title: Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities

text: Serology is a core component of the surveillance and management of viral zoonoses. Virus neutralization tests are a gold standard serological diagnostic, but requirements for large volumes of serum and high biosafety containment can limit widespread use. Here, focusing on Rabies lyssavirus, a globally important zoonosis, we developed a pseudotype micro-neutralization rapid fluorescent focus inhibition test (pmRFFIT) that overcomes these limitations. Specifically, we adapted an existing micro-neutralization test to use a green fluorescent protein–tagged murine leukemia virus pseudotype in lieu of pathogenic rabies virus, reducing the need for specialized reagents for antigen detection and enabling use in low-containment laboratories. We further used statistical analysis to generate rapid, quantitative predictions of the probability and titer of rabies virus neutralizing antibodies from microscopic imaging of neutralization outcomes. Using 47 serum samples from domestic dogs with neutralizing antibody titers estimated using the fluorescent antibody virus neutralization test (FAVN), pmRFFIT showed moderate sensitivity (78.79%) and high specificity (84.62%). Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. Our test uses a starting volume of 3.5 μL of serum, estimates titers from a single dilution of serum rather than requiring multiple dilutions and end point titration, and may be adapted to target neutralizing antibodies against alternative lyssavirus species. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained.


title: Merck KGaA to double virus manufacturing

text: Merck KGaA is investing in the contract manufacturing of viruses used in viral vaccines, gene therapy, and engineered cell therapies The firm will spend more than $100 million on a 13,000 m2 plant in Carlsbad, California, that will more than double the combined capacity of its existing facilities in Carlsbad and Glasgow, Scotland The new site will be equipped to make viruses for clinical trials and commercial products Merck recently said it will support large-scale manufacturing of a COVID-19 vaccine developed at the University of Oxford View: PDF ;Full Text HTML


title: An Extended Laboratory Validation Study and Comparative Performance Evaluation of the Abbott ID NOW COVID-19 Assay in a Coastal California Tertiary Care Medical Center

text: Abstract: The Abbott ID NOW COVID-19 assay is a rapid molecular diagnostic test particularly designed for on-site, rapid turnaround point of care (POC) testing. The utilization of rapid diagnostic tests is integral to optimizing workflow within the hospital and/or procedural-based clinics. The capability to provide both rapid disposition and correct patient classification during this COVID-19 pandemic is critically important with broad infection control implications for both patients and healthcare staff. A tightly controlled, extended laboratory validation was performed at our medical center to determine the negative test agreement of the Abbott ID NOW compared with the BD MAX analyzer, a laboratory-based, two target, molecular analyzer with a sensitive cycle threshold (Ct) positive cutoff value of 42. There was strict adoption of the procedures listed in the Abbott ID NOW Instruction for Use (IFU)1 insert delineating preferred practices for optimal test performance. Under these conditions, our institution demonstrated a significant negative percent agreement with 116 out of 117 patients correlating, which equates to a 99.1% concordance similar to a recently reported correlation study2.


title: Characterization of 100 sequential SARS-CoV-2 convalescent plasma donations

text: Transfusion of SARS-CoV-2 convalescent plasma is a promising treatment for severe COVID-19 cases, with success of the intervention based on neutralizing antibody content. Measurement by serological correlates without biocontainment needs, and an understanding of donor characteristics that may allow for targeting of more potent donors would greatly facilitate effective collection.


title: Recommendations for a safety dental care management during SARS-CoV-2 pandemic

text: As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted mainly through droplets, sneezes and aerosols, there is a high risk of transmission during dental procedures. This report describes measures that can be adopted by oral healthcare personnel to minimize the risk of cross-contamination in clinical practice during the current SARS-CoV-2 pandemic.


How Top Cancer Centers Have Responded During COVID-19


title: Prioritizing COVID-19 tests based in Participatory Surveillance and Spatial Scanning.

text: Objectives The aim of this study was to describe and analyze the generation of priority areas for Covid-19 testing combining participatory surveillance and traditional surveillance. Design The study is a descriptive transversal, where was performed in the city of Caruaru, Pernambuco state, within the period of 20/02/2020 to 05/05/2020. It was considered all official reports for flu syndromes notified by municipality health department and the data collected through the participatory surveillance platform Brasil Sem Corona. Methods To verify a correlation between Participatory Surveillance (PS) and Traditional Surveillance (TS), it was carried out a linear regression. Results The PS has showed in Caruaru 861 active users, presenting an average of 1.2 report per user per week. It was started in March 20th and is officially used by the local health authority in order to improve the quality of information from traditional surveillance system. Regarding to the respiratory syndrome cases from TS, it was found out 1,588 individuals that were positive for this clinical outcome. The spatial scanning analysis has detected 18 clusters and 6 of them have presented statistical significance (p-value < 0.1). Clusters 3 and 4 presented an overlapping and this area was chosen by local authority to deploy the Covid-19 serology, where 50 individuals were tested. From there, 32% (n=16) presented reagent results for antibodies related to Covid-19. Conclusion The use of alternative methods as participatory surveillance showed a relevant role taking advantage on the insertion at community levels to complement traditional surveillance system.


title: Factors affecting COVID-19 outcomes in cancer patients - A first report from Guys Cancer Centre in London

text: Background: There is insufficient evidence to support clinical decision-making for oncology patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a large UK Cancer Centre to assess demographic/clinical characteristics of 106 cancer patients with a confirmed COVID-19 diagnosis between 29 February-15 April 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 87 (82%) presented with mild/moderate COVID-19 and 19(18%) with severe disease. Age, sex, ethnicity, SES, and current cancer treatment were not associated with COVID-19 severity. Initial diagnosis of cancer >24m before COVID-19 (OR:3.01 (95%CI: 1.02-8.58)), presenting with fever, dyspnoea, gastro-intestinal symptoms, or higher levels of CRP and ferritin were linked with greater COVID-19 severity. During median follow-up of 17.5d, 14 patients had died of COVID-19(13%). Conclusions: Low SES, hypertension and non-malignant lung disease were common in cancer patients with COVID-19. A longer-established diagnosis of cancer was associated with increasing severity of infection, possibly reflecting effects of more advanced malignant disease on impact of this infection. Advanced age and comorbidities may be associated with an increased risk of COVID-19-related death in cancer patients, as has been reported for general populations without cancer.


title: European lockdowns and the consequences of relaxation during the COVID-19 pandemic

text: This paper investigates the lockdowns introduced in France, Germany, Italy, Spain and the UK using data on the daily number of confirmed cases, deaths and, in the case of the UK, hospital numbers. The analysis employs a two-stage SEIR model with different reproductive numbers pre- and post-lockdown, which have been estimated from the data for each country. The model is evaluated by considering its predictive accuracy on current data and it is then deployed to explore the potential consequences of partial relaxations of the lockdowns. The results suggest that there is a substantial difference between relaxations of 25% and 50% with respect to the pre-lockdown situation. The latter could lead to second peaks that are higher than the earlier peaks in all of the countries. The former would likely be very serious in the UK, would halt the decline in numbers in most countries and could lead to second peaks in some countries. Calculations also suggest that a relaxation of no more than about 10-15% would be needed if cases of COVID-19 are to continue to decline in all five countries.


title: Multiple SARS-CoV-2 introductions shaped the early outbreak in Central Eastern Europe: comparing Hungarian data to a worldwide sequence data-matrix

text: Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019 the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of the 21th of April, 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.


title: Multi-chain Fudan-CCDC model for COVID-19 in Iran

text: Background: COVID-19 has been deeply affecting people's lives all over the world. It is significant for prevention and control to model the evolution effectively and efficiently . Methods: We first propose the multi-chain Fudan-CCDC model which is based on the original single-chain model to describe the revival of COVID-19 in some countries. Multi-chains are considered as the superposition of distinctive single chains. Parameter identification is carried out by minimizing the penalty function. Results: From results of numerical simulations, the multi-chain model performs well on data fitting and reasonably interprets the revival phenomena. The band of 25% fluctuation of simulation results could contain most seemly unsteady increments. Conclusion: The multi-chain model has better performance on data fitting in revival situations compared with the single-chain model. It is predicted by the three-chain model with data by Apr 21 that the epidemic curve of Iran would level off on round May 10, and the final cumulative confirmed cases would be around 88820. The upper bound of the 95% confidence interval would be around 96000.


