title: Prehospitalization Proton Pump Inhibitor (PPI) use and Clinical Outcomes in COVID-19

text: Introduction There is a concern that proton pump inhibitors (PPI) induced hypochlorhydria could potentially predispose to severe COVID-19. Methods We studied the association between prehospitalization PPI use and clinical outcomes among hospitalized COVID-19 patients. Results In our study, 15.6% of hospitalized COVID-19 patients were on PPI. Mortality among PPI-users was 2.3 times higher than non-users, along with 2.5 times higher risk of mechanical ventilation. This relationship existed even after adjusting for confounding variables. Discussion These results warrant further investigation to evaluate if PPI-induced hypochlorhydria is associated with a higher risk of GI symptoms and worse outcomes because of the omnipresence of ACE-2 in the gastrointestinal tract.


title: Self-control Mediates the Relationship between Psychosocial Strengths and Perceived Severity of COVID-19 among Frontline Healthcare Professionals of Pakistan: A Single Center Experience

text: OBJECTIVE: To examine the relationship between psychosocial strengths (resilience, self-efficacy beliefs and social support) and perceived severity of COVID-19 and also to gauge the mediating role of self-control among frontline health care professionals of Pakistan. METHODS: A cross-sectional research design was utilized from March to April 2020 from one medical teaching hospital of South Punjab. As it was a single center experience so all the doctors were approached and asked to participate in this research. In total, 284 doctors (out of 300 approx.) completed online survey. The data were collected through online google forms consisting of self-report measures i.e. Brief Resilience Scale, Short General Self Efficacy Scale, Brief Scale for Social Support, Risk Behavior Diagnostic Scale and Brief Self-Control Scale. RESULTS: The results were analyzed by using SmartPLS (3.0), direct effect of psychosocial strengths on perceived severity of COVID-19 and indirect effect of self-control were assessed through path coefficients, t-values and r-square values. The results confirmed that there was significant negative relationship between psychosocial strengths and perceived severity of COVID-19 (β = -0.854, t =14.279) with 72% variance in perceived severity due to psychosocial strengths. Further, the results also suggest that self-control proved significant mediator between psychosocial strengths and perceived severity (β = -0.604, t = 11.004, variance in perceived severity is 74%). CONCLUSION: In the time of pandemic, medical professionals are working as frontline force and can have several uncertainties regarding the risk associated with outbreak of COVID-19. This study concludes psychosocial strengths can play a significant role in subsiding the risk associated with severity of disease. Whereas, self-control can significantly contribute to buffer the negative influence of COVID-19 among frontline medical professionals. In line with findings of this study, there is a dire need to initiate psychotherapeutic studies for medical professionals to boost up their psychosocial strengths that would make them resilient against COVID-19.


title: Estimating the establishment of local transmission and the cryptic phase of the COVID-19 pandemic in the USA

text: We use a global metapopulation transmission model to study the establishment of sustained and undetected community transmission of the COVID-19 epidemic in the United States. The model is calibrated on international case importations from mainland China and takes into account travel restrictions to and from international destinations. We estimate widespread community transmission of SARS-CoV-2 in February, 2020. Modeling results indicate international travel as the key driver of the introduction of SARS-CoV-2 in the West and East Coast metropolitan areas that could have been seeded as early as late-December, 2019. For most of the continental states the largest contribution of imported infections arrived through domestic travel flows.


title: Predicting the cumulative number of cases for the COVID-19 epidemic in China from early data

text: We model the COVID-19 coronavirus epidemic in China. We use early reported case data to predict the cumulative number of reported cases to a final size. The key features of our model are the timing of implementation of major public policies restricting social movement, the identification and isolation of unreported cases, and the impact of asymptomatic infectious cases.


Performing tracheostomy during the Covid-19 pandemic: guidance and recommendations from the Critical Care and Acute Care Surgery Committees of the American Association for the Surgery of Trauma


title: Prediction of the virus incubation period for COVID-19 and future outbreaks

text: A crucial factor in mitigating respiratory viral outbreaks is early determination of the duration of the incubation period and, accordingly, the required quarantine time for potentially exposed individuals. Here, we explore different genomic features of RNA viruses that correlate with the incubation times and provide a predictive model that accurately estimates the upper limit incubation time for diverse viruses including SARS-CoV-2, and thus, could help control future outbreaks.


Schnell publiziert


title: Capsid integrity quantitative PCR to determine virus infectivity in environmental and food applications; a systematic review

text: Capsid integrity quantitative PCR (qPCR), a molecular detection method for infectious viruses combining azo dye pretreatment with qPCR, has been widely used in recent years; however, variations in pretreatment conditions for various virus types can limit the efficacy of specific protocols. By identifying and critically synthesizing 42 recent peer-reviewed studies employing capsid integrity qPCR for viruses in the last decade (2009 to 2019) in the fields of food safety and environmental virology, we aimed to establish recommendations for the detection of infectious viruses. Intercalating dyes are effective measures of viability in PCR assays provided the viral capsid is damaged; viruses that have been inactivated by other causes, such as loss of attachment or genomic damage, are less well detected using this approach. Although optimizing specific protocols for each virus is recommended, we identify a framework for general assay conditions. These include concentrations of ethidium monoazide, propidium monoazide or its derivates between 10 and 200 uM; incubation on ice or at room temperature (20 to 25C) for 5 to 120 min; and dye activation using LED or high light (500 to 800 Watts) exposure for periods ranging from 5 to 20 min. These simple steps can benefit the investigation of infectious virus transmission in routine (water) monitoring settings and during viral outbreaks such as the current COVID-19 pandemic or endemic diseases like dengue fever.


title: The COVID-19 Pandemic, Small-Scale Fisheries and Coastal Fishing Communities

text: The COVID-19 pandemic has rapidly spread around the world with extensive social and economic effects. This editorial focuses specifically on the implications of the pandemic for small-scale fishers, including marketing and processing aspects of the sector, and coastal fishing communities, drawing from news and reports from around the world. Negative consequences to date have included complete shut-downs of some fisheries, knock-on economic effects from market disruptions, increased health risks for fishers, processors and communities, additional implications for marginalized groups, exacerbated vulnerabilities to other social and environmental stressors, and increased Illegal, Unreported and Unregulated fishing. Though much of the news is dire, there have been some positive outcomes such as food sharing, the revival of local food networks, increases in local sales through direct marketing and deliveries, collective actions to safeguard rights, collaborations between communities and governments, and reduced fishing pressure in some places. While the crisis is still unfolding, there is an urgent need to coordinate, plan and implement effective short- and long-term responses. Thus, we urge governments, development organizations, NGOs, donors, the private sector, and researchers to rapidly mobilize in support of small-scale fishers, coastal fishing communities, and associated civil society organizations, and suggest actions that can be taken by each to help these groups respond to the COVID-19 pandemic.


title: Impact of social media on knowledge dissemination between physicians during COVID-19 virus outbreak: A cross sectional survey

text: Background: Social media became an alternative platform for communicating during medical crisis as COVID-19 pandemic. Aim of the study: 1- to describe the use of social media by Physicians during Covid-19 outbreak 2- to determine how physicians obtain their medical information about the emerging disease 3- to determine physicians practice and how do they use the information received. Methods: This is a cross-sectional web-based anonymous survey. Data were collected from Health Care Professional (HCPs) via fulfilling online designed questionnaire. Descriptive statistics with frequencies and percentages are presented. Results: The response rate was 66.2% (232/350). Smart phones was the most commonly used (94.8%) followed by laptops (13.4%). Facebook was used by 65.8% and WhatsApp by 52.8%. The data shared were medical newsletters (68%) and educational movies (52.2%). Source of information were mainly professional local pages (60.8%) then WHO pages (53.7%). Physicians shared trusted information (66.7%) and they confirmed the data were correct before publishing in 55.5%. They shared mainly WHO announcements and alerts (44%), professional lectures (32.1%) and 13.3% shared comics. Overall, 71% perceived lots of data about the cause of disease, clinical picture, daily spread, fatality rate and alert of the countries. Conclusion: Physicians are active users of social media. Facebook and WhatsApp are useful platforms to spread right data about diseases during pandemics. Most physicians are positive towards data published; they watch, read and disseminate trusted informations.


title: The impact of transmission control measures during the first 50 days of the COVID-19 epidemic in China

text: Respiratory illness caused by a novel coronavirus (COVID-19) appeared in China during December 2019. Attempting to contain infection, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. Here we evaluate the spread and control of the epidemic based on a unique synthesis of data including case reports, human movement and public health interventions. The Wuhan shutdown slowed the dispersal of infection to other cities by an estimated 2.91 days (95%CI: 2.54-3.29), delaying epidemic growth elsewhere in China. Other cities that implemented control measures pre-emptively reported 33.3% (11.1-44.4%) fewer cases in the first week of their outbreaks (13.0; 7.1-18.8) compared with cities that started control later (20.6; 14.5-26.8). Among interventions investigated here, the most effective were suspending intra-city public transport, closing entertainment venues and banning public gatherings. The national emergency response delayed the growth and limited the size of the COVID-19 epidemic and, by 19 February (day 50), had averted hundreds of thousands of cases across China.


