title: AI-Driven CT-based quantification, staging and short-term outcome prediction of COVID-19 pneumonia

text: Chest computed tomography (CT) is widely used for the management of Coronavirus disease 2019 (COVID-19) 49 pneumonia because of its availability and rapidity. The standard of reference for confirming COVID-19 relies on microbiological tests but these tests might not be available in an emergency setting and their results are not immediately available, contrary to CT. In addition to its role for early diagnosis, CT has a prognostic role by allowing visually evaluating the extent of COVID-19 lung abnormalities. The objective of this study is to address prediction of short-term outcomes, especially need for mechanical ventilation. In this multi-centric study, we propose an end-to-end artificial intelligence solution for automatic quantification and prognosis assessment by combining automatic CT delineation of lung disease meeting the performance of experts and data-driven identification of biomarkers for its prognosis. AI-driven combination of variables with CT-based biomarkers offers perspectives for optimal patient management given the shortage of intensive care beds and ventilators.


title: Reduced ICU demand with early CPAP and proning in COVID-19 at Bradford: a single centre cohort

text: Background The management of hypoxic respiratory failure due to COVID-19 is not currently subject to consensus. International and national guidance has favoured early intubation, with concerns persisting over the use of CPAP. However, considering available evidence and local circumstances, early ward based CPAP and self proning was adopted in our institution. We aimed to evaluate the safety and efficacy of this approach. Methods In this retrospective observational study we included all patients admitted with a positive COVID-19 PCR. Negative patients were also included where clinical suspicion remained high. A large number of simple CPAP machines were used with entrained oxygen. Ward staff were supported in their use by physiotherapists and an intensive critical care outreach program. CPAP was initiated early via protocol, with the aim of preventing rather than responding to deterioration. Data was analysed descriptively. Results 559 patients admitted prior to 1/May/20 were included. 29.5% received CPAP, 7.2% were admitted to ICU and 4.8% were ventilated. Hospital mortality was 33.3%, ICU mortality 54.5%. Following CPAP, 64% of patients with moderate or severe ARDS at presentation, who were candidates for escalation, avoided intubation during their stay. Conclusion Figures for ICU admission, intubation and overall hospital mortality are significantly lower than those reported in a large and relevant comparator database, whilst ICU mortality is similar. This is despite our population having high levels of co-morbidity and ethnicities associated with poor outcomes. We advocate this approach as both effective and safe.


title: Performance & Quality Evaluation of Marketed COVID-19 RNA Detection Kits

text: Compared to other coronaviruses, COVID-19 has a longer incubation period and features asymptomatic infection at a high rate (>25%). Therefore, early detection of infection is the key to early isolation and treatment. Direct detection of the virus itself has advantages over indirect detection. Currently, the most sensitive and commercially validated method for COVID-19 testing is RT-qPCR, designed to detect amplified virus-specific RNA. Reliable testing has proven to be a bottleneck in early diagnosis of virus infection in all countries dealing with the pandemic. Significant performance and quality issues with available testing kits have caused confusion and serious health risks. In order to provide better understanding of the Quality and performance of COVID-19 RNA detection kits on the market, we designed a system to evaluate the specificity (quantitation), sensitivity (LOD) and robustness of the kits using positive RNA and pseudovirus controls based on COVID-19 genomic sequence. We evaluated 8 Nucleic Acid qPCR Kits approved in China, some of which are also approved in the US and EU. Our study showed that half of these 8 kits lack 1:1 linear relationship for virus RNA copy: qPCR signal. Of the 4 with linear response, 2 demonstrated sensitivity at 1 Copy viral RNA/Reaction, suitable for early detection of virus infection. Furthermore, we established the best RNA extraction, handling and qPCR procedures allowing highly sensitive and consistent performance using BGI qPCR kits. Our study provides an effective method to assess and compare performance quality of all COVID-19 nucleic acid testing kits, globally.


title: The Challenge of Managing Parkinson’s Disease Patients during the COVID-19 Pandemic

text: The 2019 novel coronavirus (nCoV) pandemic is rapidly developing across the globe and new information is emerging expeditiously and constantly, particularly in relation to neurological illnesses. Both central and peripheral nervous system involvement has been reported including headache, dizziness, hyposmia/anosmia, taste disturbances, seizures, stroke, alteration of the sensorium, and even acute hemorrhagic necrotizing leukoencephalopathy. Varying degrees of olfactory disturbances may pre-empt the diagnosis of COVID-19. Although no direct effect of 2019 nCoV has been reported yet on Parkinson’s disease, there are enormous possible indirect effects and implications. We examine the potential effects and challenges posed by this pandemic to individuals with Parkinson’s disease, particularly in the Indian context where telecommunication access or support group access may be lacking for these patients. Additionally, lockdown and social distancing may pose hurdles in the provision of optimum medical therapy, particularly if patients experience motor and non-motor deteriorations due to diverse reasons.


title: Probable causes and risk factors for positive SARS-CoV-2 test in recovered patients: Evidence from Brunei Darussalam

text: We report findings of a national study in Brunei Darussalam indicating that one in five recovered patients subsequently test positive again for SARS-CoV-2 - this risk is nearly three times higher in older patients (age 53 and above) than younger ones (below age 53). Review of clinical and epidemiological records do not support reinfection or reactivation as likely causes of the 're-positive' observation. Instead, prolonged but intermittent viral shedding is the most probable explanation. We discuss the implications of these findings for infection control and clinical practice.


Sanitation and hygiene as factors for choosing a place to stay: perceptions of the Bulgarian tourists


title: Molecular mechanism of SARS-CoV-2 components caused ARDS in murine model

text: COVID-19 has become a major challenge to global health, and until now, no efficient antiviral agents have been developed. The SARS-CoV-2 infection is characterized by pulmonary and systemic inflammation in severe patients, and acute respiratory distress syndrome (ARDS) caused respiratory failure contributes to most mortalities. There is an urgent need for developing effective drugs and vaccines against SARS-CoV-2 and COVID-19 caused ARDS. However, most researchers cannot perform SARS-CoV-2 related researches due to lacking P3 or P4 facility. We developed a non-infectious, highly safety, time-saving SARS-CoV-2 components induced murine model to study the SARS-CoV-2 caused ARDS and cytokine storm syndrome (CSS). We also investigated mAbs and inhibitors which potentially neutralize the pro-inflammatory phenotype of COVID-19, and found that anti-IL-1α, anti-IL-6, anti-TNFα, anti-GM-CSF mAbs, p38 inhibitor, and JAK inhibitor partially relieved CSS. Besides, anti-IL-6, anti-TNFα, anti-GM-CSF mAbs and inhibitors of p38, ERK, and MPO somewhat reduced neutrophilic alveolitis in the lung. In all, we established the murine model mimic of COVID-19, opening a biosafety and less time-consuming avenue for clarifying the mechanism of ARDS and CSS in COVID-19 and developing the therapeutic drugs.


title: At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR based tests?: A systematic review of individual participant data

text: Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA), using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. Methods We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. Findings Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from -6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 to 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. Interpretation RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond ten days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias so the positivity rates are probably overestimated.


title: Virus shedding patterns in nasopharyngeal and fecal specimens of COVID-19 patients

text: Diagnosis is the key point for confirmation and treatment of COVID-19. we focused on comparative analysis of virus dynamics between the upper respiratory and feces specimens in the COVID-19 patients. A total of 66 upper respiratory swabs, 51 feces, 56 urine and 56 plasma samples were sequentially collected from 23 patients in a designated hospital. The plasma and urine samples were all negative, except for urine samples from two severe cases at the latest available detection point. Conversely, virus was shed in respiratory swabs and feces samples during the diseased period. Ten of 12 (83.3%) cases were positive for feces samples, while 14 of 21 (66.7%) were positive for respiratory samples. In addition, the median duration of virus shedding was 10.0 days (IQR 8.0 to 17.0) in the upper respiratory swabs, but was 22.0 days (IQR 15.5 to 23.5) for the feces. Notably, at 26 days after discharge, case 3 (a 45-year-old) was detected positive again in the feces samples, but appears to be healthy and negative for respiratory swabs. These results indicated that beside respiratory samples, intestinal samples (e.g. feces) should be recommended for diagnosis of COVID-19, especially before a patient discharge and for monitoring the relapse of discharged patients.


