docid: fixgrdmj

title: Droplet rather than Aerosol Mediated Dispersion is the Primary Mechanism of Bacterial transmission from Contaminated Hand Washing Sink Traps

text: An alarming rise in hospital outbreaks implicating hand-washing sinks has led to widespread acknowledgement that sinks are a major reservoir of antibiotic resistant pathogens in patient-care areas. An earlier study using a GFP-expressing Escherichia coli (GFP-E. coli) as a model organism demonstrated dispersal from drain biofilm in contaminated sinks. The present study further characterizes the dispersal of microorganisms from contaminated sinks. Replicate hand-washing sinks were inoculated with GFP-E. coli, and dispersion was measured using qualitative (settle plates) and quantitative (air sampling) methods. Dispersal caused by faucet water was captured with settle plates and air sampling methods when bacteria were present on the drain. In contrast, no dispersal was captured without or in between faucet events amending earlier theory that bacteria aerosolize from P-trap and disperse. Numbers of dispersed GFP-E. coli diminished substantially within 30 minutes after faucet usage, suggesting that the organisms were associated with larger droplet-sized particles that are not suspended in the air for long periods. IMPORTANCE Among the possible environmental reservoirs in a patient care environment, sink drains are increasingly recognized as potential reservoir of multidrug resistant healthcare-associated pathogens to hospitalized patients. With increasing antimicrobial resistance limiting therapeutic options for patients, better understanding of how pathogens disseminate from sink drains is urgently needed. Once this knowledge gap has decreased, interventions can be engineered to decrease or eliminate transmission from hospital sink drains to patients. The current study further defines the mechanisms of transmission for bacteria colonizing sink drains.


title: Clinical characteristics of 34 COVID-19 patients admitted to ICU in Hangzhou, China

text: Introduction: The purpose of the study was to summarize the clinical and laboratory characteristics of the coronavirus disease 2019 patients admitted to intensive care unit. Methods: We tracked the data until March 5, 2020. The cases in our cohort were divided into cases only received noninvasive ventilation (NIV) and cases required invasive mechanical ventilation (IMV). The characteristics between the two groups were compared. Results: 34 cases were included in the study. The complications rate (including, acute liver injury, acute cardiac injury and acute kidney injury) were higher in IMV cases. Lymphocytopenia and neutrophilia occurred in most cases in both groups on the admission day, however, lymphocyte levels dropped progressively and more severe lymphopenia occurred in IMV group. Increased amounts of plasma IL-6 and IL-10 were found in both groups on the admission day, the progressive decrease of which occurred in NIV cases rather than IMV cases, and the levels were higher in IMV cases during hospitalization. Conclusions: Lymphocytopenia, neutrophilia, and increase of IL-6 and IL-10 occurred in SARS-CoV-2 infected patients in ICU, however, the dynamics of those were significantly different in IMV cases and NIV cases during hospitalization.


title: Influence factors of death risk among COVID-19 patients in Wuhan, China: a hospital-based case-cohort study

text: Background. Coronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely pandemic all over the world. The aim of this study was to analyze the influence factors of death risk among 200 COVID-19 patients. Methods. Two hundred patients with confirmed SARS-CoV-2 infection were recruited. Demographic data and clinical characteristics were collected from electronic medical records. Biochemical indexes on admission were measured and patient's prognosis was tracked. The association of demographic data, clinical characteristics and biochemical indexes with death risk was analyzed. Results. Of 200 COVID-19 patients, 163 (81.5%) had at least one of comorbidities, including diabetes, hypertension, hepatic disease, cardiac disease, chronic pulmonary disease and others. Among all patients, critical cases, defined as oxygenation index lower than 200, accounted for 26.2%. Severe cases, oxygenation index from 200 to 300, were 29.7%. Besides, common cases, oxygenation index higher than 300, accounted for 44.1%. At the end of follow-up, 34 (17%) were died on mean 10.9 day after hospitalization. Stratified analysis revealed that older ages, lower oxygenation index and comorbidities elevated death risk of COVID-19 patients. On admission, 85.5% COVID-19 patients were with at least one of extrapulmonary organ injuries. Univariable logistic regression showed that ALT and TBIL, two indexes of hepatic injury, AST, myoglobin and LDH, AST/ALT ratio, several markers of myocardial injury, creatinine, urea nitrogen and uric acid, three indexes of renal injury, were positively associated with death risk of COVID-19 patients. Multivariable logistic regression revealed that AST/ALT ratio, urea nitrogen, TBIL and LDH on admission were positively correlated with death risk of COVID-19 patients. Conclusion. Older age, lower oxygenation index and comorbidities on admission elevate death risk of COVID-19 patients. AST/ALT ratio, urea nitrogen, TBIL and LDH on admission may be potential prognostic indicators. Early hospitalization is of great significance to prevent multiple organ damage and improve the survival of COVID-19 patients.


title: Simple ventilators for emergency use based on Bag-Valve pressing systems: Lessons learned and future steps

text: As part of a plethora of global efforts to minimize the negative effects of the SARS-CoV2 (COVID-19) pandemic, we developed two different mechanisms that, after further development, could potentially be of use in the future in order to increase the capacity of ventilators with low-cost devices based on single-use-bag-valve mask systems. We describe the concept behind the devices and report a characterization of them. Finally, we make a description of the solved and unsolved challenges and propose a series of measures in order to better cope with future contingencies.


title: Pediatric coronavirus disease 2019 (COVID-19): An insight from west of Iran

text: OBJECTIVE: To study the clinical, laboratory, and radiological characteristics of the pediatric patients infected with the new emerging 2019 coronavirus virus (SARS-CoV-2) in Hamadan and Sanandaj, west of Iran. METHODS: A descriptive study was conducted in Hamadan and Kurdistan province between March 1 to April 15, 2020. Medical records of the children diagnosed as probable or confirmed cases of COVID-19 disease were extracted and analyzed in this study. We followed the WHO Guideline for the case definition of the patients. RESULTS: Thirty patients admitted to the wards specified for COVID-19 diseases. Nineteen (63%) patients categorized as confirmed by Real-Time Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) and 11 (37%) patients as probable according to Computed Tomography (CT) findings of the chest. Sixteen (53.3%) cases were female, the youngest patient was one day old, and the oldest patient was 15 years old. 11 (36.7%) cases had a definite history of close contact. The most common symptoms were fever, cough, and dyspnea, and the most common sign was tachypnea. None of our patients presented with a runny nose. Lymphopenia and marked elevation of the C-reactive Protein observed in four (13.3%) and 12 (40%) cases, respectively. There were 10 (33.3%) cases with normal chest X-rays. Ground-Glass Opacities (GGOs) were the most common CT findings (19, 73.1%). All but one of the patients discharged without sequala. An 11-yrs-old girl expired with a fulminant pneumonia. CONCLUSION: COVID-19 is not uncommon in children and could have different presentations. Concomitant use of RT-PCR and chest CT scans in symptomatic cases recommended as a modality of choice to diagnose the disease. Routine laboratory tests, like many other viral infections, may not show significant or specific changes. The superimposed bacterial infection seems not the determinant of clinical outcomes as most patients had a negative evaluation by specific laboratory tests for bacterial infections; got improved dramatically with a short or no antibiotic therapy.


title: Side by side comparison of three fully automated SARS-CoV-2 antibody assays with a focus on specificity

text: Background: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies have become available quickly. However, the clinical performance of many of them is still insufficiently described. Therefore we compared three commercial, CE-marked, SARS-CoV-2 antibody assays side by side. Methods: We included a total of 1,154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients ([≥]14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. Results: All three assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers' specifications, sensitivities only ranged from 83.1% to 89.2%. Although the three methods were in good agreement (Cohen's Kappa 0.71-0.87), McNemar's test revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictability at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Roche, Abbott, and DiaSorin, respectively. Conclusion: We find diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictability of these tests.


title: Safe contact tracing for COVID-19: A method without privacy breach using functional encryption techniques based-on spatio-temporal trajectory data

text: The COVID-19 pandemic has spread all over the globe. In the absence of a vaccine, a small number of countries have managed to control the diffusion of viruses by early detection and early quarantine. South Korea, one of the countries which have kept the epidemics well-controlled, has opened the infected patients' trajectory to the public. Such a reaction has been regarded as an effective method, however, serious privacy breach cases have been issued in South Korea. Furthermore, some suspected contacts have refused to take infection tests because they are afraid of being exposed. To solve this problem, we propose a privacy-preserving contact tracing method based on spatio-temporal trajectory which can be practically used in many quarantine systems. In addition, we develop a system to visualize the contact tracing workflow.


title: AIDCOV: An Interpretable Artificial Intelligence Model for Detection of COVID-19 from Chest Radiography Images

text: As the Coronavirus Disease 2019 (COVID-19) pandemic continues to grow globally, testing to detect COVID-19 and isolating individuals who test positive remains to be the primary strategy for preventing community spread of the disease. The current gold standard method of testing for COVID-19 is the reverse transcription polymerase chain reaction (RT-PCR) test. The RT-PCR test, however, has an imperfect sensitivity (around 70%), is time-consuming and labor-intensive, and is in short supply, particularly in resource-limited countries. Therefore, automatic and accurate detection of COVID-19 using medical imaging modalities such as chest X-ray and Computed Tomography, which are more widely available and accessible, can be beneficial. We develop a novel hierarchical attention neural network model to classify chest radiography images as belonging to a person with either COVID-19, other infections, or no pneumonia (i.e., normal). We refer to this model as Artificial Intelligence for Detection of COVID-19 (AIDCOV). The hierarchical structure in AIDCOV captures the dependency of features and improves model performance while the attention mechanism makes the model interpretable and transparent. Using a publicly available dataset of 5801 chest images, we demonstrate that our model achieves a mean cross-validation accuracy of 97.8%. AIDCOV has a sensitivity of 99.3%, a specificity of 99.98%, and a positive predictive value of 99.6% in detecting COVID-19 from chest radiography images. AIDCOV can be used in conjunction with or instead of RT-PCR testing (where RT-PCR testing is unavailable) to detect and isolate individuals with COVID-19 and prevent onward transmission to the general population and healthcare workers.


