title: Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak

text: Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R(0), of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R(0). Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403–540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18–25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R(0) of 2019-nCoV at 2.56 (95% CI: 2.49–2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation.


title: Comparison of Different Kits for SARS-CoV-2 RNA Extraction Marketed in Brazil

text: December 2019 marked the begining of the greatest pandemic since Spanish Flu, the disease named Covid-19 that cause severe pneumonia. Until May 19, 2020 more than 4 million and 700 thousand cases were oficially notified with about 316 thousand deaths. Etiological agent of the disease was identified as being a new coronavirus, Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). In this study we compared four different manual methods for RNA isolation and purification for detection of SARS-CoV-2 through qRT-PCR, as well as the extraction quality itself through detection of RNAse P. Magnetic beads-based (MagMax™) and silica column-based (Biopur®) methods presented the better performances. Concerning to the mean delay in CT values when compared to MagMax™, TRIzol™, Biopur® and EasyExtract presented 0,39, 0,95 and 5,23 respectively. Agreement between positive and negative results of different methods when compared with the one with better performance MagMax™ was 94,44% for silica column-based method (Biopur®), 88,89% for phenol-chroloform-based method (TRIzol™) and 77,78% for EasyExtract. We aimed to evaluate how reliable each method is for diagnostic purposes and to propose alternatives when usual methods are not available. In this regard, magnectic beads and silica column-based methods are convenient and reliable choices and phenol-chloroform-based method could also be chosen as an alternative.


title: Impact of COVID-19 Attributable Deaths on Longevity, Premature Mortality and DALY: Estimates of USA, Italy, Sweden and Germany

text: In a short span of four months, the COVID-19 pandemic has added over 0.4 million deaths worldwide, which are untimely, premature and unwarranted. The USA, Italy, Germany and Sweden are four worst affected countries, accounting to over 40% of COVID-19 attributable deaths on longevity, years of potential life lost (YPLL) and disability adjusted life years (DALY) in USA, Italy, Germay and Sweden. Data from United Nation Population Projection, Statista and Centre for disease control and prevention were used in the analyses. Life expectancy, YPLL and DALY were estimated under four scenarios; no COVID-19 deaths, actual number of COVID-19 deaths as of 22nd May, 2020 and anticipating COVID-19 death share of 6% and 10% , respectively. The COVID-19 attributable deaths have lowered the life expectancy by 0.4 year each in USA and Sweden, o.5 year in Italy and 0.1 year in Germany. The loss of YPLL was 1.5, 0.5, 0.1 and 0.5 million in USA, Italy, Germany and Sweden. Comapression in life expectancy and increase in YPLL and DALY may intensify further if death continues to soar. COVID-19 has a marked impact on mortality. Reduction in longevity, premature mortality and loss of DALY is higher among elderly. Key Words: COVID-19, Mortality, life expectancy, Italy, USA, Germany, Sweden


title: Implications of the reverse associations between obesity prevalence and coronavirus disease (COVID-19) cases and related deaths in the United States

text: The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was most recently discovered, quickly evolved into a global pandemic. Studies suggested that obesity was a major risk factor for its hospitalization and severity of symptoms. This study investigated the associations between obesity prevalence with overall COVID-19 cases and related deaths across states in the United States. General regression and Chi-square tests were used to examine those associations. The analyses indicated that obesity prevalence (%) across states were negatively associated with COVID-19 cases (p = 0.0448) and related deaths (p = 0.0181), with a decrease of 158 cases/100K population and 13 deaths/100K for every 5% increase of the obesity prevalence. When the states were divided based on the median of obesity prevalence (30.9%) into a group of states with low obesity prevalence and a group with high obesity prevalence, both the cases (671 vs 416 cases/100k population) and deaths (39 vs 21 deaths/100k population) were significantly different (p < 0.001) across groups. These findings provided important information for the relationship between the dual pandemic threats of obesity and COVID-19. These results should not currently be considered as an indication that obesity is a protective factor for COVID-19, and would rather be used as a warning of the public advice that obese people is more vulnerable to COVID-19 infection, which may lead to a false safety message probably given to people with normal body weight.


title: Psychological impact of COVID-19 pandemic on general population in West Bengal: A cross-sectional study

text: Background: COVID-19 pandemic poses a unique medical challenge to the humanity in recent times. The psychological impact of the pandemic itself and the lockdown in particular is likely to be huge. Aim: To assess the psychological impact of COVID-19 pandemic on general population in West Bengal. Materials and Methods: It was an online survey which was conducted using Google Forms with link sent using WhatsApp. A 38-item self-designed questionnaire was used for the study. The survey questionnaire would take around 5-7 min to complete. Total 507 responses were received by the stipulated time. Results: Near about five-seventh (71.8%) and one-fifth (24.7%) of the respondents felt more worried and depressed, respectively, in the past 2 weeks. Half of the respondents (52.1%) were preoccupied with the idea of contracting COVID-19 and one-fifth (21.1%) of the respondents were repeatedly thinking of getting themselves tested for the presence of COVID-19 despite having no symptoms. Majority (69.6%) of the respondents were worried about the financial loss they were incurring during the period of lockdown. One-fourth (25.6%) and one-third (30.8%) of the respondents found that COVID-19 pandemic had threatened their existence and they found it difficult to adjust to the new routine during 21-day lockdown period, respectively. Conclusion: The index survey suggested that worry and sleep disturbances were common among the respondents in the past 2 weeks. The pandemic threatened the existence of the respondents to a great extent and affected their mental status negatively.


The Juggle Is Unreal


title: Is the spread of COVID-19 across countries influenced by environmental, economic and social factors?

text: The SARS-CoV-2 virus, emerged from Wuhan, China is spreading all over the world in an unprecedented manner, causing millions of infections and thousands of deaths. However, the spread of the disease across countries and regions are not even. Why some countries and regions are more affected than some other countries and regions? We employ simple statistical methods to investigate any linkage between the severity of the disease and the environmental, economic and social factors of countries. The estimation results indicate that the number of confirmed cases of Coronavirus infection is higher in countries with lower yearly average temperatures, higher economic openness, and stronger political democracy. However, findings of this analysis should be interpreted carefully keeping in mind the fact that statistical relations do not necessarily imply causation. Only clinical experiments with medical expertise can confirm how the virus behaves in the environment.


title: GENOMIC CHARACTERISATION AND PHYLOGENETIC ANALYSIS OF SARS-COV-2 IN ITALY

text: This report describes the isolation, the molecular characterization and the phylogenetic analysis of the first three complete genomes of SARS-CoV-2 isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.


title: Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling

text: SARS-COV-2 and all other coronaviruses express its 3 prime genes by forming sub-genomic RNA. As the genome of these virus exist in RNA form, only by profiling the relative abundance of these sgRNAs, can the viral transcriptome be revealed. Utilizing publically available meta-transcriptomic data generated from patient samples, we were able to infer the viral transcriptome in vivo, which is distinct from the in vitro one derived from cell culture. Inter-sample diversity was also observed and a sample specific transcript was identified. By doing the same analysis to MERS and SARS data, we were able to compare the three in terms of transcription. Among the differences, SARS-COV-2 has significantly elevated expression of the Spike gene, which may contribute to its high transmissibility. Highlights The in vivo transcriptome of SARS-CoV-2 revealed by sgRNA profiling, for 25 patient samples around the globe. The Spike protein expression is an order of magnitude higher in SARS-CoV-2 than MERS-CoV or SARS-CoV, possibly contributing to the virus’ elevated transmissibility. The in vivo SARS-CoV-2 transcriptomes, as inferred from human patient data was distinct from the in vitro one derived from cell line culture, all the accessory genes were up-regulated in vivo, suggesting intricate expression regulation mechanism for the small viral genome.


title: Pressure-Regulated Ventilator Splitting (PReVentS): A COVID-19 Response Paradigm from Yale University

text: In the current COVID-19 crisis, the US and many countries in the world are suffering acute shortages of modern ventilators to care for desperately ill patients. Since modern ICU ventilators are powerful devices that can deliver very high gas flow rates and pressures, multiple physicians have attempted to ventilate more than one patient on a single ventilator -- so-called 'vent splitting'. Early applications of this approach have utilized simple concatenations of ventilator tubing and T-pieces, to provide flow to more than one patient. Additional approaches using custom flow splitters -- sometimes made using 3D printing technologies -- have also advanced into the clinic with FDA approval. However, heretofore there has been less progress made on controlling individual ventilatory pressures for patients with severe lung disease. Given the inherent variability and instability of lung compliance amongst patients with COVID-19, there remains an important need to provide a means of extending ventilator usefulness to more than one patient, but in a way that provides more tailored pressures that can be titrated over time. In this descriptive report, we provide the basis for a ventilator circuit that can support two patients with individualized peak inspiratory and end-expiratory pressures. The circuit is comprised of exclusively 'off the shelf' materials and is inexpensive to produce. The circuit can be used with typical ICU ventilators, and with anesthesia ventilators used in operating rooms. Inspiratory and end-expiratory pressures for each patient can be titrated over time, without changes for one patient affecting the ventilation parameters of the other patient. Using in-line spirometry, individual tidal volumes can be measured for each patient. This Pressure-Regulated Ventilator Splitting (PReVentS) Yale University protocol operates under a pressure-control ventilatory mode, and may function optimally when patients are not triggering breaths from the ventilator. This method has been tested thus far only in the laboratory with mock lungs, and has not yet been deployed in animals or in patients. However, given the novelty and potential utility of this approach, we deemed it appropriate to provide this information to the broader critical care community at the present time. In coming days and weeks, we will continue to characterize and refine this approach, using large animal models and proof-of-principle human studies.