title: In silico approaches to drug repositioning for COVID-19 at AMED-BINDS

text: Abstract In silico prediction based on the protein structures of SARS-CoV2 is effective to find the putative drug candidates from the approved drugs, as drug repositioning The main protease, 3CL protease, of SARS-Cov2 is essential for proteolytic maturation of the virus, and inhibiting its function could prevent the COVID-19 spreading Here, recent activities in the in-silico unit of AMED-BINDS are introduced Hirokawa et al adopted an in silico docking-based screening approach, which combines molecular docking with a protein-ligand interaction fingerprint (PLIF) scoring method, utilizing the crystal structure of SARS-Cov2 3CL protease (PDB: 6LU7) and a database of known drugs (KEGG-Drug) Selected drugs have the binding modes similar to PLIF of the known active N3 inhibitors with favorable docking scores They identified one hundred and several dozen potentially candidate drugs for 3CL protease inhibitors, which are already approved as antiviral, HIV protease inhibitors, antibacterial or antineoplastic agents Sekijima et al analyzed the interactions between 3CL protease and the drug candidate compounds using molecular dynamics simulation Through this study, they aim to elucidate the interactions between 3CL protease and the drugs The chemical compound libraries in AMED-BINDS will also be available in the future assay studies


title: Renal involvement in children with COVID-19 infection

text: Perhaps when China reported its first cases of the novel coronavirus in December 2019, few would predict that it would overwhelm the majority of the global community The first reports conveyed that the rate of infection and death from this virus among children is rare However, evidence showed that there is no particular age range for the disease and children, infants and even neonates may be infected Although COVID-19 primarily targets the host's respiratory system, complications in other organs such as heart, kidney and liver have been observed as well This mini-review attempts to consider the publications focused on the COVID-19 infection among children with emphasis on renal involvement and the treatment approach of this complication


title: Mental health status and coping strategy of medical workers in China during The COVID-19 outbreak

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


title: Social distancing and movement constraint as the most likely factors for COVID-19 outbreak control in Brazil

text: As thousands of new cases of COVID-19 have been confirmed, there is an increasing demand to understand the factors underlying the spread of this disease. Using country-level data, we modeled the early growth in the number of cases for over 480 cities in all Brazilian states. As the main findings, we found that the percentage of people respecting social distancing protocols was the main explanatory factor for the observed growth rate of COVID-19. Those cities that presented the highest spread of the new coronavirus were also those that had lower averages of social distancing. We also underline that total population of cities and connectivity, represented by the city-level importance to the air transportation of people across the country, plays important roles in the dissemination of SARS-CoV-2. Climate and socioeconomic predictors had little contribution to the big-picture scenario. Our results show that different States had high variability in their growth rates, mostly due to quite different public health strategies to retain the outbreak of COVID-19. In spite of all limitations of such a large-scale approach, our results underline that climatic conditions are likely weak limiting factors for the spread of the new coronavirus, and the circulation of people in the city- and country-level are the most responsible factors for the early outbreak of COVID-19 in Brazil. Moreover, we reinforce that social distancing protocols are fundamental to avoid critical scenarios and the collapse of healthcare systems. We also predict that economic-induced decisions for relaxing social distancing might have catastrophic consequences, especially in large cities.


title: Inferring the number of COVID-19 cases from recently reported deaths

text: We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.


title: Investigating a serious challenge in the sustainable development process: Analysis of confirmed cases of COVID-19 (new type of Coronavirus) through a binary classification using artificial intelligence and regression analysis

text: Nowadays, sustainable development is considered a key concept and solution in creating a promising and prosperous future for human societies. Nevertheless, there are some predicted and unpredicted problems that epidemic diseases are real and complex problems. Hence, in this research work, a serious challenge in the sustainable development process was investigated using the classification of confirmed cases of COVID-19 (new version of Coronavirus) as one of the epidemic diseases. Hence, binary classification modeling was used by the group method of data handling (GMDH) type of neural network as one of the artificial intelligence methods. For this purpose, the Hubei province in China was selected as a case study to construct the proposed model, and some important factors, namely maximum, minimum, and average daily temperature, the density of a city, relative humidity, and wind speed, were considered as the input dataset, and the number of confirmed cases was selected as the output dataset for 30 days. The proposed binary classification model provides higher performance capacity in predicting the confirmed cases. In addition, regression analysis has been done and the trend of confirmed cases compared with the fluctuations of daily weather parameters (wind, humidity, and average temperature). The results demonstrated that the relative humidity and maximum daily temperature had the highest impact on the confirmed cases. The relative humidity in the main case study, with an average of 77.9%, affected positively, and maximum daily temperature, with an average of 15.4 ◦C, affected negatively, the confirmed cases.


title: Development and validation of the COVID-19 severity index (CSI): a prognostic tool for early respiratory decompensation

text: Objective: The goal of this study was to create a predictive model of early hospital respiratory decompensation among patients with COVID-19. Design: Observational, retrospective cohort study. Setting: Nine-hospital health system within the Northeastern United States. Populations: Adult patients ([≥] 18 years) admitted from the emergency department who tested positive for SARS-CoV-2 (COVID-19) up to 24 hours after initial presentation. Patients meeting criteria for critical respiratory illness within 4 hours of arrival were excluded. Main outcome and performance measures: We used a composite endpoint of respiratory critical illness as defined by oxygen requirement beyond low-flow nasal cannula (e.g., non-rebreather mask, high-flow nasal cannula, bi-level positive pressure ventilation), intubation, or death within the first 24 hours of hospitalization. We developed predictive models using patient demographic and clinical data collected during those first 4 hours. Eight hospitals were used for development and internal validation (n=932) and 1 hospital for model external validation (n=240). Predictive variables were identified using an ensemble approach that included univariate regression, random forest, logistic regression with LASSO, Chi-square testing, gradient boosting information gain, and gradient boosting Shapley additive explanation (SHAP) values prior to manual curation. We generated two predictive models, a quick COVID-19 severity index (qCSI) that uses only exam and vital sign measurements, and a COVID-19 severity index (CSI) machine learning model. Using area under receiver operating characteristic (AU-ROC), precision-recall curves (AU-PRC) and calibration metrics, we compare the qCSI and CSI to three illness scoring systems: Elixhauser mortality score, qSOFA, and CURB-65. We present performance of qCSI and CSI on an external validation cohort. Results: During the study period from March 1, 2020 to April 27, 2020, 1,792 patients were admitted with COVID-19. Six-hundred and twenty patients were excluded based on age or critical illness within the first 4 hours, yielding 1172 patients in the final cohort. Of these patients, 144 (12.3%) met the composite endpoint within the first 24 hours. The qCSI (AU-ROC: 0.90 [0.85-0.96]) comprised of nasal cannula flow rate, respiratory rate, and minimum documented pulse oximetry outperformed the baseline models (qSOFA: 0.76 [0.69-0.85]; Elixhauser: 0.70 [0.62-0.80]; CURB-65: AU-ROC 0.66 [0.58-0.77]) and was validated on an external cohort (AU-ROC: 0.82). The machine learning-based CSI had superior performance on the training cohort (AU-ROC: 0.91 [0.86-0.97]), but was unlikely to provide practical improvements in clinical settings. Conclusions: A significant proportion of admitted COVID-19 patients decompensate within 24 hours of hospital presentation and these events are accurately predicted using respiratory exam findings within a simple scoring system.


title: Risk perceptions of COVID-19 around the world

text: The World Health Organization has declared the rapid spread of COVID-19 around the world a global public health emergency. It is well-known that the spread of the disease is influenced by people’s willingness to adopt preventative public health behaviors, which are often associated with public risk perception. In this study, we present the first assessment of public risk perception of COVID-19 around the world using national samples (total N = 6,991) in ten countries across Europe, America, and Asia. We find that although levels of concern are relatively high, they are highest in the UK compared to all other sampled countries. Pooled across countries, personal experience with the virus, individualistic and prosocial values, hearing about the virus from friends and family, trust in government, science, and medical professionals, personal knowledge of government strategy, and personal and collective efficacy were all significant predictors of risk perception. Although there was substantial variability across cultures, individualistic worldviews, personal experience, prosocial values, and social amplification through friends and family in particular were found to be significant determinants in more than half of the countries examined. Risk perception correlated significantly with reported adoption of preventative health behaviors in all ten countries. Implications for effective risk communication are discussed.