title: A single holiday was the turning point of the COVID-19 policy of Israel

text: Background: The impact of COVID-19 has been profound, and the public health challenge seem to be the most serious regarding respiratory viruses since the 1918 H1N1 influenza pandemic. In the absence of effective vaccine or biomedical treatment, the basic rules of public health measures have not changed, namely public distancing. Methods: We analyzed epidemiological investigation reports during the first month of the outbreak in Israel. In addition, we present a deterministic compartment model and simulations of several scenarios emphasizing quarantine and isolation policies given their efficiency. Results: We identify an abrupt change from controlled epidemic regime to an exponential growth (R_0= 2.19) in light of the actual policy-makers decisions and public behavior in Israel. Our analysis show that before the abrupt change, the new cases trend was due to returning citizens infected abroad. The abrupt change followed a holiday in which social distancing was clearly inefficient and many public gatherings were held. We further discuss three different modeled scenarios of quarantine efficiency: high-, medium-, and low-efficiency. Conclusions: Israel early lessons show that there is no allowance to compromise with the directive of social distancing. Even before the onset of the pandemic in Israel, fine-tuned but determined early decisions were taken by policy makers to monitor flight arrivals from Covid-19 affected regions and to limit public gatherings. Our analysis show that one particular holiday has shifted the occurrence curve from controlled regime to exponential growth. Therefore, even a short lapse in public responsiveness can have a dramatic effect.


title: Comparison of renin-angiotensin-aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes: systematic review and meta-analysis

text: Introduction: The effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies. This meta-analysis was undertaken to provide more conclusive evidence. Methods: A systematic search for published articles was performed in PubMed and EMBASE from January 5 2020 till May 5 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). Results: A total of 6,997 patients with COVID-19 were included, and all of them had hypertension. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). In addition, comparison of ACEIs to the rest of non-ACEI antihypertensives gave a consistently decreased risk of poor COVID-19 outcome (OR=0.77, 95% CI: [0.63-0.93]; P=0.002). However, ARBs did not decrease the risk of poor COVID-19 outcomes compared to all other non-ARB antihypertensives (OR=1.13, 95% CI: [0.95-1.35]). Conclusion: The risk of developing severe illness or death from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. ACEIs might be better in decreasing the severity and mortality of COVID-19 than ARBs.


title: Oscillations in USA COVID-19 Incidence and Mortality Data reflect societal factors

text: The COVID-19 pandemic currently in process differs from other infectious disease calamities that have previously plagued humanity in the vast amount of information that is produces each day, which includes daily estimates of the disease incidence and mortality data. Apart from providing actionable information to public health authorities on the trend of the pandemic, the daily incidence reflects the process of disease in a susceptible population and thus reflects the pathogenesis of COVID-19, the public health response and diagnosis and reporting. Both daily new cases and daily mortality data in the US exhibit periodic oscillatory patterns. By analyzing NYC and LA testing data, we demonstrate that this oscillation in the number of cases can be strongly explained by the daily variation in testing. This seems to rule out alternative hypotheses such as increased infections on certain days of the week as driving this oscillation. Similarly, we show that the apparent oscillation in mortality in the US data is mostly an artifact of reporting, which disappears in datasets that record death by episode date, such as the NYC and LA datasets. Periodic oscillations in COVID-19 incidence and mortality data reflect testing and reporting practices and contingencies. Thus, these contingencies should be considered first prior to suggesting social or biological mechanisms.


title: Analysis of factors associated early diagnosis in coronavirus disease 2019 (COVID-19)

text: Background The pandemic of coronavirus disease 2019 (COVID-19) has become the first concern in international affairs as the novel coronavirus (SARS-CoV-2) is spreading all over the world at a terrific speed. The accuracy of early diagnosis is critical in the control of the spread of the virus. Although the real-time RT-PCR detection of the virus nucleic acid is the current golden diagnostic standard, it has high false negative rate when only apply single test. Objective Summarize the baseline characteristics and laboratory examination results of hospitalized COVID-19 patients. Analyze the factors that could interfere with the early diagnosis quantitatively to support the timely confirmation of the disease. Methods All suspected patients with COVID-19 were included in our study until Feb 9th, 2020. The last day of follow-up was Mar 20th, 2020. Throat swab real-time RT-PCR test was used to confirm SARS-CoV-2 infection. The difference between the epidemiological profile and first laboratory examination results of COVID-19 patients and non-COVID-19 patients were compared and analyzed by multiple logistic regression. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the potential diagnostic value in factors, which had statistical differences in regression analysis. Results In total, 315 hospitalized patients were included. Among them, 108 were confirmed as COVID-19 patients and 207 were non-COVID-19 patients. Two groups of patients have significance in comparing age, contact history, leukocyte count, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate (p<0.10). Multiple logistic regression analysis showed age, contact history and decreasing lymphocyte count could be used as individual factor that has diagnostic value (p<0.05). The AUC of first RT-PCR test was 0.84 (95% CI 0.73-0.89), AUC of cumulative two times of RT-PCR tests was 0.92 (95% CI 0.88-0.96) and 0.96 (95% CI 0.93-0.99) for cumulative three times of RT-PCR tests. Ninety-six patients showed typical pneumonia radiological features in first CT scan, AUC was 0.74 (95% CI 0.60-0.73). The AUC of patients age, contact history with confirmed people and the decreased lymphocytes were 0.66 (95% CI 0.60-0.73), 0.67 (95% CI 0.61-0.73), 0.62 (95% CI 0.56-0.69), respectively. Taking chest CT scan diagnosis together with patients age and decreasing lymphocytes, AUC would be 0.86 (95% CI 0.82-0.90). The age threshold to predict COVID-19 was 41.5 years, with a diagnostic sensitivity of 0.70 (95% CI 0.61-0.79) and a specificity of 0.59 (95% CI 0.52-0.66). Positive and negative likelihood ratios were 1.71 and 0.50, respectively. Threshold of lymphocyte count to diagnose COVID-19 was 1.53x109/L, with a diagnostic sensitivity of 0.82 (95% CI 0.73-0.88) and a specificity of 0.50 (95% CI 0.43-0.57). Positive and negative likelihood ratios were 1.64 and 0.37, respectively. Conclusion Single RT-PCR test has relatively high false negative rate. When first RT-PCR test show negative result in suspected patients, the chest CT scan, contact history, age and lymphocyte count should be used combinedly to assess the possibility of SARS-CoV-2 infection.


title: Impact of Daily Weather on COVID-19 outbreak in India

text: The COVID-19 pandemic has outspread obstreperously in India. As of June 04, 2020, more than 2 lakh cases have been confirmed with a death rate of 2.81%. It has been noticed that, out of each 1000 tests, 53 result positively infected. In order to investigate the impact of weather conditions on daily transmission occurring in India, daily data of Maximum (TMax), Minimum (TMin), Mean (TMean) and Dew Point Temperature (TDew), Diurnal Temperature range (TRange), Average Relative Humidity, Range in Relative Humidity, and Wind Speed (WS) over 9 most affected cities are analysed in several time frames: weather of that day, 7, 10, 12, 14, 16 days before transmission. Spearman rank correlation (r) shows significant but low correlation with most of the weather parameters, however, comparatively better association exists on 14 days lag. Diurnal range in Temperature and Relative Humidity shows non-significant correlation. Analysis shows, COVID-19 cases likely to be increased with increasing air temperature, however role of humidity is not clear. Among weather parameters, Minimum Temperature was relatively better correlate than other. 80% of the total confirmed cases were registered when TMax, TMean, TMin, TRange, TDew, and WS on 12-16 days ago vary within a range of 33.6-41.3 deg C, 29.8-36.5 deg C, 24.8-30.4 deg C, 7.5-15.2 deg C, 18.7-23.6 deg C, and 4.2-5.75 m/s respectively, hence, it gives an idea of susceptible weather conditions for such transmission in India. Using Support Vector Machine based regression, the daily cases are profoundly estimated with more than 80% accuracy, which indicate that coronavirus transmission cannot be well linearly correlated with any single weather parameters, rather multivariate non-linear approach must be employed. Accounting lag of 12-16 days, the association found to be excellent, thus depict that there is an incubation period of 12-16 days for coronavirus transmission in Indian scenario.