title: LAMP-Seq: Population-Scale COVID-19 Diagnostics Using Combinatorial Barcoding

text: The ongoing SARS-CoV-2 pandemic has already caused devastating losses. Exponential spread can be slowed by social distancing and population-wide isolation measures, but those place a tremendous burden on society, and, once lifted, exponential spread can re-emerge. Regular population-scale testing, combined with contact tracing and case isolation, should help break the cycle of transmission, but current detection strategies are not capable of such large-scale processing. Here we present a protocol for LAMP-Seq, a barcoded Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP) method that is highly scalable. Individual samples are stabilized, inactivated, and amplified in three isothermal heat steps, generating barcoded amplicons that can be pooled and analyzed en masse by sequencing. Using unique barcode combinations per sample from a compressed barcode space enables extensive pooling, potentially further reducing cost and simplifying logistics. We validated LAMP-Seq on 28 clinical samples, empirically optimized the protocol and barcode design, and performed initial safety evaluation. Relying on world-wide infrastructure for next-generation sequencing, and in the context of population-wide sample collection, LAMP-Seq could be scaled to analyze millions of samples per day.


title: The 'Icarus effect' of preventative health behaviors

text: Ongoing efforts to combat the global pandemic of COVID-19 via public health policy have revealed the critical importance of understanding how individuals understand and react to infection risks. We here present a model to explore how both individual observation and social learning are likely to shape behavioral, and therefore epidemiological, dynamics over time. Efforts to delay and reduce infections can compromise their own success, especially in populations with age-structure in both disease risk and social learning - two critical features of the current COVID-19 crisis. Our results concur with anecdotal observations of age-based differences in reactions to public health recommendations. We show how shifting reliance on types of learning affect the course of an outbreak, and could therefore factor into policy-based interventions.


title: SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design

text: SARS-CoV-2 is a single-stranded RNA virus that has caused more than 0.29 million deaths worldwide as of May 2020, and influence of COVID-19 pandemic is increasing continuously in the absence of approved vaccine and drug. Moreover, very limited information is available about SARS-CoV-2 expressed regions and immune responses. In this paper an effort has been made, to facilitate vaccine development by proposing multiple epitopes as potential vaccine candidates by utilising SARS-CoV-2 transcriptome data. Here, publicly available RNA-seq data of SARS-CoV-2 infection in NHBE and A549 human cell lines were used to construct SARS-CoV-2 transcriptome to understand disease pathogenesis and immune responses. In the first step, epitope prediction, MHC class I and II gene identification for epitopes, population coverage, antigenicity, immunogenicity, conservation and crossreactivity analysis with host antigens were performed by using SARS-CoV-2 transcriptome, and in the second step, structural compatibility of identified T-and B-cell epitopes were evaluated with MHC molecules and B-cell receptors through molecular docking studies. Quantification of MHC gene expression was also performed that indicated high variation in allele types and expression level of MHC genes with respect to cell lines. In A549 cell line, HLA-A*30:01:01:01 and HLA-B*44:03:01:01 were highly expressed, whereas 92 variants of HLA-A*24 genes such as HLA-A*24:02:01:01, HLA-A*24:286, HLA-A*24:479Q, HLA-A*24:02:134 and HLA-A*24:02:116 were highly expressed in NHBE cell lines. Prevalence of HLA-A*24 alleles was suggested as risk factors for H1N1 infection, and associated with type-1 diabetes. HLA-C*03:03, linked with male infertility factors was also highly expressed in SARS-CoV-2 infected NHBE cell lines. Finally, three potential T-cell and five B-cell epitopes were selected for molecular docking studies with twenty-two MHC molecules and two B-cell receptors respectively. The results of in silico analysis indicated that proposed epitopes have high potential to recognize immune response of SARS-CoV-2 infection. This study will facilitate in vitro and in vivo vaccine related research studies.


title: Determining the optimal strategy for reopening schools, work and society in the UK: balancing earlier opening and the impact of test and trace strategies with the risk of occurrence of a secondary COVID-19 pandemic wave

text: Background In order to slow down the spread of SARS-CoV-2, the virus causing the COVID-19 pandemic, the UK government has imposed strict physical distancing (lockdown) measures including school 'dismissals' since 23 March 2020. As evidence is emerging that these measures may have slowed the spread of the pandemic, it is important to assess the impact of any changes in strategy, including scenarios for school reopening and broader relaxation of social distancing. This work uses an individual-based model to predict the impact of a suite of possible strategies to reopen schools in the UK, including that currently proposed by the UK government. Methods We use Covasim, a stochastic agent-based model for transmission of COVID-19, calibrated to the UK epidemic. The model describes individuals' contact networks stratified as household, school, work and community layers, and uses demographic and epidemiological data from the UK. We simulate a range of different school reopening strategies with a society-wide relaxation of lockdown measures and in the presence of different non-pharmaceutical interventions, to estimate the number of new infections, cumulative cases and deaths, as well as the effective reproduction number with different strategies. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. Findings We found that with increased levels of testing of people (between 25% and 72% of symptomatic people tested at some point during an active COVID-19 infection depending on scenarios) and effective contact-tracing and isolation for infected individuals, an epidemic rebound may be prevented across all reopening scenarios, with the effective reproduction number (R) remaining below one and the cumulative number of new infections and deaths significantly lower than they would be if testing did not increase. If UK schools reopen in phases from June 2020, prevention of a second wave would require testing 51% of symptomatic infections, tracing of 40% of their contacts, and isolation of symptomatic and diagnosed cases. However, without such measures, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a secondary pandemic wave, as are other scenarios for reopening. When infectiousness of <20 year olds was varied from 100% to 50% of that of older ages, our findings remained unchanged. Interpretation To prevent a secondary COVID-19 wave, relaxation of social distancing including reopening schools in the UK must be implemented alongside an active large-scale population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of symptomatic and diagnosed individuals. Such combined measures have a greater likelihood of controlling the transmission of SARS-CoV-2 and preventing a large number of COVID-19 deaths than reopening schools and society with the current level of implementation of testing and isolation of infected individuals.


title: Rational evaluation of various epidemic models based on the COVID-19 data of China

text: During the study of epidemics, one of the most significant and also challenging problems is to forecast the future trends, on which all follow-up actions of individuals and governments heavily rely. However, to pick out a reliable predictable model/method is far from simple, a rational evaluation of various possible choices is eagerly needed, especially under the severe threat of COVID-19 epidemics which is spreading worldwide right now. In this paper, based on the public COVID-19 data of seven provinces/cities in China reported during the spring of 2020, we make a systematical investigation on the forecast ability of eight widely used empirical functions, four statistical inference methods and five dynamical models widely used in the literature. We highlight the significance of a well balance between model complexity and accuracy, over-fitting and under-fitting, as well as model robustness and sensitivity. We further introduce the Akaike information criterion, root mean square errors and robustness index to quantify these three golden means and to evaluate various epidemic models/methods. Through extensive simulations, we find that the inflection point plays a crucial role in the choice of the size of dataset in forecasting. Before the inflection point, no model considered here could make a reliable prediction. We further notice the Logistic function steadily underestimate the final epidemic size, while the Gomertz's function makes an overestimation in all cases. Since the methods of sequential Bayesian and time-dependent reproduction number take the non-constant nature of the effective reproduction number with the progression of epidemics into consideration, we suggest to employ them especially in the late stage of an epidemic. The transition-like behavior of exponential growth method from underestimation to overestimation with respect to the inflection point might be useful for constructing a more reliable forecast. Towards the dynamical models based on ODEs, it is observed that the SEIR-QD and SEIR-PO models generally show a better performance than SIR, SEIR and SEIR-AHQ models on the COVID-19 epidemics, whose success could be attributed to the inclusion of self-protection and quarantine, and a proper trade-off between model complexity and fitting accuracy.


title: BRENDA: Browser Extension for Fake News Detection

text: Misinformation such as fake news has drawn a lot of attention in recent years. It has serious consequences on society, politics and economy. This has lead to a rise of manually fact-checking websites such as Snopes and Politifact. However, the scale of misinformation limits their ability for verification. In this demonstration, we propose BRENDA a browser extension which can be used to automate the entire process of credibility assessments of false claims. Behind the scenes BRENDA uses a tested deep neural network architecture to automatically identify fact check worthy claims and classifies as well as presents the result along with evidence to the user. Since BRENDA is a browser extension, it facilities fast automated fact checking for the end user without having to leave the Webpage.