title: Robot dance: a city-wise automatic control of Covid-19 mitigation levels

text: We develop an automatic control system to help to design efficient mitigation measures for the Covid-19 epidemic in cities. Taking into account parameters associated to the population of each city and the mobility among them, the optimal control framework suggests the level and duration of protective measures that must be implemented to ensure that the number of infected individuals is within a range that avoids the collapse of the health care system. Compared against other mitigation measures that are implemented simultaneously and in equal strength across cities our method has three major particularities when: Accounts for city commute and health infrastructure: It takes into account the daily commute among cities to estimate the dynamics of infected people while keeping the number of infected people within a desired level at each city avoiding the collapse of its health care system. City-specific control: It allows for orchestrating the control measures among cities so as to prevent all cities to face the same level control. The model tends to induce alternation between periods of stricter controls and periods of a more normal life in each city and among the cities. Flexible scenarios: It is flexible enough to allow for simulating the impact of particular actions. For example, one can simulate the how the control all cities change when the number of care beds increases in specific places. Therefore, our method creates an automatic dance adjusting mitigation levels within cities and alternating among cities as suggested in~cite{Pue2020}. This automatic dance may help the city economy and orchestration of resources. We provide case studies using the major cities of the state of Sao Paulo given by using estimates on the daily mobility among the cities their health care system capacity. We use official data in our case studies. However, sub-notification of infected people in Brazil is notoriously high. Hence the case study should not be considered as a real world policy suggestion. It high sub-notification is taken into account, the optimal control algorithm will suggest stricter mitigation measures, as also shown in the case studies. Surprisingly, the total duration of the protocol for the state is barely affected by the sub-notification, but the severity of such protocols is strengthened. This stresses a twofold implication, first, the protocol depends on high-quality data and, second, such optimal and orchestrated protocol is robust and can be adjusted to the demand.


title: On the corona infection model with contact restriction

text: This article presents a mathematical infection model that is designed to estimate the course of coronavirus infection in Germany for several days in advance: How many people become ill or die, what is the temporal development? If the contact restriction is perfect, then the model predicts the development of the virus infection after the initial subsidence of the infection. However, since this restriction cannot always be strictly adhered to, the model is dynamically adapted to the development. This makes it possible to estimate the number of infected people, the number of new infections and deaths in Germany about a week in advance.


title: Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

text: Background: Although the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease (COVID-19) diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients. Methods: This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value. Findings: The Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= -0.682). Interpretation: Serum SARS-CoV-2 viral load (RNAaemia) is strongly associated with cytokine storm and can be used to predict the poor prognosis of COVID-19 patients. Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response.


title: Comparative in vitro transcriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes

text: Hydroxychloroquine (HCQ) has emerged as a potential and controversial antiviral candidate therapy for COVID-19. While many clinical trials are underway to test the efficacy of HCQ as a treatment for COVID-19, underlying mechanisms of HCQ in the setting of COVID-19 remain unclear. Hence, we examined differential gene expression signatures of HCQ exposure, in vitro SARS-CoV-2 infection, and host signatures of COVID-19 in blood, bronchoalveolar lavage, and postmortem lung to evaluate whether HCQ transcriptome signatures associate with restoration of SARS-CoV-2-related host transcriptional responses. Here, we show that 24 hours of in vitro treatment of peripheral blood mononuclear cells(PBMC) with HCQ significantly impacted transcription of 16 genes involved in immune regulation and lipid metabolism. Using transcriptome data from in vitro SARS-CoV-2 infected NHBE and A549 cells and PBMC derived from confirmed COVID-19 infected patients, we determined that only 0.24% of the COVID-19 PBMC differentially expressed gene set and 0.39% of the in vitro SARS-CoV-2 cells differentially expressed gene set overlapped with HCQ-related differentially expressed genes. Moreover, we observed that HCQ treatment significantly impacted transcription of 159 genes in human primary monocyte-derived macrophages involved in cholesterol biosynthetic process and chemokine activity. Notably, when we compared the macrophage HCQ-related gene lists with genes transcriptionally altered during SARS-CoV-2 infection and in bronchoalveolar lavage of COVID-19+ patients, the CXCL6 gene was impacted in all three transcriptional signatures revealing evidence in favor of chemokine modulation. HCQ-related transcriptional changes minimally overlapped with host genes altered in postmortem lung biopsies from COVID-19 participants. These results may provide insight into the immunomodulation mechanisms of HCQ treatment in the setting of COVID-19 and suggest HCQ is not a panacea to SARS-CoV-2 infection.


title: Enhancing Colorimetric LAMP Amplification Speed and Sensitivity with Guanidine Chloride

text: Loop-mediated isothermal amplification (LAMP) is a versatile technique for detection of target DNA and RNA, enabling rapid molecular diagnostic assays with minimal equipment. The global SARS-CoV-2 pandemic has presented an urgent need for new and better diagnostic methods, with colorimetric LAMP utilized in numerous studies for SARS-CoV-2 detection. However, the sensitivity of colorimetric LAMP in early reports has been below that of the standard RT-qPCR tests, and we sought to improve performance. Here we report the use of guanidine hydrochloride and combined primer sets to increase speed and sensitivity in colorimetric LAMP, bringing this simple method up to the standards of sophisticated technique and enabling accurate and high-throughput diagnostics.


title: Adaptive split ventilator system enables parallel ventilation, individual monitoring and ventilation pressures control for each lung simulators

text: Abstract Objective: In mass crisis setting such as the COVID-19 pandemic, the number of patients requiring invasive ventilation may exceed the number of available ventilators. This challenge led to the concept of splitting ventilator between several patients, which aroused interest as well as a strong opposition from multiple professional societies (The joint statement)1.Establishment of a safe ventilator splitting setup which enables monitoring and control of each ventilated patient would be a desirable ability. Achieving independency between the Co-vent patients would enable effective coping with different individual clinical scenarios and broaden the pairing possibilities of patients connected to a single ventilator. We conducted an experiment to determine if our designed setup achieves these goals. Methods: We utilized a double two limbed modified ventilator circuits which were connected to dual lung simulators. Adding readily available pressure sensors (transducers), PEEP valves, flow control valves, one-way (check) valves and HME filters made the circuit safe enough and suitable for our goals. We first examined a single lung simulator establishing the baseline set parameters, while monitoring ventilator measures as Tidal Volume. The initial ventilator setting we chose was a controlled mandatory ventilation mode with a PIP (peak inspiratory pressure) of 25cmH2O, PEEP (Positive End Expiratory Pressure) of 5 cmH2O. In pressure control set at 20 cmH2O, the recorded mean TV( tidal volume) was 1000 mL (approximately 500 mL/lung simulator) with an average MV(minute ventilation) of 13 L/min (or 6.5 L/min/lung simulator). After examining the system with the dual modified circuits attached, and obtaining all the ventilation parameters, we simulated several clinical scenarios. We simulated clinical events such as: partial or full obstruction, disconnection, air leak and compliance differentials, which occur frequently on a ventilation course. Thus, it is a paramount system demand to keep undisturbed ventilation to the Co-vent patient A, while being challenged by patient B. Results: The adaptive split ventilator setup yields increased safety, monitoring, and controls ventilation parameters successfully for each connected simulated patient (using lung simulators).It also enables coping with several common clinical scenarios on a ventilation course, by allowing the care provider to control PIP and PEEP of each Co-Vent patient. Conclusion: In a mass crisis setting, when there is a shortage of ventilators supply, and as a last resort, this setup can be a viable option to act upon. This experiment demonstrates the ability of the split ventilator to ventilate dual lung simulators with increased safety, monitoring and ventilation pressures control of each simulated patient. This split ventilator kept supporting a simulated patient with undisturbed parameters while the CO-vent patient was simulated to be disconnected, having an air leak, or exhibiting lung compliance deterioration. To the best of our knowledge, this is the first time a split ventilator setup demonstrates these capabilities. Our pilot experiment suggests a significant potential of expanding the ventilator support resources, and is especially relevant during COVID-19 outbreak. Since this setup has not been used in a clinical setting yet, further research should be conducted to explore the safety limits and the capabilities of this model.


title: Who can go back to work when the COVID-19 pandemic remits?

text: This paper seeks to determine which workers affected by lockdown measures can return to work when a government decides to apply lockdown exit strategies. This system, which we call Sequential Selective Multidimensional Decision (SSMD), involves deciding sequentially, by geographical areas, sectors of activity, age groups and immunity, which workers can return to work at a given time according to the epidemiological criteria of the country as well as that of a group of reference countries, used as a benchmark, that have suffered a lower level of lockdown de-escalation strategies. We apply SSMD to Spain, based on affiliation to the Social Security system prior to the COVID-19 pandemic, and conclude that 98.37% of the population could be affected. The proposed system makes it possible to accurately identify the target population for serological IgG antibody tests in the work field, as well as those affected by special income replacement measures due to lockdown being maintained over a longer period.