title: Evaluation of 30-day mortality for 500 patients undergoing non-emergency surgery in a COVID-19 cold site within a multicentre regional surgical network during the COVID-19 pandemic

text: Background Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. Objective To determine whether it is feasible and safe to continue non-emergency surgery in the COVID-19 pandemic Design, setting and participants This is a cohort study of 500 consecutive patients undergoing non-emergency surgery in a dedicated COVID-19 cold site following the first case of COVID-19 that was reported in the institution. The study was carried out during the peak of the pandemic in the United Kingdom, which currently has one of the highest number of cases and deaths from COVID-19 globally. We set up a hub-and-spoke surgical network amongst 14 National Health Service institutions during the pandemic. The hub was a cancer centre, which was converted into a COVID-19 cold site, performing urological, thoracic, gynaecological and general surgical operations. Outcomes The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. Results 500 patients underwent surgery with median age 62.5 (IQR 51-71). 65% were male and 60% had a known diagnosis of cancer. 44% of surgeries were performed with robotic or laparoscopic assistance and 61% were considered complex or major operations. None of the 500 patients undergoing surgery died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. Conclusion It is safe to continue non-emergency surgery during the COVID-19 pandemic with appropriate service reconfiguration.


title: A high efficient hospital emergency responsive mode is the key of successful treatment of 100 COVID-19 patients in Zhuhai

text: Background: Since December 2019, Coronavirus Disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. The mortality of novel coronavirus pneumonia (NCP) in severe and critical cases is very high. Facing this kind of public health emergency, high efficient administrative emergency responsive mode in designated hospital is needed. Method: As an affiliated hospital of Sun Yat-sen University, our hospital is the only designated one for diagnosis and treatment of COVID-19 in Zhuhai, a medium-sized city. Novel coronavirus pneumonia department, which is administrative led by the president of hospital directly, has been established at early stage of epidemic crisis in my hospital. In NCP department, there are core members of Pulmonary and Critical Care Medicine (PCCM) specialist and multidisciplinary team. Don't stick to national guidelines of NCP, based on professional opinion by respiratory professor and expert group, we focused on individualized treatment and timely adjustment of treatment and management strategies in working about COVID-19 patients. Results: 1. High working efficiency: By Mar 02, 2020, we have completed 2974 citywide consultations and treatment of 366 inpatients, including 101 patients diagnosed with COVID-19. 2. Excellent therapeutic effectAmong 101 hospitalized patients with confirmed COVID-19, all were cured and discharged, except for one death. No secondary hospital infection, no pipeline infection and no pressure sore were found in all patients. 3. Finding and confirming person-to-person transmission characteristic of COVID-19 prior to official release conference: Strengthened protection is key point to zero infection in healthcare group and medical faculty and lower rate of second generation infectious patients. 4. Timely adjustment management and treatment strategy prior to guideline update: The first evidence of digestive tract involvement in COVID-19 has been found, and the earliest clinical trial of chloroquine in the treatment of COVID-19 has been carried out in our hospital. Conclusions: In our hospital, establishment of NCP department, which is administratively led by the president of hospital directly and specialized conduct by respiratory professor, is the key to success in management and treatment of COVID-19 patients. This hospital emergency responsive mode could provide reference for other hospitals and cities in epidemic situation.


title: Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota

text: The immediate call for translational research in the field of coronavirus disease (COVID-19) pandemic, needs new and unexplored angles to support and contribute to this important worldwide health problem. The aim of this study is to better understand the pathogenic mechanisms underlying COVID-19, deciphering the carbohydrate-mediated interactions of the SARS-CoV-2 spike protein. We studied the carbohydrate-binding receptors that could be important for viral entry and for immune-modulatory responses, and we studied the interactions of the spike protein with the host lung microbiota. Exploring solid-phase immunoassays, we evaluated the interactions between the SARS-CoV-2 spike protein and a library of 12 different human carbohydrate-binding proteins (C-type lectins and Siglecs) involved in binding, triggering and modulation of innate and adaptive immune-responses. We revealed a specific binding of the SARS-CoV-2 spike protein to the receptors DC-SIGN, MGL, Siglec-9 and Siglec-10 that are all expressed on myeloid immune cells. In addition, because the lung microbiota can promote or modulate viral infection, we studied the interactions between the SARS-CoV-2 spike protein and a library of Streptococcus pneumoniae capsular polysaccharides, as well as other bacterial glyco-conjugates. We show specific binding of the spike protein to different S. pneumoniae capsular polysaccharides (serotypes 19F and 23F but not to serotype 14). Moreover we demonstrated a specific binding of SARS-CoV-2 spike protein to the lipopolysaccharide from the opportunistic human pathogen Pseudomonas aeruginosa, one of the leading cause of acute nosocomial infections and pneumonia. Interestingly, we identified rhamnosylated epitopes as one of the discriminating structures in lung microbiota to bind SARS-CoV-2 spike protein. In conclusion, we revealed novel ACE2-independent carbohydrate-mediated interactions with immune modulating lectins expressed on myeloid cells, as well as host lung microbiota glyco-conjugates. Our results identified new molecular pathways using host lectins and signalling, that may contribute to viral infection and subsequent immune exacerbation. Moreover we identified specific rhamnosylated epitopes in lung microbiota to bind SARS-CoV-2, providing a hypothetical link between the presence of specific lung microbiota and SARS-CoV-2 infection and severity.


title: The effectiveness and perceived burden of nonpharmaceutical interventions against COVID-19 transmission: a modelling study with 41 countries

text: Background: Existing analyses of nonpharmaceutical interventions (NPIs) against COVID19 transmission have focussed on the joint effectiveness of large-scale NPIs. With increasing data, we can move beyond estimating aggregate effects, to understanding the effects of individual interventions. In addition to effectiveness, policy decisions ought to reflect the burden different NPIs put on the population. Methods: To our knowledge, this is the largest data-driven study of NPI effectiveness to date. We collected chronological data on 9 NPIs in 41 countries between January and April 2020, using extensive fact-checking to ensure high data quality. We infer NPI effectiveness with a novel semi-mechanistic Bayesian hierarchical model, modelling both confirmed cases and deaths to increase the signal from which NPI effects can be inferred. Finally, we study the burden imposed by different NPIs with an online survey of preferences using the MaxDiff method. Results: Six NPIs had a >97.5% posterior probability of being effective: closing schools (mean reduction in R: 58%; 95% credible interval: 50% - 64%), limiting gatherings to 10 people or less (24%; 6% - 39%), closing nonessential businesses (23%; 5% - 38%), closing high-risk businesses (19%; 1% - 34%), testing patients with respiratory symptoms (18%; 8% - 26%), and stay-at-home orders (17%; 5% - 28%). These results show low sensitivity to 12 forms of varying the model and the data. The model makes sensible forecasts for countries and periods not seen during training. We combine the effectiveness and preference results to estimate effectiveness-to-burden ratios. Conclusions: Our results suggest a surprisingly large role for schools in COVID-19 transmission, a contribution to the ongoing debate about the relevance of asymptomatic carriers in disease spreading. We identify additional interventions with good effectiveness-burden tradeoffs, namely symptomatic testing, closing high-risk businesses, and limiting gathering size. Closing most nonessential businesses and issuing stay-at-home orders impose a high burden while having a limited additional effect.


title: Epidemic analysis of COVID-19 in China by dynamical modeling

text: The outbreak of the novel coronavirus (2019-nCoV) epidemic has attracted world- wide attention. Herein, we propose a mathematical model to analyzes this epidemic, based on a dynamic mechanism that incorporating the intrinsic impact of hidden la- tent and infectious cases on the entire process of transmission. Meanwhile, this model is validated by data correlation analysis, predicting the recent public data, and back- tracking, as well as sensitivity analysis. The dynamical model reveals the impact of various measures on the key parameters of the epidemic. According to the public data of NHCs from 01/20 to 02/09, we predict the epidemic peak and possible end time for 5 different regions. The epidemic in Beijing and Shanghai, Mainland/Hubei and Hubei/Wuhan, are expected to end before the end of February, and before mid- March respectively. The model indicates that, the outbreak in Wuhan is predicted to be ended in the early April. As a result, more effective policies and more efforts on clinical research are demanded. Moreover, through the backtracking simulation, we infer that the outbreak of the epidemic in Mainland/Hubei, Hubei/Wuhan, and Wuhan can be dated back to the end of December 2019 or the beginning of January 2020.