title: Consensus Statement – Suggested Recommendations for Acute Stroke Management during the COVID-19 Pandemic: Expert Group on Behalf of the Indian Stroke Association

text: The ongoing pandemic of COVID-19 is a global public health emergency. This has led to challenges for healthcare facilities to optimally manage other important medical emergencies. Stroke is an important public health emergency with significant mortality and morbidity. Timely treatment of acute stroke is critical to prevent disability. The current expert consensus statement on behalf of the Indian Stroke Association outlines the issues and suggestions related to the management of stroke during this ongoing COVID-19 pandemic.


title: Sample Pooling as a Strategy of SARS-COV-2 Nucleic Acid Screening Increases the False-negative Rate

text: Identification of less costly and accurate methods for monitoring novel coronavirus disease 2019 (CoViD-19) transmission has attracted much interest in recent times. Here, we evaluated a pooling method to determine if this could improve screening efficiency and reduce costs while maintaining accuracy in Guangzhou, China. We evaluated 8097 throat swap samples collected from individuals who came for a health check-up or fever clinic in The Third Affiliated Hospital, Southern Medical University between March 4, 2020 and April 26, 2020. Samples were screened for CoViD-19 infection using the WHO-approved quantitative reverse transcription PCR (RT-qPCR) primers. The positive samples were classified into two groups (high or low) based on viral load in accordance with the CT value of COVID-19 RT-qPCR results. Each positive RNA samples were mixed with COVID-19 negative RNA or ddH2O to form RNA pools. Samples with high viral load could be detected in pool negative samples (up to 1/1000 dilution fold). In contrast, the detection of RNA sample from positive patients with low viral load in a pool was difficult and not repeatable. Our results show that the COVID-19 viral load significantly influences in pooling efficacy. COVID-19 has distinct viral load profile which depends on the timeline of infection. Thus, application of pooling for infection surveillance may lead to false negatives and hamper infection control efforts.


title: Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera

text: Emergence of the novel pathogenic coronavirus Sars-CoV-2 and its rapid pandemic spread presents numerous questions and challenges that demand immediate attention. Among these is the urgent need for a better understanding of humoral immune response against the virus and assessment of seroprevalence levels in the population, both of which form the basis for developing public health strategies to control viral spread. For this, sensitive, specific and quantitative serological assays are required. Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in improvement of sensitivity and specificity compared to an approved ELISA-based diagnostic test. Combining both methods resulted in maximum specificity in a negative control cohort, while maintaining high sensitivity. The procedure described here is compatible with high-throughput microscopy approaches and may be applied for serological analysis of other virus infections.


title: The Chest CT Features of Coronavirus Disease 2019 (COVID-19) in China: A Meta-analysis of 19 Trials

text: Objective: This study aimed to summarize the characteristics of chest CT imaging in Chinese patients with Coronavirus Disease 2019 (COVID-19) to provide reliable evidence for further guiding clinical routine. Methods: PubMed, Embase and Web of Science databases were thoroughly searched to identified relevant articles involving the features of chest CT imaging in Chinese patients with COVID-19. All data were analyzed utilizing R software version i386 4.0.0. Random-effects models were employed to calculate pooled mean differences. Results: 19 trials incorporating 1332 cases were included in the study. The results demonstrated that the incidence of ground-glass opacities (GGO) was 0.79, consolidation was 0.34; mixed GGO and consolidation was 0.46; air bronchogram sign was 0.41; crazy paving pattern was 0.32; interlobular septal thickening was 0.55; reticulation was 0.30; bronchial wall thickening was 0.24; vascular enlargement was 0.74. subpleural linear opacity was 0.28; intrathoracic lymph node enlargement was 0.03; pleural effusions was 0.03. The distribution in lung: the incidence of central was 0.05; peripheral was 0.74; peripheral involving central was 0.38; diffuse was 0.19; unifocal involvement was 0.09; multifocal involvement was 0.57; unilateral was 0.16; bilateral was 0.83; The incidence of lobes involved (>2) was 0.70; lobes involved ([less double equals]2) was 0.35. Conclusion: GGO, vascular enlargement, interlobular septal thickening more frequently occurred in patients with COVID-19. Peripheral, bilateral, involved lobes >2 might be the features of COVID-19 in the distribution aspect. Therefore, based on the aboved features of COVID-19 in chest CT imaging, it might be a promising means for identifying COVID-19.


The Plague: Human resilience and the collective response to catastrophe


title: ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS

text: COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 3.6 million people and caused the death of around 252,000 people. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Currently around 50,000 patients are in a seriously critical situation. Although 1.2 million patients recovered from the disease there are still more than 2.1 Million active cases. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative naso-oropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis.


title: Interim Analysis of Pandemic Coronavirus Disease 2019 (COVID-19) and the SARS-CoV-2 virus in Latin America and the Caribbean: Morbidity, Mortality and Molecular Testing Trends in the Region

text: Background: The relentless advance of the SARS-CoV-2 virus pandemic has resulted in a significant burden on countries, regardless of their socio-economic conditions. The virus has infected more than 2.5 million people worldwide, causing to date more than 150,000 deaths in over 210 countries. Objective: The aim of this study was to describe the trends in cases, tests and deaths related to novel coronavirus disease (COVID-19) in Latin American and Caribbean (LAC) countries. Methodology: Data were retrieved from the WHO-Coronavirus Disease (COVID-2019) situation reports and the Center for Systems Science and Engineering (CSSE) databases from Johns Hopkins University. Descriptive statistics including death rates, cumulative mortality and incidence rates, as well as testing rates per population at risk were performed. A comparison analysis among countries with [≥]50 confirmed cases was performed from February 26th, 2020 to April 8th, 2020. Results: Brazil had the greatest number of cases and deaths in the region. Panama experienced a rapid increase in the number of confirmed cases with Trinidad and Tobago, Bolivia and Honduras having the highest case fatality rates. Panama and Chile conducted more tests per million inhabitants and more tests per day per million inhabitants, followed by Uruguay and El Salvador. Dominican Republic, Bolivia, Ecuador and Brazil had the highest positive test rates. Conclusions: The COVID-19 disease pandemic caused by the SARS-CoV-2 virus has progressed rapidly in LAC countries. Some countries have been affected more severely than others, with some adopting similar disease control methods to help slow down the spread of the virus. With limited testing and other resources, social distancing is needed to help alleviate the strain on already stretched health systems.


CORONAVIRUS COVID‐19 ROILS DISPLAY SUPPLY CHAIN


title: Combination of Antibody based rapid diagnostic tests used in an algorithm may improve their performance in SARS CoV-2 diagnosis.

text: Background: Globally response to the SARS-CoV-2 pandemic is highly limited by diagnostic methods. Currently, World Health Organization (WHO) recommends the use of molecular assays for confirmation of SARS-CoV-2 infection which are highly expensive and require specialized laboratory equipment. This is a limitation in mass testing and in low resource settings. SARS CoV-2 IgG/IgM antibody tests have had poor diagnostic performance that do not guarantee their use in diagnostics. In this study we demonstrate a concept of using a combination of RDTs in an algorithm to improve their performance for diagnostics. Method: Eighty six (86) EDTA whole blood samples were collected from SARS-CoV-2 positive cases admitted at Masaka and Mbarara Regional Referral Hospitals in Uganda. These were categorized from day when confirmed positive as follows; category A (0-3 days, 10 samples), category B (4-7 days, 20 samples), Category C (8-17 days, 11 samples) and Category D (18-28 days, 20 samples). Plasma was prepared, transported to the testing laboratory and stored at -200C prior to testing. A total of 13 RDTS were tested following manufacturers instructions. Data was entered in Microsoft Excel exported to STATA for computation of sensitivity and specificity. We computed for all possible combinations of 2 of the 13 RDTS (13C2) that were evaluated in parallel algorithm. Results: The individual sensitives of the RDTs ranged between 74% and 18% and there was a general increasing trend across the categories with days since PCR confirmation. A total of 78 possible combinations of the RDTs to be used in parallel was computated. The combinations of the 2 RDTS improved the sensitivities to 90%. Discussion: We demonstrate that use of RDTs in combinations can improve their overall sensitivity. This approach when used on a wider range of combination of RDTs may yield combinations that can give sensitivities that are of diagnostics relevance in mass testing and low resource setting.


