proteomic changes in bacteria caused by exposure to environmental conditions can be detected by Matrix-Assisted Laser Desorption/Ionization – Time of Flight (MALDI-ToF) Mass Spectrometry

text: In the past decade, matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry (MS) has become a timely and cost-effective alternative to bacterial identification. The MALDI-ToF MS technique analyzes the total protein of culturable microorganisms at the species level and produces a mass spectra based on peptides which is compared to a database of identified profiles. Consequently, unique signatures of each microorganism are produced allowing identification at the species and, more importantly, strain level. Our present study proposes that the MALDI-ToF MS can be further used to screen functional and metabolic differences. While other studies applied the MALDI-ToF technique to identify subgroups within species, we investigated how various environmental factors could alter the unique bacterial signatures. We found that genetic and phenotypic differences between microorganisms belonging to the same species can be reflected in peptide-mass fingerprints generated by MALDI-ToF MS. These results suggest that MALDI-ToF MS can screen intra-species phenotypic differences of several microorganisms.


title: Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic COVID-19. It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV and MERS-CoV. Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2.


title: Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis

text: Background The pathogenesis of COVID-19, caused by a novel strain of coronavirus (SARS-CoV-2), involves a complex host-virus interaction and is characterised by an exaggerated immune response, the specific components of which are poorly understood. Here we report the outcome of a longitudinal immune profiling study in hospitalised patients during the peak of the COVID-19 pandemic in the UK and show the relationship between immune responses and severity of the clinical presentation. Methods The Coronavirus Immune Response and Clinical Outcomes (CIRCO) study was conducted at four hospitals in Greater Manchester. Patients with SARS-CoV-2 infection, recruited as close to admission as possible, provided peripheral blood samples at enrolment and sequentially thereafter. Fresh samples were assessed for immune cells and proteins in whole blood and serum. Some samples were also stimulated for 3 hours with LPS and analysed for intracellular proteins. Results were stratified based on patient-level data including severity of symptoms and date of reported symptom onset. Findings Longitudinal analysis showed a very high neutrophil to T cell ratio and abnormal activation of monocytes in the blood, which displayed high levels of the cell cycle marker, Ki67 and low COX-2. These properties all reverted in patient with good outcome. Unexpectedly, multiple aspects of inflammation were diminished as patients progressed in severity and time, even in ITU patients not recovering. Interpretation This is the first detailed longitudinal analysis of COVID-19 patients of varying severity and outcome, revealing common features and aspects that track with severity. Patients destined for a severe outcome can be identified at admission when still displaying mild-moderate symptoms. We provide clues concerning pathogenesis that should influence clinical trials and therapeutics. Targeting pathways involved in neutrophil and monocyte release from the bone marrow should be tested in patients with COVID-19. Funding: The Kennedy Trust for Rheumatology Research, The Wellcome Trust, The Royal Society, The BBSRC, National Institute for Health Research (NIHR) Biomedical Research Centres (BRC).


title: Is Nigeria really on top of COVID-19? Message from effective reproduction number

text: Following the importation of Covid-19 into Nigeria on the 27 February 2020 and then the outbreak, the question is: how do we anticipate the progression of the ongoing epidemics following all the intervention measures put in place? This kind of question is appropriate for public health responses and it will depend on the early estimates of the key epidemiological parameters of the virus in a defined population. In this study, we combined a likelihood-based method using a Bayesian framework and compartmental model of the epidemic of Covid-19 in Nigeria to estimate the effective reproduction number (R(t)) and basic reproduction number (R_0). This also enables us to estimate the daily transmission rate ({beta}) that determines the effect of social distancing. We further estimate the reported fraction of symptomatic cases. The models are applied to the NCDC data on Covid-19 symptomatic and death cases from 27 February 2020 and 7 May 2020. In this period, the effective reproduction number is estimated with a minimum value of 0.18 and a maximum value of 1.78. Most importantly, the R(t) is strictly greater than one from April 13 till 7 May 2020. The R_0 is estimated to be 2.42 with credible interval: (2.37, 2.47). Comparing this with the R(t) shows that control measures are working but not effective enough to keep R(t) below one. Also, the estimated fractional reported symptomatic cases are between 10 to 50%. Our analysis has shown evidence that the existing control measures are not enough to end the epidemic and more stringent measures are needed.