Genetic susceptibility to pneumonia: A GWAS meta-analysis between UK Biobank and FinnGen


title: Closed form solution of the SIR model for the COVID-19 outbreak in Italy

text: The CODIV-19 outbreak in early 2020 generated a tremendous effort of epidemiologists and researchers to fit the experimental data with the solutions of the SIR model equations or with more sophisticated models. In this paper we show that under same hypotheses, a closed form solution exists that reasonably fits the experimental data for Italy, and the results can be extended to any other area.


title: Insufficient social distancing may be related to a future COVID-19 outbreak in Ijui-Brazil: Predictions of further social interventions.

text: The coronavirus disease that initiates in 2019 (COVID-19) has proven to be highly contagious since it became pandemic quickly and nowadays presents higher transmission rates worldwide, including small Brazilian cities, as Ijui. Located in the northwestern of the State of Rio Grande do Sul (RS) with 83,475 inhabitants, Ijui was selected to receive a population-based survey divided into four steps separated by 15 days each that involved 1,750 subjects. Subjects were tested for the presence of antibodies against coronavirus (SARS CoV-2) and answered questions about social distance adherence, daily routine, comorbidities, and sociodemographic characteristics. In parallel, the local government registered the official COVID-19 cases in Ijui. In this study, we demonstrated the levels of social distancing adherence and the beginning of COVID-19 community transmission in Ijui and showed some predictions for cases, hospitalization, and deaths. We concluded that the insufficient social distancing registered in the population-based study might be related to the rapid increase of COVID-19 cases in Ijui. Our study predicts a closer outbreak of community infection of COVID-19, which could be avoided or attenuated if the levels of the social distancing in the population increase in the next weeks.


title: Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route

text: In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis. According to the nucleotide C28144T variation, the SARS-CoV-2 can be divided into group A (117 strains) and group B (256 strains). The spike protein gene (S gene) coding region 1841 (total 23403) A1841G, formed a B1 subgroup (40 strains) in group B, of which 30 strains were from European and American countries in March (especially Washington, USA). These mutations are likely to be influenced by the environment or the immunization selection pressure of different populations. Although the mutation is not in the receptor binding region (RBD) and alkaline cleavage region, it may also affect the ability of transmission and pathogenicity; however, the significance is not yet clear. As the ratio of A / B strains in the epidemic months showed an increasing trend (0.35: 1 in January, 0.62: 1 in February and 0.76: 1 in March), it seems that the transmissibility of group A strains becomes stronger with time. Based on the variation of 11 nucleotide sites during the epidemic process, it is speculated that the Washington strain is more like an ancestor type, and the Wuhan strain is the offspring of the group A virus strain. By comparing the detection capabilities of primers in different countries, the SARS-CoV-2 nucleotide variation may only affect molecular detection of very few strains. The differences in the transmissibility, pathogenicity and clinical manifestations of different types of strains require further investigations.


title: Knowledge and Awareness-based Survey of COVID-19 within the Eye Care Profession in Nepal: Misinformation is Hiding the Truth.

text: Abstract Background: Nepal is currently under lockdown due to the COVID-19 pandemic with misinformation circulating on social media. This study aimed to analyse the knowledge and awareness of COVID-19 amongst eye care professionals in Nepal. Methodology: We invited 600 participants from 12 ophthalmic centres across Nepal to complete a qualitative, anonymous online survey. Results: Of the 600 eye care professionals invited, 310 (51%) participated in the survey. The symptoms of COVID-19 were known to 94%, whilst only 49% were aware of disease transmission. 98% of participants recognised the World Health Organization (WHO) awareness message, yet 41% of participants felt that consumption of hot drinks helps to destroy the virus. 41% disagreed that PPE should be mandatory for eye care practitioners. Conclusion: There is still considerable scope to improve the knowledge of COVID-19 amongst ophthalmic professionals in Nepal. Opinion is also split on measures to prevent transmission, with misinformation potentially fuelling confusion.


title: The current update of vaccines for SARS-COV-2

text: Late 2019 witnessed the appearance of coronavirus disease 2019 (COVID-19) outbreak triggered by a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 spread across China from Wuhan and has been circulated to a broader variety of countries. Seeing that COVID-19 has caused tremendous human casualties posing a global danger, an awareness of the current situation and the strategies to curtail the spread of the virus are desperately required. As the most natural way to preserve public wellbeing, preventive and therapeutic vaccinations must have essential roles. Large organizations and companies have started implementing SARS-CoV-2 preventive vaccinations. Hence, in this study, we aimed to update the vaccine evolution for SARS-CoV-2.


title: An open resource for T cell phenotype changes in COVID-19 identifies IL-10-producing regulatory T cells as characteristic of severe cases

text: The pandemic spread of the novel coronavirus SARS-CoV-2 is due, in part, to the immunological properties of the host-viral interaction. The clinical presentation varies greatly from individual to individual, with asymptomatic carriers, mild to moderate-presenting patients and severely affected patients. Variation in immune response to SARS-CoV-2 may underlie this clinical variation. Using a high dimensional systems immunology platform we have analysed the peripheral blood compartment of 6 healthy individuals, 23 mild-to-moderate COVID-19 patients and 20 severe COVID-19 patients. We identify distinct immunological signatures in the peripheral blood of the mild-to-moderate and severe COVID-19 patients, including T cell lymphopenia, more consistent with peripheral hypo- than hyper-immune activation. Unique to the severe COVID-19 cases was a large increase in the proportion of IL-10-secreting regulatory T cells, a lineage known to possess anti-inflammatory properties in the lung. Annotated data is openly available (https://flowrepository.org/experiments/2713) with clinical correlates, as a systems immunology resource for the COVID-19 research community.


title: Curbing the AI-induced enthusiasm in diagnosing COVID-19 on chest X-Rays: the present and the near-future

text: In the current context of COVID-19 pandemic, a rapid and accessible screening tool based on image processing of chest X-rays (CXRs) using machine learning (ML) approaches would be much needed. Initially, we intended to create and validate an ML software solution able to discriminate on the basis of the CXR between SARS-CoV-2-induced bronchopneumonia and other bronchopneumonia etiologies. A systematic search of PubMed, Scopus and arXiv databases using the following search terms ["artificial intelligence" OR "deep learning" OR "neural networks"], AND ["COVID-19" OR "SARS-CoV-2"] AND ["chest X-ray" OR "CXR" OR "X-ray"] found 14 recent studies. Most of them declared to be able to confidently identify COVID-19 based on CXRs using deep neural networks. Firstly, weaknesses of artificial intelligence (AI) solutions were analyzed, tackling the issues with datasets (from both medical and technical points of view) and the vulnerability of used algorithms. Then, arguments were provided for why our study design is stronger and more realistic than the previously quoted papers, balancing the possible false expectations with facts. The authors consider that the potential of AI use in COVID-19 diagnosis on CXR is real. However, scientific community should be careful in interpreting statements, results and conclusions regarding AI use in imaging. It is therefore necessary to adopt standards for research and publication of data, because it seems that in the recent months scientific reality suffered manipulations and distortions. Also, a call for responsible approaches to the imaging methods in COVID-19 is raised. It seems mandatory to follow some rigorous approaches in order to provide with adequate results in daily routine. In addition, the authors intended to raise public awareness about the quality of AI protocols and algorithms and to encourage public sharing of as many CXR images with common quality standards.


title: Haplotype of RNASE 3 polymorphisms is associated with severe malaria in an Indian population

text: Severe malaria (SM) caused by Plasmodium falciparum (Pf) infection has been associated with life-threatening anemia, metabolic acidosis, cerebral malaria and multiorgan dysfunction. It may lead to death if not treated promptly. RNASE 3 has been linked to Pf growth inhibition and its polymorphisms found associated with SM and cerebral malaria in African populations. This study aimed to assess the association of RNASE 3 polymorphisms with SM in an Indian population. RNASE 3 gene and flanking regions were amplified followed by direct DNA sequencing in 151 Indian patients who visited Wenlock District Government Hospital, Mangalore, Karnataka, India. Allele, genotype and haplotype frequencies were compared between patients with SM (n=47) and uncomplicated malaria (UM; n=104). Homozygous mutant genotype was only found for rs2233860 polymorphism (<1% frequency). No significant genetic associations were found for RNASE 3 polymorphism genotypes and alleles in Indian SM patients. C-G-G haplotype of rs2233859, rs2073342 and rs2233860 polymorphisms was correlated significantly with SM patients (OR=3.03; p<0.001). Overall, these results suggest that RNASE 3 gene plays a role in susceptibility to severe malaria.


Should vets join the Covid frontline response?


title: From ‘Chinky’ to ‘Coronavirus’: racism against Northeast Indians during the Covid-19 pandemic

text: The outbreak of Covid-19 has been highly racialised and stigmatised around the world based on the origin of the virus and its highly infectious nature. Profiling of Asians or mongoloid looking individuals as a suspect carrier of the virus and the resultant taunts and discriminations occur worldwide. In India, the pandemic has reinforce racism against Northeast Indians, which the country has been grappling with this social problem in the last one decade or so. Such discriminations were overt acts of racial prejudice that primarily stems from the nonrecognition or misrecognition of Northeast Indians, who are mainly mongoloid race, as Indians. During the pandemic, the fight by Northeast Indians was with the mindset of the rest of Indians as much as the virus itself. It was a fight not only against the presumption of being ‘non-Indian’ with negative affiliation, or worse ‘unwanted Indians’, but also to get due recognition and acceptance as equal Indians. The absence of stringent anti-racism laws may have resulted in the pervasiveness of overt acts of racism during the pandemic. However, such actions are best understood on the structural elements that underpin Indian societies. The legal measures to address this social problem will reduce overt acts of racism but addressing covert racial acts, which are structural in nature, is a long way to go.


title: Sentinel surveillance of SARS-CoV-2 in wastewater anticipates the occurrence of COVID-19 cases

text: SARS-CoV-2 was detected in Barcelona sewage long before the declaration of the first COVID-19 case, indicating that the infection was present in the population before the first imported case was reported. Sentinel surveillance of SARS-CoV-2 in wastewater would enable adoption of immediate measures in the event of future COVID-19 waves.


title: SARS-CoV-2 Seroprevalence Among Parturient Women

text: Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ~1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.


title: Noisy Pooled PCR for Virus Testing

text: Fast testing can help mitigate the coronavirus disease 2019 (COVID-19) pandemic. Despite their accuracy for single sample analysis, infectious diseases diagnostic tools, like RT-PCR, require substantial resources to test large populations. We develop a scalable approach for determining the viral status of pooled patient samples. Our approach converts group testing to a linear inverse problem, where false positives and negatives are interpreted as generated by a noisy communication channel, and a message passing algorithm estimates the illness status of patients. Numerical results reveal that our approach estimates patient illness using fewer pooled measurements than existing noisy group testing algorithms. Our approach can easily be extended to various applications, including where false negatives must be minimized. Finally, in a Utopian world we would have collaborated with RT-PCR experts; it is difficult to form such connections during a pandemic. We welcome new collaborators to reach out and help improve this work!