title: Controlled Avalanche: A Regulated Voluntary Exposure Approach for Addressing Covid19

text: Background: The ongoing Covid-19 pandemic has driven many countries to take radical suppression measures. While reducing mortality, these measures result in severe economic repercussions, and inhibit the development of herd immunity. Until an effective vaccine will be available, we propose an alternative approach, akin to avalanche control at ski resorts, a practice which intentionally triggers small avalanches in order to prevent a singular catastrophic one. Its main goal is to approach herd immunity faster than the current alternatives, with lower mortality rates and lower demand for critical health-care resources. According to this approach, individuals whose probability of developing serious health conditions is low (i.e. 20-49 years old with no comorbidities) will be offered the option to be voluntarily exposed to the virus under controlled supervision, and will then be issued 'immunity certificates' if they are confirmed to have developed SARS-CoV-2 antibodies. Methods: Using a compartmental model we examine the implications of the controlled avalanche (CA) strategy over the population in Israel. We compare four scenarios: in two scenarios the CA program is applied to the low-risk population (with the rest of the population subject to mitigation measures), followed by mitigation for the entire population or by uncontrolled spread. These are compared to mitigated and uncontrolled scenarios without the CA program. We discuss the economic, ethical and public health implications of the CA strategy. Findings: We show that compared to mitigation of the entire population, the CA strategy reduces the overall mortality by 43%, reduces the maximum number of people in need for ICUs by 62% and decreases the time required for release of 50% of the low-risk population by more than 2 months. Interpretation: This study suggests an ethically acceptable practice, that enables reaching herd immunity faster than the current alternatives, with low mortality and minimal economic damage.


title: Do Face Masks Create a False Sense of Security? A COVID-19 Dilemma

text: Face masks have become an emblem of the public response to COVID-19, with many governments mandating their use in public spaces. The logic is that face masks are low cost and might help prevent some transmission. However, from the start, the assumption that face masks are "low cost" was questioned. Early on, there were warnings of the opportunity cost of public use of medical masks given shortages of personal protective equipment for healthcare providers. This led to recommendations for cloth masks and other face coverings, with little evidence of their ability to prevent transmission. However, there may also be a high cost to these recommendations if people rely on face masks in place of other more effective ways to break transmission, such as staying home. We use SafeGraph smart device location data to show that the representative American in states that have face mask mandates spent 20-30 minutes less time at home, and increase visits to a number of commercial locations, following the mandate. Since the reproductive rate of SAR-COV2, the pathogen that causes COVID-19 is hovering right around one, such substitution behavior could be the difference between controlling the epidemic and a resurgence of cases.


title: Lifestyle acquired immunity, decentralized intelligent infrastructures and revised healthcare expenditures may limit pandemic catastrophe: a lesson from COVID-19

text: Human race has often faced pandemic with substantial number of fatalities. As COVID-19 pandemic reached and endured in every corner on earth, countries with moderate to strong healthcare support and expenditure seemed to struggle in containing disease transmission and casualties. COVID-19 affected countries have variability in demographic, socioeconomic and life style health indicators. At this context it is important to find out at what extent these parametric variations are actually modulating disease outcomes. To answer this, we have selected demographic, socioeconomic and health indicators e.g. population density, percentage of urban population, median age, health expenditure per capita, obesity, diabetes prevalence, alcohol intake, tobacco use, case fatality of non communicable diseases (NCDs) as independent variables. Countries were grouped according to these variables and influence on dependent variables e.g. COVID-19 test positive, case fatality and case recovery rates were statistically analyzed. The results suggest that countries with variable median age has significantly different outcome on test positive rate (P<0.01). Both median age (P=0.0397) and health expenditure per capita (P=0.0041) has positive relation with case recovery. Increasing number of test per 100K population showed positive and negative relation with number of positives per 100K population (P=0.0001) and percentage of test positives (P<0.0001) respectively. Alcohol intake per capita in liter (P=0.0046), diabetes prevalence (P=0.0389) and NCDs mortalities (P=0.0477) also showed statistical relation with case fatality rate. Further analysis revealed that countries with high healthcare expenditure along with high median age and increased urban population showed more case fatality but also had better recovery rate. Investment in health sector alone is insufficient in controlling pandemic severity. Intelligent and sustainable healthcare both in urban and rural settings and healthy lifestyle acquired immunity may reduce disease transmission and comorbidity induced fatalities respectively.


title: Turbulence characteristics of the B\"{o}dewadt layer in a large enclosed rotor-stator system

text: A three-dimensional (3D) direct numerical simulation is combined with a laboratory study to describe the turbulent flow in an enclosed annular rotor-stator cavity characterized by a large aspect ratio G=(b-a)/h=18.32 and a small radius ratio a/b=0.152, where a and b are the inner and outer radii of the rotating disk and h is the interdisk spacing. The rotation rate Omega under consideration is equivalent to the rotational Reynolds number Re=Omegab2/nu=9.5 x 104, where nu is the kinematic viscosity of the fluid. This corresponds to a value at which an experiment carried out at the laboratory has shown that the stator boundary layer is turbulent, whereas the rotor boundary layer is still laminar. Comparisons of the 3D computed solution with velocity measurements have given good agreement for the mean and turbulent fields. The results enhance evidence of weak turbulence at this Reynolds number, by comparing the turbulence properties with available data in the literature. An approximately self-similar boundary layer behavior is observed along the stator side. The reduction of the structural parameter a1 under the typical value 0.15 and the variation in the wall-normal direction of the different characteristic angles show that this boundary layer is three-dimensional. A quadrant analysis of conditionally averaged velocities is performed to identify the contributions of different events (ejections and sweeps) on the Reynolds shear stress producing vortical structures. The asymmetries observed in the conditionally averaged quadrant analysis are dominated by Reynolds stress-producing events in this B\"{o}dewadt layer. Moreover, case 1 vortices (with a positive wall induced velocity) are found to be the major source of generation of special strong events, in agreement with the conclusions of Lygren and Andersson.


title: Sofosbuvir protects human brain organoids against SARS-CoV-2

text: COVID-19 was rapidly declared a pandemic by the World Health Organization, only three months after the initial outbreak in Wuhan, China. Early clinical care mainly focused on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are also emerging. To determine whether SARS-CoV-2 could target the human brain, we infected iPSC-derived human brain organoids. Our findings show that SARS-CoV-2 was able to infect and kill neural cells, including cortical neurons. This phenotype was accompanied by impaired synaptogenesis. Finally, Sofosbuvir, an FDA-approved antiviral drug, was able to rescue these alterations. Given that there are currently no vaccine or antiviral treatments available, urgent therapies are needed. Our findings put Sofosbuvir forward as a potential treatment to alleviate COVID-19-related neurological symptoms. One Sentence Summary SARS-CoV-2 infection causes neuronal death and impaired synaptogenesis, both rescued by Sofosbuvir treatment.