title: Multivariate Analysis of Factors Affecting COVID-19 Case and Death Rate in U.S. Counties: The Significant Effects of Black Race and Temperature

text: Objectives: Coronavirus disease-19 (COVID-19) has spread rapidly around the world, and many risk factors including patient demographics, social determinants of health, environmental variables, underlying health conditions, and adherence to social distancing have been hypothesized to affect case and death rates. However, little has been done to account for the potential confounding effects of these factors. Using a large multivariate analysis, this study illuminates modulators of COVID-19 incidence and mortality in U.S. counties while controlling for risk factors across multiple domains. Methods: Data on COVID-19 and various risk factors in all U.S. counties was collected from publicly available data sources through April 14, 2020. Counties with at least 50 COVID-19 cases were included in case analyses and those with at least 10 deaths were included in mortality models. The 661 counties meeting inclusion criteria for number of cases were grouped into quartiles and comparisons of risk factors were made using t-tests between the highest and lowest quartiles. Similar comparisons for 217 counties were made for above average and below average deaths/100,000. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of factors that significantly impacted cases and deaths. Results: Univariate analyses demonstrated numerous significant differences between cohorts for both cases and deaths. Risk factors associated with increased cases and/or deaths per 100,000 included increased GDP per capita, decreased social distancing, increased age, increased percent Black, decreased percent Hispanic, decreased percent Asian, decreased health, increased poverty, increased diabetes, increased coronary heart disease, increased physical inactivity, increased alcohol consumption, increased tobacco use, and decreased access to primary care. Multivariate regression analyses demonstrated Black race is a risk factor for worse COVID-19 outcome independent of comorbidities, poverty, access to health care, and other mitigating factors. Lower daily temperatures was also an independent risk factor in case load but not deaths. Conclusions: U.S. counties with a higher proportion of Black residents are associated with increased COVID-19 cases and deaths. However, the various suggested mechanisms, such as socioeconomic and healthcare predispositions, did not appear to drive the effect of race in our model. Counties with higher average daily temperatures are also associated with decreased COVID-19 cases but not deaths. Several theories are posited to explain these findings, including prevalence of vitamin D deficiency. Additional studies are needed to further understand these effects.


title: Organizing Pneumonia of COVID-19: Time-dependent Evolution and Outcome in CT Findings

text: Objective: As a pandemic, a most-common pattern resembled organizing pneumonia (OP) has been identified by CT findings in novel coronavirus disease (COVID-19). We aimed to delineate the evolution of CT findings and outcome in OP of COVID-19. Materials and Methods: 106 COVID-19 patients with OP based on CT findings were retrospectively included and categorized into non-severe (mild/common) and severe (severe/critical) groups. CT features including lobar distribution, presence of ground glass opacities (GGO), consolidation, linear opacities and total severity CT score were evaluated at three time intervals from symptom-onset to CT scan (day 0-7, day 8-14, day>14). Discharge or adverse outcome (admission to ICU or death), and pulmonary sequelae (complete absorption or lesion residuals) on CT after discharge were analyzed based on the CT features at different time interval. Results: 79(74.5%) patients were non-severe and 103(97.2%) were discharged at median day 25 (range, day 8-50) after symptom-onset. Of 67 patients with revisit CT at 2-4 weeks after discharge, 20(29.9%) had complete absorption of lesions at median day 38 (range, day 30-53) after symptom-onset. Significant differences between complete absorption and residuals groups were found in percentages of consolidation (1.5% vs. 13.8%, P=0.010), number of involved lobe >3 (40.0% vs. 72.5%, P=0.030), CT score >4 (20.0% vs. 65.0%, P=0.010) at day 8-14. Conclusions: Most OP cases had good prognosis. Approximately one-third of cases had complete absorption of lesions during 1-2 months after symptom-onset while those with increased frequency of consolidation, number of involved lobe>3, and CT score >4 at week 2 after symptom-onset may indicate lesion residuals on CT.


title: SARS-CoV-2 in environmental samples of quarantined households

text: The role of environmental transmission of SARS-CoV-2 remains unclear. Particularly the close contact of persons living together or cohabitating in domestic quarantine could result in high risk for exposure to the virus within the households. Therefore, the aim of this study was to investigate the whereabouts of the virus and whether useful precautions to prevent the dissemination can be given. 21 households under quarantine conditions were randomly selected for this study. All persons living in each household were recorded in terms of age, sex and time of household quarantine. Throat swabs for analysis were obtained from all adult individuals and most of the children. Air, wastewater samples and surface swabs (commodities) were obtained and analysed by RT-PCR. Positive swabs were cultivated to analyse for viral infectivity. 26 of all 43 tested adults (60.47 %) tested positive by RT-PCR. All 15 air samples were PCR-negative. 10 of 66 wastewater samples were positive for SARS-CoV-2 (15.15 %) as well as 4 of 119 object samples (3.36 %). No statistically significant correlation between PCR-positive environmental samples and the extent of infection spread inside the household could be observed. No infectious virus could be isolated under cell culture conditions. As we cannot rule out transmission through surfaces, hygienic behavioural measures are important in the households of SARS-CoV-2 infected individuals to avoid potential transmission through surfaces. The role of the domestic environment, in particular the wastewater load in washbasins and showers, in the transmission of SARS CoV-2 should be further clarified.


title: Concordance of "rapid" serological tests and IgG and IgM chemiluminescence for SARS-COV-2

text: Background The COVID-19 serological tests for IgG and IgM have been developed with several methodologies: Immunoenzymatic Assay (ELISA), Chemiluminescence, Electro Chemiluminescence, Fluorescent Lateral Flow Immunoassays and Immunochromatography. None of these tests should be used for the diagnosis or population screening of the disease, considering that the antibodies appear only on the 8th - 14th day of the disease onset. The present study evaluates a sample of immunofluorescent and immunochromatographic rapid tests to show their agreement in relation to Chemiluminescence. Methods A diagnostic test evaluation assay was performed to establish the performance of five rapid tests (4 immunochromatographic and 1 immunofluorescent tests) for IgG and IgM serology for SARS-CoV-2 using a panel of 30 serum samples from patients received in the laboratory analysis routine. For the evaluation of clinical performance, the qualitative results of the rapid tests were compared against those obtained by chemiluminescence, dichotomized as positives (>>10 AU / mL) or negative (<10 UA / mL). Findings The best agreement is seen in the immunofluorescent assay, for the IgG contrast, with a particularly good kappa index (0.85), without positive disagreements and a negative disagreement of about 15%. In the immunochromatographic methods Kappa index was 0.61 at best, with disagreements in negative findings of {approx}35% and in positive cases of up to {approx}70%. The IgM concordance behavior, on the other hand, reflects a weak to moderate Kappa concordance value (Kappa 0.2 to 0.6), with negative disagreements reaching up to 55% and positives of up to 84%, without any evaluated test reaching Kappa performance equal to or greater than 0.8. Interpretation Serological studies should be used in the clinical and epidemiological context and of other diagnostic tests. Given the high demand and supply in the market of "rapid serological tests", its evaluation against panels of serologically positive or negative samples established by Chemiluminescence or Electro chemiluminescence is essential to authorize its extensive use in populations Funding None


title: A multidisciplinary approach for managing the infraglottic difficult airway in the settings of the Coronavirus pandemic

text: Management of a difficult airway caused by pathology below the glottis is high-risk and requires a shared approach to airway planning and surgical treatment. Access to the trachea requires a careful assessment of the airway since the end-point of laryngoscopy for infraglottic airway management is not visualization of the larynx for tube placement, but access to the laryngotracheal complex in cases where intubation may not be feasible or may preclude surgical access. This work 23 provides a common framework for creating multidisciplinary shared-airway management plans and presents devices and strategies that have in recent years improved airway management safety in this difficult patient group and may prove useful in the settings of the novel Coronavirus Disease 2019 (COVID-19).


title: Potential Neutralizing Antibodies Discovered for Novel Corona Virus Using Machine Learning

text: The fast and untraceable virus mutations take lives of thousands of people before the immune system can produce the inhibitory antibody. Recent outbreak of novel coronavirus infected and killed thousands of people in the world. Rapid methods in finding peptides or antibody sequences that can inhibit the viral epitopes of COVID-19 will save the life of thousands. In this paper, we devised a machine learning (ML) model to predict the possible inhibitory synthetic antibodies for Corona virus. We collected 1933 virus-antibody sequences and their clinical patient neutralization response and trained an ML model to predict the antibody response. Using graph featurization with variety of ML methods, we screened thousands of hypothetical antibody sequences and found 8 stable antibodies that potentially inhibit COVID-19. We combined bioinformatics, structural biology, and Molecular Dynamics (MD) simulations to verify the stability of the candidate antibodies that can inhibit the Corona virus.