A Significance of High Prevalence of Diabetes and Hypertension in Severe COVID-19 Patients


title: MantisCOVID: Rapid X-Ray Chest Radiograph and Mortality Rate Evaluation With Artificial Intelligence For COVID-19

text: The novel coronavirus pandemic has negative impacts over the health, economy and well-being of the global population. This negative effect is growing with the high spreading rate of the virus. The most critical step to prevent the spreading of the virus is pre-screening and early diagnosis of the individuals. This results in quaranteeing the patients not to effect the healthy population. COVID-19 is the name of the disease caused by the novel coronavirus. It has a high infection rate and it is urgent to diagnose many patients as we can to prevent the spread of the virus at the early stage. Rapid diagnostic tools development is urgent to save lives. MantisCOVID is a cloud-based pre-diagnosis tool to be accessed from the internet. This tool delivers a rapid screening test by analyzing the X-ray Chest Radiograph scans via Artificial Intelligence (AI) and it also evaluates the mortality rate of patients with the synthesis of the patient history with the machine learning methods. This study reveals the methods used over the platform and evaluation of the algorithms via open datasets.


title: Triage of Acute Ischemic Stroke in Confirmed COVID-19: Large Vessel Occlusion Associated With Coronavirus Infection

text: The outbreak of COVID-19 has posed a significant challenge to global healthcare. Acute stroke care requires rapid bedside attendance, imaging, and intervention. However, for acute stroke patients who have a diagnosis of or are under investigation for COVID-19, the concern for nosocomial transmission moderates operational procedures for acute stroke care. We present our experience with an in-hospital stroke code called on a COVID-19-positive patient with a left middle cerebral artery syndrome and the challenges faced for timely examination, imaging, and decision to intervene. The outlook for the ongoing COVID-19 pandemic necessitates the development of protocols to sustain timely and effective acute stroke care while mitigating healthcare-associated transmission.


title: A multivariate spatiotemporal spread model of COVID-19 using ensemble of ConvLSTM networks

text: The high R-naught factor of SARS-CoV-2 has created a race against time for mankind and it necessitates rapid containment actions to control the spread. In such scenario short term accurate spatiotemporal predictions can help understanding the dynamics of the spread in a geographic region and identify hotspots. We propose an ensemble of convolutional LSTM based spatiotemporal model to forecast spread of the epidemic with high resolution and accuracy in a large geographic region. A data preparation method is proposed to convert spatial causal features into set of 2D images with or without temporal component. The model has been trained with available data for USA and Italy. It achieved 5.57% and 0.3% mean absolute percent error for total number of predicted infection cases in a 5day prediction period for USA and Italy respectively.


Lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors in the era of the COVID-19 pandemic


title: U.S. faculty and administrators’ experiences and approaches in the early weeks of the COVID-19 pandemic

text: The COVID-19 pandemic has had a profound and rapid impact on higher education institutions across the world. In this study, we report the findings of a survey investigating the rapid transition to emergency remote teaching in the early weeks of the pandemic at public and private post-secondary institutions in the United States. Participants consisted of 897 faculty and administrators at 672 U.S. institutions. Findings reveal that with few exceptions nearly all reporting institutions transitioned to emergency teaching and learning approaches. Administrators reported that faculty with and without online teaching experience pivoted to online teaching, and nearly all administrators indicated that those who did not have online teaching experience were in the process of learning how to teach online. Regardless of whether faculty had previous experience teaching online or not, many faculty reported that they were using new teaching methods. A majority of faculty reported making changes to their assignments or exams as a result of transitioning to a new mode of delivery. Nearly half reported lowering the expected volume of work for students (including dropping assignments or exams) and/or shifting to a pass/fail model for this semester. The primary areas where faculty and administrators identified a need for assistance related to student support, greater access to online digital materials, and guidance for working from home. This study provides an early snapshot of efforts towards teaching and learning continuity at a large scale and provides some insights for future research and practice.


title: The impact of testing and infection prevention and control strategies on within-hospital transmission dynamics of COVID-19 in English hospitals

text: Nosocomial transmission of SARS-CoV-2 is a key concern and evaluating the effect of testing and infection prevention control strategies is essential for guiding policy in this area. Using a within-hospital SEIR transition model of SARS-CoV-2 in a typical UK hospital, we predict that approximately 20% of infections in inpatients, and 89% of infections in HCWs were due to nosocomial transmission. Placing suspected COVID-19 patients in single rooms or bays has the potential to reduce hospital-acquired infections in patients by up to 80%. Periodic testing of HCWs has a smaller effect on the patient-burden of COVID-19 but would considerably reduce infection in HCWs by as much as 64% and result in only a small proportion of staff absences (approximately 1% per day). This is considerably fewer than currently observed due to suspected COVID-19 and self-isolation.


title: SARS-CoV-2 (COVID-19): New discoveries and current challenges

text: SARS-CoV-2 (COVID-19) has today multiplied globally and various governments are attempting to stop the outbreak of the disease escalation into a worldwide health crisis. At this juncture, readiness, candor, clarity, and partaking of data are of paramount importance to speed up factual evaluation and starting pattern control activities, including serendipitous findings. Owing to the involvement of COVID-19, many facts regarding virulence, pathogenesis, and the real viral infection source and/or transmission mode still need to be addressed. The infected patients often present clinical symptoms with fever, dyspnea, fatigue, diarrhea, vomiting, and dry cough, as well as pulmonary, infiltrates on imaging. Extensive measures to decrease person-to-person transmission of COVID-19 are being implemented to prevent, recognize, and control the current outbreak as it is very similar to SARS-CoV in its clinical spectrum, epidemiology, and pathogenicity. In response to this fatal disease and disruptive outbreak, it is extremely vital to expedite the drug development process to treat the disease and vaccines for the prevention of COVID-19 that would help us defeat this pandemic expeditiously. This paper sums up and unifies the study of virological aspects, disease transmission, clinically administered techniques, therapeutics options, managements, future directions, designing of vaccines, and news dissemination pertaining to COVID-19.


title: On Reliability of the COVID-19 Forecasts

text: In this expository article, we are aiming to show with an example that even short term forecasts regarding the COVID-19 spread pattern may sometimes not be very reliable. We have studied data published by Worldometers.info to get numerically an approximate formula of the spread pattern for a short period. We have observed that in the United States of America, there was a nearly exponential spread pattern for a very short period from May 3 to May 8, 2020. From May 9 to May 13, the nearly exponential character of the spread was found to be absent. Hence it can be concluded that the COVID-19 spread pattern, even after more than four months from the start of the outbreak, is not quite predictable. Therefore even short term forecasts regarding the spread may not be very reliable. We have found that forecasts using the assumption of an exponential pattern of spread may actually lead to overestimation.


title: Forecasting of COVID-19 Cases and Deaths Using ARIMA Models

text: After the outbreak of severe acute respiratory syndrome (SARS-2002/2003) and middle east respiratory syndrome (MERS-2012/2014) in the world, new public health crisis, called new coronavirus disease (COVID-19), started in China in December 2019 and has spread all over countries. COVID-19 coronavirus has been global threat of the disease and infected humans rapidly. Control of the pandemi is urgently essential, and science community have continued to research treatment agents. Support therapy and intensive care units in hospitals are also efective to overcome of COVID-19. Statistic forecasting models could aid to healthcare system in preventation of COVID-19. This study aimed to compose of forecasting model that could be practical to predict the spread of COVID-19 in Italy, Spain and Turkey. For this purpose, we performed Auto Regressive Integrated Moving Average (ARIMA) model on the European Centre for Disease Prevention and Control COVID-19 data to predict the number of cases and deaths in COVID-19. According to the our results, while number of cases in Italy and Spain is expected to decrease as of July, in Turkey is expected to decline as of September. The number of deaths in Italy and Spain is expected to be the lowest in July. In Turkey, this number is expected to reach the highest in July. In addition, it is thought that if studies in which the sensitivity and validity of this method are tested with more cases, they will contribute to researchers working in this field. KEYWORDS: COVID-19, pandemi, ARIMA, time series analysis


title: Cluster analysis of epidemiological characteristic features of confirmed cases with the novel coronavirus (COVID-19) outside China: a descriptive study

text: Background: Novel coronavirus COVID-19 has caused significant global outbreaks outside China. Many countries have closed their borders with China and performed obligate protective procedures, however, this disease was still rising worldwide. In this report, we aim to identify transmission patterns from China to other countries, along with describing the disease control situation of countries. Methods: We retrospectively collected information about infected cases with COVID-19 from WHO situation reports, official notification websites of health ministries and reliable local newspapers from each country. Descriptive and cluster analysis was performed to describe the transmission characteristics while the logistic regression test was used to estimate the risk factors for the occurrence of an infected individual with an unknown source. Results: A total of 446 infected cases were recorded from 24 countries outside China until 12 February 2020, with the number of reported infected cases were doubled every 3.08 days (range from 2.6 to 3.9). Besides the spread from China, the transmission was originated from sub-endemic countries (Japan, Thailand, Singapore, Malaysia, France, German). Out of 6 countries got occurrence of an infected individual with unknown source and possible potential factors contributed to this occurrence was a time of epidemic circulating, number of patients and number of clusters when the occurrence still has not happened, and notably, the unreported situation of Chinese tourists information. Conclusions: The situational reports of each country about COVID-19 should be more detailed mentioning the transmissions routes with keeping contact tracing of the unknown cases to increase the control of this disease.