Does the direct renin inhibitor have a role to play in attenuating severity of the outbreak coronavirus disease 2019 (COVID-19)?


title: EARLY ESTIMATION OF REPRODUCTION NUMBER OF COVID-19 IN VIETNAM

text: Reproduction number is an epidemiologic indicator that reflects the contagiousness and transmissibility of infectious agents. This paper aims to estimate the reproduction number of in the early phase of COVID-19 outbreak in Vietnam.


docid: xdxhsdyz

title: Distinguish Coronavirus Disease 2019 Patients in General Surgery Emergency by CIAAD Scale: Development and Validation of a Prediction Model Based on 822 Cases in China

text: IMPORTANCE In the epidemic, surgeons cannot distinguish infectious acute abdomen patients suspected COVID-19 quickly and effectively. OBJECTIVE To develop and validate a predication model, presented as nomogram and scale, to distinguish infectious acute abdomen patients suspected coronavirus disease 2019 (COVID-19). DESIGN Diagnostic model based on retrospective case series. SETTING Two hospitals in Wuhan and Beijing, China. PTRTICIPANTS 584 patients admitted to hospital with laboratory confirmed SARS-CoV-2 from 2 Jan 2020 to15 Feb 2020 and 238 infectious acute abdomen patients receiving emergency operation from 28 Feb 2019 to 3 Apr 2020. METHODS LASSO regression and multivariable logistic regression analysis were conducted to develop the prediction model in training cohort. The performance of the nomogram was evaluated by calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA) and clinical impact curves in training and validation cohort. A simplified screening scale and managing algorithm was generated according to the nomogram. RESULTS Six potential COVID-19 prediction variables were selected and the variable abdominal pain was excluded for overmuch weight. The five potential predictors, including fever, chest computed tomography (CT), leukocytes (white blood cells, WBC), C-reactive protein (CRP) and procalcitonin (PCT), were all independent predictors in multivariable logistic regression analysis (p[≤]0.001) and the nomogram, named COVID-19 Infectious Acute Abdomen Distinguishment (CIAAD) nomogram, was generated. The CIAAD nomogram showed good discrimination and calibration (C-index of 0.981 (95% CI, 0.963 to 0.999) and AUC of 0.970 (95% CI, 0.961 to 0.982)), which was validated in the validation cohort (C-index of 0.966 (95% CI, 0.960 to 0.972) and AUC of 0.966 (95% CI, 0.957 to 0.975)). Decision curve analysis revealed that the CIAAD nomogram was clinically useful. The nomogram was further simplified into the CIAAD scale. CONCLUSIONS We established an easy and effective screening model and scale for surgeons in emergency department to distinguish COVID-19 patients from infectious acute abdomen patients. The algorithm based on CIAAD scale will help surgeons manage infectious acute abdomen patients suspected COVID-19 more efficiently.


title: Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank

text: Background: Coronavirus disease 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown. Objective: To investigate the association between circulating IGF-1 concentrations and mortality risk among COVID-19 patients. Design: Prospective analysis. Setting: UK Biobank. Participants: 1425 COVID-19 patients who had pre-diagnostic serum IGF-1 measurements at baseline (2006-2010). Main outcome measures: COVID-19 mortality (available death data updated to 22 May 2020). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality across the IGF-1 quartiles. Results: Among 1425 COVID-19 patients, 365 deaths occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 37% lower risk of mortality (OR: 0.63, 95% CI: 0.43-0.93, P-trend=0.03). The association was stronger in women and nonsmokers (both P-interaction=0.01). Conclusions: Higher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.


title: Cytosine deamination in SARS-CoV-2 leads to progressive CpG depletion

text: RNA viruses use CpG reduction to evade the host cell defense, but the driving mechanism is still largely unknown. To address this, we used rapidly growing genomic dataset of SARS-CoV-2 with relevant metadata information. SARS-CoV-2 genomes show a progressive increase of C-to-U substitutions resulting in CpG loss over just a few months. This is consistent with APOBEC-mediated RNA editing resulting in CpG reduction, thus allowing the virus to escape ZAP-mediated RNA degradation. Our results thus link the dynamics of target sequences in viral genome for two known host molecular defense mechanisms, the APOBEC and ZAP proteins.


title: Genes Encoding ACE2, TMPRSS2 and Related Proteins Mediating SARS-CoV-2 Viral Entry are Upregulated with Age in Human Cardiomyocytes

text: Age is an independent risk factor for adverse outcome in patients following COVID-19 infection. We hypothesised that differential expression of genes encoding proteins proposed to be required for entry of SARS-Cov-2 in aged compared to younger cardiomyocytes might contribute to the susceptibility of older individuals to COVID-19-associated cardiovascular complications. We generated strand-specific RNA-sequencing libraries from RNA isolated from flow-sorted cardiomyocyte nuclei from left ventricular tissue. RNASeq data were compared between five young (19-25yr) and five older (63-78yr) Caucasian males who had not been on medication or exhibited evidence of cardiovascular disease post-mortem. Expression of relevant genes encoding ACE2, TMPRSS2, TMPRS11D, TMPRS11E, FURIN, CTSL, CTSB and B0AT1/SLC6A19 were upregulated in aged cardiomyocytes and the combined relative cardiomyocyte expression of these genes correlated positively with age. Genes encoding proteins in the RAAS and interferon/interleukin pathways were also upregulated such as ACE, AGTR1, MAS1 and IL6R. Our results highlight SARS-CoV-2 related genes that have higher expression in aged compared with young adult cardiomyocytes. These data may inform studies using selective enzyme inhibitors/antagonists, available as experimental compounds or clinically approved drugs e.g. remdesivir that has recently been rapidly accepted for compassionate use, to further understand the contribution of these pathways in human cardiomyocytes to disease outcome in COVID-19 patients.


title: Assessing functional propagation patterns in COVID-19

text: Among the many efforts done by the scientific community to help coping with the COVID-19 pandemic, one of the most important has been the creation of models to describe its propagation, as these are expected to guide the deployment of containment and health policies. These models are commonly based on exogenous information, as e.g. mobility data, whose limitedness always compromise the reliability of obtained results. In this contribution we propose a different approach, based on extracting relationships between the evolution of the disease in different regions through information theoretical metrics. In a way similar to what is commonly done in neuroscience, propagation is understood as information transfer, and the resulting propagation patterns are represented and studied as functional networks. By applying this methodology to the dynamics of COVID-19 in several countries and regions thereof, we were able to reconstruct static and time-varying propagation graphs. We further discuss the advantages, promises and open research questions associated with this functional approach.


Is case fatality rate an appropriate index to represent the status of case-finding process for COVID-19 in different countries?


docid: zwyueevh

title: Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in Uganda

text: Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of COVID-19 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.


title: A Light-weight Text Summarizer for Fast Access to Medical Evidence

text: The performances of current medical text summarization systems rely on resource-heavy domain-specific knowledge sources, and preprocessing methods (e.g., classification or deep learning) for deriving semantic information. Consequently, these systems are often difficult to customize, extend or deploy in low-resource settings, and are operationally slow. We propose a fast summarization system that can aid practitioners at point-of-care, and, thus, improve evidence-based healthcare. At runtime, our system utilizes similarity measurements derived from pre-trained domain-specific word embeddings in addition to simple features, rather than clunky knowledge bases and resource-heavy preprocessing. Automatic evaluation on a public dataset for evidence-based medicine shows that our system's performance, despite the simple implementation, is statistically comparable with the state-of-the-art.


title: Impacts of Early Interventions on the Age-Specific Incidence of COVID-19 in New York, Los Angeles, Daegu and Nairobi