title: Differential impacts of contact tracing and lockdowns on outbreak size in COVID-19 model applied to China

text: Rapid growth of the COVID-19 epidemic in China induced extensive efforts of contact tracing and social-distancing/lockdowns, which quickly contained the outbreak and has been replicated to varying degrees around the world. We construct a novel infectious disease model incorporating these distinct quarantine measures (contact tracing and self-quarantine) as reactionary interventions dependent on current infection levels. Derivation of the final outbreak size leads to a simple inverse proportionality relationship with self-quarantine rate, revealing a fundamental principle of exponentially increasing cumulative cases when delaying mass quarantine or lockdown measures beyond a critical time period. In contrast, contact tracing results in a proportional reduction in reproduction number, flattening the epidemic curve but only having sizable impact on final size when a large proportion of contacts are "perfectly" traced. We fit the mathematical model to data from China on reported cases and quarantined contacts, finding that lockdowns had an overwhelming influence on outbreak size and duration, whereas contact tracing played a role in reducing peak number of infected. Sensitivity analysis and simulations under different re-opening scenarios illustrate the differential effects that responsive contact tracing and lockdowns can have on current and second wave outbreaks.


title: The impact of COVID-19 control measures on social contacts and transmission in Kenyan informal settlements

text: Background Many low- and middle-income countries have implemented control measures against coronavirus disease 2019 (COVID-19). However, it is not clear to what extent these measures explain the low numbers of recorded COVID-19 cases and deaths in Africa. One of the main aims of control measures is to reduce respiratory pathogen transmission through direct contact with others. In this study we collect contact data from residents of informal settlements around Nairobi, Kenya to assess if control measures have changed contact patterns, and estimate the impact of changes on the basic reproduction number (R0). Methods We conducted a social contact survey with 213 residents of five informal settlements around Nairobi in early May 2020, four weeks after the Kenyan government introduced enhanced physical distancing measures and a curfew between 7pm and 5am. Respondents were asked to report all direct physical and non-physical contacts made the previous day, alongside a questionnaire asking about the social and economic impact of COVID-19 and control measures. We examined contact patterns by demographic factors, including socioeconomic status. We described the impact of COVID-19 and control measures on income and food security. We compared contact patterns during control measures to patterns from non-pandemic periods to estimate the change in R0. Findings We estimate that control measures reduced physical and non-physical contacts, reducing the R0 from around 2.6 to between 0.5 and 0.7, depending on the pre-COVID-19 comparison matrix used. Masks were worn by at least one person in 92% of contacts. Respondents in the poorest socioeconomic quintile reported 1.5 times more contacts than those in the richest. 86% of respondents reported a total or partial loss of income due to COVID-19, and 74% reported eating less or skipping meals due to having too little money for food. Interpretation COVID-19 control measures have had a large impact on direct contacts and therefore transmission, but have also caused considerable economic and food insecurity. Reductions in R0 are consistent with the linear epidemic growth in Kenya and other sub-Saharan African countries that implemented similar, early control measures. However, negative and inequitable impacts on economic and food security may mean control measures are not sustainable in the longer term.


title: Clinical characteristics of 51 patients discharged from hospital with COVID-19 in Chongqing，China