title: Engineering of extracellular vesicles for display of protein biotherapeutics

text: Extracellular vesicles (EVs) have recently emerged as a highly promising cell-free bio-therapeutics. While a range of engineering strategies have been developed to functionalize the EV surface, current approaches fail to address the limitations associated with endogenous surface display, pertaining to the heterogeneous display of commonly used EV-loading moieties among different EV subpopulations. Here we present a novel engineering platform to display multiple protein therapeutics simultaneously on the EV surface. As proof-of-concept, we screened multiple endogenous display strategies for decorating the EV surface with cytokine binding domains derived from tumor necrosis factor receptor 1 (TNFR1) and interleukin 6 signal transducer (IL6ST), which can act as decoys for the pro-inflammatory cytokines TNFα and IL6, respectively. Combining synthetic biology and systematic screening of loading moieties, resulted in a three-component system which increased the display and decoy activity of TNFR1 and IL6ST, respectively. Further, this system allowed for combinatorial functionalization of two different receptors on the same EV surface. These cytokine decoy EVs significantly ameliorated disease phenotypes in three different inflammatory mouse models for systemic inflammation, neuroinflammation, and intestinal inflammation. Importantly, significantly improved in vitro and in vivo efficacy of these engineered EVs was observed when compared directly to clinically approved biologics targeting the IL6 and TNFα pathways.


title: CLINICAL CHARACTERISTICS AND PROGNOSTIC FACTORS FOR ICU ADMISSION OF PATIENTS WITH COVID-19 USING MACHINE LEARNING AND NATURAL LANGUAGE PROCESSING

text: There remain many unknowns regarding the onset and clinical course of the ongoing COVID-19 pandemic. We used a combination of classic epidemiological methods, natural language processing (NLP), and machine learning (for predictive modeling), to analyse the electronic health records (EHRs) of patients with COVID-19. We explored the unstructured free text in the EHRs within the SESCAM Healthcare Network (Castilla La-Mancha, Spain) from the entire population with available EHRs (1,364,924 patients) from January 1st to March 29th, 2020. We extracted related clinical information upon diagnosis, progression and outcome for all COVID-19 cases, focusing in those requiring ICU admission. A total of 10,504 patients with a clinical or PCR-confirmed diagnosis of COVID-19 were identified, 52.5% males, with a mean age of 58.2 and S.D. 19.7 years. Upon admission, the most common symptoms were cough, fever, and dyspnoea, but all in less than half of cases. Overall, 6% of hospitalized patients required ICU admission. Using a machine-learning, data-driven algorithm we identified that a combination of age, fever, and tachypnoea was the most parsimonious predictor of ICU admission: those younger than 56 years, without tachypnoea, and temperature <39 C, (or >39 C without respiratory crackles), were free of ICU admission. On the contrary, COVID-19 patients aged 40 to 79 years were likely to be admitted to the ICU if they had tachypnoea and delayed their visit to the ER after being seen in primary care. Our results show that a combination of easily obtainable clinical variables (age, fever, and tachypnoea with/without respiratory crackles) predicts which COVID-19 patients require ICU admission.


title: Effects of Chinese strategies for controlling the diffusion and deterioration of novel coronavirus-infected pneumonia in China

text: Background: In December 2019, an outbreak of new type of coronavirus named COVID-19 occurred in Wuhan, Hubei Province, China. In a very short time, this virus spread rapidly over China, greatly threatening public health and economic development. The Chinese government acted quickly and implemented a series of strategies to prevent diffusion of this disease. We therefore sought to evaluate the effects of these Chinese strategies for controlling the spread of COVID-19. Methods: From the data of cumulative confirmed cases from provincial Health Commission websites of China, we performed model fitting and calculated the growth speed of cumulative confirmed patients. We further analyzed the time when this growth speed, the rate of the number of new cases, reached its maximum (Speedmax). Comparing different times to Speedmax of different areas in China, we calculated the dates at which the growth speed began to decline in different areas. Also, The number of plateaus were analyzed. Results: The quartic model showed the best fit. For almost all areas in mainland China, the speed of infections reached Speedmax and began to decline within 14 days; exceptions were Hebei, Heilongjiang, Hainan, Guizhou, and Hubei. The number of plateaus was significantly correlated with the emigration index. However, the distance from other areas to Hubei and the number of plateaus had little influence on when a province or area arrived at Speedmax. Once strict intervention strategies were implemented, diffusion and deterioration of COVID-19 were inhibited quickly and effectively over China. Conclusion: Our study suggests that Chinese strategies are highly effective on controlling the diffusion and deterioration of the novel coronavirus-infected pneumonia. These strategies supply experience and guidelines for other countries to control the COVID-19 epidemic.


title: Prediction of SARS-CoV interaction with host proteins during lung aging reveals a potential role for TRIB3 in COVID-19

text: COVID-19 is prevalent in the elderly. Old individuals are more likely to develop pneumonia and respiratory failure due to alveolar damage, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 (TRIB3) during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein and RNA-dependent RNA polymerase. Using publicly available lung single-cell data, we found TRIB3 expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 was previously reported to decrease virus infection and replication, the decreased expression of TRIB3 in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19. Thus, drugs that stimulate TRIB3 expression should be evaluated as a potential therapy for the disease.


title: A handheld point-of-care system for rapid detection of SARS-CoV-2 in under 20 minutes

text: The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (< 20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 90.55% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 {+/-} 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n=40), showing average detection times of 12.89 {+/-} 2.59 min for positive samples (n=34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geo-localization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.


title: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate forCOVID-19: Meta-analysis and sensitivity analysis

text: The coronavirus disease 2019 (COVID-19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensive knowledge of COVID-19 remains incomplete and many important features are still unknown. This manuscripts conduct a meta-analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% interval (2.41, 3.90), the average incubation time to be 5.08 days with the 95% confidence interval (4.77, 5.39) (in day), the asymptomatic infection rate to be 46% with the 95% confidence interval (18.48%, 73.60%), and the case fatality rate to be 2.72% with 95% confidence interval (1.29%, 4.16%) where asymptomatic infections are accounted for.


title: Predicting the number of reported and unreported cases for the COVID-19 epidemic in South Korea, Italy, France and Germany

text: We model the COVID-19 coronavirus epidemic in South Korea, Italy, France, and Germany. 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.


title: Who is wearing a mask? Gender-, age-, and location-related differences during the COVID-19 pandemic

text: Masks are an effective tool in combatting the spread of COVID-19 but wearing them remains controversial and has not been studied in the United States. To understand the demographics of mask wearers in the US, we observed shoppers (n = 5517) entering retail stores. 41.5% of the observed sample wore a mask. The odds of an individual wearing a mask increased significantly with age, and was also 1.5x greater for females than males. Additionally, the odds of observing a mask on an urban or suburban shopper were ~4x that for rural areas. Thus, gender, age, and location factor into whether American shoppers wear a mask or face covering. Regardless, all demographics wore masks at substantially lesser rates than required to stop the spread of COVID-19.


title: Syndromic detectability of haemorrhagic fever outbreaks

text: Late detection of emerging viral transmission allows outbreaks to spread uncontrolled, the devastating consequences of which are exemplified by recent epidemics of Ebola virus disease. Especially challenging in places with sparse healthcare, limited diagnostic capacity, and public health infrastructure, syndromes with overlapping febrile presentations easily evade early detection. There is a clear need for evidence-based and context-dependent tools to make syndromic surveillance more efficient. Using published data on symptom presentation and incidence of 21 febrile syndromes, we develop a novel algorithm for aetiological identification of case clusters and demonstrate its ability to identify outbreaks of dengue, malaria, typhoid fever, and meningococcal disease based on clinical data from past outbreaks. We then apply the same algorithm to simulated outbreaks to systematically estimate the syndromic detectability of outbreaks of all 21 syndromes. We show that while most rare haemorrhagic fevers are clinically distinct from most endemic fevers in sub-Saharan Africa, VHF detectability is limited even under conditions of perfect syndromic surveillance. Furthermore, even large clusters (20+ cases) of filoviral diseases cannot be routinely distinguished by the clinical criteria present in their case definitions alone; we show that simple syndromic case definitions are insensitive to rare fevers across most of the region. We map the estimated detectability of Ebola virus disease across sub-Saharan Africa, based on geospatially mapped estimates of malaria, dengue, and other fevers with overlapping syndromes. We demonstrate "hidden hotspots" where Ebola virus is likely to spill over from wildlife and also transmit undetected for many cases. Such places may represent both the locations of past unobserved outbreaks and potential future origins for larger epidemics. Finally, we consider the implications of these results for improved locally relevant syndromic surveillance and the consequences of syndemics and under-resourced health infrastructure for infectious disease emergence.