text: Background COVID-19 has caused an unprecedented public health crisis and economic shock to the global economy. While many countries were affected, regions with an older population and weaker public health interventions tended to suffer more morbidity and mortality. Here we model and quantify the age-specific incidence of COVID-19 in four pandemic cities under different interventions. Methods We developed an age-specific and multiple-stage susceptible-exposed-infected-recovered-hospitalized-quarantined-dead (SEIR-HQD) dynamical systems model expanded from the more basic SEIR model by incorporating location- and age-specific contact matrices to estimate the outcomes of COVID-19. Utilizing latest estimates of epidemiological parameters and demographic data, we model the potential effects of various interventions in four representative cities with different population structures - New York, Los Angeles, Daegu and Nairobi. We compared the effects of different interventions in the age-structure populations specific to each city. These policy options are then applied to determine the potential for effective containment. We model these dynamic policy scenarios to assess the risks of less-stringent social distancing, as has been proposed by those arguing to enhance economic activity over public health and safety. Finally, we explored the health impacts of different policy action timelines to understand the benefits of early interventions. Findings We find the spread of COVID-19 to be dramatically different in the regions modeled, with the primary drivers the variation of population age structures, and the dynamics of interactions of the younger demographics, whose higher interaction rates can lead to increasing transmission rates across these communities. A city with younger citizens may also have fewer hospitalized cases and deaths. Our modeling quantifies the value of early interventions, which avoided an additional 5%, 16%, 37% and 43% of the infections in Daegu, Nairobi, New York and Los Angeles, respectively, compared to what has been observed in the four cities. The finding is clear: in the absence of pharmaceutical options, delaying strict social policy interventions has resulted in substantial public health cost. This modeling can, and will, be applied to other cities and regions, and conducted in conjunction with other health insults, such as exposure to air pollution. Critically, we find that school closures, working from home, and reduction in other mobility were most beneficial for younger population (0-19 years old), middle-age (20-59 years old) population and older population (60 years and older), respectively across each city. Specifically, school closure avoided 25%, 18%, 16% and 12% of the infections for the population under 20 years old in Daegu, Los Angeles, New York and Nairobi, respectively. A 50% and 80% population working from home policy avoids 8% and 15% of the infections. Reduction in mobility was more effective than the working from home strategy. Any single social distancing policy if enacted alone can delay the spread of COVID-19 but was unable to totally suppress the infection. Coordinated policy action can be highly effective. Increasing the quarantine rate to 10% of infectious cases was more effective than strict social distancing alone in this study, although together they can suppress 80% of the epidemic. A combination of moderate social distancing and quarantine strategies was able to avoid 99% of the infections. Interpretation Moderate social distancing together with high quarantine rates was effective in each of the four cities. COVID-19 caused more deaths and hospitalization in cities with an ageing population than those with a younger population. However, in the cities with a younger population, there is a clear need to implement a social distancing strategy that is even more strict due to the higher transmission rates among younger people. Cities with more older people should prepare more hospital beds and healthcare facilities to save people who are in critical conditions. Cities with ageing population should take targeted action for the elderly to avoid the severe impacts on the vulnerable populations. Increasing quarantine rate is an effective strategy to avoid the substantial infection while also does not influence the economy fiercely. We recommend countries or regions experiencing, or likely to experience the rapid spread of COVID-19, to implement combination of multiple strategies in the early stage of the breakout which can avoid over 90% of infected cases.


title: Contact tracing strategies for COVID-19 containment with attenuated physical distancing

text: Contact tracing has been recommended as a critical component of containment strategies for COVID-19. We used a simple epidemic model to evaluate how contact tracing might enable partial relaxation of current physical distancing restrictions. Testing and tracing coverage need to exceed 50% in order for contact tracing to reduce transmission by at least 10%. With high isolation and quarantine efficacy, contact tracing could reduce overall transmission by >40%, which would allow for substantial loosening of physical distancing measures. Benefits of contact tracing could be enhanced by testing all contacts rather than only those with symptoms and by policies to support high adherence to voluntary isolation and quarantine.


title: A Review of Neurological Complications of COVID-19

text: The SARS-CoV-2, a novel virus has shown an association with central nervous system (CNS) symptoms. Initial retrospective studies emerging from China and France, as well as case reports from different parts of the world revealed a spectrum of neurological symptoms ranging from a simple headache to more serious encephalitis and dysexecutive syndromes. Authors have tried to explain this neurotropism of the virus by comparing invasion mechanisms with prior epidemic coronavirus like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Concrete evidence on those viruses has been limited. This review attempts to discuss various pathophysiological mechanisms as it relates to neurological complications of SARS-CoV-2. We will also discuss the neurological manifestations seen in various retrospective studies, systemic reviews, and case reports.


title: Effect of Temperature on the Transmission of COVID-19: A Machine Learning Case Study in Spain

text: The novel coronavirus (COVID-19) has already spread to almost every country in the world and has infected over 3 million people. To understand the transmission mechanism of this highly contagious virus, it is necessary to study the potential factors, including meteorological conditions. Here, we present a machine learning approach to study the effect of temperature, humidity and wind speed on the number of infected people in the three most populous autonomous communities in Spain. We find that there is a moderate inverse correlation between temperature and the daily number of infections. This correlation manifests for temperatures recorded up to 6 days before the onset, which corresponds well to the known mean incubation period of COVID-19. We also show that the correlation for humidity and wind speed is not significant.


docid: bzoelucz

title: A simple Stochastic model for the SARS-CoV-2 Epidemic curve

text: An epidemic curve is a graphic depiction of the number of outbreak cases by date of illness onset, ordinarily constructed after the disease outbreak is over. However, a good estimate of the epidemic curve early in an outbreak would be invaluable to health care officials. On the other hand, from the end of February, the SARS-CoV-2 epidemic in Brazil seems to not following the Europe, or in particular, Italy or Spain. Even if less tests have been applied, there are less deaths occurring in Brazil than in both cited countries. However, due to the few applied tests, there is no certain planning on the real number of active cases. To estimate the number of future cases, epidemiologists make an educated guess as to how many people might become affected. We have proposed a simple fitting model using a simulated annealing technique, testing it with the South Korea data. We have tested and discussed the uncertainties of the model. We also have analyzed the trends in the confirmed cases using this model for the five most affected countries plus Brazil along several epidemic weeks.


title: Room Temperature Isothermal Colorimetric Padlock Probe Rolling Circle Amplification for Viral RNA Detection

text: Seasonal flu and pandemics, which account for millions of infections and hundreds of thousands of deaths, require rapid and reliable detection mechanisms for preventive and therapeutic measures. Current methods of viral detection have limitations in speed, accuracy, accessibility, and usability. This project presents a novel, widely applicable viral diagnosis that uses a modified version of the traditional rolling circle amplification (RCA) to be sensitive, specific, direct, colorimetric, and operable at room temperature. We are specifically aiming to detect SARS-CoV-2, Influenza A (H1N1pdm09), and Influenza B (Victoria Lineage). Results using synthetic viral DNA sequences show that the diagnostic test could take as fast as 30 minutes and detect up to picomolar concentrations of DNA strands. The next step for this project is to test the assay with synthetic viral RNA to verify the results. We envision that the implementation of this type of diagnostic test could allow faster responses to outbreaks of related viruses and quicker societal recovery.


docid: iwkuwnun

title: Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19

text: Abstract Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any ”normal” post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart. Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.


COVID-19 and Epilepsy


title: Liver Chemistries in COVID-19 Patients with Survival or Death: A Meta-Analysis

text: Background and Aims: Although abnormal liver chemistries are linked to higher risk of death related to coronavirus disease (COVID-19), liver manifestations may be diverse and even confused. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19 patients with death or survival. Methods: We searched PubMed, Google Scholar, medRxiv, bioRxiv, Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19 using a fixed or random-effects model. Results: In the meta-analysis of 18 studies, which included a total of 2,862 patients, the pooled mean alanine aminotransferase (ALT) was 30.9 IU/L in the COVID-19 patients with death and 26.3 IU/L in the COVID-19 patients discharged alive (p < 0.0001). The pooled mean aspartate aminotransferase (AST) level was 45.3 IU/L in the COVID-19 patients with death while 30.1 IU/L in the patients discharged alive (p < 0.0001). Compared with the discharged alive cases, the dead cases tended to have lower albumin levels but longer prothrombin time, and international standardized ratio. Conclusions: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively described three patterns of liver impairment related to COVID-19, hepatocellular injury, cholestasis, and hepatocellular disfunction. Patients died from COVID-19 tend to have different liver chemistries from those are discharged alive. Close monitoring of liver chemistries provides an early warning against COVID-19 related death.