text: Abstract Background：Since December 2019, Severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）-infected disease (Coronavirus Disease 2019，COVID-19) emerged in Wuhan , China，and rapidly spread throughout China，even throughout the world. We try to describe the epidemiological and clinical characteristics of COVID-19 in non-Wuhan area，and explore its effective treatment. Methods：Retrospective, single-center case series of the 51 hospitalized patients with confirmed COVID-19 at Chongqing University Three Gorges Hospital in Chongqing, China, from January 20 to February 3, 2020；The discharge time was from January 29 to February 11, 2020. The main results and indicators of epidemiology, demography, clinical manifestation, laboratory examination, imaging data and treatment data of 51 patients with covid-19 were collected and analyzed. The changes of blood routine and biochemical indexes at discharge and admission were compared. Compare the clinical characteristics of severe patients (including severe and critical patients) and non- severe patients (general patients). Results： Of 51 hospitalized patients with COVID-19, the median age was 45 years (interquartile range, 34-51; range, 16-68 years) and 32 (62.7%) were men.43（84.3%）patients had been to Wuhan or Other Hubei areas outside Wuhan，and 4（7.7%） patients had a clear contact history of COVID-19 patients before the onset of the disease, and 4（7.7%） patients had no clear epidemiological history of COVID-19.Common symptoms included fever (43 [84.3%]), cough (38 [74.5%]) and fatigue (22 [43.1%]). Lymphopenia was observed in 26 patients (51.0%), and elevated C-reactive protein level in 32 patients (62.7%). Ground-glass opacity was the typical radiological finding on chest computed tomography (41 [80.4%])，Local consolidation of pneumonia in some patients(17 [33.3%]).Most of the patients were treated with traditional Chinese medicine decoction (28 [54.9%])，all of them received aerosol inhalation of recombinant human interferon a-1b for injection and oral antiviral therapy with Lopinavir and Ritonavir tablets (51 [100%]); Most of the patients were given Bacillus licheniformis capsules regulated intestinal flora treatment (44 [86.3%]). 10 patients (19.6%) received short-term (3-5 days) glucocorticoid treatment. Compared with non-severe patients (n = 44), severe patients (n = 7) were older (median age, 52 years vs 44 years), had a higher proportion of diabetes mellitus (4 [57.1%] vs 0 [0.0%]), most of them needed antibiotic treatment (7 [100%] vs 4 [9.1%], most of them needed nutritional diet (6 [85.7%) vs 0 [0.0%], and were more likely to have dyspnea (6 [85.7%] vs 5 [11.4%])，most of them needed noninvasive mechanical ventilation (6 [85.7%] vs 0 [0.0%]). Except one patient died, the remaining 50 patients were discharged according to the discharge standard, the common clinical symptoms disappeared basically, the lymphocyte increased significantly (P=0.008), CRP decreased significantly (P <0.001). The median length of stay was 12 days (IQR, 9-13). Conclusion：In 51 single center cases confirmed as COVID-19 and discharged from the hospital, 13.7% of the patients were severe. The main clinical symptoms of patients with COVID-19 were fever, cough and asthenia，Some patients had obvious dyspnea. They had clinical laboratory and radiologic characteristics. There is no specific drug treatment for the disease. For the treatment of COVID-19, in addition to oxygen inhalation and antiviral treatment, attention should be paid to the dialectical treatment of traditional Chinese medicine, regulation of intestinal flora, nutritional support treatment and other comprehensive treatment.


title: Thoughts on prevention and treatment of coronavirus disease 2019 (COVID-19) by traditional Chinese medicine/ 新型冠状病毒肺炎（COVID-19）中医药防治的思考

text: The etiology and pathogenesis of coronavirus disease 2019 (COVID-19), which was discovered in Wuhan in late 2019 and has spread to the world, were expounded. In view of the application of traditional Chinese medicine (TCM) in the plague over these years, the therapeutic advantages of TCM in different stages of COVID-19 were expounded as “strengthening body resistance and eliminating evil, meeting changes with constancy”, “Syndrome differentiation and treatment, meeting change with variance”, with aim to reduce the sequelae caused by hormone and other drugs and the mortality. It is suggested that Chinese medicine of clearing heat and removing toxin should be used to prevent the uninfected people from COVID-19, and intervene in the early stage of the disease and control the development of it to be severe by inhibiting the “cytokine storm”. In order to refine the dialectical classification according to the theory of “defensing-qi-nutrient-blood syndrome differentiation”, to give full play to the individual advantages of TCM in the prevention and treatment of COVID-19. We should pay attention to the rational use of TCM in the prevention and treatment of COVID-19, collect the real world clinical data, and integrate TCM and Western medicine with TCM as the main part. The COVID-19 database of integrated TCM and Western medicine can be used to prepare for the prevention and treatment of COVID-19.


title: Isolation and quarantine in South Africa during COVID-19: Draconian measures or proportional response?

text: In the midst of an unprecedented public health crisis, extraordinary containment measures must be implemented. These include both isolation and quarantine, either on a voluntary basis or enforced. In the transition from voluntary to mandatory isolation, conflicts arise at the intersection of ethics, human rights and the law. The Siracusa Principles adopted by the United Nations Economic and Social Council in 1985 and enshrined in international human rights legislation and guidelines specify conditions under which civil liberties may be infringed. In order for isolation processes in South Africa to claim legitimacy, it is important that these principles as well as national laws and constitutional rights are embedded in state action.