A Silver Linings Playbook, COVID-19 Edition


title: The Efficacy of IL-6 Inhibitor Tocilizumab in Reducing Severe COVID-19 Mortality: A Systematic Review

text: Without proven, targeted therapies against SARS-CoV-2, it is crucial to counter the known pathophysiological causes of severe COVID-19, potentially utilizing existing drugs. Severe COVID-19 is largely the result of a dysregulated immune response characterized by lymphocytopenia, neutrophilia and critical hypercytokinemia, also called a cytokine storm. The IL-6 inhibitor tocilizumab (TCZ) could potentially suppress effects of the pro-inflammatory cytokine which drives the cytokine storm and thereby lower mortality from the disease. This systematic analysis aimed to investigate and synthesize existing evidence for the efficacy of TCZ in reducing COVID-19 mortality. PubMed and SearchWorks searches were performed to locate clinical studies with primary data on TCZ treatment for severe COVID-19. 9 case-control studies comparing mortality between TCZ and standard of care (SOC) were identified for a qualitative synthesis. In all of the studies, the odds ratio of mortality from COVID-19 pointed towards lower fatality with TCZ versus the SOC and a combined random effects odds ratio calculation yielded an odds ratio of 0.482 (p<0.001, 95% CI 0.326-0.713). Additionally, 12 uncontrolled trials were identified for a qualitative analysis producing a raw combined mortality rate of 13.6%. Results from the systematic analysis provide positive evidence for the potential efficacy of TCZ, validating the merit and need for ongoing clinical trials of the drug to treat severe COVID-19.


title: In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication

text: A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this study, we screened the Prestwick Chemical Library® composed of 1,520 approved drugs in an infected cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. The hits were sorted according to their chemical composition and their known therapeutic effect, then EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, Opipramol, Quinidine or Omeprazol present antiviral potency with 2<EC50<20µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study could contribute to the short-term repurposing of drugs against Covid-19.


title: A one-enzyme RT-qPCR assay for SARS-CoV-2, and procedures for reagent production

text: Given the scale of the ongoing COVID-19 pandemic, the need for reliable, scalable testing, and the likelihood of reagent shortages, especially in resource-poor settings, we have developed a RT-qPCR assay that relies on an alternative to conventional viral reverse transcriptases, a thermostable reverse transcriptase / DNA polymerase (RTX)1. Here we show that RTX performs comparably to the other assays sanctioned by the CDC and validated in kit format. We demonstrate two modes of RTX use – (i) dye-based RT-qPCR assays that require only RTX polymerase, and (ii) TaqMan RT-qPCR assays that use a combination of RTX and Taq DNA polymerases (as the RTX exonuclease does not degrade a TaqMan probe). We also provide straightforward recipes for the purification of this alternative reagent. We anticipate that in low resource or point-of-need settings researchers could obtain the available constructs from Addgene or our lab and begin to develop their own assays, within whatever regulatory framework exists for them. We lay out protocols for dye-based and TaqMan probe-based assays, in order to best compare with ‘gold standard’ reagents. These protocols should form the basis of further modifications that can simplify the assay to the use of overexpressing cells themselves as reagents. Developing dye-based and TaqMan probe-based RT-qPCR assays with RTX


title: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals

text: SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.


title: New York clinical trial quietly tests heartburn remedy against coronavirus

text: The fast-growing list of possible treatments for the novel coronavirus includes an unlikely candidate: famotidine, the active compound in the over-the-counter heartburn drug Pepcid On 7 April, the first COVID-19 patients at Northwell Health in the New York City area began receiving famotidine intravenously, at nine times the heartburn dose Unlike other drugs the 23-hospital system is testing, including Regeneron’s sarilumab and Gilead Science’s remdesivir, Northwell kept the famotidine study under wraps to secure a research stockpile before other hospitals, or even the federal government, started buying it “If we talked about this to the wrong people or too soon, the drug supply would be gone,” says Kevin Tracey, a former neurosurgeon in charge of the hospital system’s research


title: Deep convolutional approaches for the analysis of Covid-19 using chest X-Ray images from portable devices

text: The recent human coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared as a global pandemic on 11 March 2020 by the World Health Organization. Given the effects of COVID-19 in pulmonary tissues, chest radiography imaging plays an important role for the screening, early detection and monitoring of the suspected individuals. Hence, as the pandemic of COVID-19 progresses, there will be a greater reliance on the use of portable equipment for the acquisition of chest X-Ray images due to its accessibility, widespread availability and benefits regarding to infection control issues, minimizing the risk of cross contamination. This work presents novel fully automatic approaches specifically tailored for the classification of chest X-Ray images acquired by portable equipment into 3 different clinical categories: normal, pathological and COVID-19. For this purpose, two complementary deep learning approaches based on a densely convolutional network architecture are herein presented. The joint response of both approaches allows to enhance the differentiation between patients infected with COVID-19, patients with other diseases that manifest characteristics similar to COVID-19 and normal cases. The proposed approaches were validated over a dataset provided by the Radiology Service of the Complexo Hospitalario Universitario A Coru&ntildea (CHUAC) specifically retrieved for this research. Despite the poor quality of chest X-Ray images that is inherent to the nature of the portable equipment, the proposed approaches provided satisfactory results, allowing a reliable analysis of portable radiographs, to support the clinical decision-making process.


title: Estimate of the development of the epidemic reproduction number Rt from Coronavirus SARS-CoV-2 case data and implications for political measures based on prognostics

text: The novel Coronavirus SARS-CoV-2 (CoV) has induced a world-wide pandemic and subsequent non-pharmaceutical interventions (NPI) in order to control the spreading of the virus. NPIs are considered to be critical in order to at least delay the peak number of infected individuals and to prevent the health care system becoming overwhelmed by the number of patients to treat in hospitals or in intensive care units (ICUs). However, there is also increasing concern that the NPIs in place would increase mortality because of other diseases, increase the frequency of suicide and increase the risk of an economic recession with unforeseeable implications. It is therefore instrumental to evaluate the necessity of NPIs and to monitor the progress of containment of the virus spreading. We used a data-driven estimation of the evolution of the reproduction number for viral spreading in Germany as well as in all its federal states. Based on an extended infection-epidemic model, parameterized with data from the Robert Koch-Institute and, alternatively, with parameters stemming from a fit to the initial phase of CoV spreading in different regions of Italy, we consistently found that the reproduction number was turned down to a range near 1 in all federal states. We used the latest reproduction number as a starting point for the simulation of epidemic progression and varied the reproduction number, mimicking either release or strengthening of NPIs. Germany is currently, April 3rd, 2020, at the border line of a reproduction number between the scenarios of major immunisation of the population or eradication of the virus. We strongly recommend to keep all NPIs in place and suggest to even strengthen the measures in order to accelerate reaching the state of full control, thus, also limiting collateral damage of the NPIs in time.


title: A Research on the Results of Viral Nucleic Acid Tests and CT Imaging Variation of Patients with COVID-19

text: Background: Coronavirus disease 2019 (COVID-19) has become a global health problem. We aim to investigate the changes in the results of viral nucleic acid tests on pharyngeal swabs and feces of patients with COVID-19 and CT imaging of lungs as the disease progresses. Methods: Seven patients with COVID-19 in the third affiliated hospital of Sun Yat-sen University Yuedong Hospital were retrospectively enrolled with clinical features, including imaging staging, and performance characteristics of viral nucleic acid test results of pharyngeal swabs and feces. The dynamic changes of these features were observed during hospitalization, and therapeutic effect and prognosis of patients were evaluated. Results: The results of seven confirmed cases were positive for viral nucleic acid tests on pharyngeal swabs early after the onset of symptoms, and then turned negative; while the results of viral nucleic acid tests on feces were persistently positive in the mid-term clinical treatment and recovery period. And the viral nucleic acid test results were capricious in three cases. Pulmonary CT imaging showed characteristic changes in early, advanced and recovery phases. Conclusion: The application of viral nucleic acid detection and pulmonary CT imaging can be used for screeningof suspected cases, and early diagnosis and dynamic condition assessment of patients.


title: Initial characterisation of ELISA assays and the immune response of the clinically correlated SARS-CoV-2 biobank SERO-BL-COVID-19 collected during the pandemic onset in Switzerland

text: Background: To accurately measure seroprevalance in the population, boththe expected immune response as well as the assay performances have to be well characterised. Here, we describe the collection and initial characterisation of a blood and saliva biobank obtained after the initial peak of the SARS-CoV-2 pandemic in Switzerland. Methods: Two laboratory ELISA assays measuring IgA & IgG (Euroimmun), and IgM & IgG (Epitope Diagnostics) were used to characterise the biobank collected from 349 re- and convalescent patients from the canton of Basel-Landschaft. Findings: The antibody response in terms of recognized epitopes is diverse, especially in oligosymptomatic patients, while the average strength of the antibody response of the population does correlate with the severity of the disease at each time point. Interpretation: The diverse immune response presents a challenge when conducting epidemiological studies as the used assays only detect 90% of the oligosymptomatic cases. This problem cannot be rectified by using more sensitive assays or lower cut-offs as they concomitantly reduce specificity. Funding Funding was obtained from the Amt fur Gesundheit of the canton Basel-Landschaft, Switzerland.


title: Care of patients with pulmonary arterial hypertension during the coronavirus (COVID-19) pandemic

text: The COVID-19 pandemic presents many unique challenges when caring for patients with pulmonary hypertension. The COVID-19 pandemic has altered routine standard of care practice and the acute management particularly for those patients with pulmonary arterial hypertension, where pulmonary arterial hypertension-specific treatments are used. It is important to balance the ongoing care and evaluation of pulmonary arterial hypertension patients with “exposure risk” to COVID-19 for patients coming to clinic or the hospital. If there is a morbidity and mortality benefit from starting pulmonary arterial hypertension therapies, for example in a patient with high-likelihood of pulmonary arterial hypertension, then it remains important to complete the thorough evaluation. However, the COVID-19 outbreak may also represent a unique time when pulmonary hypertension experts have to weigh the risks and benefits of the diagnostic work-up including potential exposure to COVID-19 versus initiating targeted pulmonary arterial hypertension therapy in a select high-risk, high likelihood World Symposium Pulmonary Hypertension Group 1 pulmonary arterial hypertension patients. This document will highlight some of the issues facing providers, patients, and the pulmonary arterial hypertension community in real-time as the COVID-19 pandemic is evolving and is intended to share expected common clinical scenarios and best clinical practices to help the community at-large.