title: Mechanism of Tanreqing Injection on treatment of coronavirus disease 2019 based on network pharmacology and molecular docking/ 基于网络药理学和分子对接探讨痰热清注射液治疗新型冠状病毒肺炎（COVID-19）的机制

text: Objective: To study the mechanism of Tanreqing Injection (TRQI) on treatment of coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking, so as to provide theoretical basis for clinical treatment. Methods: The active compounds of TRQI were searched by literature, BATMAN-TCM, and TCMSP database. The potential targets of TRQI active compounds were searched by TCMSP. In Genecards database, “coronavirus” was used as the key word to search for coronavirus targets and the common targets were selected by mapping with TRQI. The network between the active compounds and common targets was established by Cytoscape 3.2.1. The common targets were imported into a STRING database for protein-protein interaction analysis, and the target protein interaction network diagram (PPI) was constructed. The key antiviral targets of TRQI were screened by combining two networks. “GlueGO 2.5.5” plug-in unit in Cytoscape 3.2.1 was used to perform GO biological process and KEGG pathway enrichment analysis. Results: A total of 54 components of TRQI were obtained and corresponding to 287 targets. Among them, there were 54 common targets and 34 key targets. GO analysis obtained 29 biological processes related to the treatment effect of TRQI, and KEGG analysis obtained 70 pathways. The results of molecular docking showed that kaempferol, quercetin, baicalein luteolin, and wogonin had good affinity with SARS-CoV-2 3CL hydrolase. Conclusion: The active compounds in TRQI may act as an antiviral agent by binding SARS-CoV-2 3CL hydrolase and regulating multiple signaling pathways. The molecular mechanism of TRQI in the treatment of COVID-19 indicated the synergistic features of multi-component, multi-target, and multi-pathway of traditional Chinese medicine, which provided an important scientific basis for further elucidating the mechanism of TRQI in the treatment of COVID-19.


title: Antigenic evolution on global scale reveals potential natural selection of SARS-CoV-2 by pre-existing cross-reactive T cell immunity

text: The mutation pattern of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is constantly changing with the places of transmission, but the reason remains to be revealed. Here, we presented the study that comprehensively analyzed the potential selective pressure of immune system restriction, which can drive mutations in circulating SARS-CoV-2 isolates. The results showed that the most common mutation sites of SARS-CoV-2 proteins were located on the non-structural protein ORF1ab and the structural protein Spike. Further analysis revealed mutations in cross-reactive epitopes between SARS-CoV-2 and seasonal coronavirus may help SARS-CoV-2 to escape cellular immunity under the long-term and large-scale community transmission. Meanwhile, the mutations on Spike protein may enhance the ability of SARS-CoV-2 to enter the host cells and escape the recognition of B-cell immunity. This study will increase the understanding of the evolutionary direction and warn about the potential immune escape ability of SARS-CoV-2, which may provide important guidance for the potential vaccine design.


title: Coronavirus cases have dropped sharply in South Korea. What’s the secret to its success?

text: Europe is now the epicenter of the COVID-19 pandemic Case counts and deaths are soaring in Italy, Spain, France, and Germany, and many countries have imposed lockdowns and closed borders Meanwhile, the United States, hampered by a fiasco with delayed and faulty test kits, is just guessing at its COVID-19 burden, though experts believe it is on the same trajectory as countries in Europe


title: Burden of COVID-19 pandemic in India: Perspectives from Health Infrastructure

text: The coronavirus (COVID-19) is spreading rapidly across the country but testing regime of India is far from the global standards. It is important to identify the states where testing needs expansion and the magnitudes of active COVID cases are higher focusing on current health infrastructure to meet the pandemic. The data on COVID-19 was extracted from the Application Programming Interface. Test positive rate, test per confirmed case, recovery rate, case fatality rate, and percent distribution of active cases were computed. Availability of hospitals, hospital beds, intensive care unit and ventilators per lakh population was also computed by public and private sector. The result revealed that, Maharashtra constitutes more than one-third positive cases in the country. More than a quarter of the active cases in India belonged to the Mumbai district of Maharashtra, followed by the Chennai district (9.4%) and Ahmedabad district (9.1%). Further, about 40 percent of the active cases in India belonged to the 11 districts of Maharashtra. The increased test positive rate in Maharashtra and Gujarat to almost double in last one month is a concern. In order to bring the states and the country in right track, the test positive rate need to be brought down to below 2 percent. The procurement of higher number of high throughput machine, the Cobas 6800 testing machine, is need of the hour. Only few states have adequate health infrastructure. The priority should be the laid on expansion of more laboratories and hospitals, storage of PPE kit, testing kit, and indigenously developed vaccines.


title: Identification and classification of differentially expressed genes reveals potential molecular signatures associated with SARS-CoV-2 infection in lung adenocarcinoma cells

text: Genomic techniques such as next-generation sequencing and microarrays have facilitated the identification and classification of molecular signatures inherent in cells upon viral infection, for possible therapeutic targets. Therefore, in this study, we performed a differential gene expression analysis, pathway enrichment analysis, and gene ontology on RNAseq data obtained from SARS-CoV-2 infected A549 cells. Differential expression analysis revealed that 753 genes were up-regulated while 746 down-regulated. SNORA81, OAS2, SYCP2, LOC100506985, and SNORD35B are the top 5 upregulated genes upon SARS-Cov-2 infection. Expectedly, these genes have been implicated in the immune response to viral assaults. In the Ontology of protein classification, a high percentage of the genes are classified as Gene-specific transcriptional regulator, metabolite interconversion enzyme, and Protein modifying enzymes. Twenty pathways with P-value lower than 0.05 were enriched in the up-regulated genes while 18 pathways are enriched in the down-regulated DEGs. The toll-like receptor signalling pathway is one of the major pathways enriched. This pathway plays an important role in the innate immune system by identifying the pathogen-associated molecular signature emanating from various microorganisms. Taken together, our results present a novel understanding of genes and corresponding pathways upon SARS-Cov-2 infection, and could facilitate the identification of novel therapeutic targets and biomarkers in the treatment of COVID-19.


docid: nbzbmrsd

title: A citizen science initiative for open data and visualization of COVID-19 outbreak in Kerala, India

text: India, the second most populated country in the world, reported its first COVID-19 case in the state of Kerala with a travel history from Wuhan. Subsequently, a surge of cases was observed in the state mainly through the individuals who traveled from Europe and the Middle East to Kerala, thus initiating an outbreak. Since public awareness through dissemination of reliable information plays a significant role in controlling the spread of the disease, the Department of Health Services, Government of Kerala initially released daily updates through daily textual bulletins. However, this unstructured data requires refinement and enrichment for upstream applications, such as visualization, and/or analysis. Here we reported a citizen science initiative that leveraged publicly available and crowd-verified data on COVID-19 outbreak in Kerala from the government bulletins, supplemented with the information from media outlets to generate reusable datasets. This data was further used to provide real-time analysis, and daily updates of COVID-19 cases in Kerala, through a user-friendly bilingual dashboard (https://covid19kerala.info/) for non-specialists. We ensured longevity and reusability of the dataset by depositing it in a public repository, aligning with open source principles for future analytical efforts. Finally, to show the scope of the sourced data, we also provided a snapshot of outbreak trends and demographic characteristics of the individuals affected with COVID-19 in Kerala during the first 99 days of the outbreak.


Computed tomography (CT) intestinal alterations of Coronavirus Disease 2019 (COVID-19) from the imaging perspective: A case description


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

text: The novel coronavirus (SARS-CoV-2), identified in China at the end of December 2019 and causing the disease COVID-19, has meanwhile led to outbreaks all over the globe with about 2.2 million confirmed cases and more than 150,000 deaths as of April 17, 2020. In view of most recent information on testing activity, we present here an update of our initial work. In this work, mathematical models have been developed to study the spread of COVID-19 among the population in Germany and to asses the impact of non-pharmaceutical interventions. Systems of differential equations of SEIR type are extended here to account for undetected infections, as well as for stages of infections and age groups. The models are calibrated on data until April 5, data from April 6 to 14 are used for model validation. We simulate different possible strategies for the mitigation of the current outbreak, slowing down the spread of the virus and thus reducing the peak in daily diagnosed cases, the demand for hospitalization or intensive care units admissions, and eventually the number of fatalities. Our results suggest that a partial (and gradual) lifting of introduced control measures could soon be possible if accompanied by further increased testing activity, strict isolation of detected cases and reduced contact to risk groups.


title: My journey in coping research and practice_ The impetus and the relevance

text: My journey in the field of stress and coping began in the mid 1980s when I was researching the rather new field of childhood depression. It was a relatively under-explored field, and as a clinical and educational psychologist it was becoming increasingly apparent that there were concerns of young people, with some of these reflected in their experiences of sadness and despair. However, as I researched and measured the depression construct, I became aware of despair as a growing phenomenon, with an increased focus and emphasis on stress, anxiety and depression. In time, the statistics would bear out the concerns, as one in four young people have identified as being or are likely to be depressed in their lifetime in some Western communities like Australia, the United States and the United Kingdom (WHO, 2018). Given the growing 'ill health' of our Western communities, something had to change. In the 1980s, young people were concerned about their future with the fear of nuclear war. As I was writing this invited retrospective in late 2019, there were widespread concerns about global warming, and in the first half of 2020 concerns arising from the pandemic of COVID-19 are dominating. Coping theory research and practice can make a significant contribution to how we cope with our world in general and the specifics of our lives in particular. This article reports a body of work in the field of coping to illustrate the value of the core constructs and their applications in diverse settings providing opportunities for helpful adaptation and development in the face of whatever circumstances arise.