title: A potential role for Galectin-3 inhibitors in the treatment of COVID-19

text: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), has been declared a global pandemic by the World Health Organization. With no standard of care for the treatment of COVID-19, there is an urgent need to identify therapies that may be effective in treatment. Recent evidence has implicated the development of cytokine release syndrome as the major cause of fatality in COVID-19 patients, with elevated levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) observed in patients. Galectin-3 (Gal-3) is an animal lectin that has been implicated in the disease process of a variety of inflammatory conditions. Inhibitors of the small molecule Gal-3 have been shown to reduce the levels of both IL-6 and TNF-α in vitro and have shown anti-inflammatory effects in vivo. Additionally, a key domain in the spike protein of β-coronaviridae, a genus which includes SARS-CoV2, is nearly identical in morphology to human Gal-3. These spike proteins are critical for the virus’ entry into host cells. Here we provide a systematic review of the available literature and an impetus for further research on the use of Gal-3 inhibitors in the treatment of COVID-19. Further, we propose a dual mechanism by which Gal-3 inhibition may be beneficial in the treatment of COVID-19, both suppressing the host inflammatory response and impeding viral attachment to host cells.


title: A Brief Review on 3D Bioprinted Skin Substitutes

text: Abstract The global escalating cases of skin donor shortage for patients with severe wounds warn the vital need for alternatives to skin allografts. Over the last three decades, research in the skin regeneration area has addressed the unmet need for artificial skin substitutes. 3D bioprinting is a promising innovative technology to accurately fabricate skin constructs based on natural or synthetic bioinks, whether loaded or not loaded with native skin cells (i.e., keratinocytes and fibroblasts) or stem cells in the prescribed 3D hierarchal structure to create artificial multilayer and single cell-laden construct. In this paper, the recent developments in 3D bioprinting for skin regeneration are reviewed to discuss different aspects of skin bioprinted substitutes, including 3D printing technology, bioink composition, and cell-laden constructs. The impact of 3D printing parameters on functionality of the skin substitute and cell viability is reviewed to provide insight into controlled fabrication as the critical component of advanced wound healing. We highlight the recent and ongoing research in skin bioprinting to address the progress in the translation of advanced wound healing from lab to clinic.


title: Alpha-1 antitrypsin inhibits SARS-CoV-2 infection

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). To identify factors of the respiratory tract that suppress SARS-CoV-2, we screened a peptide/protein library derived from bronchoalveolar lavage, and identified α1-antitrypsin (α1-AT) as specific inhibitor of SARS-CoV-2. α1-AT targets the viral spike protein and blocks SARS-CoV-2 infection of human airway epithelium at physiological concentrations. Our findings show that endogenous α1-AT restricts SARS-CoV-2 and repurposes α1-AT-based drugs for COVID-19 therapy.


title: Importance of Interaction Structure and Stochasticity for Epidemic Spreading: A COVID-19 Case Study

text: In the recent COVID-19 pandemic, computer simulations are used to predict the evolution of the virus propagation and to evaluate the prospective effectiveness of non-pharmaceutical interventions. As such, the corresponding mathematical models and their simulations are central tools to guide political decision-making. Typically, ODE-based models are considered, in which fractions of infected and healthy individuals change deterministically and continuously over time. In this work, we translate an ODE-based COVID-19 spreading model from literature to a stochastic multi-agent system and use a contact network to mimic complex interaction structures. We observe a large dependency of the epidemic's dynamics on the structure of the underlying contact graph, which is not adequately captured by existing ODE-models. For instance, existence of super-spreaders leads to a higher infection peak but a lower death toll compared to interaction structures without super-spreaders. Overall, we observe that the interaction structure has a crucial impact on the spreading dynamics, which exceeds the effects of other parameters such as the basic reproduction number R0. We conclude that deterministic models fitted to COVID-19 outbreak data have limited predictive power or may even lead to wrong conclusions while stochastic models taking interaction structure into account offer different and probably more realistic epidemiological insights.


title: Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications

text: IMPORTANCE How to appropriately care for patients who become PCR-negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still not known. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system if a subset were to be PCR-positive again with reactivated SARS-CoV-2. OBJECTIVE To characterize a single center COVID-19 cohort with and without recurrence of PCR positivity, and develop an algorithm to identify patients at high risk of retest positivity after discharge to inform health care policy and case management decision-making. DESIGN, SETTING, AND PARTICIPANTS A cohort of 414 patients with confirmed SARS-CoV-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. EXPOSURES Polymerase chain reaction (PCR) and IgM-IgG antibody confirmed SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Univariable and multivariable statistical analysis of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data to develop an algorithm to predict patients at risk of recurrence of PCR positivity. RESULTS 16.7% (95CI: 13.0%-20.3%) patients retest PCR positive 1 to 3 times after discharge, despite being in strict quarantine. The driving factors in the recurrence prediction model included: age, BMI; lowest levels of the blood laboratory tests during hospitalization for cholinesterase, fibrinogen, albumin, prealbumin, calcium, eGFR, creatinine; highest levels of the blood laboratory tests during hospitalization for total bilirubin, lactate dehydrogenase, alkaline phosphatase; the first test results during hospitalization for partial pressure of oxygen, white blood cell and lymphocyte counts, blood procalcitonin; and the first test episodic Ct value and the lowest Ct value of the nasopharyngeal swab RT PCR results. Area under the ROC curve is 0.786. CONCLUSIONS AND RELEVANCE This case series provides clinical characteristics of COVID-19 patients with recurrent PCR positivity, despite strict quarantine, at a 16.7% rate. Use of a recurrence prediction algorithm may identify patients at high risk of PCR retest positivity of SARS-CoV-2 and help modify COVID-19 case management and health policy approaches.


title: Caution on Kidney Dysfunctions of COVID-19 Patients

text: Summary Background: To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality. Methods: In this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses. Findings: We included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6th and February 21th,2020; the final date of follow-up was March 4th, 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospital admission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ~5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (~1.5 times risk of those without comorbid chronic illnesses). Interpretation: To prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm. Funding: None.


title: Validity of Wrist and Forehead Temperature in Temperature Screening in the General Population During the Outbreak of 2019 Novel Coronavirus: a prospective real-world study

text: Aims: Temperature screening is important in the population during the outbreak of 2019 Novel Coronavirus (COVID-19). This study aimed to compare the accuracy and precision of wrist and forehead temperature with tympanic temperature under different circumstances. Methods: We performed a prospective observational study in a real-life population. We consecutively collected wrist and forehead temperatures in Celsius (C) using a non-contact infrared thermometer (NCIT). We also measured the tympanic temperature using a tympanic thermometers (IRTT) and defined fever as a tympanic temperature ≥37.3C. Results: We enrolled a total of 528 participants including 261 indoor and 267 outdoor participants. We divided outdoor participants into four types according to their means of transportation to the hospital as walk, bicycle, electric vehicle, car, and inside the car. Under different circumstance, the mean difference ranged from -1.72 to -0.56C in different groups for the forehead measurements, and -0.96 to -0.61C for the wrist measurements. Both measurements had high fever screening abilities in inpatients (wrist: AUC 0.790; 95% CI: 0.725-0.854, P <0.001; forehead: AUC 0.816; 95% CI: 0.757-0.876, P <0.001). The cut-off value of wrist measurement for detecting tympanic temperature ≥37.3C was 36.2C with a 86.4% sensitivity and a 67.0% specificity, and the best threshold of forehead measurement was also 36.2C with a 93.2% sensitivity and a 60.0% specificity. Conclusions: Wrist measurement is more stable than forehead measurement under different circumstance. Both measurements have great fever screening abilities for indoor patients. The cut-off value of both measurements was 36.2C.