What does “crisis” education look like?


title: Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Review

text: Since its origin in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a pandemic and spread to 209 countries. As coronavirus disease 2019 (COVID-19) is a very rapidly emerging disease, organ-specific studies related to it have been reported. Apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. Cardiac involvement in COVID-19 seems to be a result of an inflammatory storm in response to the infection. Moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in COVID-19. Nevertheless, the mechanism of heart injury in COVID-19 is not clear yet. However, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (AMI) in COVID-19-affected individuals have been published. In this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports.


title: Using simulation to assess the potential effectiveness of implementing screening at national borders during international outbreaks of influenza, SARS, Ebola virus disease and COVID-19

text: The effectiveness of screening travellers for signs of infection during times of international disease outbreak is contentious, especially as the reduction of the risk of disease importation can be very small. Border screening typically consists of arriving individuals being thermally scanned for signs of fever and/or completing a survey to declare any possible symptoms, and while more thorough testing typically exists, these would generally prove more disruptive to deploy. In this paper, we utilise epidemiological data and Monte Carlo simulation to calculate the potential success rate of deploying border screening for a range of diseases (including the current COVID-19 pandemic) in varying outbreak scenarios. We negate the issue of testing precision by assuming a perfect test is used; our outputs then represent the best-case scenario. We then use these outputs to briefly explore the types of scenarios where the implementation of border screening could prove most effective. Our models only considers screening implemented at airports, due to air travel being the predominant method of international travel. Primary results showed that in the best-case scenario, screening has the potential to detect 46.4%, 12.9% and 4.0% of travellers infected with influenza, SARS and ebola respectively, while screening for COVID-19 could potentially detect 12.0% of infected travellers. We compare our results to those already in the published literature.


title: Modelling Singapore COVID-19 pandemic with a SEIR multiplex network model

text: In this paper, we have implemented a large-scale agent-based model to study the outbreak of coronavirus infectious diseases (COVID-19) in Singapore, taking into account complex human interaction pattern. In particular, the concept of multiplex network is utilized to differentiate between social interactions that happen in households and workplaces. In addition, weak interactions among crowds, transient interactions within social gatherings, and dense human contact between foreign workers in dormitories are also taken into consideration. Such a categorization in terms of a multiplex of social network connections together with the Susceptible-Exposed-Infectious-Removed (SEIR) epidemic model have enabled a more precise study of the feasibility and efficacy of control measures such as social distancing, work from home, and lockdown, at different moments and stages of the pandemics.


title: Biotechnology Applied to the Diagnosis of Animal Diseases. Revue Scientifique et Technique 1993 Office International des Epizooties Paris Vol. 12, No. 2. 376 pages, Soft cover, FrF 200,-; US$ 40.-

text: Unknown


title: Genetic Variability of Human Angiotensin-Converting Enzyme 2 (hACE2) Among Various Ethnic Populations

text: There appears to be large regional variations for susceptibility, severity and mortality for Covid-19 infections. We set out to examine genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS- CoV-2. By comparing 56,885 Non-Finnish European and 9,197 East Asians (including 1,909 Koreans) four missense mutations were noted in the hACE2 gene. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also examined hACE2 gene expression in eight global populations from the HapMap3 and noted marginal differences in expression for some populations as compared to the Chinese population. However, for both of our studies, the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.


title: ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection

text: In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.


title: Temperature and Humidity Do Not Influence Global COVID-19 Incidence as Inferred from Causal Models

text: The relationship between meteorological factors such as temperature and humidity with COVID-19 incidence is still unclear after 6 months of the beginning of the pandemic. Some literature confirms the association of temperature with disease transmission while some oppose the same. This work intends to determine whether there is a causal association between temperature, humidity and Covid-19 cases. Three different causal models were used to capture stochastic, chaotic and symbolic natured time-series data and to provide a robust & unbiased analysis by constructing networks of causal relationships between the variables. Granger-Causality method, Transfer Entropy method & Convergent Cross-Mapping (CCM) was done on data from regions with different temperatures and cases greater than 50,000 as of 13th May 2020. From the Granger-Causality test we found that in only Canada, the United Kingdom, temperature and daily new infections are causally linked. The same results were obtained from Convergent Cross Mapping for India. Again using Granger-Causality test, we found that in Russia only, relative humidity is causally linked to daily new cases. Thus, a Generalized Additive Model with a smoothing spline function was fitted for these countries to understand the directionality. Using the combined results of the said models, we were able to conclude that there is no evidence of a causal association between temperature, humidity and Covid-19 cases.


Sociologiska perspektiv på coronakrisen: Fyra sociologer om samhällets reaktion på covid-19


title: How many patients will need ventilators tomorrow?

text: This paper develops an algorithm to predict the number of Covid-19 patients who will start to use ventilators tomorrow. This algorithm is intended to be utilized by a large hospital or a group of coordinated hospitals at the end of each day (e.g. 8pm) when the current number of non-ventilated Covid-19 patients and the predicated number of Covid-19 admissions for tomorrow are available. The predicted number of new admissions can be replaced by the numbers of Covid-19 admissions in the previous d days (including today) for some integer d [≥] 1 when such data is available. In our simulation model that is calibrated with New York City's Covid-19 data, our predictions have consistently provided reliable estimates of the number of the ventilator-starts next day. This algorithm has been implemented through a web interface at covidvent.github.io, which is available for public usage. Utilizing this algorithm, our paper also suggests a ventilator ordering and returning policy. The policy will dictate at the end of each day how many ventilators should be ordered tonight from a central stockpile so that they will arrive by tomorrow morning and how many ventilators should be returned tomorrow morning to the central stockpile. In 100 runs of operating our ventilator order and return policy, no patients were denied of ventilation and there was no excessive inventory of ventilators kept at hospitals.


title: Indian Economy Amid COVID-19 Lockdown: A Prespective

text: COVID-19 virus has resulted in the lockdown of schools, offices, factories, temples, railway stations, and even the airspace It is estimated that due to the lockdown, the Indian economy may face prolonged adverse impact The paper is an attempt to ascertain the impact of lockdown on the Indian economy and explore future perspective The study has addressed important issues like consumption expenditure, demand & supply, unemployment rate, purchasing power, financial market, etc Under the given circumstances, the lockdown will cost India around USD 120 bn The manufacturing and service sector has come to an abrupt stop and interrupted domestic supply chains If this crisis continuous it will indirectly affect all economic sectors The study has given suggestions as a learning curve which can be used by different stakeholder to improve the economic situation of the country and minimize negative effect of lockdown


Washington State Medical Oncologist Offers COVID-19 Perspective, Guidance


title: BIP4COVID19: Releasing impact measures for articles relevant to COVID-19

text: Since the beginning of the 2019-20 coronavirus pandemic, a large number of relevant articles has been published or become available in preprint servers. These articles, along with earlier related literature, compose a valuable knowledge base affecting contemporary research studies, or even government actions to limit the spread of the disease and treatment decisions taken by physicians. However, the number of such articles is increasing at an intense rate making the exploration of the relevant literature and the identification of useful knowledge in it challenging. In this work, we describe BIP4COVID19, an open dataset compiled to facilitate the coronavirus-related literature exploration, by providing various indicators of scientific impact for the relevant articles. Finally, we provide a publicly accessible Web interface on top of our data, allowing the exploration of the publications based on the computed indicators.


title: Appendix 2 List of Abbreviations

text: Unknown


title: EFFECTS OF COVID-19 INFECTION DURING PREGNANCY AND NEONATAL PROGNOSIS: WHAT IS THE EVIDENCE?

text: Background: Little is known about how COVID-19 infection affects pregnant women, as well as about the possibility of vertical transmission or that of premature labor. Thus, this studys objective was to identify existing evidence to directive public policies. Method: Systematic literature review assessing papers published in the most comprehensive databases in the field of health. Results: 12 papers were eligible. A total of 119 pregnant women aged between 22 and 42 years old and between the 12th and 41st weeks were analyzed; 90 children were born. Most pregnant women acquired the infection in the third trimester of pregnancy, 97.4% were diagnosed before hospitalization based on signs and symptoms. There was no maternal death and no vertical transmission was confirmed. Conclusions: pregnant women must be cautious and vigilant because their exposure to the virus, even if at the end of a pregnancy, has important repercussions, especially for the type of labor.