title: Trauma-spectrum symptoms among the Italian general population in the time of the COVID-19 outbreak.

text: Background: Recent evidence showed substantial negative mental health outcomes associated with the current COVID-19 pandemic, including trauma-related symptoms although the effects on the Italian population who were subjected to unprecedented nationwide lockdown measure remains unknown. The Global Psychotrauma Screen (GPS) is a brief instrument designed to assess a broad range of trauma-related symptoms with no available validation in the Italian population. Aims: This study aimed at examining the factor structure of the Italian version of the GPS in a general population sample exposed to the COVID-19 pandemic and at evaluating trauma-related symptoms in the Italian population in the context of specific COVID-19 related risk factors associated with the implementation of lockdown measures and social distancing. Methods: Cross-sectional web-based observational study, as part of a long-term monitoring programme of mental health outcomes in the general population. 18147 participants completed a self-report online questionnaire to collect key demographic data and to evaluate trauma-related symptoms using the GPS, PHQ-9, GAD-7, ISI and PSS. Validation analyses included both exploratory and confirmatory factor analysis, and correlation analyses. Results: Exploratory factor analyses supported both a two-factor and a three-factor model. Confirmatory factor analysis showed that a one-factor solution that was used as a baseline comparison showed acceptable fit indices, the two-factor solution showed good fit indices, but the best fitting model was a three-factor solution, with Negative Affect (symptoms of depressed mood, anxiety, irritability), core Post-traumatic Stress Symptoms (PTSS) (avoidance, re-experiencing, hyperarousal and insomnia) and Dissociative symptoms. GPS Risk factors as well as specific COVID-19 related stressful events, were associated with GPS total as well as the three factor scores. Conclusions: Our data suggest that a wide range of trauma-spectrum symptoms were reported by a large Italian sample during the COVID-19 pandemic. The GPS symptoms clustered best in three factors: Negative Affect symptoms, Core PTSS, and Dissociative symptoms. In particular high rates of core PTSS and negative affect symptoms were associated with the COVID-19 pandemic in Italy and should be routinely assessed in clinical practice.


title: Epigenetic regulator miRNA pattern differences among SARS-CoV, SARS-CoV-2 and SARS-CoV-2 world-wide isolates delineated the mystery behind the epic pathogenicity and distinct clinical characteristics of pandemic COVID-19

text: Detailed molecular mechanism of SARS-CoV-2 pathogenesis is still elusive to address its deadlier nature and to design effective theraputics. Here, we present our study elucidating the interplay between the SARS-CoV and SARS-CoV-2 viruses’; and host’s miRNAs, an epigenetic regulator, as a mode of pathogenesis, and enlightened how the SARS-CoV and SARS-CoV-2 infections differ in terms of their miRNA mediated interactions with host and its implications in the disease complexity. We have utilized computational approaches to predict potential host and viral miRNAs, and their possible roles in different important functional pathways. We have identified several putative host antiviral miRNAs that can target the SARS viruses, and also SARS viruses’ encoded miRNAs targeting host genes. In silico predicted targets were also integrated with SARS infected human cells microarray and RNA-seq gene expression data. Comparison of the host miRNA binding profiles on 67 different SARS-CoV-2 genomes from 24 different countries with respective country’s normalized death count surprisingly uncovered some miRNA clusters which are associated with increased death rates. We have found that induced cellular miRNAs can be both a boon and a bane to the host immunity, as they have possible roles in neutralizing the viral threat, parallelly, they can also function as proviral factors. On the other hand, from over representation analysis, interestingly our study revealed that although both SARS-CoV and SARS-CoV-2 viral miRNAs could target broad immune signaling pathways; only some of the SARS-CoV-2 miRNAs are found to uniquely target some immune signaling pathways like-autophagy, IFN-I signaling etc, which might suggest their immune-escape mechanisms for prolonged latency inside some hosts without any symptoms of COVID-19. Further, SARS-CoV-2 can modulate several important cellular pathways which might lead to the increased anomalies in patients with comorbidities like-cardiovascular diseases, diabetes, breathing complications, etc. This might suggest that miRNAs can be a key epigenetic modulator behind the overcomplications amongst the COVID-19 patients. Our results support that miRNAs of host and SARS-CoV-2 can indeed play a role in the pathogenesis which can be further concluded with more experiments. These results will also be useful in designing RNA therapeutics to alleviate the complications from COVID-19.


title: Lactate arterial-central venous gradient among COVID-19 patients in ICU: a potential tool in the clinical practice.

text: Objective. In physiological conditions arterial blood lactate concentration is equal or lower than central venous. The aim of this study was to explore if the COVID-19 induced lung cells damage was mirrored by an arterial lactatemia higher than the central venous one; then if the administration of immunosuppressant drugs (i.e. canakinumab) could normalize such abnormal lactate a-cv difference. Methods. Prospective cohort study started on March 25th 2020 for a duration of 10 days, enrolling 21 patients affected by severe COVID-19 pneumonia undergoing mechanical ventilation consecutively admitted to the ICU of the Rimini Hospital, Italy. Arterial and central venous blood samples were contemporary collected to calculate the difference between arterial and central venous lactate (Delta a-cv lactate) concentration within 24 h from tracheal intubation (T0), and 24 hours after canakinumab administration (T1). Results. At the T0 19/21 (90.5%) patients showed a pathologic Delta a-cv lactate (median 0.22 mmol/L; IQR 0.07-0.36), suggesting severe inflammation. In the 13 patients undergoing canakinumab administration, at the T1 Delta a-cv lactate decreased in 92.3% of cases, being the decrease statistically significant (T0: median 0.15, IQR 0.07-0.25 mmol/L; T1: median -0.01, IQR -0.09-0.04 mmol/L; p=0.002). Conclusion. A reversed Delta a-cv lactate is likely to be one of the effects of COVID-19 related cytokine storm, that could reflect a derangement in the lung cells mitochondrial metabolism induced by inflammation or other uncoupling mediators. Delta a-cv lactate decrease may reflect the anti-inflammatory activity of canakinumab. Our preliminary findings need to be confirmed by larger outcome studies.


title: Epidemiological Risk Factors Associated with Death and Severe Disease in Patients Suffering From COVID-19: A Comprehensive Systematic Review and Meta-analysis

text: Introduction: Progression of COVID-19 to severe disease and death is insufficiently understood. Objective: Summarize the prevalence adverse outcomes, risk factors, and association of risk factors with adverse outcomes in COVID-19 patients. Methods: We searched Medline, Embase and Web of Science for case-series and observational studies of hospitalized COVID-19 patients through May 22, 2020. Data were analyzed by fixed-effects meta-analysis, using Shore adjusted confidence intervals to address heterogeneity. Results: Forty-four studies comprising 20594 hospitalized patients met inclusion criteria; 12591 from the US-Europe and 7885 from China. Pooled prevalence of death [%(95% CI)] was 18% (15-22%). Of those that died, 76% were aged>=60 years, 68% were males, and 63%, 38%, and 29% had hypertension, diabetes and heart disease, respectively. The case fatality risk [%(95% CI)] were 62% (48-78) for heart disease, 51% (36-71) for COPD, and 42% (34-50) for age>=60 years and 49% (33-71) for chronic kidney disease (CKD). Summary relative risk (sRR) of death were higher for age>=60 years [sRR=3.8; 95% CI: 2.9-4.8; n=12 studies], males [1.3; 1.2-1.5; 17], smoking history [1.9; 1.1-3.3; n=6], COPD [2.0; 1.6-2.4; n=9], hypertension [1.8; 1.7-2.0; n=14], diabetes [1.5; 1.4-1.7; n=16], heart disease [2.0; 1.7-2.4; 16] and CKD [2.0; 1.3-3.1; 8]. The overall prevalence of hypertension (55%), diabetes (31%) and heart disease (16%) among COVODI-19 patients in the US were substantially higher than the general US population. Conclusions: Public health screening for COVID-19 can be prioritized based on risk-groups. A higher prevalence of cardiovascular risk factors in COVID-19 patients can suggest increased risk of SARS-CoV-2 acquisition in the population.


title: Feeling Like It is Time to Reopen Now? COVID-19 New Normal Scenarios based on Reopening Sentiment Analytics

text: The Coronavirus pandemic has created complex challenges and adverse circumstances. This research discovers public sentiment amidst problematic socioeconomic consequences of the lockdown, and explores ensuing four potential sentiment associated scenarios. The severity and brutality of COVID-19 have led to the development of extreme feelings, and emotional and mental healthcare challenges. This research identifies emotional consequences - the presence of extreme fear, confusion and volatile sentiments, mixed along with trust and anticipation. It is necessary to gauge dominant public sentiment trends for effective decisions and policies. This study analyzes public sentiment using Twitter Data, time-aligned to COVID-19, to identify dominant sentiment trends associated with the push to 'reopen' the economy. Present research uses textual analytics methodologies to analyze public sentiment support for two potential divergent scenarios - an early opening and a delayed opening, and consequences of each. Present research concludes on the basis of exploratory textual analytics and textual data visualization, that Tweets data from American Twitter users shows more trust sentiment support, than fear, for reopening the US economy. With additional validation, this could present a valuable time sensitive opportunity for state governments, the federal government, corporations and societal leaders to guide the nation into a successful new normal future.