Following the evidence, from coronavirus to terrorism response


title: Automatic Identification of SARS Coronavirus using Compression-Complexity Measures

text: Finding vaccine or specific antiviral treatment for global pandemic of virus diseases (such as the ongoing COVID-19) requires rapid analysis, annotation and evaluation of metagenomic libraries to enable a quick and efficient screening of nucleotide sequences. Traditional sequence alignment methods are not suitable and there is a need for fast alignment-free techniques for sequence analysis. Information theory and data compression algorithms provide a rich set of mathematical and computational tools to capture essential patterns in biological sequences. In 2013, our research group (Nagaraj et al., Eur. Phys. J. Special Topics 222(3-4), 2013) has proposed a novel measure known as Effort-To-Compress (ETC) based on the notion of compression-complexity to capture the information content of sequences. In this study, we propose a compression-complexity based distance measure for automatic identification of SARS coronavirus strains from a set of viruses using only short fragments of nucleotide sequences. We also demonstrate that our proposed method can correctly distinguish SARS-CoV-2 from SARS-CoV-1 viruses by analyzing very short segments of nucleotide sequences. This work could be extended further to enable medical practitioners in automatically identifying and characterizing SARS coronavirus strain in a fast and efficient fashion using short and/or incomplete segments of nucleotide sequences. Potentially, the need for sequence assembly can be circumvented. Note The main ideas and results of this research were first presented at the International Conference on Nonlinear Systems and Dynamics (CNSD-2013) held at Indian Institute of Technology, Indore, December 12, 2013. In this manuscript, we have extended our preliminary analysis to include SARS-CoV-2 virus as well.


Sport psychology services to high performance athletes during COVID-19


title: Evolution of COVID-19 pandemic: Power law growth and saturation

text: In this paper, we analyze the real-time infection data of COVID-19 epidemic for 21 nations up to April 20, 2020. We observe that China, South Korea, Australia, Hong Kong, and Switzerland have flattened their infection curves. For these nations, the total number of infected individuals (I(t)) exhibits a succession of exponential growth and power-law growth (t2,t,{surd}t in sequence) before flattening of the curve. USA, Italy, UK, France, Spain, Germany, Belgium, Israel, Netherlands, India, and Sri Lanka have reached up to the linear growth (I(t) [~] t), but they are yet to flatten their curves. Russia and Singapore are still in the exponential growth regime. Such features of I(t) curves could be used for understanding and forecast of the epidemic evolution. Besides this detailed analysis, we compare the predictions of an extended SEIR model and a delay differential equation-based model with the reported infection data, and observed a general agreement between them.


title: Clinical characteristics and predictors of disease progression in severe patients with COVID-19 infection in Jiangsu Province, China: a descriptive study

text: Background We studied patients with coronavirus disease 2019 (COVID-19) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that originated in Wuhan, China, and is spreading over the country including Jiangsu Province We studied the clinical characteristics and therapies of severe cases in Jiangsu Province Methods A multicenter retrospective cohort study was conducted to analyze clinical, laboratory data and treatment of 60 severe cases with COVID-19 infection in Jiangsu Province between January 24, 2020 and April 20, 2020 The improvement and deterioration subgroups were compared to identify predictors of disease progression Results A total of 653 infected cases with COVID-19 were reported in Jiangsu Province, of which 60 severe cases were included in this study Up until April 20, 2020, the mortality of severe patients was 0% The median age was 57 years The average body mass index (BMI) of these patients was 25 kg/m² White blood cell counts decreased in 45 0% of patients, lymphopenia in 63 3%, thrombocytopenia in 13 3%, and procalcitonin levels in 88 3% of the patients were less than 0 5 ng/mL There were no statistically significant differences in immunoglobulin therapy and glucocorticoids therapy between the improvement and deterioration subgroups Logistic regression analysis identified higher levels of troponin T (odds ratio [OR]: 1 04;95% confidence interval [CI]: 1 00-1 08;P=0 04), antiviral therapy with aerosol inhalation of interferon (OR: 6 33;95% CI: 1 18-33 98;P=0 03), and the application of non-invasive mechanical ventilation (OR: 1 99;95%CI: 1 17-3 41;P=0 01) as predictors of disease progression, whereas higher lymphocyte count (OR: 0 11;95% CI: 0 02-0 57;P=0 01) and early prone ventilation were associated with improvement (OR: 0 11;95% CI: 0 01-0 98;P=0 04) Conclusions COVID-19 infection had a low mortality rate in Jiangsu Province, China The higher levels of troponin T and lower lymphocyte count were predictors of disease progression Early prone ventilation may be an effective treatment for severe cases


title: Impact of meteorological parameters on the Covid-19 incidence. The case of the city of Oran, Algeria.

text: Several studies have confirmed the impact of weather conditions on the evolution of the Covid-19 pandemic. We wanted to verify this phenomenon in the city of Oran in Algeria, which experienced its first case of Covid19 on March 19, 2020. The data studied are the new Covid19 cases, the average, minimum and maximum temperatures, as well as the relative humidity rate. A first analysis of the data with a Spearman rank correlation test did not yield significant results. Taking into account the average incubation period to adjust the data made it possible, during a second analysis, to show that the minimum temperature is significantly correlated with the new cases of Covid19 in Oran. This study can help establish prevention policies against Covid19, especially during fall in temperatures in autumn and winter.


title: Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: Findings from a population-based study

text: Background The novel COVID-19 pandemic has affected over 2.4 million people worldwide. Little is known about COVID-19 testing rates and COVID-19 test outcomes in people with mental illness. We hypothesized that people with psychiatric disorders are less likely to undergo COVID-19 testing and more likely to test positive. Methods We used data on COVID-19 testing in the UK Biobank (UKB) cohort to compare the prevalence of COVID-19 testing and test outcomes among individuals with psychiatric disorders to those without such diagnoses. We further investigated associations of testing probability and outcome with psychiatric diagnostic categories. Outcomes Individuals with psychiatric disorders were overrepresented among the 1 474 UKB participants with test data: 23% of the COVID-19 test sample had a psychiatric diagnosis compared to 10% in the full cohort (p<0.0001). This overrepresentation persisted for each of the specific psychiatric disorders tested. Furthermore, individuals with a psychiatric disorder (p=0.01), particularly with substance use disorder (p<0.005), had negative test results significantly more often than individuals without psychiatric disorders. Sensitivity analyses confirmed our results. Interpretation In contrast with our hypotheses, UKB participants with psychiatric disorders have been tested for COVID-19 more frequently than individuals without a psychiatric history, pleading against the notion that limited health care access is preventing them from undergoing testing. Among those tested, test outcomes were more frequently negative for UKB participants with psychiatric disorders than in others, countering arguments that people with mental illness are more prone to contract the virus. Funding No external funding sources participated in any stage of the present study.


title: Multi-site Validation of a SARS-CoV-2 IgG/IgM Rapid Antibody Detection Kit

text: Deaths from coronavirus disease (COVID-19) have exceeded 300,000 persons globally, calling for rapid development of mobile diagnostics that can assay widespread prevalence and infection rates. Data provided in this study supports the utility of a newly-designed lateral flow immunoassay (LFA) for detecting SARS-CoV-2 IgM and IgG antibodies. We employed a clinical cohort of 1,892 SARS-CoV-2 patients and controls, including individuals diagnosed by RT-qPCR at Yale New Haven Hospital, The First Affiliated Hospital of Anhui Medical University, the Chinese Center for Disease Control and Prevention of Hefei City (Hefei CDC), Anhui Province (Anhui Province CDC), and Fuyang City (Fuyang CDC). The LFA studied here detects SARS-CoV-2 IgM and IgG antibodies with a specificity of 97.9-100% for IgM, 99.7-100% for IgG, and sensitivities ranging from 94.1-100% for patients >14-days post symptom onset. Sensitivity decreases in patients <14-days post symptom onset, which is likely due to lower IgG/IgM antibody levels in this population. Finally, we developed a visual intensity reporting system that we believe will be suitable for laboratory and point-of-care settings, and will provide granular information about antibody levels. Overall our results support the widespread utility of this and other LFAs in assessing population-level epidemiological statistics.