title: Syndromic Surveillance for COVID-19 in Canada

text: Background: Syndromic surveillance through web or phone-based polling has been used to track the course of infectious diseases worldwide. Our study objective was to describe the characteristics, symptoms, and self-reported testing rates of respondents in three different COVID-19 symptom surveys in Canada. Methods: Data sources consisted of two distinct Canada-wide web-based surveys, and phone polling in Ontario. All three sources contained self-reported information on COVID-19 symptoms and testing. In addition to describing respondent characteristics, we examined symptom frequency and the testing rate among the symptomatic, as well as rates of symptoms and testing across respondent groups. Results: We found that 1.6% of respondents experienced a symptom on the day of their survey, 15% of Ontario households had a symptom in the previous week, and 44% of Canada-wide respondents had a symptom in the previous month over March-April 2020. Across the three surveys, SARS-CoV-2-testing was reported in 2-9% of symptomatic responses. Women, younger and middle-aged adults (versus older adults) and Indigenous/First nations/Inuit/Metis were more likely to report at least one symptom, and visible minorities were more likely to report the combination of fever with cough or shortness of breath. Interpretation: The low rate of testing among those reporting symptoms suggests significant opportunity to expand testing among community-dwelling residents of Canada. Syndromic surveillance data can supplement public health reports and provide much-needed context to gauge the adequacy of current SARS-CoV-2 testing rates.


title: Limiting Spread of COVID-19 in Ghana: Compliance audit of selected transportation stations in the Greater Accra region of Ghana

text: Globally, little evidence exists on transmission patterns of COVID-19. Recommendations to prevent infection include appropriate and frequent handwashing plus physical and social distancing. We conducted an exploratory observational study to assess compliance with these recommendations in selected transportation stations in Ghana. A one-hour audit of 45 public transport stations in the Greater Accra region was carried out between 27th and 29th March 2020. Using an adapted World Health Organization (WHO) hand hygiene assessment scale, the availability and use of handwashing facilities, social distancing, and ongoing public education on COVID-19 prevention measures were assessed, weighted and scored to determine the level of compliance of stations. Compliance with recommendations was categorized as 'inadequate', 'basic', 'intermediate' and 'advanced', based on the overall score. Majority (80%) of stations in Accra have at least one Veronica Bucket with flowing water and soap, but the number of washing places at each station is not adequate. Only a small minority (18%) of stations were communicating the need to wash hands frequently and appropriately, and to practice social/physical distancing while at the station. In most stations (95%), hand washing practice was either not observed, or only infrequently. Almost all stations (93%) did not have alcohol-based hand sanitizers available for public use, while social distancing was rarely practiced (only 2%). In over 90% of the stations, face masks were either not worn or only worn by a few passengers. Compliance with COVID-19 prevention measures was inadequate in 13 stations, basic in 16 stations, intermediate in 7 stations, and advanced in 9 stations. Compliance with COVID-19 prevention measures in public transportation stations in the Greater Accra region remains a challenge. Awareness creation should aim to elevate COVID-19 risk perception of transportation operators and clients. Transport operators and stations need support and guidance to enforce hand washing and social distancing.


COVID‐19 and the digestive system: More than just a “flu”


title: The haunting figure of the useless academic: Critical thinking in coronavirus time

text: A critical intellectual, someone whose job is to think, reflect and critique can be the last thing one needs in times of practical urgency. If anything such people can be a hindrance to the recovery effort. Pardoxically, in such times, critical intellectuals are more necessary than ever. Pandemics, for instance, invite war metaphors, and unleash reactionary themes of ‘cohesion’, ‘unity’ and ‘common purpose’ that require being challenged. To be a critical intellectual in such times is to be aware of, and learn how to negotiate, such a contradiction.


Out of the Urban Shadows: Uneven Development and Spatial Politics in Immigrant Suburbs


title: Antibody Profiling and Prevalence in the US population during the SARS-CoV2 Pandemic

text: ABSTRACT Background: Antibody diagnostics play an important role in disease detection and can potentially aid in monitoring of the immune responses to see if an individual has developed immunity. Developing high throughput diagnostics which does not involve handling of infectious material becomes imperative in the case of pandemics such as the recent outbreak of SARS-CoV2. Methods: A protein microarray technology was used to detect the plurality of antibody response to four novel antigens namely S1 glycoprotein, Receptor binding domain (RBD), S2 glycoprotein and Nucleoprotein of the novel coronavirus named SARS-CoV2 using serum samples. A DBS card was additionally used to compare its performance with a venipuncture-based serum separator tube (SST) draw. Results: The three main subclasses of antibodies IgM, IgA and IgG were analyzed to see the variations in immune responses in the affected population and compared to their microbial RT-PCR based NP swab results. The clinical sensitivity and specificity were determined to be 98.1% and 98.6%. In the matrix comparison study, which would enable patients to test without risk of transmitting the virus, DBS matched with higher than 98% accuracy to a venipuncture-based SST collection. Conclusion: Multiplex testing enables higher sensitivity and specificity which is essential while establishing exposure on a population scale. This flexible platform along with a discrete collection methodology would be crucial and broadly useful to scale up testing in current and future pandemics. Minimum sample volume that can be collected using DBS cards can be processed in this multiplex pillar plate format enabling the capacity to provide the reliability of high throughput analyzers while having the ease of collection similar to rapid tests. Keywords: COVID19, SARS-CoV2, Antibody, Multiplex, serology, biomarker, immune modulation, prevalence, high sensitivity, high specificity, Dried blood spot, pandemic, venipuncture


title: Prevalence and mortality of Lung Comorbidities Among Patients with COVID-19: A systematic review and meta-analysis

text: Abstract Background The World Health Organization declared COVID-19 associated infections as a global health public emergency that has led to more than 3,50,000 deaths worldwide. COVID-19 infections are seen across all age groups but they have shown to have a predisposition for the elderly and those with underlying comorbidities. Specifically, these include cardiovascular diseases, diabetes and underlying lung conditions. Further, patients with severe COVID-19 infections and comorbidities are more prone to respiratory distress syndrome (ARDS), mechanical ventilator use and ultimately succumb to these complications. Little evidence exists of the prevalence of underlying lung comorbidities among COVID-19 patients and associated mortality. Methods We performed a systematic review of the literature including PubMed (Medline), Embase (Ovid), Google Scholar and Cochrane Library. The last date for our search was 29th April 2020. We included all original research articles on COVID-19 and calculated prevalence of chronic lung disease patients among COVID-19 patients using random effects model. Further we assessed for mortality rates among COVID-19 patients associated with these lung comorbidities. We calculated pooled prevalence of these conditions among COVID-19 patients using random effects model. Results The authors identified 29 articles that reported the prevalence of chronic lung conditions among COVID-19 patients. Among those, 26 were from China and 3 from the United States. The pooled prevalence of lung comorbidities including Asthma, COPD, and lung cancer was 3% (95% CI=0-14%), 2.2% (95% CI=0.02-0.03%) and 2.1% (95% CI=0.00-0.21%) respectively. Mortality rates associated with these comorbidities was 30% (41/137) for COPD and 19% (7/37) for lung cancer respectively. No mortality rates were reported for patients with asthma. Conclusion This study provides preliminary evidence of the prevalence of chronic lung conditions among patients with COVID-19. Future studies are needed to assess other lung comorbidities and associated mortality among patients diagnosed with COVID-19.


title: New blood tests for antibodies could show true scale of coronavirus pandemic

text: How many COVID-19 cases have gone undetected? And are those who had mild cases of the disease—perhaps so mild they dismissed it as a cold or allergies—immune to new infections? If so, they could slow the spread of the burgeoning pandemic Labs and companies around the world have raced to develop antibody tests, and a few have been used in small studies and received commercial approval, including several from China But so far, large-scale data from such tests—for example showing what fraction of people in the hard-hit city of Wuhan, China, might now be immune—is still lacking or at least not public Scientists hope that will soon change as more tests become available


The importance of widespread testing for COVID-19 pandemic: systems thinking for drive-through testing sites


Impact of COVID-19 pandemic on HTA


title: A mechanistic population balance model to evaluate the impact of interventions on infectious disease outbreaks: Case for COVID19

text: Infectious diseases, especially when new and highly contagious, could be devastating producing epidemic outbreaks and pandemics. Predicting the outcomes of such events in relation to possible interventions is crucial for societal and healthcare planning and forecasting of resource needs. Deterministic and mechanistic models can capture the main known phenomena of epidemics while also allowing for a meaningful interpretation of results. In this work a deterministic mechanistic population balance model was developed. The model describes individuals in a population by infection stage and age group. The population is treated as in a close well mixed community with no migrations. Infection rates and clinical and epidemiological information govern the transitions between stages of the disease. The present model provides a steppingstone to build upon and its current low complexity retains accessibility to non experts and policy makers to comprehend the variables and phenomena at play. The impact of specific interventions on the outbreak time course, number of cases and outcome of fatalities were evaluated including that of available critical care. Data available from the COVID19 outbreak as of early April 2020 was used. Key findings in our results indicate that (i) universal social isolation measures appear effective in reducing total fatalities only if they are strict and the number of daily social interactions is reduced to very low numbers; (ii) selective isolation of only the elderly (at higher fatality risk) appears almost as effective in reducing total fatalities but at a much lower economic damage; (iii) an increase in the number of critical care beds could save up to eight lives per extra bed in a million population with the current parameters used; (iv) the use of protective equipment (PPE) appears effective to dramatically reduce total fatalities when implemented extensively and in a high degree; (v) infection recognition through random testing of the population, accompanied by subsequent (self) isolation of infected aware individuals, can dramatically reduce the total fatalities but only if conducted extensively to almost the entire population and sustained over time; (vi) ending isolation measures while R0 values remain above 1.0 (with a safety factor) renders the isolation measures useless and total fatality numbers return to values as if nothing was ever done; (vii) ending the isolation measures for only the population under 60 y/o at R0 values still above 1.0 increases total fatalities but only around half as much as if isolation ends for everyone; (viii) a threshold value, equivalent to that for R0, appears to exist for the daily fatality rate at which to end isolation measures, this is significant as the fatality rate is (unlike R0) very accurately known. Any interpretation of these results for the COVID19 outbreak predictions and interventions should be considered only qualitatively at this stage due to the low confidence (lack of complete and valid data) on the parameter values available at the time of writing. Any quantitative interpretation of the results must be accompanied with a critical discussion in terms of the model limitations and its frame of application.