Editorial: Studying the effects of the coronavirus pandemic on intercultural relations


title: Studying the effect of lockdown using epidemiological modelling of COVID-19 and a quantum computational approach using the Ising spin interaction

text: COVID-19 is a respiratory tract infection that can range from being mild to fatal. In India, the countrywide lockdown has been imposed since 24th march, 2020, and has got multiple extensions with different guidelines for each phase. Among various models of epidemiology, we use the SIR(D) model to analyze the extent to which this multi-phased lockdown has been active in `flattening the curve' and lower the threat. Analyzing the effect of lockdown on the infection may give us a better insight into the evolution of epidemic while implementing the quarantine procedures as well as improving the healthcare facilities. For accurate modelling, incorporating various parameters along with sophisticated computational facilities, are required. Parallel to SIRD modelling, we tend to compare it with the Ising model and derive a quantum circuit that incorporates the rate of infection and rate of recovery, etc as its parameters. The probabilistic plots obtained from the circuit qualitatively resemble the shape of the curve for the spread of Coronavirus. We also demonstrate how the curve flattens when the lockdown is imposed. This kind of quantum computational approach can be useful in reducing space and time complexities of a huge amount of information related to the epidemic.


Protect our healthcare workers


title: A simple criterion to design optimal nonpharmaceutical interventions for epidemic outbreaks

text: To mitigate the COVID-19 pandemic, much emphasis exists on implementing non-pharmaceutical interventions to keep the reproduction number below one. But using that objective ignores that some of these interventions, like bans of public events or lockdowns, must be transitory and as short as possible because of their significative economic and societal costs. Here we derive a simple and mathematically rigorous criterion for designing optimal transitory non-pharmaceutical interventions. We find that reducing the reproduction number below one is sufficient but not necessary. Instead, our criterion prescribes the required reduction in the reproduction number according to the maximum health services' capacity. To explore the implications of our theoretical results, we study the non-pharmaceutical interventions implemented in 16 cities during the COVID-19 pandemic. In particular, we estimate the minimal reduction of the contact rate in each city that is necessary to control the epidemic optimally. We also compare the optimal start of the intervention with the start of the actual interventions applied in each city. Our results contribute to establishing a rigorous methodology to guide the design of non- pharmaceutical intervention policies.


title: Modelling of Systemic versus Pulmonary Chloroquine Exposure in Man for COVID-19 Dose Selection

text: Chloroquine has attracted intense attention as a potential clinical candidate for prevention and treatment of COVID-19 based on reports of in-vitro efficacy against SARS-CoV-2. While the pharmacokinetic-pharmacodynamic (PK-PD) relationship of chloroquine is well established for malaria, there is sparse information regarding its dose-effect relationship in the context of COVID-19. Here, we explore the PK-PD relationship of chloroquine for COVID-19 by modelling both achievable systemic and pulmonary drug concentrations. Our data indicate that the standard anti-malarial treatment dose of 25mg/kg over three days does not deliver sufficient systemic drug exposures for the inhibition of viral replication. In contrast, PK predictions of chloroquine in the lungs using in-vivo data or human physiologically-based PK models, suggest that doses as low as 3mg/kg/day for 3 days could deliver exposures that are significantly higher than reported antiviral-EC90s for up to a week. Moreover, if pulmonary exposure is a driver for prevention, simulations show that chronic daily dosing of chloroquine may be unnecessary for prophylaxis purposes. Instead, once weekly doses of 5mg/kg would be sufficient to achieve a continuous cover of therapeutically active pulmonary exposures. These findings reveal a highly compartmentalised distribution of chloroquine in man that may significantly affect its therapeutic potential against COVID-19. The systemic circulation is shown as one site where chloroquine exposure is insufficient to inhibit SARS-CoV-2 replication. However, if therapeutic activity is driven by pulmonary exposure, it should be possible to reduce the chloroquine dose to safe levels. Carefully designed randomized controlled trials are urgently required to address these outstanding issues.


title: In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and Other Nidovirales Suggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

text: Noncanonical nucleic acid structures play important roles in the regulation of molecular processes. Considering the importance of the ongoing coronavirus crisis, we decided to evaluate genomes of all coronaviruses sequenced to date (stated more broadly, the order Nidovirales) to determine if they contain noncanonical nucleic acid structures. We discovered much evidence of putative G-quadruplex sites and even much more of inverted repeats (IRs) loci, which in fact are ubiquitous along the whole genomic sequence and indicate a possible mechanism for genomic RNA packaging. The most notable enrichment of IRs was found inside 5′UTR for IRs of size 12+ nucleotides, and the most notable enrichment of putative quadruplex sites (PQSs) was located before 3′UTR, inside 5′UTR, and before mRNA. This indicates crucial regulatory roles for both IRs and PQSs. Moreover, we found multiple G-quadruplex binding motifs in human proteins having potential for binding of SARS-CoV-2 RNA. Noncanonical nucleic acids structures in Nidovirales and in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.


docid: kwddyctk

title: An investigation into respiratory tract viruses in children with acute lower respiratory tract infection or wheezing

text: BACKGROUND: This study aimed to determine the frequencies of respiratory tract viruses in patient (acute lower respiratory tract infection [LRTI] or wheezing) and control (history of asthma without symptoms) groups. METHODS: Using multiplex-polymerase chain reaction (PCR), respiratory tract viruses were investigated in the respiratory tract specimens from patient and control groups followed in the Pediatric Clinic. RESULTS: The viruses detected in the patient and control groups (P=0.013) were as follows, respectively: Rhinoviruses A, B, C (25.6% and 36.7%), influenza virus A (21.1% and 0.0%), parainfluenza virus type 1 (7.8% and 1.7%), parainfluenza virus type 4 (5.6% and 0.0%), adenoviruses A, B, C, D, E (4.4% and 1.7%), parainfluenza virus type 3 (4.4% and 1.7%), coronaviruses 229E and NL63 (4.4% and 1.7%), coronavirus OC43 (3.3% and 0.0%), respiratory syncytial virus A (3.3% and 0.0%), parainfluenza virus type 2 (2.2% and 0.0%), influenza virus B (2.2% and 0.0%), and respiratory syncytial virus B (1.1% and 1.7%). No bocavirus, metapneumovirus or enterovirus was found in any specimen. Statistically significant differences in the detection of influenza virus A (P=0.000), the total detection of parainfluenza viruses (P=0.008) and coinfection (P=0.004) were observed between the patient and control groups. CONCLUSIONS: The advantage of our study compared with other studies is the inclusion of not only wheezing patients but also children with asthma without symptom. The higher detection of rhinoviruses both in patient and control groups give rise to thought that these viruses may be responsible for asthma exacerbations and may be related with long duration of virus shedding.


title: A Novel Approach to Monitoring the COVID-19 Pandemic using Emergency Department Discharge Diagnoses

text: Introduction Tracking the COVID-19 pandemic using existing metrics such as confirmed cases and deaths are insufficient for understanding the trajectory of the pandemic and identifying the next wave of cases. In this study, we demonstrate the utility of monitoring the daily number of patients with COVID-like illness (CLI) who present to the Emergency Department (ED) as a tool that can guide local response efforts. Methods Using data from two hospitals in King County, WA, we examined the daily volume of CLI visits, and compare them to confirmed COVID cases and COVID deaths in the County. A linear regression model with varying lags is used to predict the number of daily COVID deaths from the number of CLI visits. Results CLI visits appear to rise and peak well in advance of both confirmed COVID cases and deaths in King County. Our regression analysis to predict daily deaths with a lagged count of CLI visits in the ED showed that the R2 value was maximized at 14 days. Conclusions ED CLI visits are a leading indicator of the pandemic. Adopting and scaling up a CLI monitoring approach at the local level will provide needed actionable evidence to policy makers and health officials struggling to confront this health challenge.


title: COVID-19 pandemic scenario in India compared to China and rest of the world: a data driven and model analysis

text: The COVID-19 is a rapidly spreading respiratory illness caused with the infection of SARS-CoV-2. The COVID-19 data from India was compared with China and rest of the world. The average values of daily growth rate (DGR), case recovery rate (CRR), case fatality rate (CFR), serial interval (SI) of COVID-19 in India was 17%, 8.25%, and 1.87%, and 5.76 days respectively, as of April 9, 2020. The data driven estimates of basic reproduction number (R0), average reproduction number (R) and effective reproduction number (Re) were 1.03, 1.73, and 1.35, respectively. The results of exponential and SIR model showed higher estimates of R0, R and Re. The data driven as well as estimated COVID-19 cases reflect the growing nature of the epidemic in India and world excluding China, whereas the same in China reveal the involved population became infected with the disease and moved into the recovered stage. The epidemic size of India was estimated to be ~30,284 (as of April 15, 2020 with 12,370 infectious cases) with an estimated end of the epidemic on June 9, 2020. The Re values in India before and after lockdown were 1.62 and 1.37 respectively, with SI 5.52 days and 5.98 days, respectively, as of April 17, 2020, reflecting the effectiveness of lockdown strategies. Beyond April 17, 2020, our estimate of 24,431 COVID-19 infected cases with lockdown is 78% lower compared to the 112,042 case estimates in absence of lockdown, on April 27, 2020. To early end of the COVID-19 epidemic, strong social distancing is important.


docid: cdmoazrl

title: A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-Pertussis toxoid antibodies

text: Due to their shared genetic history, antibodies from the same clonotype often bind to the same epitope. This knowledge is used in immune repertoire mining, where known binders are used to search bulk sequencing repertoires to identify new binders. However current computational methods cannot identify epitope convergence between antibodies from different clonotypes, limiting the sequence diversity of antigen-specific antibodies which can be identified. We describe how the antibody binding site, the paratope, can be used to cluster antibodies with common antigen reactivity from different clonotypes. Our method, paratyping, uses the predicted paratope to identify these novel cross clonotype matches. We experimentally validated our predictions on a Pertussis toxoid dataset. Our results show that even the simplest abstraction of the antibody binding site, using only the length of the loops involved and predicted binding residues, is sufficient to group antigen-specific antibodies and provide additional information to conventional clonotype analysis.


title: RSI model: COVID-19 in Germany Alternating quarantine episodes and normal episodes

text: Pandemic containment is essential to prevent overloading of the medical care system. Limitation of the pandemic is mainly facilitated by reducing infections. An effective strategy is social distancing. However, this strategy draws more and more criticism, in Germany as elsewhere, because of its economic and psychological consequences for society. How can the number of infected person be held below the medical care capacity while restrictions affecting the general public are minimized? Various approaches exist to retarding the infection rate during the current coronavirus (COVID-19) outbreak until vaccine has been developed, without overloading medical capacity. Options being discussed include large-scale testing, contact tracing and social distancing. A study published by the Imperial College contains a model calculation of the effects of alternating school closings and openings in the United States and the United Kingdom. However, no satisfactory solution was developed. Variables which describe the medical care resources in Germany and the age and occupational structure of its population contrast sharply with American and British conditions. This study attempts to apply the Imperial College approach of alternating quarantine and normal episodes for the entire population. Mathematically, an oscillation in hospitalization can be imposed. The difficulty lies in determining the non-controllable parameters related to the virus. Varying the ambiguously quantified input variables is investigated in an attempt to devise a strategy for all combinations that does not overload the clinical system.