title: Fuzzy logic assisted COVID 19 safety assessment of dental care

text: Uncertainty is significant when assessing a risk of certain health care facility conditions especially the facility that prone to the COVID 19 risk. One solution to deal with an uncertainty in health situation assessment is through fuzzy inference system. For that reason, this study aims to develop fuzzy assisted system to assess the safety of dental care related to the sets of patient and environmental conditions. The fuzzy system allows assessment based on the patient body temperature, travel history, dental care ventilation rate, and disinfection frequency. The fuzzy system incorporates several steps including fuzzification, fuzzy regulation, and defuzzification. As a result of this study, the fuzzy system is able to assess and identify the risk of dental care according to the patient health status and hygiene conditions of dental care as well. To conclude, fuzzy system used in this study has offered the advantage of assessing at any situation as for patient and environmental factor predicts the safety of dental care.


title: Lopinavir/ritonavir for the treatment of COVID-19: A living systematic review protocol

text: Objective To assess the efficacy and safety of lopinavir/ritonavir for the treatment of patients with COVID-19. Design This is the protocol of a living systematic review. Data sources We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomised trials evaluating the effect of lopinavir/ritonavir - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating lopinavir/ritonavir in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.


title: Validation of N95 filtering facepiece respirator decontamination methods available at a large university hospital

text: Importance: Filtering facepiece respirators, including N95 masks, are a critical component of infection prevention in hospitals. Due to unprecedented shortages in N95 respirators, many healthcare systems have explored reprocessing of N95 respirators. Data supporting these approaches are lacking in real hospital settings. In particular, published studies have not yet reported an evaluation of multiple viruses, bacteria, and fungi along with respirator filtration and fit in a single, full-scale study. Objective: We initiated a full-scale study to evaluate different N95 FFR decontamination strategies and their impact on respirator integrity and inactivating multiple microorganisms, with experimental conditions informed by the needs and constraints of the hospital. Methods: We explored several reprocessing methods using new 3MTM 1860 N95 respirators, including dry (<10% relative humidity) and moist (62-66% relative humidity) heat (80-82 oC) in the drying cycle of industrial instrument washers, ethylene oxide (EtO), pulsed xenon UV (UV-PX), hydrogen peroxide gas plasma (HPGP), and vaporous hydrogen peroxide (VHP). Respirator samples were treated and analyzed for biological indicator inactivation using four viruses (MS2, phi6, influenza A virus, murine hepatitis virus), three bacteria (Escherichia coli, Staphylococcus aureus, Geobacillus stearothermophilus), and the fungus Aspergillus niger. The impact of different application media was also evaluated. In parallel, decontaminated respirators were evaluated for filtration integrity and fit. Results: VHP resulted in >2 log10 inactivation of all tested biological indicators. The combination of UV-PX + moist heat resulted in >2 log10 inactivation of all biological indicators except G. stearothermohphilus. Greater than 95% filtration efficiency was maintained following 2 (UV-PX + <10% relative humidity heat) or 10 (VHP) cycles of treatment, and proper fit was also preserved. UV-PX + dry heat was insufficient to inactivate all biological indicators. Although very effective at virus decontamination, HPGP resulted in decreased filtration efficiency after 3 cycles, and EtO treatment raised potential toxicity concerns. The observed inactivation of viruses with UV-PX, heat, and hydrogen peroxide treatments varied as a function of which culture media (PBS buffer or DMEM) they were deposited in. Conclusions and Relevance: High levels of biological indicator inactivation were achieved following treatment with either moist heat or VHP. These same treatments did not significantly impact mask filtration or fit. Hospitals have a variety of scalable options to safely reprocess N95 masks. Beyond value in the current Covid-19 pandemic, the broad group of microorganisms and conditions tested make these results relevant in potential future pandemic scenarios.


title: Wading through Molasses: A qualitative examination of the experiences, perceptions, attitudes, and knowledge of Australian medical practitioners regarding medical billing

text: Background The WHO has stated that all health systems haemorrhage money, citing one of the causes of financial leakage as non-compliant billing and fraud. In Australia, it has been estimated that leakage from Medicare caused by non-compliant medical billing may be 10-15% of the schemes total cost. Despite a growing body of international research suggesting that rather than deliberately abusing the health financing systems they operate within, medical practitioners may be struggling to understand complex and highly interpretive medical billing rules, there is a lack of research in this area in Australia. The aim of this study was to address this research gap by examining the experiences of Australian medical practitioners as they interact with Australias Medicare by engaging in conversations with them about their lived experiences conducting medical billing in grass roots practice. Method This study interviewed 27 specialist and general medical practitioners who claim Medicare reimbursements in their daily practice. Interviews were recorded, transcribed, and analysed using thematic analysis. Results The qualitative data revealed five themes including inadequate induction, poor legal literacy, absence of reliable advice and support, fear and deference, and unmet opportunities for improvement. Conclusion The qualitative data presented in this study suggest Australian medical practitioners are ill-equipped to manage their Medicare compliance obligations, have low levels of legal literacy and desire education, clarity and certainty around complex billing standards and rules. Non-compliant medical billing under Australias Medicare scheme is a nuanced phenomenon that may be far more complex than previously thought. Strategies to address the barriers and deficiencies identified by participants in this study will require a multi-pronged approach. The data suggest that the current system of ensuring compliance by Australian medical practitioners is not fit for purpose.