title: COVID-19 Trend and Forecast in India: A Joinpoint Regression Analysis

text: This paper analyses the trend in daily reported confirmed cases of COVID-19 in India using joinpoint regression analysis. The analysis reveals that there has been little impact of the nation-wide lockdown and subsequent extension on the progress of the COVID-19 epidemic in the country and there is no empirical evidence to suggest that relaxations under the third and the fourth phase of the lockdown has resulted in spiking the reported confirmed cases of COVID-19. The analysis also suggests that if the current trend continues, in the immediate future, then the daily reported confirmed cases of COVID-19 in the country is likely to increase to 21 thousand by 15 June 2020 whereas the total number of confirmed cases of COVID-19 will increase to around 422 thousand.


title: Would India Really Touch the Peak of SARS COVID 19 Cases or Deaths in Near Future?

text: Background: The Government, Health System and even an individual citizen of India is alarmed expecting the height of pandemic of SARS-COVID-19 in near future. Many experts worldwide predict it to happen in India between end of May and end of July. Objectives: The aim of this research was to find an answer that whether India would come across the looming conditions of SARS-COVID-19 in coming days given the prevailing circumstances so far. Methods: The proposed approach used fundamental concept of Statistics by fixing the standard reference to the number of daily new tests conducted by a country. We thus computed the percentage of daily new cases and daily new deaths, in using such references. The trends were studied using simple line chart. The theory of three sigma was also used to build the upper bound for daily new cases and deaths, specifically for India to see the extreme conditions. Results: The analysis was done using data from January to till May 18, 2020 for India, Italy, USA and UK. The trend of India was almost fix between ~2% to ~6% till May 18, 2020. On contrary, Italy, USA and UK were touched the Peak on March 29, 2020 (24.38%), April 26, 2020 (23.51%) and April 24, 2020 (24.91%), respectively and declining since then. Similar trends were also noted in daily new deaths, except Italy. Conclusions: The proposed new concept for fixing universal reference provides a consistent and coherent results. It is thus clear from observed data so far that India is not going to encounter the frightened conditions or peak, like, Italy, USA, and UK for pandemic SARS-COVID-19, given the existing conditions, excluding the current migration.


Immer mehr Kliniken steuern Intensivkapazitäten in Echtzeit


title: COVID-19 outbreak response: a first assessment of mobility changes in Italy following national lockdown

text: Italy is currently experiencing the largest COVID-19 outbreak in Europe so far, with more than 100,000 confirmed cases. Following the identification of the first infections, on February 21, 2020, national authorities have put in place an increasing number of restrictions aimed at containing the outbreak and delaying the epidemic peak. Since March 12, the whole country is under lockdown. Here we provide the first quantitative assessment of the impact of such measures on the mobility and the spatial proximity of Italians, through the analysis of a large-scale dataset on de-identified, geo-located smartphone users. With respect to pre-outbreak averages, we estimate a reduction of 50% of the total trips between Italian provinces, following the lockdown. In the same week, the average users' radius of gyration has declined by about 50% and the average degree of the users' proximity network has dropped by 47% at national level.


Life under lockdown: A Kashmiri journalist: A Kashmiri journalist speaks about the difficulties – personal and professional - of living in the state with an internet shutdown during lockdown


title: Reverse Pneumatic Artificial Muscles for Application in Low-Cost Artificial Respirators

text: One of the main challenges associated with mechanical ventilators is their limited availability in pandemics and other emergencies. Therefore, there is a great demand for mechanical ventilators to address this issue. In this work, we propose a low-cost, portable, yet high-performance design for a volume-controlled mechanical ventilator. We are employing pneumatic artificial muscles, such as air cylinders, in the reverse mode of operation to achieve mechanical ventilation. The current design of the device can operate in two modes: controlled mode and assisted mode. Unlike most ICU ventilators, our device does not need a high-pressure air pipeline to operate. With the current design, mechanical ventilation for respiration rate ranging from 10 b/min to 30 b/min with a tidal volume range of 150 mL to 1000 mL and I:E ratio of 1:1 to 1:5 can be performed. We achieved a total cost of less $400 USD to make one device. We estimate the device to cost less than $250 USD when produced in larger volumes.


title: Abdominal Pain: A Real Challenge in Novel COVID-19 Infection

text: COVID-19 (coronavirus disease 19) is an infectious disease caused by coronavirus 2019-nCoV. Since its detection in China at the end of 2019, the novel coronavirus has rapidly spread throughout the world and has caused an international public health emergency. The most common manifestation is flu-like symptoms. Mild infections usually improve within a few days, but COVID-19 can cause severe pneumonia with acute respiratory distress syndrome and death. Gastrointestinal symptoms are less common but possible and more difficult to recognize as part of a COVID-19 syndrome. In line with the current opinion of the WHO, we strongly believe that preventive measures and early diagnosis of COVID-19 are crucial to interrupt virus spread and avoid local outbreaks. We report the cases of COVID-19 patients admitted to our Emergency Department who complained of gastrointestinal symptoms at admission. LEARNING POINTS: The novel COVID-19 infection is a severe public health problem which is causing an increasing number of deaths worldwide. Although uncommon, there may be a relationship between gastrointestinal symptoms and COVID-19, as reported in recent studies. Early detection and isolation of patients with COVID-19 infection is the only way to control and limit the global spread of this virus.


title: Forecasting Covid-19 dynamics in Brazil: a data driven approach

text: This paper has a twofold contribution. The first is a data driven approach for predicting the Covid-19 pandemic dynamics, based on data from more advanced countries. The second is to report and discuss the results obtained with this approach for Brazilian states, as of May 4th, 2020. We start by presenting preliminary results obtained by training an LSTM-SAE network, which are somewhat disappointing. Then, our main approach consists in an initial clustering of the world regions for which data is available and where the pandemic is at an advanced stage, based on a set of manually engineered features representing a country's response to the early spread of the pandemic. A Modified Auto-Encoder network is then trained from these clusters and learns to predict future data for Brazilian states. These predictions are used to estimate important statistics about the disease, such as peaks. Finally, curve fitting is carried out on the predictions in order to find the distribution that best fits the outputs of the MAE, and to refine the estimates of the peaks of the pandemic. Results indicate that the pandemic is still growing in Brazil, with most states peaks of infection estimated between the 25th of April and the 19th of May 2020. Predicted numbers reach a total of 240 thousand infected Brazilians, distributed among the different states, with Sao Paulo leading with almost 65 thousand estimated, confirmed cases. The estimated end of the pandemics (with 97 % of cases reaching an outcome) starts as of May 28th for some states and rests through August 14th, 2020.


Electric Scooters during a Pandemic: Cutting out Emergency Room Visits and Coronavirus Disease 2019 Transmission


title: Global analysis of daily new COVID-19 cases reveals many static-phase countries including US and UK potentially with unstoppable epidemics

text: The COVID-19 epidemics are differentially progressing in different countries. Here, comparative analyses of daily new cases reveal that 61 most affected countries can be classified into four types: downward (22), upward (20), static-phase (12) and uncertain ones (7). In particular, the 12 static-phase countries including US and UK are characterized by largely constant numbers of daily new cases in the past over 14 days. Furthermore, these static-phase countries are overall significantly lower in testing density but higher in the level of positive COVID-19 tests than downward countries. These findings suggest that the testing capacity in static-phase countries is lagging behind the spread of the outbreak, i.e., daily new cases (confirmed) are likely less than daily new infections and the remaining undocumented infections are thus still expanding, resulting in unstoppable epidemics. As such, increasing the testing capacity and/or reducing the COVID-19 transmission are urgently needed to stop the severing crisis in static-phase countries.


title: Associations between ambient air pollutants exposure and case fatality rate of COVID-19: a multi-city ecological study in China.

text: Background: Environmental factors, including air pollution, can strongly impact on spatio-temporal patterns of infectious diseases outbreak. In this study, we aimed to investigate the association and correlation between ambient air pollutants and case fatality rate (CFR) of the novel coronavirus disease (COVID-19) in China.Methods: Publicly accessible data on COVID-19 average CFR were utilized in the data analysis.The ambient daily air pollution including fine particulate matter(PM2.5), inhalable particles(PM10)and nitrogen dioxide(NO2)during the period from December 25,2019 to March 5,2020 were obtained from National Air Quality Real-time Publishing System of China.Ecological analysis was performed to explore the association and correlation between the cumulative average exposure of ambient air pollutants at different lags(14 and 28 days)and average CFR in China outside Hubei and cities in Hubei provinces via model fitting.Results:The average case fatality rate was highest in Wuhan city(4.53%) and the cumulative average exposure of ambient PM2.5, PM10 and NO2 at lag 28 days was 55.8{+/-} 12.1g/m3,66.8{+/-}9.2g/m3, 20.7{+/-}4.4g/m3, respectively in Hubei province during the study period.Ecological analysis showed that ambient PM2.5, PM10 and NO2 exposure at both lag 14 and 28 days was positively correlated with average CFR in China outside Hubei(province-level).For city-level analysis in Hubei,significant associations were only found between cumulative ambient NO2 exposure and average CFR(r=0.693 for Lag0-14,r=0.697 for Lag0-28,respectively)during the same period.Conclusions: Our findings suggest ambient PM2.5, PM10 and NO2 exposure, especially at 28 lag days,positively associated with the case fatality rate of COVID-19 in China.These results could help provide guidance for identifying potential exposure windows and preventing and controlling the epidemic.