EXPRESS: The course of COVID-19 in a 55-year-old patient diagnosed with severe idiopathic pulmonary arterial hypertension


title: Health care workers seek to flatten COVID-19’s ‘second curve’—their rising mental anguish

text: Health care workers are experiencing a crushing psychological burden in the COVID-19 pandemic When intensive care unit (ICU) nurse Núria Burló Arévalo first heard about the coronavirus outbreak in Wuhan, China, she never thought it would reach her small city of Tarragona, Spain, some 100 kilometers west of Barcelona But 1 month ago, the virus hit her city hard Within 1 week, her hospital went from having one case of COVID-19 to 14 seriously ill patients, including young people without any underlying conditions Since March, 63 members of the hospital staff have been infected with coronavirus Long hours, high risk of infection, and crushing uncertainty about how the pandemic will progress—and who will get the disease next—have led to high anxiety among health care workers at John XXIII University Hospital “We’re in a warlike situation,” Burló Arévalo says “You feel like you’re in a trench ”


title: Clinical Characteristics and Short-Term Outcomes of Severe Patients with COVID-19 in Wuhan, China

text: Objective. A novel pneumonia (COVID-19) which is sweeping the globe was started in December, 2019, in Wuhan, China. Most deaths occurred in severe and critically cases, but information on prognostic risk factors for severe ill patients is incomplete. Further research is urgently needed to guide clinicians, so we prospectively evaluate the clinical outcomes of 114 severe ill patients with COVID-19 for short-term in the Union Hospital in Wuhan, China. Methods. In this single-centered, prospective and observational study, we enrolled 114 severe ill patients with confirmed COVID-19 from Jan 23, 2020 to February 22, 2020. Epidemiological, demographic and laboratory information were collected at baseline, data on treatment and outcome were collected until the day of death or discharge or for the first 28 days after severe ill diagnosis, whichever was shorter. Univariate and multivariate Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of poor outcome. Results. Among enrolled 114 patients, 94 (82.5%) had good outcome while 20 (17.5%) had poor outcome. No significant differences were showed in age, gender and the prevalence of coexisting disorders between outcome groups. Results of multivariate Cox analyses indicated that higher levels of oxygen saturation (HR, 0.123; 95% CI, 0.041-0.369), albumin (HR, 0.060; 95% CI, 0.008-0.460) and arterial partial pressure of oxygen (HR, 0.321; 95% CI, 0.106-0.973) were associated with decreased risk of developing poor outcome within 28 days. In the other hand, higher levels of leucocytes (HR, 5.575; 95% CI, 2.080-14.943), neutrophils (HR, 2.566; 95% CI, 1.022-6.443), total bilirubin (HR, 6.171; 95% CI, 2.458-15.496), globulin (HR, 2.526; 95% CI, 1.027-6.211), blood urea nitrogen (HR, 5.640; 95% CI, 2.193-14.509), creatine kinase-MB (HR, 3.032; 95% CI, 1.203-7.644), lactate dehydrogenase (HR, 4.607; 95% CI, 1.057-20.090), hypersensitive cardiac troponin I (HR, 5.023; 95% CI, 1.921-13.136), lactate concentration (HR,15.721; 95% CI, 2.099-117.777), Interleukin-10 (HR, 3.551; 95% CI, 1.280-9.857) and C-reactive protein (HR, 5.275; 95% CI, 1.517-18.344) were associated with increased risk of poor outcome development. We also found that traditional Chinese medicine can significantly improve the patient's condition, which is conducive to the transformation from severe to mild. Conclusion. In summary, we firstly reported this single-centered, prospective and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storm and uncontrolled inflammation responses, liver, kidney, cardiac dysfunction may play important roles in final outcome of severe ill patients with COVID-19. Our study will provide clinicians to be benefit to rapidly estimate the likelihood risk of short-term poor outcome for severe patients.


title: Social, Psychological, and Philosophical Reflections on Pandemics and Beyond

text: This conceptual paper presents social, psychological and philosophical (ethical and epistemological) reflections regarding the current (COVID-19) pandemic and beyond, using an analytic and comparative approach For example, Taiwan and Canada are compared, addressing Taiwan’s learning from SARS Suggestions are made in relation to current and future relevant practice, policy, research and education For example, highly exposed individuals and particularly vulnerable populations, such as health care providers and socially disadvantaged (homeless and other) people, respectively, are addressed as requiring special attention In conclusion, more reflection on and study of social and psychological challenges as well as underlying philosophical issues related to the current pandemic and more generally to global crises is needed


title: Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19

text: Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 90 individuals were enrolled in this study, 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC). Using two comprehensive 11-color flow cytometric panels conforming to Good Laboratory Practice (GLP) and approved for clinical diagnostics, we longitudinally examined cell count differences in lymphocyte populations and T cell activation in COVID-19 patients. Findings: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and {gamma}{delta} T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Interestingly, follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. Interpretation: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Our data imply that the presence of SARS-CoV-2 responsive T cells contributes to convalescence in MD. Thus, understanding the T cell-response in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control.


title: Viral load dynamics in transmissible symptomatic patients with COVID-19

text: To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19), we reviewed epidemiological and clinical data obtained from immunocompetent laboratory-confirmed patients with COVID-19 at Toyama University Hospital. In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in adults than in children and in symptomatic than in asymptomatic patients. Among symptomatic patients, non-linear regression models showed that the estimated viral load at onset was higher in the index (patients who transmitted the disease to at least one other patient) than in the non-index patients (patients who were not the cause of secondary transmission; median [95% confidence interval]: 6.6 [5.2-8.2] vs. 3.1 [1.5-4.8] log copies/{micro}L, respectively). High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19.


title: Fauci mania! His voice for science during pandemic inspires bobblehead, other kitsch … and SNL

text: Anthony Fauci’s burgeoning fame as a steady voice for science within White House corridors and beyond reached new heights in April, with the release of a raft of merchandise in his honor, including a bobblehead The National Bobblehead Hall of Fame and Museum has been taking orders for the plastic figurine of Fauci, longtime director of the U S National Institute of Allergy and Infectious Diseases, as a fundraiser for COVID-19 masks and recently posted images of the finished product Although President Donald Trump this week scaled back the daily White House briefings about the pandemic that often featured Fauci, the Hall of Fame says the bobblehead remains its best-selling ever


title: Specific mutations in SARS-CoV2 RNA dependent RNA polymerase and helicase alter protein structure, dynamics and thus function: Effect on viral RNA replication

text: The open reading frame (ORF) 1ab of SARS-CoV2 encodes non-structural proteins involved in viral RNA functions like translation and replication including nsp1-4; 3C like proteinase; nsp6-10; RNA dependent RNA polymerase (RdRp); helicase and 3’-5’ exonuclease. Sequence analyses of ORF1ab unravelled emergence of mutations especially in the viral RdRp and helicase at specific positions, both of which are important in mediating viral RNA replication. Since proteins are dynamic in nature and their functions are governed by the molecular motions, we performed normal mode analyses of the SARS-CoV2 wild type and mutant RdRp and helicases to understand the effect of mutations on their structure, conformation, dynamics and thus function. Structural analyses revealed that mutation of RdRp (at position 4715 in the context of the polyprotein/ at position 323 of RdRp) leads to rigidification of structure and that mutation in the helicase (at position 5828 of polyprotein/ position 504) leads to destabilization increasing the flexibility of the protein structure. Such structural modifications and protein dynamics alterations might alter unwinding of complex RNA stem loop structures, the affinity/ avidity of polymerase RNA interactions and in turn the viral RNA replication. The mutation analyses of proteins of the SARS-CoV2 RNA replication complex would help targeting RdRp better for therapeutic intervention.


title: Lessons learnt from 288 COVID-19 international cases: importations over time, effect of interventions, underdetection of imported cases

text: 288 cases have been confirmed out of China from January 3 to February 13, 2020. We collected and synthesized all available information on these cases from official sources and media. We analyzed importations that were successfully isolated and those leading to onward transmission. We modeled their number over time, in relation to the origin of travel (Hubei province, other Chinese provinces, other countries) and interventions. We characterized importations timeline to assess the rapidity of isolation, and epidemiologically linked clusters to estimate the rate of detection. We found a rapid exponential growth of importations from Hubei, combined with a slower growth from the other areas. We predicted a rebound of importations from South East Asia in the upcoming weeks. Time from travel to detection has considerably decreased since the first importation, however 6 cases out of 10 were estimated to go undetected. Countries outside China should be prepared for the possible emergence of several undetected clusters of chains of local transmissions.