title: Potential material basis of Kangbingdu Granules for treatment of coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking technology/ 基于网络药理学和分子对接技术的抗病毒颗粒治疗新型冠状病毒肺炎（COVID-19）的潜在物质基础研究

text: Objective: To explore the potential material basis of Kangbingdu Granules for the treatment of coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking technology. Methods: The chemical constituents and action targets of Isatidis Radix, Forsythiae Fructus, Gypsum Fibrosum, Anemarrhenae Rhizoma, Phragmitis Rhizoma, Rehmanniae Radix Praeparata, Pogostemon cablin, Acoritataninowii Rhizoma and Curcumae Radix in Kangbingdu Granules were searched by TCMSP. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.6.1 was used to build a medicinal material-compound-target (gene) network. DAVID was used to perform gene ontology (GO) function enrichment analysis and KEGG pathway enrichment analysis to predict its mechanism. Molecular docking of the top 15 components was carried out in the medicinal material-compound-target network with SARS-CoV-2 3CL hydrolase, and molecular docking with bicuculline, luteolin, quercetin and angiotensin-converting enzyme II (ACE2) was performed. Results: The medicinal material-compound-target (gene) network contained eight medicinal materials, 75 compounds and 255 targets. GO function enrichment analysis revealed 161 GO items (P < 0.05), including 65 biological process (BP) items, 36 cell composition (CC) items, and 60 molecular function (MF) items. KEGG pathway enrichment screened 131 signaling pathways (P < 0.05). The results of molecular docking showed that the core active compounds such as bicuculline, luteolin, and quercetin in the Kangbingdu Granules had similar affinities with those recommended by COVID-19. Conclusion: The active compounds in Kangbingdu Granules can interact with angiotensin-converting enzyme II (ACE2) via targets PTGS2, HSP90AB1, and PTGS1 to regulate multiple signaling pathways, thereby exerting therapeutic effects on COVID-19.


title: A multi-level influence model of COVID-19 themed cybercrime

text: The recent severity and frequency of cybercrime has been dominated by a single theme–the COVID-19 pandemic. This research develops a multi-level influence model to explore how cybercriminals are exploiting the COVID-19 pandemic by assessing situational factors, identifying victims, impersonating trusted sources, selecting attack methods, and employing social engineering techniques. The model extends upon prior work on influence techniques and emotional appeals that cybercriminals employ, by bringing into sharper focus the role of situational factors in COVID-19 related cybercrime attacks. Content and thematic analysis was conducted on 185 distinct COVID-19 cybercrime scam incident documents, including text, images, and photos, provided by a global online fraud and cybersecurity company tracking COVID-19 related cybercrime. The analysis reveals interesting patterns about the sheer breadth and diversity of COVID-19 related cybercrime and how these crimes are continually evolving in response to changing situational factors. It is hoped that these insights and recommendations for end-users and organisations can contribute to a safer digital world as we cope with many other pressing challenges during the COVID-19 pandemic.


title: Community responses during early phase of the COVID-19 epidemic: a cross-sectional study

text: Community responses are important for outbreak management during the early phase when preventive interventions are the major options. Therefore, this study aims to examine the behavioral responses of the community during the early phase of the COVID-19 epidemic in the Razavi Khorasan Province of Iran. A cross-sectional online survey was proceeded after confirmed COVID-19 in Iran. The population of the study was 500 residents of Razavi Khorasan areas were randomly surveyed. The research tool was demographic and risk perception questionnaire and Anxiety was assessed using the 7item GAD Scale. The data analyzed using the SPSS statistical version (V.20). The means of age participants was 31.9 11.9. The mean GAD-7 scores were 6.4 5.2 and 92.4% had moderate or severe anxiety (GAD-7 score ≥10). Many respondents reported their health status were very good or good (62.2 %; 311/500). About a quarter of them had respiratory symptoms in the past 14 days and experienced 20% of them travelled outside the Razavi Khorasan Province in the previous. Risk perception toward COVID-19 in the community of the Razavi Khorasan Province was moderate. Most participants are alert to disease progression. This study suggested timely behavioral assessment of the community is beneficial and effective to inform next intervention, and risk communication strategies in epidemic disease.