title: Widespread use of face masks in public may slow the spread of SARS CoV-2: an ecological study

text: Background The reasons for the large differences between countries in the sizes of their SARS CoV2 epidemics is unknown. Individual level studies have found that the use of face masks was protective for the acquisition and transmission of a range of respiratory viruses including SARS CoV1. We hypothesized that population level usage of face masks may be negatively associated SARS CoV2 spread. Methods At a country level, linear regression was used to assess the association between COVID19 diagnoses per inhabitant and the national promotion of face masks in public (coded as a binary variable), controlling for the age of the COVID19 epidemic and testing intensity. Results Eight of the 49 countries with available data advocated wearing face masks in public: China, Czechia, Hong Kong, Japan, Singapore, South Korea, Thailand and Malaysia. In multivariate analysis face mask use was negatively associated with number of COVID19 cases/inhabitant (coef. -326, 95% CI -601- -51, P=0.021). Testing intensity was positively associated with COVID-19 cases (coef. 0.07, 95% CI 0.05-0.08, P<0.001). Conclusion Whilst these results are susceptible to residual confounding, they do provide ecological level support to the individual level studies that found face mask usage to reduce the transmission and acquisition of respiratory viral infections.


title: Identification of Human Immune Cell Subtypes Most Vulnerable to IL-1β-induced Inflammatory Signaling Using Mass Cytometry

text: IL-1β has emerged as a key mediator of the cytokine storm linked to high morbidity and mortality from COVID-19 and blockade of the IL-1 receptor (IL-1R) with Anakinra has entered clinical trials in COVID-19 subjects. Yet, knowledge of the specific immune cell subsets targeted by IL-1β and IL-1β-induced signaling pathways in humans is limited. Utilizing mass cytometry (CyTOF) of human peripheral blood mononuclear cells, we identified effector memory CD4 T cells and CD4−CD8low/-CD161+ T cells as the circulating immune subtypes with the greatest expression of p-NF-κB in response to IL-1β stimulation. Notably, CCR6 distinctly identified T cells most responsive to IL-1β. Other subsets including CD11c myeloid dendritic cells (mDCs), classical monocytes (CM), two subsets of natural killer cells (CD16−CD56brightCD161− and CD16−CD56dimCD161+) and a population of lineage−(Lin-) cells expressing CD161 and CD25 also showed IL-1β-induced expression of p-NF-kB. The IL-1R antagonist, Anakinra significantly inhibited IL-1β-induced p-NF-kB in the CCR6+ T cells and CD11c mDCs with a trending inhibition in CD14 monocytes and Lin−CD161+CD25+ cells. IL-1β also induced a rapid but much less robust increase in p-p38 expression as compared to p-NF-kB in the majority of these same immune cell subsets. Prolonged IL-1β stimulation greatly increased p-STAT3 and to a much lesser extent p-STAT1 and p-STAT5 in T cell subsets, monocytes, DCs and the Lin−CD161+CD25+ cells suggesting IL-1β-induced production of downstream STAT-activating cytokines, consistent with its role in cytokine storm. Interindividual heterogeneity and inhibition of this activation by Anakinra raises the intriguing possibility that assays to measure IL-1β-induced p-NF-kB in CCR6+ T cell subtypes could identify those at higher risk of cytokine storm and those most likely to benefit from Anakinra therapy.


title: PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection

text: Summary PoSeiDon is an easy-to-use pipeline that helps researchers to find recombination events and sites under positive selection in protein-coding sequences. By entering homologous sequences, PoSeiDon builds an alignment, estimates a best-fitting substitution model, and performs a recombination analysis followed by the construction of all corresponding phylogenies. Finally, significantly positive selected sites are detected according to different models for the full alignment and possible recombination fragments. The results of PoSeiDon are summarized in a user-friendly HTML page providing all intermediate results and the graphical representation of recombination events and positively selected sites. Availability and implementation PoSeiDon is freely available at https://github.com/hoelzer/poseidon. The pipeline is implemented in Nextflow with Docker support and processes the output of various tools. Contact hoelzer.martin@gmail.com


COVID-19 and people with intellectual disabilities


title: Comparison of SARS-CoV-2 Exit Strategies Building Blocks

text: We consider and compare various exit strategy building blocks and key measures to mitigate the current SARS-CoV-2 pandemic, some already proposed as well as improvements we suggest. Our comparison is based on a computerized simulation integrating accumulated SARS-CoV-2 epidemiological knowledge. Our results stress the importance of immediate on-symptom isolation of suspected cases and household members, and the beneficial effects of prompt testing capacity. Our findings expose significant epidemic-suppression differences among strategies with seemingly similar economic cost stressing the importance of not just the portion of population and business that is released, but also the pattern. The most effective building blocks are the ones that integrate several base strategies - they allow to release large portions of the population while still achieving diminishing viral spread. However, it may come with a price on somewhat more complex schemes. For example, our simulations indicate that dividing the population into two groups completely released except for taking turns on a long weekend (Fri-Tue) self-isolation once every two weeks, while protecting the 5% most sensitive population would reduce R below 1 even if ten percent of the population does not follow it. We further simulate the contrasting approach of a stratified population release in a hope to achieve herd immunity, which for the time being seems inferior to other suggested building blocks. Knowing the tradeoff between building blocks could help optimize exit strategies to be more effective and suitable for a particular area or country, while maximizing human life as well as economic value. Given our results, we believe that pandemic can be controlled within a reasonable amount of time and at a reasonable socio-economic burden.


title: Saliva as a Candidate for COVID-19 Diagnostic Testing: A Meta-Analysis

text: Objectives: Our aim was to conduct a meta-analysis on the reliability and consistency of SARS-CoV-2 viral RNA detection in saliva specimens. Methods: We reported our meta-analysis according to the Cochrane Handbook. We searched the Cochrane Library, Embase, Pubmed, Scopus, Web of Science and clinical trial registries for eligible studies published between 1 January and 25 April 2020. The number of positive tests and total number of conducted tests were collected as raw data. The proportion of positive tests in the pooled data were calculated by score confidence interval estimation with the Freeman-Tukey transformation. Heterogeneity was assessed using the I2 measure and the Chi2 test. Results: The systematic search revealed 96 records after removal of duplicates. 26 records were included for qualitative analysis and 5 records for quantitative synthesis. We found 91% (95%CI = 80%-99%) sensitivity for saliva tests and 98% (95%CI 89%-100%) sensitivity for nasopharyngeal swab (NPS) tests in previously confirmed COVID-19 infected patients, with moderate heterogeneity among studies. Additionally, we identified 18 registered, ongoing clinical trials on saliva-based tests for detection of the virus. Conclusion: Saliva tests offer a promising alternative to NPS for COVID-19 diagnosis. However, further diagnostic accuracy studies are needed to improve their specificity and sensitivity.


title: The effect of non-pharmaceutical interventions on COVID-19 cases, deaths and demand for hospital services in the UK: a modelling study

text: Background Non-pharmaceutical interventions have been implemented to reduce transmission of SARS-CoV-2 in the UK. Projecting the size of an unmitigated epidemic and the potential effect of different control measures has been critical to support evidence-based policymaking during the early stages of the epidemic. Methods We used a stochastic age-structured transmission model to explore a range of intervention scenarios, including the introduction of school closures, social distancing, shielding of elderly groups, self-isolation of symptomatic cases, and extreme "lockdown"-type restrictions. We simulated different durations of interventions and triggers for introduction, as well as combinations of interventions. For each scenario, we projected estimated new cases over time, patients requiring inpatient and critical care (intensive care unit, ICU) treatment, and deaths. Findings We found that mitigation measures aimed at reducing transmission would likely have decreased the reproduction number, but not sufficiently to prevent ICU demand from exceeding NHS availability. To keep ICU bed demand below capacity in the model, more extreme restrictions were necessary. In a scenario where "lockdown"-type interventions were put in place to reduce transmission, these interventions would need to be in place for a large proportion of the coming year in order to prevent healthcare demand exceeding availability. Interpretation The characteristics of SARS-CoV-2 mean that extreme measures are likely required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs.