title: Validation of an extraction-free RT-PCR protocol for detection of SARS-CoV2 RNA

text: In light of supply chain failures for reagents and consumables needed for purification of nucleic acid for detection of SARS-CoV-2 RNA by RT-PCR, we aim to verify the performance and utility of a non-extraction protocol for RT-PCR ("direct RT-PCR"). We report improved sensitivity compared to earlier reports of direct RT-PCR testing of swab samples, in particular at the lower limit of detection (sensitivity 93% overall; 100% for specimens with high to moderate viral titre, Ct <34; 81% for specimens with a low viral titre, Ct [≥]34). Sensitivity is improved (from 90 to 93%) by testing in duplicate. We recommend swabs are re-suspended in water to minimise PCR inhibition. A cellular target is necessary to control for PCR inhibition and specimen quality. Direct RT-PCR is best suited to population level screening where results are not clinically actionable, however in the event of a critical supply chain failure direct RT-PCR is fit for purpose for the detection of SARS-CoV-2 infection. The results from our study offer front-line laboratories additional reagent options for performing extraction-free RT-PCR protocols.


title: Window of Opportunity for Mitigation to Prevent Overflow of ICU capacity in Chicago by COVID-19

text: We estimate the growth in demand for ICU beds in Chicago during the emerging COVID-19 epidemic, using state-of-the-art computer simulations calibrated for the SARS-CoV-2 virus. The questions we address are these: (1) Will the ICU capacity in Chicago be exceeded, and if so by how much? (2) Can strong mitigation strategies, such as lockdown or shelter in place order, prevent the overflow of capacity? (3) When should such strategies be implemented? Our answers are as follows: (1) The ICU capacity may be exceeded by a large amount, probably by a factor of ten. (2) Strong mitigation can avert this emergency situation potentially, but even that will not work if implemented too late. (3) If the strong mitigation precedes April 1st, then the growth of COVID-19 can be controlled and the ICU capacity could be adequate. The earlier the strong mitigation is implemented, the greater the probability that it will be successful. After around April 1 2020, any strong mitigation will not avert the emergency situation. In Italy, the lockdown occurred too late and the number of deaths is still doubling every 2.3 days. It is difficult to be sure about the precise dates for this window of opportunity, due to the inherent uncertainties in computer simulation. But there is high confidence in the main conclusion that it exists and will soon be closed. Our conclusion is that, being fully cognizant of the societal trade-offs, there is a rapidly closing window of opportunity to avert a worst-case scenario in Chicago, but only with strong mitigation/lockdown implemented in the next week at the latest. If this window is missed, the epidemic will get worse and then strong mitigation/lockdown will be required after all, but it will be too late.


title: Quantification of the South African Lockdown Regimes, for the SARS-CoV-2 Pandemic, and the Levels of Immunity They Require to Work

text: This research quantifies the various South African lockdown regimes, for the SARS-CoV-2 pandemic, in terms of the basic reproduction number, r0. It further calculates the levels of immunity required for these selfsame lockdown regimes to begin to work, then predicts their perceived values, should infections have been underestimated by a factor of 10. The first, level-5 lockdown was a valiant attempt to contain the highly infectious, SARS-CoV-2 virus, based on a limited knowledge. Its basic reproduction number (r0 = 1.93) never came anywhere close to the requirement of being less than unity. Obviously, it could be anticipated that the same would apply for subsequent, lower levels of lockdown. The basic reproduction number for the level-3 lockdown was found to be 2.34 and that of the level-4 lockdown, 1.69. The suggestion is therefore that the level-4 lockdown might have been marginally 'smarter' than the 'harder', level-5 lockdown, although its basic reproduction number may merely reflect an adjustment by the public to the new normal, or the ever-present error associated with data sets, in general. The pandemic's basic reproduction number was calculated to be 3.16, in the Swedish context. The lockdowns therefore served to ensure that the medical system was not overwhelmed, bought it valuable time to prepare and provided useful data. The lockdowns nonetheless failed significantly in meeting any objective to curtail the pandemic.


title: Arterial Mesenteric Thrombosis as a Complication of SARS-CoV-2 Infection

text: A 52-year-old patient with SARS-CoV-2 was diagnosed with interstitial pneumonia and treated with darunavir/ritonavir, hydroxychloroquine, azithromycin and low molecular weight heparin (LMWH). After LMWH cessation, he developed superior mesenteric arterial thrombosis. An abdominal CT scan showed arterial thrombosis of vessels efferent of the superior mesenteric artery with bowel distension. COVID-19 may predispose to venous and arterial thromboembolism. Anticoagulation prophylaxis should be considered in hospitalized patients with COVID-19, and potential thromboembolism investigated in each symptomatic patient affected by SARS-CoV-2. LEARNING POINTS: Potential thromboembolism must be investigated in each symptomatic patient with SARS-CoV-2 infection. The preventive and therapeutic use of antithrombotic agents should be strongly considered in order to mitigate thrombotic and haemorrhagic events in patients with SARS-CoV-2 infection.


title: Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity

text: To dissect the mechanisms underlying the observed inflation of variants in SARS-CoV-2 genome, we present the largest up-to-date analysis of intra-host genomic diversity, which reveals that the majority of samples present a complex sublineage architecture, due to the interplay between host-related mutational processes and transmission dynamics. Strikingly, the deconvolution of the entire set of intra-host variants reveals the existence of mutually exclusive viral mutational signatures, which prove that distinct hosts differently respond to SARS-CoV-2 infections. In particular, two signatures are likely ruled by APOBEC and Reactive Oxygen Species (ROS), which induce hypermutation in a significant number of samples, and appear to be affected by severe purifying selection. Conversely, several mutations linked to low-rate mutational processes appear to transit to clonality in the population, eventually leading to the definition of new viral genotypes and to an increase of overall genomic diversity. Finally, we demonstrate that a high number of variants are observed in samples associated to independent lineages, likely due to signature-related mutational hotspots or to positive selection.


title: Harmonizing heterogeneous endpoints in COVID-19 trials without loss of information - an essential step to facilitate decision making

text: Background: Many trials are now underway to inform decision-makers on potential effects of treatments for COVID-19. To provide sufficient information for all involved decision-makers (clinicians, public health authorities, drug regulatory agencies) a multiplicity of endpoints must be considered. It is a challenge to generate detailed high quality evidence from data while ensuring fast availability and evaluation of the results. Methods: We reviewed all interventional COVID-19 trials on Remdesivir, Lopinavir/ritonavir and Hydroxychloroquine registered in the National Library of Medicine (NLM) at the National Institutes of Health (NIH) and summarized the endpoints used to assess treatment effects. We propose a multistate model that harmonizes heterogeneous endpoints and differing lengths of follow-up within and between trials. Results: There are currently, March 27, 2020, 23 registered interventional trials investigating the potential benefits of Remdesivir, Lopinavir/ritonavir and Hydroxychloroquine. The endpoints are highly heterogeneous. Follow-up for the primary endpoints ranges from four to 168 days. A detailed precisely defined endpoint has been proposed by the global network REMAP-CAP, which is specialized on community-acquired pneumonia. Their seven-category endpoint accounts for major clinical events informative for all decision-makers. Moreover, the Core Outcome Measures in Effectiveness Trials (COMET) Initiative is currently working on a core outcome set. We propose a multistate model that accommodates analysis of these recommended endpoints. The model allows for a detailed investigation of treatment effects for various endpoints over the course of time thereby harmonizing differing endpoints and lengths of follow-up. Conclusion: Multistate model analysis is a powerful tool to study clinically heterogeneous endpoints (mortality, discharge) as well as endpoints influencing hospital capacities (duration of hospitalization and ventilation) simultaneously over time. Our proposed model extracts all information available in the data and is - by harmonizing endpoints within and between trials - a step towards faster decision making. All ongoing clinical trials, especially those with severe cases, should accommodate primary analysis with a stacked probability plot of the major events mechanical ventilation, discharge alive and death.


title: Scrutinising the COVID-19 data on 590.000 cases. A retrospective, population-based descriptive study for data quality surveillance and a review at 4.540.000 cases.

text: Reports on the detected positive patients with COVID-19 are as per today the best estimation of a country spread of the pandemic. In order to evaluate the early indicators for true lethality and recovery time, the data where the model is built must be quality checked. Each country sets different procedures and criteria for fatality count due to COVID-19 and the health system is stressed by having insufficient testing, untracked patients and premature discharge. In this paper the dynamics behind such data quality issues are discussed throughout the disease course to support better modeling and decision-making processes in a stressed healthcare system. From 593.291 cases in the sample, and its 7 representative groups, the recovery time and the local CFR are negatively correlated, having the highest fatality rates (21%, Spain) the countries with shorter recovery time (11 days, Spain). Also, CFR can be an indicator of Infection inconsistencies (i.e. South Korea, CFR 1%, Time to recovery 25 days). At the review part, focus is made on the inconsistencies detected in Germany and South Korea datasets as well as the potential misfits on China and Spain. Overall, the Time to Fatality ranges between 4 and 8 days, and the mean is of 6 days (South Korea, 7 days; Japan, 6days). Only Germany and France are detecting earlier than other countries and admit 10 days before fatality occurs. One simple explanation for the local CFR and Recovery time correlation is to define such rate as a measure of the healthcare system overload. Anomalous CFR indexes point to a stressed healthcare system. The higher the overload, the more focus on critical cases and hence the higher local CFR. The COVID-19 intrinsic CFR is unlikely to change by a factor of 10x from countries with similar lifestyle, GDP per capita and health services (i.e. the Mediterranean Basin, Northern Europe, etc.). Because of this fact, early CFR measured before Healthcare system overwhelming (COVID-19 free flow) are considered to be more accurate than the measured CFR while the outbreak is still ongoing, Finally, the synthetic Infection indexes may be a helpful indirect measure of the real population infection rate and also used for data quality audit. Any model built upon inconsistent data will be complex to explain and justify.