title: On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

text: A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.


title: Health literacy in the general population in the context of epidemic or pandemic coronavirus outbreak situations: rapid scoping review

text: BACKGROUND: Authorities responded with contact restrictions and other measures to the global spread of SARS-CoV-2. Health literacy (HL) has been linked to health outcomes and refers to the ability to access, understand, appraise and apply health information in order to make good health decisions. When restrictions are gradually lifted, individual HL becomes essential to control the pandemic and to prevent the resumption of these restriction, should infection numbers surge again. The aim of this rapid scoping review, for which only studies from the general population were considered, was to describe the extent of existing research on HL in the context of previous coronavirus outbreaks (SARS-CoV-1, MERS-CoV and SARS-CoV-2). Facets of HL that were of particular interest were: type of assessment of HL (theory-based versus proxy assessment; validated instrument versus ad hoc assessment), domains of HL, interventions aiming to improve HL during outbreak situations, and HL surveillance during outbreak. METHODS: We searched two major databases and included publications of quantitative and qualitative studies in English and German on any type of research on the functional, critical and communicative domains of HL conducted in the context of the three outbreaks in the general population. We extracted and tabulated relevant data and narratively reported where and when the study was conducted, the design and method used, and how HL was measured. FINDINGS: 72 studies were included. Three investigated HL or explicitly referred to the concept of HL, 14 were guided by health behaviour theory. We did not find any study designed to develop or psychometrically evaluate pandemic HL instruments, or relate pandemic or general HL to a pandemic outcome, or any controlled intervention study. Type of assessment of the domains of HL varied widely. INTERPRETATION: Theory-driven observational studies as well as interventions, examining whether pandemic-related HL can be improved are needed. In addition, the development and validation of instruments that measure pandemic-related HL is desirable.


title: Trends of SARS-Cov-2 infection in 67 countries: Role of climate zone, temperature, humidity and curve behavior of cumulative frequency on duplication time

text: Summary Objective. To analyze the role of temperature, humidity, date of first case diagnosed (DFC) and the behavior of the growth-curve of cumulative frequency (CF) [number of days to rise (DCS) and reach the first 100 cases (D100), and the difference between them (ΔDD)] with the doubling time (Td) of Covid-19 cases in 67 countries grouped by climate zone. Design. Retrospective incident case study. Setting. WHO based register of cumulative incidence of Covid-19 cases. Participants. 1,706,914 subjects diagnosed between 12-29-2019 and 4-15-2020. Exposures. SARS-Cov-2 virus, ambient humidity, temperature and climate areas (temperate, tropical/subtropical). Main outcome measures. Comparison of DCS, D100, ΔDD, DFC, humidity, temperature, Td for the first (Td10) and second (Td20) ten days of the CF growth-curve between countries according to climate zone, and identification of factors involved in Td, as well as predictors of CF using lineal regression models. Results. Td10 and Td20 were ≥3 days longer in tropical/subtropical vs. temperate areas (2.8[plusmn]1.2 vs. 5.7[plusmn]3.4; p=1.41E-05 and 4.6[plusmn]1.8 vs. 8.6[plusmn]4.2; p=9.7E-05, respectively). The factors involved in Td10 (DFC and ΔDD) were different than those in Td20 (Td10 and climate areas). After D100, the fastest growth-curves during the first 10 days, were associated with Td10<2 and Td10<3 in temperate and tropical/subtropical countries, respectively. The fold change Td20/Td10 >2 was associated with earlier flattening of the growth-curve. In multivariate models, Td10, DFC and ambient temperature were negatively related with CF and explained 44.7% (r2 = 0.447) of CF variability at day 20 of the growth-curve, while Td20 and DFC were negatively related with CF and explained 63.8% (r2 = 0.638) of CF variability towards day 30 of the growth-curve. Conclusions. The larger Td in tropical/subtropical countries is positively related to DFC and temperature. Td and environmental factors explain 64% of CF variability in the best of cases. Therefore, other factors, such as pandemic containment measures, would explain the remaining variability.