How to cite this article: Bhosale S, Kulkarni AP. Is A Problem Shared, A Problem Halved? Not Always! The Novel Coronavirus COVID-19 Outbreak. Indian J Crit Care Med 2020;24(2):88–89.


title: Sphingolipid Biosynthesis Inhibition As A Host Strategy Against Diverse Pathogens

text: Chloroquine is an anti-malarial and immunosuppressant drug that has cationic amphipathic chemical properties. We performed genome-wide screens in human cells with chloroquine and several other widely used cationic amphipathic drugs (CADs) including the anti-depressants, sertraline (Zoloft) and fluoxetine (Prozac), the analgesic nortriptyline (Pamelor), the anti-arrhythmic amiodarone (Cordarone), and the anti-hypertensive verapamil (Calan) to characterize their molecular similarities and differences. Despite CADs having different disease indications but consistent with them sharing key chemical properties, we found CADs to have remarkably similar phenotypic profiles compared with non-CADs we and others have previously screened (1–5). The most significant genetic interaction for all CADs was the initiating step in sphingolipid biosynthesis catalyzed by serine palmitoyltransferase (SPT). A comparison of genome-wide screens performed with diverse pathogens from viruses, bacteria, plants, and parasites including Ebola (6), adeno-associated virus AAV2 (7), HIV (8), Rotavirus (9), Influenza A (10), Zika virus (11), Picornavirus (12), Exotoxin A (13), Cholera toxin (14), Type III secretion system and Shiga toxin (15, 16), Ricin toxin (17), and Toxoplasma gondii (18) showed SPT as a top common host factor and 80% overlap overall in top hits specifically with CADs. Potential sphingolipid-mediated mechanisms for the host response- and virulence-modulating effects of CADs involve autophagy and SERPINE1/PAI-1 (plasminogen activator inhibitor-1). Chloroquine has recently shown potential as an anti-viral agent for the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease (19, 20). Our study demonstrates that numerous readily available drugs molecularly function highly similar to chloroquine, which suggests they might be considered for further pre-clinical investigation in the context of SARS-CoV-2. More generally, our work suggests the diverse pathogen mitigating potential of drugs that inhibit host sphingolipid biosynthesis such as CADs. Brief Summary Our study demonstrates that numerous readily available drugs molecularly function highly similar to chloroquine, which suggests they might be considered for further pre-clinical investigation in the context of SARS-CoV-2.


title: Effect of different resumption strategies to flatten the potential COVID-19 outbreaks amid society reopens: a modeling study

text: The effect of the COVID-19 outbreak has led policymakers around the world to attempt transmission control. However, lockdown and shutdown interventions have caused new social problems and designating policy resumption for infection control when reopening society remains a crucial issue. We investigated the effects of different resumption strategies on COVID-19 transmission using a modeling study setting. We employed a susceptible-exposed-infectious-removed model to simulate COVID-19 outbreaks under five reopening strategies based on the business resumption progress in China. The effect of each strategy was evaluated using the peak values of the epidemic curves with respect to confirmed active cases and cumulative cases. We found that a hierarchy-based reopen strategy performed best when current epidemic prevention measures were maintained save for lockdown, reducing the peak number of active cases and cumulative cases by 50% and 44%, respectively. However, the modeled effect of each strategy decreased when the current intervention was lifted somewhat. Additional attention should be given to regions with significant numbers of migrants, as the potential risk of COVID-19 outbreaks amid society reopening is intrinsically high. Business resumption strategies have the potential to eliminate COVID-19 outbreaks amid society reopening without special control measures. The proposed resumption strategies focused mainly on decreasing the number of imported exposure cases, guaranteeing medical support for epidemic control, or decreasing active cases.


title: Analysis of psychological state and clinical psychological intervention model of patients with COVID-19

text: Background:Patients with the 2019 coronavirus disease (COVID-19) have different degrees of psychological pain, such as anxiety and depression, which may related to their prognosis. Psychological intervention can be conducted in different ways to improve psychological pain and improve the treatment effect. Objective:The present study aimed to investigate and analyze the psychological status of patients with COVID-19 during the course of illness, and to evaluate the effect and influencing factors of psychological crisis intervention, so as to explore the effective mode of clinical psychological intervention in acute patients under isolation environment. Methods:A total of 143 persons participated in the study, including 26 patients diagnosed with COVID-19 in the isolation ward (COVID-19 group), 87 patients with general pneumonia in the observation ward (General Pneumonia group) and 30 healthy volunteers (Normal group). All the patients in the ward received comprehensive psychological intervention, including telephone psychological counseling (active and passive), self-adjustment of written materials and one-to-one psychological crisis intervention. Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were used to evaluate the mental health status of all patients on the day of admission and 1 week after treatment. Results:The scores of HAMA and HAMD of all patients (including isolation ward and observation ward) were significantly higher than the healthy volunteers at the time of admission. The total score of HAMA and HAMD in CVOID-19 group were both higher than that General Pneumonia group. After 1 week`s hospitalization with comprehensive psychological intervention, the scores of HAMA and HAMD in CVOID-19 group were significantly decreased. Conclusion:Patients those who diagnosed with COVID-19 in the isolation ward and/or general pneumonia in observation ward have different degrees of anxiety, depression and sleep problems. While receiving antiviral treatment, patients also need psychological intervention. Comprehensive psychological intervention model has been proved to be effective.


docid: wyqxxluh

title: COVID-19 management in a UK NHS Foundation Trust with a High Consequence Infectious Diseases centre: a detailed descriptive analysis

text: Background: Recent large national and international cohorts describe the baseline characteristics and outcome of hospitalised patients with COVID-19, however there is little granularity to these reports. We aimed to provide a detailed description of a UK COVID-19 cohort, focusing on clinical decisions and patient journeys. Methods: We retrospectively analysed the management and 28-day outcomes of 316 consecutive adult patients with SARS-CoV-2 PCR-confirmed COVID-19 admitted to a large NHS Foundation Trust with a tertiary High Consequence Infectious Diseases centre in the North of England. Findings: Most patients were elderly (median age 75) with multiple comorbidities. One quarter were admitted from residential or nursing care. Symptoms were consistent with COVID-19, with cough, fever and/or breathlessness in 90.5% of patients. Two thirds of patients had severe disease on admission. Mortality was 81/291 (27.8%). Most deaths were anticipated; decisions to initiate respiratory support were individualised after consideration of patient wishes, premorbid frailty and comorbidities, with specialist palliative care input where appropriate. 22/291 (7.6%) patients were intubated and 11/22 (50%) survived beyond discharge. Multiple logistic regression identified age as the most significant risk factor for death (OR 1.09 [95% CI 1.06 - 1.12] per year increase, p < 0.001). Interpretation: These findings provide important clinical context to outcome data. Deaths were anticipated, occurring in patients with advance decisions on ceilings of treatment. Age was the most significant risk factor for death, confirming that demographic factors in the population are a major influence on hospital mortality rates. Funding: Funding was not required.


title: Clinical Outcomes of Patients with COVID-19 and Chronic Inflammatory and Autoimmune Rheumatic Diseases: A Multicentric Matched-Cohort Study

text: ABSTRACT Background The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. Methods In this comparative cohort study, we identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. Results The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID were increased age (OR 5.31; CI 3.14-8.95), male sex (2.13; CI 1.35-3.36) and having an AI/IMID (OR 1.98; CI 1.15-3.41). Conclusion In patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19.


docid: auzioqyz

title: Estimating the size of COVID-19 epidemic outbreak

text: In this work, we analyze the epidemic data of cumulative infected cases collected from many countries as reported by WHO starting from January 21st,2020 and up till March 21st,2020. Our inspection is motivated by the renormalization group (RG) framework. Here we propose the RG-inspired logistic function of the form αE(t) = a(1 + ec(t-t0))-n as an epidemic strength function with n being asymmetry in the modified logistic function. We perform the non-linear least-squares analysis with data from various countries. The uncertainty for model parameters is computed using the squared root of the corresponding diagonal components of the covariance matrix. We carefully divide countries under consideration into 2 categories based on the estimation of the inflection point: the maturing phase and the growth-dominated phase. We observe that long-term estimations of cumulative infected cases of countries in the maturing phase for both n=1 and n≠ 1 are close to each other. We find from the value of root mean squared error (RMSE) that the RG-inspired logistic model with n≠ 1 is slightly preferable in this category. We also argue that n determines the characteristic of the epidemic at an early stage. However, in the second category, the estimated asymptotic number of cumulative infected cases contain rather large uncertainty. Therefore, in the growth-dominated phase, we focus on using n≠ 1 for countries in this phase. Some of them are in an early stage of an epidemic with an insufficient amount of data leading to a large uncertainty on parameter fits. In terms of the accuracy of the size estimation, the results do strongly depend on limitations on data collection and the epidemic phase for each country.


title: COVID-19: A Chronological Review of the Neurological Repercussions - What do We Know by May, 2020?