title: Treating Influenza and SARS-CoV-2 via mRNA-encoded Cas13a

text: Here, Cas13a has been used to target and mitigate influenza virus A (IAV) and SARS-CoV-2 using a synthetic mRNA-based platform. CRISPR RNAs (crRNA) against PB1 and highly conserved regions of PB2 were screened in conjunction with mRNA-encoded Cas13a. Screens were designed such that only guides that decreased influenza RNA levels in a Cas13-mediated fashion, were valid. Cas13a mRNA and validated guides, delivered post-infection, simulating treatment, were tested in combination and across multiplicities of infection. Their function was also characterized over time. Similar screens were performed for guides against SARS-CoV-2, yielding multiple guides that significantly impacted cytopathic effect. Last, the approach was utilized in vivo, demonstrating the ability to degrade influenza RNA in a mouse model of infection, using polymer-formulated, nebulizer-based mRNA delivery. Our findings demonstrate the applicability of Cas13a in mitigating respiratory infections both in vitro and in a mouse model, paving the way for future therapeutic use.


title: How to Flatten the post-lockdown epidemic trajectory

text: Populations are locked down during an epidemic to slow down the rate of infection so that epidemic trajectory is flattened. This helps to keep cases at a manageable level. Given the enormous economic damage and misery caused by a lockdown, it is imperative to keep the lockdown period limited . A lockdown is useful only if it can be ensured that after the lockdown is lifted, the epidemic trajectory does not rise sharply again. We present here the results from a mathematical model of the epidemic which examines how the timing, strength and duration of the lockdown affects the post-lockdown epidemic trajectory. Our results show the following:


title: Pre-treatment of the clinical sample with Proteinase K allows detection of SARS-CoV-2 in the absence of RNA extraction

text: COVID-19 (Coronavirus Disease 2019) outbreak was declared a pandemic, by World Health Organization, on March 11, 2020. Viral detection using RT-qPCR has been among the most important factors helping to control local spread of SARS-CoV-2 and it is considered the “gold standard” for diagnosis. Nevertheless, the RNA extraction step is both laborious and expensive, thus hampering the diagnosis in many places where there are not laboratory staff of funds enough to contribute for diagnosis efforts. Thus, the need to simplify procedures, reduce costs of the techniques used, and expand the capacity of the number of diagnostics of COVID-19 is imperative. In this study, detection of SARS-CoV-2 in the absence of RNA extraction has been successfully achieved through pre-treatment of the clinical sample with Proteinase K. The results show that only the use of proteinase K, without the need to perform the whole standard protocol for sample extraction and purification, can be an efficient technique for the diagnosis of COVID-19, since 91% of the samples matched the results with the standard procedure, with an average increase of 5.64 CT in the RT-qPCR.


title: Revealing the influence of national public health policies for the outbreak of the SARS-CoV-2 epidemic in Wuhan, China through status dynamic modeling

text: Background The epidemic caused by SARS-CoV-2 was first reported in Wuhan, China, and now is spreading worldwide. The Chinese government responded to this epidemic with multiple public health policies including locking down the city of Wuhan, establishing multiple temporary hospitals, and prohibiting public gathering events. Here, we constructed a new real-time status dynamic model of SEIO (MH) to reveal the influence of national public health policies and to model the epidemic in Wuhan. Methods A real-time status dynamic model was proposed to model the population of Wuhan in status Susceptible (S), Exposed (E), Infected with symptoms (I), with Medical care (M), and Out of the system (O) daily. Model parameters were fitted according to the daily report of new infections from Jan. 27th, 2020 to Feb. 2nd, 2020. Using the fitted parameters, the epidemic under different conditions was simulated and compared with the current situation. Finding According to our study, the first patient is most likely appeared on Nov. 29th, 2019. There had already been 4,153 infected people and 6,536 exposed ones with the basic reproduction number R_0 of 2.65 before lockdown, whereas R_0 dropped to 1.98 for the first 30 days after the lockdown. The peak point is Feb. 17th, 2020 with 24,115 infected people and the end point is Jun. 17th, 2020. In total, 77,453 people will be infected. If lockdown imposed 7 days earlier, the total number of infected people would be 21,508, while delaying the lockdown by 1-6 days would expand the infection scale 1.23 to 4.94 times. A delay for 7 days would make the epidemic finally out of control. Doubling the number of beds in hospitals would decrease the total infections by 28%, and further investment in bed numbers would yield a diminishing return. Last, public gathering events that increased the transmission parameter by 5% in one single day would increase 4,243 infected people eventually. Interpretation Our model forecasted that the peak time in Wuhan was Feb. 17th, 2020 and the epidemic in Wuhan is now under control. The outbreak of SARS-CoV-2 is currently a global public health threat for all nations. Multiple countries including South Korea, Japan, Iran, Italy, and the United States are suffering from SARS-CoV-2. Our study, which simulated the epidemic in Wuhan, the first city in the world fighting against SARS-CoV-2, may provide useful guidance for other countries in dealing with similar situations.


title: Design and regulation of the surface and interfacial behavior of protein molecules

text: Surface and interfacial behavior of protein molecules are crucial for the protein function involved in many biochemical processes and biomedical products such as enzyme design, bio-separation, drug design and delivery This article is devoted to an overview of design and regulation of the surface and interfacial behavior of protein molecules The improvement of enzyme surface such as the directed evolution and the rational design of enzymes is introduced at first, followed by the rational design of protein interface for the protein assembly Thereafter, the design of micro-environment and ligands are described as two examples for the design guided by protein surface Then the design of protein surface and interface with the help of artificial intelligence will be discussed


title: Heterogeneity in risk, testing and outcome of COVID-19 across outbreak settings in the Greater Toronto Area, Canada: an observational study

text: Background: We compared the risk of, testing for, and death following COVID-19 infection across three settings (long-term care homes (LTCH), shelters, the rest of the population) in the Greater Toronto Area (GTA), Canada. Methods: We sourced person-level data from COVID-19 surveillance and reporting systems in Ontario, and examined settings with population-specific denominators (LTCH residents, shelters, and the rest of the population). We calculated cumulatively, the diagnosed cases per capita, proportion tested for COVID-19, daily and cumulative positivity, and case fatality proportion. We estimated the age- and sex-adjusted relative rate ratios for test positivity and case fatality using quasi-Poisson regression. Results: Between 01/23/2020-05/25/2020, we observed a shift in the proportion of cases: from travel-related and into LTCH and shelters. Cumulatively, compared to the rest of the population, the number of diagnosed cases per 100,000 was 59-fold and 18-fold higher among LTCH and shelter residents, respectively. By 05/25/2020, 77.2% of LTCH residents compared to 2.4% of the rest of the population had been tested. After adjusting for age and sex, LTCH residents were 2.5 times (95% confidence interval (CI): 2.3-2.8) more likely to test positive. Case fatality was 26.3% (915/3485), 0.7% (3/402), and 3.6% (506/14133) among LTCH residents, shelter population, and others in the GTA, respectively. After adjusting for age and sex, case fatality was 1.4-fold (95%CI: 1.1-1.9) higher among LTCH residents than the rest of the population. Interpretation: Heterogeneity across micro-epidemics among specific populations in specific settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies.


The SARS-CoV-2 coronavirus that causes the COVID-19 disease led to the most significant change in the world order over the past century, destabilizing the global economy and financial stock markets, the world’s economy, social development, business, risk, financial management and financial markets, among others COVID-19 has generated great uncertainty, and dramatically affected tourism, travel, hospitality, supply chains, consumption, production, operations, valuations, security, financial stress and the prices of all products, including fossil fuel and renewable energy sources This Editorial introduces a Special Issue of the Journal of Risk and Financial Management (JRFM) on the “Risk and Financial Management of COVID-19 in Business, Economics and Finance” This Special Issue will attract practical, state-of-the-art applications of mathematics, probability and statistical techniques on the topic, including empirical applications This paper investigates important issues that have been discussed in tourism, global health security and risk management in business as well as the social and medical sciences


title: A data driven epidemic model to analyse the lockdown effect and predict the course of COVID-19 progress in India

text: We propose a data driven epidemic model using the real data on the infection, recovery and death cases for the analysis of COVID-19 progression in India. The model assumes continuation of existing control measures such as lockdown and quarantines, the suspected and confirmed cases and does not consider the scenario of 2nd surge of the epidemic due to any reason. The model is arrived after least square fitting of epidemic behaviour model based on theoretical formulation to the real data of cumulative infection cases reported between 24 March 2020 and 15 May 2020. The predictive capability of the model has been validated with real data of infection cases reported during May 15-30, 2020. A detailed analysis of model predictions in terms of future trend of COVID-19 progress individually in 18 states of India and India as a whole has been attempted. Infection rate in India as a whole is continuously decreasing with time and has reached 3 times lower than the initial infection rate after 6 weeks of lock down suggesting the effectiveness of the lockdown in containing the epidemic. Results suggest that India as a whole could see the peak and end of the epidemic in the month of July 2020 and January 2021. As per the current trend in the data, active infected cases in India may reach 2 lakhs at the peak time and total infected cases may reach around 14 lakhs. State-wise results have been discussed in the manuscript. However, the prediction may deviate particularly for longer dates, as assumptions of model cannot be met always in a real scenario. In view of this, a real time application (COV-IND Predictor) has been developed which automatically syncs the latest data from COVID19 dash board on daily basis and update the model input parameters and predictions of relevant results on daily basis. This application can serve as a practical tool for epidemic management decisions


title: Association of Cardiovascular Manifestations with In-hospital Outcomes in Patients with COVID-19: A Hospital Staff Data