title: Scrutinizing the heterogeneous spreading of COVID-19 outbreak in Brazilian territory

text: After the spread of COVID-19 out of China, the evolution of the pandemic shows remarkable similarities and differences among countries across the world. Eventually, such characteristics are also observed between different regions of the same country. Herewith, we study the heterogeneous spreading of the confirmed infected cases and deaths by the COVID-19 until May 30th, 2020, in the Brazilian territory, which has been seen as the current epicenter of the pandemic in South America. Our first set of results is related to the similarities and it shows that: (i) a power-law growth of the cumulative number of infected people is observed for federative units of the five regions of Brazil; and (ii) the Distance Correlation (DC) calculated between the time series of the most affected federative units and the curve that describes the evolution of the pandemic in Brazil remains about 1 in most of the time, while such quantity calculated for the federative units with a low incidence of newly infected people remains about 0.95. In the second set of results, we focus on the heterogeneous distribution of the confirmed cases and deaths, which is demonstrated by the fact that only three regions concentrate 92% of the cases. By applying the epidemiological SIRD model we estimated the effective reproduction number Re during the pandemic evolution and found that: (i) the mean value of Re for the eight most affected federative units in Brazil is about 2; (ii) the current value of Re for Brazil is greater than 1, which indicates that the epidemic peak is far; and (iii) Ceara was the only federative unit for which the current Re < 1. Based on these findings, we projected the effects of increase or decrease the effective reproduction number and concluded that if the value of Re increases 20%, not only the peak might grow at least 40% but also its occurrence might be anticipated, which hastens the collapse of the public health care system. In all cases, to keep the effective reproduction number 20% below the current one can save thousands of people in the long term.


title: Report 21: Estimating COVID-19 cases and reproduction number in Brazil

text: Brazil is an epicentre for COVID-19 in Latin America. In this report we describe the Brazilian epidemic using three epidemiological measures: the number of infections, the number of deaths and the reproduction number. Our modelling framework requires sufficient death data to estimate trends, and we therefore limit our analysis to 16 states that have experienced a total of more than fifty deaths. The distribution of deaths among states is highly heterogeneous, with 5 states---Sao Paulo, Rio de Janeiro, Ceara, Pernambuco and Amazonas---accounting for 81% of deaths reported to date. In these states, we estimate that the percentage of people that have been infected with SARS-CoV-2 ranges from 3.3% (95% CI: 2.8%-3.7%) in Sao Paulo to 10.6% (95% CI: 8.8%-12.1%) in Amazonas. The reproduction number (a measure of transmission intensity) at the start of the epidemic meant that an infected individual would infect three or four others on average. Following non-pharmaceutical interventions such as school closures and decreases in population mobility, we show that the reproduction number has dropped substantially in each state. However, for all 16 states we study, we estimate with high confidence that the reproduction number remains above 1. A reproduction number above 1 means that the epidemic is not yet controlled and will continue to grow. These trends are in stark contrast to other major COVID-19 epidemics in Europe and Asia where enforced lockdowns have successfully driven the reproduction number below 1. While the Brazilian epidemic is still relatively nascent on a national scale, our results suggest that further action is needed to limit spread and prevent health system overload.


title: Indian Publications on SARS-CoV-2: A Bibliometric Study of WHO COVID-19 Database

text: Nowadays, the whole World is under threat of Coronavirus disease (COVID-19). The ongoing COVID-19 pandemic has resulted in many fatalities and forced scientific communities to foster their Research and Development (R & D) activities. As a result, there is an enormous growth of scholarly literature on the subject. In order to combat this novel coronavirus, the open access to scientific literature is essential. On this line, many reputed academic institutions and publication firms have made their literature on COVID-19 accessible to all. By maintaining the database of updated information on global literature on Coronavirus disease, the World Health Organization (WHO) is playing a pivotal role. The present study analyzed 89 Indian publications on SARS-CoV-2 accessible through WHO COVID-19 database. The research data was restricted for the period of 2/3/2020 to 12/5/2020. The analysis was carried out in light of the objectives of the study. The study found the considerable and constant growth of Indian publications on COVID-19 from mid-April. It is interesting to note that the prolific authors belong to either AIIMS or ICMR institutes. Majority of the COVID-19 articles were found to be collaborative publications. The study noticed that no research publications on COVID-19 have appeared from North Eastern region. Regarding the research output on COVID-19, the performance of largest states like Uttar Pradesh, Madhya Pradesh and Bihar was found to be poor. Delhi state contributed highest publications on COVID-19. The All India Institute of Medical Sciences (AIIMS), New Delhi was the most productive institution in terms of publications. It is also important to note that the central government undertakings like AIIMS and ICMR, New Delhi and its affiliated institutions shared largest proportion of publications on COVID-19. The Indian Journal of Medical Research has emerged as the productive journal contributing highest number of the publications. The highest contribution in COVID-19 research takes the form of journal articles. In terms of research area, the majority of the publications were related to Epidemiology. The study reported covid, coronavirus, India, pandemic, sars etc. as the frequently occurred keywords in the COVID-19 publications. The highly cited publications were of evidenced based studies. It is observed that the studies pertaining to virology, diagnosis and treatment, clinical features etc. have received highest citations than general studies on epidemiology or pandemic


title: Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs

text: Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard for COVID-19 diagnosis is real-time RT-PCR detection of SARS-CoV-2 from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, and global shortages of swabs and personal protective equipment, however, necessitate the validation of new diagnostic approaches. Saliva is a promising candidate for SARS-CoV-2 diagnostics because (1) collection is minimally invasive and can reliably be self-administered and (2) saliva has exhibited comparable sensitivity to nasopharyngeal swabs in detection of other respiratory pathogens, including endemic human coronaviruses, in previous studies. To validate the use of saliva for SARS-CoV-2 detection, we tested nasopharyngeal and saliva samples from confirmed COVID-19 patients and self-collected samples from healthcare workers on COVID-19 wards. When we compared SARS-CoV-2 detection from patient-matched nasopharyngeal and saliva samples, we found that saliva yielded greater detection sensitivity and consistency throughout the course of infection. Furthermore, we report less variability in self-sample collection of saliva. Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing.


title: Clinical characteristics of imported and second-generation COVID-19 cases outside Wuhan, China: A multicenter retrospective study

text: Background The mortality of COVID-19 differs between countries and regions. By now, reports on COVID-19 are largely focused on first-generation cases. This study aimed to clarify the clinical characteristics of imported and second-generation cases. Methods This retrospective, multicenter cohort study included 134 confirmed COVID-19 cases from 9 cities outside Wuhan. Epidemiological, clinical and outcome data were extracted from medical records and were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. Results 34.3% of the 134 patients were severe cases, and 11.2% had complications. As of March 7, 2020, 91.8% patients were discharged and one patient (0.7%) died. The median age was 46 years. The median interval from symptom onset to hospital admission was 4.5 (IQR 3-7) days. The median lymphocyte count was 1.1*109/L. Age, lymphocyte count, CRP, ESR, DBIL, LDH, HBDH showed difference between severe and no-severe cases (all P<0.05). Baseline lymphocyte count was higher in the survived patients than in the non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The IL-6 level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest CT images in 51.5% of the pneumonia cases. Conclusion Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.


title: SARS-CoV-2 Infection Associated Hemophagocytic Lymphohistiocytosis: An autopsy series with clinical and laboratory correlation.