title: The impact of Covid-19 pandemic on corporate social responsibility and marketing philosophy

text: In this article, we offer some initial examination on how Covid-19 pandemic can influence the developments of CSR and marketing. We argue that Covid-19 pandemic offers a great opportunity for businesses to shift towards more genuine and authentic CSR and contribute to address urgent global social and environmental challenges. We also discuss some potential directions of how consumer ethical decision making will be shifted to due to the pandemic. In our discussion of marketing, we outline how we believe marketing is being affected by this pandemic and how we think this will change, not only the context of marketing, but how organizations approach their strategic marketing efforts. We end the paper with a identifying a number of potentially fruitful research themes and directions.


title: Multinational modeling of SARS-CoV-2 spreading dynamics: Insights on the heterogeneity of COVID-19 transmission and its potential healthcare burden

text: Background: Modelling and projections of COVID-19 using a single set of transmission parameters can be an elaborated because the application of different levels of containment measures at different stages of the worldwide COVID-19 outbreak. Methods: We developed a piecewise fitting SEIR methodology to fit the progress of the COVID-19 that can be applied on any of the 185 countries listed in John Hopkins Coronavirus Resource Center. The contagious contact rate, the rate of removal and the initially exposed population were obtained at three different stages of the pandemic for a set of 18 countries, and globally for the total number of cases worldwide. The active number of infections and the removed populations were fitted simultaneously to validate the SEIR model against the available time series reports on the number of confirmed infections, recoveries and deaths. We evaluate the effect of a reduction of contagious contact rate on the level of burden put on local healthcare infrastructure considering different levels of intervention. As a guideline for future public health interventions, we also estimated the maximum number of future cases and its potential peak date. Findings: We project that the peak in the number of infections worldwide will take place after the third quarter of 2020 with a decline rate that might extend beyond 2020. For 12 out of the 18 countries analyzed, we observe that, following the trend at the date of this study, the number of severe infections will surpass their healthcare capacity. For a 90% reduction scenario of the contagious contact rate, four out of the 18 countries analyzed will undergo a significant delay in the peak of infection, extending the course of the epidemic further than our simulation window (365 days). Interpretation: We identify three stages for the COVID-19 transmission dynamics, which suggest that it is highly heterogeneous between countries and its contagious contact rate, is currently affected by both local responses of the public health interventions and to the population's adherence to the measures. Funding: No funding received.


title: Perioperative care of pediatric anesthesia for children with suspected or confirmed COVID-19

text: COVID-19 is a pandemic disease that recently been spreading all over the globe. Health-care bodies recognize that organized and written protocols are essential tools to help in fighting this highly contagious virus. In this review, we published our protocol and recommendations in the pediatric anesthesia department in our hospital in preparation for the management of children who are confirmed or suspected in perioperative periods.


Characteristic feature in COVID-19 statistics in China


title: COVID-19 Pandemic & Skin Care Guidelines for Health Care Professionals

text: The Novel corona virus is bringing multiple challenges for health care professionals. Skin is the biggest organ and the first line of defense against different infections and external factors. Being the front line warriors, health care professionals are susceptible to various skin conditions due to prolonged use of personal protective equipment. These adverse skin conditions are redness, irritation, itching, contact dermatitis, and aggravation of underlying skin conditions like seborrheic dermatitis and acne vulgaris. In the current global situation, the potential incidence of such adverse dermatological effects does not in any manner cause the HCPs to deviate from the strict specific precautionary hygiene rules. These skin problems are manageable with the few precautionary measures. This article explores the different skin conditions that result from personal hygiene measures and usage of protective gear and will suggest some practical advice about how to manage and protect from these different adverse skin conditions.


title: Value of chest CT screening in the early COVID-19 outbreak/ 胸部CT筛查在新型冠状病毒肺炎暴发早期的价值

text: Objective: In view of the shortage of new coronavirus nucleal acid test in the early COVID-19 outbreak, the application value of chest CT in screening COVID-19 patients was explored. Methods: Retrospective analysis was performed on the data of patients with fever who received chest CT and new coronavirus nucleal acid test during January 25, 2020 to February 2, 2020 in Zhongnan Hospital of Wuhan University. A total of 587 patients were enrolled, including 290 males and 297 females, aged from 11.0 to 96.0 (51.3±17.1) years old. Taking the nucleic acid test results as the gold standard, the sensitivity, specificity and rate of misdiagnosis of CT screening were calculated. Results: Among the 587 patients, there were 433 positive cases (73.8%, 433/587) and 154 negative cases (26.2%, 154/587) of novel coronavirus nucleic acid test. Using CT screening, 494 cases (84.2%, 494/587) were positive and 93 cases (15.8%, 93/587) were negative. The sensitivity of CT screening was 97.7% (423/433), specificity was 53.9% (83/154) and rate of misdiagnosis was 2.3% (10/433). Conclusions: In the early COVID-19 outbreak, CT screening has the advantages of high sensitivity and low rate of misdiagnosis, which can compensate for the shortage of new coronavirus nucleal acid test and can be used as a rapid screening for early prevention and control.


title: Predicted COVID-19 fatality rates based on age, sex, comorbidities, and health system capacity

text: Early reports suggest the fatality rate from COVID-19 varies greatly across countries, but non-random testing and incomplete vital registration systems render it impossible to directly estimate the infection fatality rate (IFR) in many low- and middle-income countries. To fill this gap, we estimate the adjustments required to extrapolate estimates of the IFR from high- to lower-income regions. Accounting for differences in the distribution of age, sex, and relevant comorbidities yields substantial differences in the predicted IFR across 21 world regions, ranging from 0.11% in Western Sub-Saharan Africa to 0.95% for High Income Asia Pacific. However, these predictions must be treated as lower bounds, as they are grounded in fatality rates from countries with advanced health systems. In order to adjust for health system capacity, we incorporate regional differences in the relative odds of infection fatality from childhood influenza. This adjustment greatly diminishes, but does not entirely erase, the demography-based advantage predicted in the lowest income settings, with regional estimates of the predicted COVID-19 IFR ranging from 0.43% in Western Sub-Saharan Africa to 1.74% for Eastern Europe.


title: Estimation of the number of general anesthesia cases based on a series of nationwide surveys on Twitter during COVID-19 in Japan: A statistical analysis

text: Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has since spread to more than 200 other countries at the time of writing. In light of this situation, the Japanese Government declared a state of emergency in seven regions of Japan on the April 7, 2020 under the provisions of the law. The medical care delivery system has been under pressure. Although various surgical societies have published guidelines on which to base their surgical decisions, it is not clear how general anesthesia has been performed and will be performed in Japan. Social networks such as Twitter are becoming a part of society, as various information is accumulated on the web. One of the services provided by Twitter is a voting function-Twitter Polls-through which anonymous surveys can be conducted. We analyzed the results of a series of surveys on Twitter on the status of operating restrictions using a mathematical model, and public data provided by the Japanese Government were used to estimate the current and future changes in the number of general anesthesia performed in Japan. The number of general anesthesia was estimated as 2.77*104 cases per week on 2nd May 2020 and 0.68*104 cases in 24 weeks.


title: Evaluation of heating and chemical protocols for inactivating SARS-CoV-2

text: Clinical samples collected in COVID-19 patients are commonly manipulated in BSL-2 laboratories for diagnostic purpose. We used the French norm NF-EN-14476+A2 derived from the European standard EN-14885. To avoid the risk of exposure of laboratory workers, we showed that Triton-X100 must be added to guanidinium thiocyanate-lysis buffers to obtain a 6-log reduction of infectious virus. Although heating protocol consisting of 92°C-15min was more effective rather than 56°C-30min and 60°C-60min to achieve 6-log reduction, it is not amenable for molecular detection on respiratory specimens because of important decrease of detectable RNA copies in the treated sample vs untreated sample. The 56°C-30min and 60°C-60min should be used for inactivation of serum / plasma samples for serology because of the 5log10 reduction of infectivity and low viral loads in blood specimens.


title: ARIMA modelling of predicting COVID-19 infections

text: The World Health Organization (WHO) Director-General, Dr. Tedros Adhanom Ghebreyesus on March 11, 2020 declared the novel coronavirus (COVID-19) outbreak a global pandemic [4] the reason being the number of cases outside China increased 13-fold and the number of countries with cases increased threefold. In this paper a time series model to predict short-term prediction of the transmission of the exponentially growing COVID-19 time series is modelled and studied. Auto Regressive Integrated Moving Average (ARIMA) model prediction is performed on the number of cumulative cases over a time period and is validated over Akaike information criterion (AIC) statistics.


title: Improving pandemic mitigation policies across communities through coupled dynamics of risk perception and infection

text: Decisions to adhere to health-protective behaviors (e.g. mask-wearing, social distancing, etc.) that impact the spread of COVID-19 are not made in isolation by each individual. They are instead the result of the social construction of perceived risks and resulting community norms. In populations in which disease is unlikely to spread throughout all communities simultaneously, community-driven perception of risk can drastically alter collective outcomes. A community could respond to a few infections by becoming fearful and adopting anticipatory behaviors that protect them from disease spread. Similarly, there could be false reassurance, in which low disease incidence over time leads to community consensus that protective actions are unnecessary (even if they are the reason cases remains rare). We therefore model COVID-19 spread with three synergistic dynamics governing individual behavioral choices: (1) Social construction of concern, (2) Awareness of disease incidence, and (3) Reassurance by lack of disease. We use a multiplex network approach that captures social communication and epidemiological spread. We find that effective protective policies enacted too early may backfire by allowing a community to become reassured and therefore unwilling to adopt or maintain further protective behaviors. Based on these insights, we propose that public health policies for which success relies on collective action should be designed to exploit the behaviourally receptive phase; the period between the generation of sufficient concern as to foster adoption of novel protective behaviors and the relaxation of adherence driven by reassurance fostered by avoidance of negative outcomes over time.