title: Ecological and evolutionary drivers of hemoplasma infection and bacterial genotype sharing in a Neotropical bat community

text: Most emerging pathogens can infect multiple species, underscoring the importance of understanding the ecological and evolutionary factors that allow some hosts to harbor greater infection prevalence and share pathogens with other species. However, our understanding of pathogen jumps is primarily based around viruses, despite bacteria accounting for the greatest proportion of zoonoses. Because bacterial pathogens in bats (Order: Chiroptera) can have conservation and human health consequences, studies that examine the ecological and evolutionary drivers of bacterial prevalence and barriers to pathogen sharing are crucially needed. We here studied hemotropic Mycoplasma spp. (i.e., hemoplasmas) across a species-rich bat community in Belize over two years. Across 469 bats spanning 33 species, half of individuals and two-thirds of species were hemoplasma positive. Infection prevalence was higher for males and for species with larger body mass and colony sizes. Hemoplasmas displayed high genetic diversity (21 novel genotypes) and strong host specificity. Evolutionary patterns supported co-divergence of bats and bacterial genotypes alongside phylogenetically constrained host shifts. Bat species centrality to the network of shared hemoplasma genotypes was phylogenetically clustered and unrelated to prevalence, further suggesting rare—but detectable—bacterial sharing between species. Our study highlights the importance of using fine phylogenetic scales when assessing host specificity and suggests phylogenetic similarity may play a key role in host shifts for not only viruses but also bacteria. Such work more broadly contributes to increasing efforts to understand cross-species transmission and epidemiological consequences of bacterial pathogens.


title: Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8+ T cells

text: The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was ‘exhausted’ or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the non-exhausted subsets from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features. Cells with such features were mostly absent in SARS-CoV-2 responsive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.


title: Cumulative Active and Recovery Rates Based Criterion for Gradual Lockdown Exit: A Global Observation of SARS Cov-2 Management

text: On March 11, 2020 the World Health Organization (WHO) had declared SARS-CoV-2 pandemic; and at present there are over 6 million cases across the globe. Based on the interim guidelines of WHO, most of the countries opted for social distancing with lockdown as the only way to control the pandemic. This led to Manufacturing shut down, which acted as a spanner in the wheel for international supply chain leading to pressure on governments to review the protocols of the lockdown. We studied epidemiological parameters for 18 countries and obtained crossover time point referring to cumulative case active and case recovery rates and the time point for the peak positive confirmation rate in a time window of 92 days; and linked with the respective governmental decisions. For countries awaiting crossover, time series non-linear models could be used for predicting the crossover point. A sample study was carried out for India. The median time for reaching crossover for 12 countries was 37 days, while peak positive confirmation rate was 30 days after their first intervention. These countries enforced strict lockdown regulations and have shown constant improvement in their recovery rate even after crossover time point. A phase wise relaxation of lockdown is evident after crossover point in most of these countries. The crossover time point with the subsequent increasing recovery rate can be a strategy for lockdown relaxation as evident from the experiences of few countries. Also, we propose a criterion based on cumulative recovery and fatality rate for micro-management of lockdown.


title: Genetic variability in the expression of the SARS-CoV-2 host cell entry factors across populations

text: The entry of SARS-CoV-2 into host cells is dependent upon angiotensin-converting enzyme 2 (ACE2), which serves as a functional attachment receptor for the viral spike glycoprotein, and the serine protease TMPRSS2 which allows fusion of the viral and host cell membranes. We devised a quantitative measure to estimate genetic determinants of ACE2 and TMPRSS2 expression and applied this measure to >2,500 individuals. Our data show significant variability in genetic determinants of ACE2 and TMPRSS2 expression among individuals and between populations, and demonstrate a genetic predisposition for lower expression levels of both key viral entry genes in African populations. These data suggest that genetic factors might lead to lower susceptibility for SARS-CoV-2 infection in African populations and that host genetics might help explain inter-individual variability in disease susceptibility and severity of COVID-19.


title: Clinical Characteristics of Coronavirus Disease 2019 in Hainan, China

text: Background: Since January 2020, coronavirus disease 2019 (Covid-19) has spread rapidly and developing the pandemic model around the world. Data have been needed on the clinical characteristics of the affected patients in an imported cases as model in island outside Wuhan. Methods: We conducted a retrospective study included all 168 confirmed cases of Covid-19 in Hainan province from 22 January 2020 to 13 March 2020. Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, radiological and laboratory data. Results: Of 168 patients, 160 have been discharged, 6 have died and 2 remain hospitalized. The median age was 51.0 years and 51.8% were females. 129 (76.8%) patients were imported cases, and 118 (70.2%), 51 (30.4%) and 52 (31%) of patients lived in Wuhan or traveled to Wuhan, had contact with Covid-19 patients, or had contact with Wuhan residents, respectively. The most common symptoms at onset of illness were fever (65.5%), dry cough (48.8%) and expectoration (32.1%). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (60.2%). The elderly people with diabetes, hypertension and CVD are more likely to develop severe cases. Follow-up of 160 discharged patients found that 20 patients (12.5%) had a positive RT-PCR test results of pharyngeal swabs or anal swabs or fecal. Conclusions: In light of the rapid spread of Covid-19 around the world, early diagnosis and quarantine is important to curb the spread of Covid-19 and intensive treatments in early stage is to prevent patients away from critical condition.


title: A stochastic, individual-based model for the evaluation of the impact of non-pharmacological interventions on COVID-19 transmission in Slovakia

text: The COVID-19 pandemic represents one of the most significant healthcare challenges that humanity faces. We developed a stochastic, individual-based model of transmission of COVID-19 in Slovakia. The proposed model is based on current clinical knowledge of the disease and takes into account the age structure of the population, distribution of the population into the households, interactions within the municipalities, and interaction among the individuals travelling between municipalities. Furthermore, the model incorporates the effect of age-dependent severity of COVID-19 and realistic trajectories of patients through the healthcare system. We assess the impact of the governmental non-pharmacological interventions, such as population-wide social distancing, social distancing within specific subsets of population, reduction of travel between the municipalities, and self-quarantining of the infected individuals. We also evaluate the impact of relaxing of strict restrictions, efficacy of the simple state feedback-based restrictions in controlling the outbreak, and the effect of superspreaders on the disease dynamics. Our simulations show that non-pharmacological interventions reduce the number of infected individuals and the number of fatalities, especially when the social distancing of particularly susceptible subgroups of the population is employed along with case isolation.


title: Associations of Global Country Profiles and Modifiable Risk Factors with COVID-19 Cases and Deaths

text: Modifiable risk factors affect SARS-CoV-2 infection and mortality raising the possibility that lifestyle modification could play a role. This has not been studied at a global level. We analysed publicly available data from countries reporting COVID-19 cases and deaths. Associations of modifiable risk factors with total cases and excess deaths were determined with and without adjustment for confounders. 4,670,832 cases and 311,384 deaths were reported by 181 countries by 18th May 2020. Wealthier countries had the greatest caseload. Obesity was the primary modifiable risk factor for infection and greater age, male sex, physical inactivity and low salt consumption were associated with excess deaths. Obesity was less influential on mortality than physical inactivity. Globally, obesity confers vulnerability to SARS-CoV-2 infection and physical inactivity likely explains the greater mortality in the obese. High salt consumption may induce reductions in tissue ACE2 expression and subsequently reduce mortality rates.


title: SARS-CoV-2 Nsp1 binds ribosomal mRNA channel to inhibit translation

text: The non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, is the first viral protein that is synthesized in SARS-CoV-2 infected human cells to suppress host innate immune functions1,2. By combining cryo-electron microscopy and biochemical experiments, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes including the 43S pre-initiation complex. The protein inserts its C-terminal domain at the entrance to the mRNA channel where it interferes with mRNA binding. We observe potent translation inhibition in the presence of Nsp1 in lysates from human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5’ untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines inhibition of translation by Nsp1 with efficient translation of the viral mRNA to achieve expression of viral genes3.