text: Background: A subset of COVID-19 patients exhibit clinical features of cytokine storm. However, clinicopathologic features diagnostic of hemophagocytic lymphohistiocytosis (HLH) have not been reported. Pathologic studies to date have largely focused on the pulmonary finding of diffuse alveolar damage (DAD). To this aim, we study the reticuloendothelial organs of four consecutive patients dying of COVID-19 and correlate with clinical and laboratory parameters to detect HLH. Methods: Autopsies restricted to chest and abdomen were performed on four patients who succumbed to COVID-19. Spleen, liver, and multiple pulmonary hilar/mediastinal lymph nodes were sampled in all cases. Bone marrow was obtained by rib squeeze in a subset of cases. Routine H&E staining as well as immunohistochemical staining for CD163 was performed to detect hemophagocytosis. Clinical and laboratory results from pre-mortem blood samples were used to calculate H-scores. Findings: All four cases demonstrated DAD within the lungs. Three of the four cases had histologic evidence of hemophagocytosis within pulmonary hilar/mediastinal lymph nodes. One case showed hemophagocytosis in the spleen but none showed hemophagocytosis in liver or bone marrow. Lymphophagocytosis was the predominant form of hemophagocytosis observed. One patient showed diagnostic features of HLH with an H-score of 217 while a second patient was likely HLH with a partial H-score of 145 due to missing triglyceride level. Both patients exhibited high fever and early onset rise in serum ferritin; however, neither bicytopenia, pancytopenia, nor hypofibrinogenemia were observed in either. The remaining two patients had H-scores of 131 and 96. Interpretation: This is the first report of SARS-CoV-2 associated HLH. Identification of HLH in a subset of patients with severe COVID-19 will inform clinical trials of therapeutic strategies.


title: Early Impact of COVID-19 Pandemic on Paediatric Surgical Practice in Nigeria: a National Survey of Paediatric Surgeons.

text: Introduction The novel Coronavirus disease has had significant impact on healthcare globally. Knowledge of this virus is evolving, definitive care is not yet known, and mortality is increasing. We assessed its initial impact on paediatric surgical practice in Nigeria, creating a benchmark for recommendations and future reference. Methods Survey of 120 paediatric surgeons from 50 centres to assess socio-demographics and specific domains of impact of COVID-19 on their services and training in Nigeria. Seventy four surgeons adequately responded. Responses have been analysed. Duplicate submissions for centres were excluded by combining and averaging the responses from centres with multiple respondents. Results Forty-six (92%) centres had suspended elective surgeries. All centres continued emergency surgeries but volume reduced in March by 31%. Eleven (22%) centres reported 13 suspended elective cases presenting as emergencies in March, accounting for 3% of total emergency surgeries. Nine (18%) centres adopted new modalities for managing selected surgical conditions: non-operative reduction of intussusception in 1(2%), antibiotic management of uncomplicated acute appendicitis in 5(10%), more conservative management of trauma and replacement of laparoscopic appendectomy with open surgery in 3(6%) respectively. Low perception of adequacy of Personal Protective Equipment (PPE) was reported in 35(70%) centres. Forty (80%) centres did not offer telemedicine for patients follow up. Twenty-nine (58%) centres had suspended academic training. Perception of safety to operate was low in 37(50%) respondents, indifferent in 24% and high in 26%. Conclusion Majority of paediatric surgical centres reported cessation of elective surgeries whilst continuing emergencies. There is however an acute decline in the volume of emergency surgeries. Adequate PPE need to be provided and preparations towards handling backlog of elective surgeries once the pandemic recedes. Further study is planned to more conclusively understand the full impact of this pandemic on children's surgery. Key words pandemic, COVID-19, children's surgery.


title: Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

text: COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress syndrome characterized by extensive pulmonary inflammation and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. Highlights Nine potential PIPs were predicted exclusive from the SARS-CoV-2. SARS-CoV-2 PIPs showed homology against T cell recognition epitopes. Most of PIPs were produced by enzymatic cleavage of the spike glycoproteins. The release of these PIPs might be related to the increased inflammatory response observed in the patients. Graphical abstract


title: Molecular docking analyses of CYP450 monooxygenases of Tribolium castaneum (Herbst) reveal synergism of quercetin with paraoxon and tetraethyl pyrophosphate: in vivo and in silico studies

text: Pest management in stored grain industry is a global issue due to the development of insecticide resistance in stored grain insect pests Excessive use of insecticides at higher doses poses a serious threat of food contamination and residual toxicity for grain consumers Since the development of new pesticide incurs heavy costs, identifying an effective synergist can provide a ready and economical tool for controlling resistant pest populations Therefore, the synergistic property of quercetin with paraoxon and tetraethyl pyrophosphate has been evaluated against the larvae and adults of Tribolium castaneum (Herbst) Comparative molecular docking analyses were carried out to further identify the possible mechanism of synergism It was observed that quercetin has no insecticidal when applied at the rate of 1 5 and 3 0 mg/g;however, a considerable synergism was observed when applied in combination with paraoxon The comparative molecular docking analyses of CYP450 monooxygenase (CYP15A1, CYP6BR1, CYP6BK2, CYP6BK3) family were performed with quercetin, paraoxon and tetraethyl pyrophosphate which revealed considerable molecular interactions, predicting the inhibition of CYP450 isoenzyme by all three ligands The study concludes that quercetin may be an effective synergist for organophosphate pesticides depending upon the dose and type of the compound In addition, in silico analyses of the structurally diversified organophosphates can effectively differentiate the organophosphates which are synergistic with quercetin


title: Predicted effects of summer holidays and seasonality on the SARS-Cov-2 epidemic in France

text: The SARS-CoV-2 epidemic in France has had a large death toll. It has not affected all regions similarly, since the death rate can vary several folds between regions where the epidemic has remained at a low level and regions where it got an early burst. The epidemic has been slowed down by a lockdown that lasted for almost eight weeks, and individuals can now move between metropolitan French regions without restriction. In this report we investigate the effect on the epidemic of summer holidays, during which millions of individuals will move between French regions. Additionally, we evaluate the effect of strong or weak seasonality and of several values for the reproduction number on the epidemic, in particular on the timing, the height and the spread of a second wave. To do so, we extend a SEIR model to simulate the effect of summer migrations between regions on the number and distribution of new infections. We find that the model predicts little effect of summer migrations on the epidemic. However, all the reproduction numbers above 1.0 and the seasonality parameters we tried result in a second epidemic wave, with a peak date that can vary between October 2020 and April 2021. If the sanitary measures currently in place manage to keep the reproduction number below 1.0, the second wave will be avoided. If they keep the reproduction number at a low value, for instance at 1.1 as in one of our simulations, the second wave is flattened and could be similar to the first wave.


title: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

text: The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 than any other organ. The large intestine, kidney and testis showed moderate signals, whereas the signal was weak in the lung. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung. IMPORTANCE Vaccines and new medicines are urgently needed to prevent spread of COVID-19 pandemic, reduce the symptoms, shorten the duration of disease, prevent virus spread in the body, and most importantly to save lives. One of the key drug targets could be angiotensin-converting enzyme 2 (ACE2), which is a crucial receptor for the corona virus (SARS-CoV-2). It is known that SARS coronavirus infections lead to worse outcome in the elderly and in males. Therefore, one aim of the present study was to investigate whether age or sex could contribute to the regulation of ACE2 expression. We also decided to explore the transcriptional regulation of ACE2 gene expression. Since data on ACE2 distribution is still conflicting, we aimed to get a more comprehensive view of the cell types expressing the receptor of SARS-CoV-2. Finally, we studied the coexpression of ACE2 with other genes and explored its putative functions using gene ontology enrichment analysis.


title: COVID-19 Management and Arrhythmia: Risks and Challenges for Clinicians Treating Patients Affected by SARS-CoV-2

text: The COVID-19 pandemic is an unprecedented challenge and will require novel therapeutic strategies. Affected patients are likely to be at risk of arrhythmia due to underlying comorbidities, polypharmacy and the disease process. Importantly, a number of the medications likely to receive significant use can themselves, particularly in combination, be pro-arrhythmic. Drug-induced prolongation of the QT interval is primarily caused by inhibition of the hERG potassium channel either directly and/or by impaired channel trafficking. Concurrent use of multiple hERG-blocking drugs may have a synergistic rather than additive effect which, in addition to any pre-existing polypharmacy, critical illness or electrolyte imbalance, may significantly increase the risk of arrhythmia and Torsades de Pointes. Knowledge of these risks will allow informed decisions regarding appropriate therapeutics and monitoring to keep our patients safe.


title: SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

text: Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 μg/mL and IC50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85×10−7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.


title: Accounting for symptomatic and asymptomatic in a SEIR-type model of COVID-19

text: A mathematical model was developed describing the dynamic of the COVID-19 virus over a population considering that the infected can either be symptomatic or not The model was calibrated using data on the confirmed cases and death from several countries like France, Philippines, Italy, Spain, United Kingdom, China, and the USA First, we derived the basic reproduction number,R(0)R0, and estimated the effective reproductionR(eff)Refffor each country Second, we were interested in the merits of interventions, either by distancing or by treatment Results revealed that total and partial containment is effective in reducing the transmission However, its duration may be long to eradicate the disease (104 days for France) By setting the end of containment as the day when hospital capacity is reached, numerical simulations showed that the duration can be reduced (up to only 39 days for France if the capacity is 1000 patients) Further, results pointed out that the effective reproduction number remains large after containment Therefore, testing and isolation are necessary to stop the disease