Wider collateral damage to children in the UK because of the social distancing measures designed to reduce the impact of COVID-19 in adults


title: Modeling the Covid-19 Epidemic using Time Series Econometrics

text: The classic logistic model has provided a realistic model of the behavior of Covid-19 in China and many East Asian countries. Once these countries passed the peak, the daily case count fell back, mirroring its initial climb in a symmetric way, just as the classic model predicts. However, in Italy and Spain, and now the UK and many other Western countries, the experience has been very different. The daily count has fallen back gradually from the peak but remained stubbornly high. The reason for the divergence from the classical model remain unclear. We take an empirical stance on this issue and develop a model that is based upon the statistical characteristics of the time series. With the possible exception of China, the workhorse logistic model is decisively rejected against more flexible alternatives.


title: Tracking the COVID-19 pandemic in Australia using genomics

text: BACKGROUND: Whole-genome sequencing of pathogens can improve resolution of outbreak clusters and define possible transmission networks. We applied high-throughput genome sequencing of SARS-CoV-2 to 75% of cases in the State of Victoria (population 6.24 million) in Australia. METHODS: Cases of SARS-CoV-2 infection were detected through active case finding and contact tracing. A dedicated SARS-CoV-2 multidisciplinary genomic response team was formed to enable rapid integration of epidemiological and genomic data. Phylodynamic analysis was performed to assess the putative impact of social restrictions. RESULTS: Between 25 January and 14 April 2020, 1,333 COVID-19 cases were reported in Victoria, with a peak in late March. After applying internal quality control parameters, 903 samples were included in genomic analyses. Sequenced samples from Australia were representative of the global diversity of SARS-CoV-2, consistent with epidemiological findings of multiple importations and limited onward transmission. In total, 76 distinct genomic clusters were identified; these included large clusters associated with social venues, healthcare facilities and cruise ships. Sequencing of sequential samples from 98 patients revealed minimal intra-patient SARS-CoV-2 genomic diversity. Phylodynamic modelling indicated a significant reduction in the effective viral reproductive number (Re) from 1.63 to 0.48 after the implementation of travel restrictions and population-level physical distancing. CONCLUSIONS: Our data provide a comprehensive framework for the use of SARS-CoV-2 genomics in public health responses. The application of genomics to rapidly identify SARS-CoV-2 transmission chains will become critically important as social restrictions ease globally. Public health responses to emergent cases must be swift, highly focused and effective.


title: Forecasting Hospital Staff Availability During The COVID-19 Epidemic

text: The COVID-19 pandemic poses two challenges to healthcare providers. Firstly, a high number of patients require hospital admission. Second, a high number of healthcare staff are either falling ill with the infection, or self-isolating. This poses significant problems for the staffing of busy hospital departments. We have created a simple model which allows users to stress test their rota. The model provides plots of staff availability over time using either a constant infection rate, or a changing infection rate fitted to population-based infection curves. It allows users to gauge the extent and timing of dips in staff availability. The basic constant infection rate model is available within an on-line web application (https://covid19.shef.ac.uk). As for any model, our work is imperfect. However, it allows a range of infection rates to be simulated quickly across different work patterns. We hope it will be useful to those planning staff deployment and will stimulate debate on the most effective patterns of work during the COVID-19 epidemic.


title: Reduced COVID-19-Related Critical Illness and Death, and High Risk of Epidemic Resurgence, After Physical Distancing in Ontario, Canada

text: We explored the impact of physical distancing measures on COVID-19 transmission in the population of Ontario, Canada using a previously described age- and health-status stratified transmission model. The model was fit to confirmed cases occupying intensive care unit (ICU) beds and mortality among hospitalized COVID-19 cases for the time period 19 March to 26 April 2020. We projected that mortality would have been 4.6-fold what was observed had physical distancing measures not been implemented in the province. Relaxation of physical distancing measures without compensatory increases in case detection, isolation, and/or contact tracing was projected to result in resurgence of disease activity. Return to normal or near-normal levels of contact would rapidly result in cases exceeding ICU capacity. Maintaining physical distancing for a longer period of time, allowing for the initial wave of infections to subside, delayed this resurgence, but the level of contacts post-restrictive distancing was the major factor determining how quickly ICU capacity was expected to be overwhelmed. Using a model, we demonstrate the marked impact strong public health measures had in reducing ICU admissions and mortality in Ontario. We also show that this hard-earned success is tenuous: relaxation of physical distancing measures in the near-term is projected to result in a rapid resurgence of disease activity.


title: Universality in COVID-19 spread in view of the Gompertz function

text: We demonstrate that universal scaling behavior is observed in the current coronavirus (COVID-19) spread in various countries. We analyze the numbers of infected people in selected eleven countries (Japan, USA, Russia, Brazil, China, Italy, Indonesia, Spain,South Korea, UK, and Sweden). By using the double exponential function called the Gompertz function, fG(x)=exp(-e-x), the number of infected people is well described as N(t)=N0 fG({gamma}(t-t0)), where N0, {gamma} and t0 are the final total number of infected people, the damping rate of the infection probability and the peak time of dN(t)/dt, respectively. The scaled data of infected people in most of the analyzed countries are found to collapse onto a common scaling function fG(x) with x={gamma}(t-t0) in the range of fG(x) {+/-} 0.05. The recently proposed indicator so-called the K value, the increasing rate of infected people in one week, is also found to show universal behavior. The mechanism for the Gompertz function to appear is discussed from the time dependence of the produced pion numbers in nucleus-nucleus collisions, which is also found to be described by the Gompertz function.


docid: ebwxryai

title: Cellular senescence limits acute lung injury induced by mechanical ventilation

text: Different forms of lung injury can activate senescence pathways. Senescence has been involved in chronic lung diseases, but its role in the acute phase is less known. Acute lung injury activates a large variety of pathogenetic mechanisms that can lead to respiratory insufficiency. In some cases, mechanical ventilation may help to maintain gas exchange, but positive airway pressures can cause regional overdistension of alveolar units and further damage. Here, we report that acute lung injury and alveolar overstretching activate a lung senescent program aimed to limit apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of a specific senescence signature. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed the activation of the Tp53/Cdkn1a (p21) senescence pathway, increases in senescence-associated heterochromatin foci in alveolar cells and markers of DNA damage, chromatin reorganization and changes in the nuclear envelope. Autopsy samples from lungs of critically ill patients showed the increase in senescence-associated heterochromatin foci. Cell stretch per se was also able to activate the senescence response in an ex-vivo model. Absence of Cdkn1a decreased the senescent response, but worsened lung injury by a significant increase in apoptosis. In opposite, treatment with lopinavir/ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. Collectively, these results suggest that acute injury promotes lung senescence. This response plays a protective role against acute lung injury in the short term, but its long-term consequences remain unexplored.


title: High excess mortality during the COVID-19 outbreak in Stockholm Region areas with young and socially vulnerable populations

text: Background: We aimed to describe the distribution of excess mortality (EM) during the first weeks of the COVID-19 outbreak in the Stockholm Region, Sweden, according to individual age and sex, and the sociodemographic context Methods: Weekly all-cause mortality data were obtained from Statistics Sweden for the period 01/01/2015 to 17/05/2020. EM during the first 20 weeks of 2020 was estimated by comparing observed mortality rates with expected mortality rates during the five previous years (N=2,379,792). EM variation by socioeconomic status (tertiles of income, education, Swedish-born, gainful employment) and age distribution (share of 70+ year-old persons) was explored based on Demographic Statistics Area (DeSO) data. Findings: An EM was first detected during the week of March 23-29 2020. During the peaking week of the epidemic (6-12 April 2020), an EM of 160% was observed: 211% in 80+ year-old women; 179% in 80+ year-old men. During the same week, the highest EM was observed for DeSOs with lowest income (171%), lowest education (162%), lowest share of Swedish-born (178%), and lowest share of gainfully employed (174%). There was a 1.2 to 1.7-fold increase in EM between those areas with a higher vs. lower proportion of young people. Interpretation: Living in areas with lower socioeconomic status and younger populations is linked to COVID-19 EM. These conditions might have facilitated the viral spread. Our findings add to the well-known biological vulnerability linked to increasing age, the relevance of the sociodemographic context when estimating the individual risk to COVID-19.


title: Predicting the impact of asymptomatic transmission, non-pharmaceutical intervention and testing on the spread of COVID19 COVID19

text: We introduce a novel mathematical model to analyze the effect of removing non-pharmaceutical interventions on the spread of COVID19 as a function of disease testing rate. We find that relaxing interventions has a strong impact on the size of the epidemic peak as a function of intervention re- moval time. We show that it is essential for predictive models to explicitly capture transmission from asymptomatic carriers and important to obtain precise information on asymptomatic transmission by testing. The asymptomatic reservoir, reported to account for as much as 85% of transmission, will contribute to resurgence of the epidemic if public health interventions are removed too soon. Use of more basic models that fail to capture asymptomatic transmission can result in large errors in predicted clinical caseload or in fitted epidemiological parameters and, therefore, may be unreliable in estimating the risk of a second wave based on the timing of terminated interventions.


title: Cotton tipped plastic swabs for SARS-CoV-2 RT-qPCR diagnosis to prevent supplies shortage.

text: Nasopharyngeal sampling protocols for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis guidelines only recommend synthetic fiber swabs. We show that simple and cheap cotton tipped plastic swabs do not inhibit PCR and have equivalent performance to rayon swabs. Cotton tipped plastic swabs are massively produced worldwide and would prevent swabs supplies shortage during current high SARS-CoV-2 testing demands, particularly on developing countries.