title: Development and application of Pandemic Projection Measures (PPM) for forecasting the COVID-19 outbreak

text: This study aims to provide an accessible and dynamic estimate method to project the Covid-19 trend and hopefully it will help inform policymakers to allocate the needed medical equipment and supplies for saving more lives. A set of newly developed Pandemic Projection Measures (PPM) had been successfully applied to project daily new cases across countries. During the development, numerous trial and error iterations had been performed and then improved with live data. The procedures and computations for the PPM including Uphill Index (UHI), Downhill Indices (DHI), and Error Band Projection (EBP) estimates were explained and discussed along with graphical projections. The PPM was computed with daily live data for the USA, four U.S. states (Illinois, Massachusetts, New Jersey, and New York), France, Italy, Spain, Germany, and China. The results indicated that with the PPM estimations, the daily projections for the future trend were robust to reflect the most plausibility, since the PPM can be updated frequently. With the most up-to-date predictions, governments should be able to monitor the values of UHI and DHI for making a better decision for flattening the curve. Based on the empirical data, policymakers should pay more attentions for the following two scenarios: a) When expecting an apex of the outbreak, the UHI is higher than 1.20; and b) After passing a peak day, the DHI is still larger than 0.925. The applications of the PPM estimates are not designed for a one-time projection rather than updated frequently to improve the prediction precisions. With the same concepts from the PPM computations, the peak day and the number of new deaths could be predictable if more data are collected. Like many country leaders saying, We will win the battle of coronavirus pandemic, the author hopes to use this easily applicable estimate method to save more lives and to win. The results, currently presented with the data on April 16 and 17, 2020, were only used to explain how to apply the PPM estimates for predictions. The outdated results should not be used to compared with today's outbreak trend.


title: Compliance and containment in social distancing: mathematical modeling of COVID-19 across townships

text: In the early development of COVID-19, large-scale preventive measures, such as border control and air travel restrictions, were implemented to slow international and domestic transmissions. When these measures were in full effect, new cases of infection would be primarily induced by community spread, such as the human interaction within and between neighboring cities and towns, which is generally known as the meso-scale. Existing studies of COVID-19 using mathematical models are unable to accommodate the need for meso-scale modeling, because of the unavailability of COVID-19 data at this scale and the different timings of local intervention policies. In this respect, we propose a meso-scale mathematical model of COVID-19 using town-level infection data in the state of Connecticut. We consider the spatial interaction in terms of the inter-town travel in the model. Based on the developed model, we evaluated how different strengths of social distancing policy enforcement may impact future epidemic curves based on two evaluative metrics: compliance and containment. The developed model and the simulation results will establish the foundation for community-level assessment and better preparation for COVID-19.


title: Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal–oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak.


title: SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus

text: Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=212 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across clinical and convalescent samples collected [≥]28 days post symptom onset, 0/244 (0%, 95%CI 0.0-1.5%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.


title: Linear epitope landscape of SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients

text: Neutralization antibodies and vaccines for treating COVID-19 are desperately needed. For precise development of antibodies and vaccines, the key is to understand which part of SARS-CoV-2 Spike protein is highly immunogenic on a systematic way. We generate a linear epitope landscape of Spike protein by analyzing serum IgG response of 1,051 COVID-19 patients with a peptide microarray. We reveal two regions that rich of linear epitopes, i.e., CTD and a region close to the S2' cleavage site and fusion peptide. Unexpectedly, we find RBD is lack of linear epitope. Besides 3 moderate immunogenic peptides from RBD, 16 highly immunogenic peptides from other regions of Spike protein are determined. These peptides could serve as the base for precise development of antibodies and vaccines for COVID-19 on a systematic level.


title: Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in 2019, is responsible for the COVID-19 pandemic. It is now accepted that the wild fauna, probably bats, constitute the initial reservoir of the virus, but little is known about the role pets can play in the spread of the disease in human communities, knowing the ability of SARS-CoV-2 to infect some domestic animals. We tested 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. Although a few pets presented many clinical signs indicative for a coronavirus infection, no animal tested positive for SARS-CoV-2 by RT-PCR and no antibodies against SARS-CoV-2 were detectable in their blood using an immunoprecipitation assay. These original data can serve a better evaluation of the host range of SARS-CoV-2 in natural environment exposure conditions.


title: Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

text: Viruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug.


title: HIGH LIVER FAT ASSOCIATES WITH HIGHER RISK OF DEVELOPING SYMPTOMATIC COVID-19 INFECTION - INITIAL UK BIOBANK OBSERVATIONS

text: Background A high proportion of COVID-19 patients develop acute liver dysfunction. Early research has suggested that pre-existing fatty liver disease may be a significant risk factor for hospitalisation. Liver fat, in particular, is a modifiable parameter and can be a target for public health policy and individual patient plans. In this study we aimed to assess pre-existing liver disease as a risk factor for developing symptomatic COVID-19. Methods From 502,506 participants from the UK Biobank, 42,146 underwent MRI (aged 45-82), and had measures of liver fat, liver fibroinflammatory disease and liver iron. Patients were censored on May 28th to determine how many had tested for COVID-19 with symptomatic disease. UK testing was restricted to those with symptoms in hospital. COVID-19 symptoms included fever, dry cough, sore throat, diarrhoea and fatigue. Univariate analysis was performed on liver phenotypic biomarkers to determine if these variables increased risk of symptomatic COVID-19, and compared to previously described risk factors associated with severe COVID-19, including to age, ethnicity, gender and obesity, Findings Increased liver fat was associated with a higher risk for symptomatic confirmed COVID-19 in this population in univariate analysis(OR:1.85, p=0.03). In obese participants, only those with concomitant fatty liver([≥]10%) were at increased risk(OR:2.96, p=0.02), with those having normal liver fat (<5%) showing no increased risk(OR:0.36, p=0.09). Conclusions UK Biobank data demonstrated an association between pre-existing liver disease and obesity with severe COVID-19, with higher proportions of liver fat in obese individuals a likely risk factor for symptomatic disease and severity. Public policy measures to protect patients with liver disease who may have almost double the risk of the general population should be considered, especially as dietary and pharmacological strategies to reduce body weight and liver fat already exist. Funding University of Oxford, Innovate UK, UK Biobank. Authors are employees of Perspectum Ltd.


title: Humoral immune response and prolonged PCR positivity in a cohort of 1343 SARS-CoV 2 patients in the New York City region

text: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The percentage of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can still be detected at considerable time post symptom resolution. Here we investigated both seroconversion and PCR-positivity in a large cohort of convalescent serum donors in New York City. Methods: Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via enzyme-linked immunosorbent assay for presence of anti SARS-CoV-2 spike antibodies. Results: All but three confirmed SARS-CoV-2 patients seroconverted to the SARS-CoV-2 spike while only 37.4% of suspected SARS-CoV-2 patients seroconverted. PCR-positivity was detected up to 28 days from symptom resolution. Conclusions: Here we show that the vast majority of confirmed COVID19 patients seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks post symptom resolution, but it is unclear if this signal represents infectious virus.


title: COVID-19 lockdown: if, when and how

text: Background: With the lack of an effective SARS-CoV-2 vaccine, mathematical modeling has stepped up in the COVID-19 management to guide non-pharmaceutical intervention (NPI) policies. Complete lockdown has been characterized as the most powerful strategy for the epidemic; anyhow, it is associated with undeniable negative consequences. Not aware that global panic could make countries adopt premature and lengthy lockdowns, previous studies only warned about the inefficacy of late quarantine sets. Therefore, we proposed ourselves to find the optimal timing and lasting for COVID-19 suppressive measures. Methods: We used our previously elaborated compartmental SEIR (Susceptible-Exposed-Infected-Recovered) model to scan different timings for lockdown set and various lockdown lengths under different reproduction number (R0) scenarios. We explored healthcare parameters focusing on ICU occupation and deaths since they condition the sanitary system and reflect the severity of the epidemic. Results: The timing for the lockdown trigger varies according to the original R0 and has great impact on ICU usage and fatalities. The less the R0 the later the lockdown should be for it to be effective. The lockdown length is also something to consider. Too short lockdowns (~15 days) have minimal effect on healthcare parameters, but too long quarantines (>45 days) do not benefit healthcare parameters proportionally when compared to more reasonable 30 to 45-day lockdowns. We explored the outcome of the combination of a 45-day lockdown followed by strict mitigation measures sustained in time, and interestingly, it outperformed the lengthy quarantine. Additionally, we show that if strict mitigation actions were to be installed from the very beginning of the epidemic, lockdown would not benefit substantially regarding healthcare parameters. Conclusion: Lockdown set timing and lasting are non-trivial variables to COVID-19 management.