text: Background: The outbreaks of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain a huge threat to the public health worldwide. Clinical data is limited up to now regarding the risk factors in favor of severe conversion of non-severe case with COVID-19. Aims: This study analyzed a hospital staff data to figure out general clinical features of COVID-19 in terms of the association of cardiovascular manifestations (CVMs) with in-hospital outcomes of COVID-19 cases. Methods: Retrospective, single-center case series of 41 consecutive hospitalized health staff with confirmed COVID-19 were collected at the Central Hospital of Wuhan in Wuhan, China, from January 15 to January 24, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment data and in-hospital adverse events were collected and analyzed. Final date of follow-up was March 3, 2020. A comparative study was applied between cases with CVMs and those without CVMs. Results: Of all, clinicians and clinical nurses accounted for 80.5%, while 87.8% of all had history of patient contact. The population was presented with a mean age of 39.1 +- 9.2 and less comorbidities than community population. The three most frequent symptoms of COVID-19 cases analyzed were fever (82.9%), myalgia or fatigue (80.5%) and cough (63.4%). While, the three most frequent initial symptoms were myalgia or fatigue (80.5%), fever (73.2%) and cough (41.5%). There were 95.1% cases featured as non-severe course of disease according to the official standard in China. Patients with CVMs and those without CVMs accounted for 58.5% and 41.5%, respectively. Compared with cases without CVMs, patients with CVMs were presented with lower baseline lymphocyte count (0.99 +- 0.43 and 1.55 +- 0.61, P<0.001), more who had at least once positive nucleic acid detection of throat swab during admission (50.0% and 11.8%, P=0.011), and more received oxygen support (79.2% and 23.5%, P<0.001). The rate of in-hospital adverse events was significantly higher in patients with CVMs group (75.0% and 23.5%, P=0.001). Multivariable logistic regression model indicated that, coexisting with CVMs in COVID-19 patients was not independently associated with in-hospital adverse events. Conclusions: Most of hospital staff with COVID-19 had history of patient contact, featured non-severe course of disease. Cases with CVMs suffered from more in-hospital adverse events than those without CVMs. But concomitant CVMs were not independently associated with in-hospital adverse events in COVID-19 patients.


title: Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage

text: Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body in correlation to tissue damage can help understanding the pathophysiology of SARS-CoV-2 infection. We present a detailed mapping of viral RNA in 61 tissues and organs of 11 deceased patients with the diagnosis COVID-19. The autopsies were performed within the (very) early postmortem interval (mean: 5.6 hours) to avoid bias due to viral RNA and tissue degradation. Viral loads, blood levels of cytokines, prothrombotic factors as well as macro- and micro-morphology were correlated. Very high (> 104 copies/ml) viral loads were detected in the lungs of most patients and then correlated to severe tissue damage. Intact viral particles could be verified in the lung tissue by transmission electron microscopy. Viral loads in the lymph nodes were associated with a loss of follicular architecture. Viral RNA was detected throughout further extra-pulmonary tissues and organs without visible tissue damage. Inflammatory cytokines as well as the prothrombotic factors were elevated in all patients. In conclusion, the dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis of a maladaptive host response with viremia and multi-organ dysfunction.


What’s the use? On the uses of use


title: Preliminary evaluation of the safety and efficacy of oral human antimicrobial peptide LL-37 in the treatment of patients of COVID-19, a small-scale, single-arm, exploratory safety study

text: Background& Aims: The Coronavirus Disease 2019 (COVID-19) has become a global epidemic and has caused a lasting and huge loss of life security, economic development and social stability in more than 180 countries around the world. Unfortunately, there is still no specific treatment for COVID-19 till now, therefore, at this point, all potential therapies need to be critically considered. LL-37 is one of the best-studied human antimicrobial peptide (AMPs) that has a broad-spectrum activity against bacteria and viruses. The use of living, genetically modified organisms (GMOs) is an effective approach for delivery of therapeutic proteins. The aim of this study was to determine the safety and efficacy of the Lactococcus lactis which has been genetically modified to produce the therapeutic human antimicrobial peptide LL-37 (herein after referred to cas001) in the patients of COVID-19. Methods: Firstly we constructed genetically modified food-grade probiotic, Lactococcus lactis, with sequence of seven tandem repeats of mature human LL-37 under control of the nisin-inducible nisA promoter to produce the cas001. A total of 20 healthy SD rats, half male and half female (There were five male and five female in the control group, the same in treatment group) were used to observe the acute toxic reaction and death after daily administration of cas001 for three weeks, which helps to provide necessary reference basis for clinical dose selection, verificaition of toxic reaction and possible target organs. According to the estimated clinical dosage of 1 x 108CFU /kg/day, considering the conversion of body surface area, the dose for rats should be multiplied by 6.17 to 6 x 108 CFU/kg/day. We administrated 100 times higher dose at 6 x 1010 CFU/kg/day to rats. In order to investigate the pharmacokinetics of cas001, male SD rats (body weight 250-300g, 1 x 1010 /animal, n=3) were given oral administration of LL-37 bacteria powder. The concentration of LL-37 in the blood before and after gavage was detected by ELISA kit (Hycult biotechnology Cat# HK321). Human clinical study was approved by Ethics committee of Chinese PLA General Hospital (S2020-074-04) and a total of 11 patients with mild symptoms were enrolled in Wuhan hankou hospital and Huoshenshan hospital. They were enrolled voluntarily and all patients signed informed consent. Among them, there were 5 males and 6 females, aged 55 {+/-} 12 (36-70) years old, and the duration from onset to medication enrollment was 35 {+/-} 19 (5-68) days. 6 patients were nucleic acid positive and 5 patients were nucleic acid negative when they were enrolled. All patients received the oral drug cas001 treatment according to requirement(1 x 109 CFU/capsule, 3 capsules/time, three times a day for 3weeks), with an average follow-up time of 33 {+/-} 15 days (see table 1 for the results). Findings: Western blot analysis shows that reasonable amount of LL-37 were induced by different concentrations of nisin, which means we have successfully constructed cas001. In the pre-clinical safety evaluation test, after three weeks administration of cas001, no adverse effects were observed on the rat's body weight, food and water intake, hematological or serum biochemical parameters. The results showed that the LD50 of cas001 was higher than that of the 100 times of the expected clinical dose of 6 x 1010 CFU/day. These results showed that cas001 could be safe in animal experiments. In addition, rat pharmacokinetics results showed that the serum concentration of LL-37 reached peak 2 hours after gavage of cas001 and returned to basal level 6 hours after gavage. During study period, the volunteers did not feel any discomfort while taking the cas001 capsules, and two hours after oral administration, the concentration of LL-37 were increased in healthy volunteers. cas001 shows definite effect in the improvement of gastrointestinal symptoms and is possible to have effects in improving the systemic symptoms and respiratory symptoms and may play a role in the improvement of results of nucleic acid test and lung CT test. 11 patients enrolled showed good compliance, tolerance, subjective feeling and actively interacted with the doctors. None of the patients had any adverse reactions. Conclusions Based on above observations, we conclude here that as an oral anti-viral agent, cas001 displayed good safety profiles. It is very hard to reach conclusion of clinical outcomes related to the cas001, although changes of several symptoms indicate encouraging findings.


title: ARB/ACEI use and severe COVID-19: a nationwide case-control study

text: Background: Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) have anti-inflammatory effects. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane protein angiotensin-converting enzyme 2 (ACE2), which is increased by ARB/ACEI treatment, as a cell entry receptor. Therefore, the use of ARBs/ACEIs for COVID-19 remains controversial. Methods: A retrospective case-control study was conducted using COVID-19 patients previously diagnosed with hypertension before COVID-19 onset. The primary outcome was severe infection or all-cause mortality. Cases included ARB/ACEI use for 30 days or longer during the 6 months before COVID-19 onset. Primary controls included antihypertensive use other than ARBs/ACEIs (narrow control); secondary controls included all other hypertension patients (broad control). We investigated ARB/ACEI association with outcomes in general and by subgroups (age, sex, and presence of diabetes) using logistic regression models with propensity score matching. Findings: Of 234427 suspected COVID-19 patients we screened, 1585 hypertension patients were analyzed. In the 892 cases, 428 narrow controls, and 693 broad controls, severe infection or death occurred in 8.6%, 22.2%, and 16.7%, respectively. ARB/ACEI use was associated with a reduced risk of severe infection or death relative to the narrow control group (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.28-0.65) and broad control group (aOR 0.49, 95% CI 0.33-0.71). The association was smaller for newly diagnosed hypertension patients (aOR 0.11, 95% CI 0.03-0.42 compared to narrow control group). ARB/ACEI protective effects against severe infection or death were significantly observed in male and diabetic patients. Interpretation: ARB/ACEI use was associated with a lower risk of severe infection or mortality compared to other antihypertensives or ARB/ACEI nonuse.


title: COVID-19 epidemic: Power law spread and flattening of the curve

text: In this paper, we analyze the real-time infection data of COVID-19 epidemic for nine nations. Our analysis is up to 7 April 2020. For China and South Korea, who have already flattened their infection curves, the number of infected individuals (I(t)) exhibits power-law behavior before flattening of the curve. Italy has transitioned to the power-law regime for some time. For the other six nations-USA, Spain, Germany, France, Japan, and India-a power-law regime is beginning to appear after exponential growth. We argue that the transition from an exponential regime to a power-law regime may act as an indicator for flattening of the epidemic curve. We also argue that long-term community transmission and/or the transmission by asymptomatic carriers traveling long distances may be inducing the power-law growth of the epidemic.