text: Abstract Introduction: Despite the new SARS-CoV-2 (COVID-19) be the seventh of the coronavirus family viruses known to cause human disease, little is known about potential symptoms and syndromes secondary to the compromise of the central and peripheral nervous systems. We reviewed neurological manifestations due to the new coronavirus, thus far published in the literature, as well as guidelines issued by sub-specialties in Neurology, to tackle the disease. Methods: we searched medical databases, such as PubMed, PubMed Central, LILACS and Google scholar for papers (case reports, short letters, case series, etc) describing neurological symptoms in patients with confirmed or suspect COVID-19 diagnosis and also searched webpages of associations and organizations that deal with neurological disorders. Results: we describe briefly each article considered for this review. Forty-one papers were found associating neurological conditions and COVID-19. Cases are divided by disease groups and, within each disease group, results are listed in chronological order or publication date. We also discuss briefly recommendations for neurological patients, according to disease group. Conclusion: Although there is evidence of neurological manifestations with previous coronaviruses, COVID-19 is assuring a volume of published papers not seen before for other coronavirus infections. Most neurological cases are not life-threatening, but 10 to 20% of cases will require hospitalization and are in risk for sequelae and death. Although a lot of data coming from these papers is amassing, researchers must bear in mind that many papers currently published are not yet peer-reviewed, and thus are prone to further corrections.


title: Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses

text: Introduction: Rapid diagnosis and isolation are key to containing the rapid spread of a pandemic agent like SARS-CoV-2, which has spread globally since its initial outbreak in Wuhan province in China. SARS-CoV-2 is novel to most parts of the world including USA and the effect on normally prevalent viruses is just becoming apparent. We present our initial data on the prevalence of respiratory viruses in the month of March, 2020. Methods: This is a retrospective cohort study post launching of SARS-CoV-2 testing at BSWH, Temple TX. Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions. Results: More than 3500 tests were performed during the first two weeks of testing for SARS-CoV-2 and identified 168 (4.7%) positive patients. Sixty-two (3.2%) of the 1,912 ambulatory patients and 106 (6.3%) of the 1,659 ED/inpatients were tested positive. Higher rate of infection (6.9%) were noted in the patients belonging to age group 25-34 years and least number of positive cases were noted in <25 years old (2%) group. The TX State county specific patient demographic information was shared with respective public health departments for epidemiological interventions. Incidentally, this study showed that there was a sudden decrease in the occurrence of other infections due to seasonal viruses, perhaps due to increased epidemiological awareness, about SARS-CoV-2, among general public. Authors would also like to share a small study on SARS-CoV-2 serological assay for the detection of IgG antibodies. Conclusions: This study was intended to provide an initial experience of dealing with a pandemic and the role of laboratories in crisis management. Epidemiological interventions depend on timely availability of accurate diagnostic tests and throughput capacity of such systems during large outbreaks like SARS-CoV-2.


title: Clinical meanings of rapid serological assay in patients tested for SARS-Co2 RT-PCR

text: Background RT-PCR test for identifiction of viral nucleic acid is the current standard diagnostic method for the diagnosis of COVID-19 disease but technical reasons limit the utilization of this assay on large scale screenings. Method We verified in a consecutive series of 191 symptomatic patients the clinical information that new rapid serological colorimetric test qualitatively analyzing IgM/IgG expression can provide with respect to standard assay and with respect to clinical outcome of patients. Results Rapid serological test showed a sensitivity of 30% and a specificity of 89% with respect to the standard assay but, interestingly, these performances improve after 8 days of symptoms appearance. After 10 days of symptoms the predictive value of rapid serological test is higher than that of standard assay. When the behaviour of the two immunoglobulins was evaluated with respect to time length of symptoms appearance, no significant difference in immunoglobulins behaviour was shown. Conclusions The rapid serological test analyzed in the present study is candidate to provide information on immunoreaction of the subject to COVID-19 exposure.


docid: vyzuxupg

title: Supplementing the National Early Warning Score (NEWS2) for anticipating early deterioration among patients with COVID-19 infection

text: Importance: An early minimally symptomatic phase is often followed by deterioration in patients with COVID-19 infection. This study shows that the addition of age and a minimal set of common blood tests taken in patients on admission to hospital significantly improves the National Early Warning Score (NEWS2) for risk-stratification of severe COVID disease. Objective: To supplement the NEWS2 score with a small number of easily obtained additional demographic, physiological and blood variables indicative of severity of COVID-19 infection. Design: Retrospective observational cohort with internal and temporal held-out external validation. Setting: Acute secondary care. Participants: 708 patients admitted to an acute multi-site UK NHS hospital with confirmed COVID-19 disease from 1st March to 5th April 2020. Intervention: Not applicable. Main outcome and measures: The primary outcome was patient status at 14 days after symptom onset categorised as severe disease (WHO-COVID-19 Outcomes Scales 6-8: i.e. transferred to intensive care unit or death). 218 of the 708 patients reached the primary end point. A range of physiological and blood biomarkers were assessed for their association with the primary outcome. Adjustments included age, gender, ethnicity and comorbidities (hypertension, diabetes, heart, respiratory and kidney diseases). Results: NEWS2 total score was a weak predictor for severity of COVID-19 infection at 14 days (internally validated AUC = 0.628). The addition of age and common blood tests (CRP, neutrophil count, estimated GFR and albumin) provided substantial improvements to a risk stratification model but performance was still only moderate (AUC = 0.75). Common comorbidities hypertension, diabetes, heart, respiratory and kidney diseases have minor additional predictive value. Conclusions and relevance: Adding age and a minimal set of common blood parameters to NEWS2 improves the risk stratification of patients likely to develop severe COVID-19 outcomes. The addition of a few common parameters is likely to be much easier to implement in a short time-scale than a novel risk-scoring system.


title: Recommendations: Mechanical ventilation in anesthesia. what an intensivist has to tell to an anesthesiologist/ Recomendaciones covid-19: Ventilación mecánica en anestesia. lo que un intensivista tiene que contarle a un anestesiólogo

text: The objective of these recommendations is that they are within the reach of any anesthesiologist, in order to carry out protective ventilation in the patient during the COVID-19 pandemic, in which a patient with unique characteristics is confronted, with difficult ventilatory management in a setting crisis of scarcity of resources, lack and fatigue of health personnel. We do not recommend using these guides in a different setting.


title: A Systematic Review and Meta-analysis of D-Dimer Levels in Patients Hospitalized with Coronavirus Disease 2019 (COVID-19)

text: Aim To determine if the d-dimer levels are elevated in individuals with COVID 19 having worse clinical outcomes including all-cause mortality, ICU admission or ARDS Methods We conducted a systematic review and meta-analysis of published literature in Pubmed, Embase and Cochrane database through April 9, 2020 for studies evaluating the d-dimer levels in patients with and without a worse clinical outcome (all-cause mortality, ICU admission and ARDS). A total of 6 studies included in the meta-analysis. Results The values of d-dimer were found to be significantly increased in patients with the composite clinical end point than in those without (SMD, 1.67 ug/ml (95% CI, 0.72-2.62 ug/ml). The SMD of the studies (Tang et al, Zhou et al, Chen et al), which used only mortality as an outcome measure was 2.5 ug/mL (95% CI, 0.62-4.41). Conclusion The results of this concise meta-analysis suggest that d-dimer is significantly increased in patients having a worse clinical outcome (all-cause mortality, ICU admission or ARDS).


docid: ymzlhsai

title: Rotational Thromboelastometry predicts care level in Covid-19

text: Background High rates of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolisation of vital organs may be direct causes of death in COVID-19 positive individuals. If patients at high risk of developing thrombosis may be identified early, more effective prophylactic treatment could be applied. Objectives To test whether Rotational Thromboelastometry (ROTEM) indicates hypercoagulopathy in hospitalized COVID-19 patients, and whether patients with severe disease have a more pronounced hypercoagulopathy compared with less severely ill patients. Methods COVID-19 positive patients over 18 years admitted to St Gorans Hospital, Stockholm, Sweden were eligible for inclusion. Patients were divided into two groups depending on care level: 1) regular wards or 2) wards with specialized ventilation support. ROTEM was taken as soon after admission to hospital as possible (median day 1 after hospitalization). The data were compared with healthy controls. Results The ROTEM variables Maximum Clot Firmness (EXTEM-MCF and FIBTEM-MCF) were significantly higher in both groups of COVID-19 patients compared with healthy controls (p<0.001) and higher in severely ill patients compared with patients at regular wards (p<0.05). Coagulation Time (EXTEM-CT) was significantly longer and Clot Formation Time (EXTEM-CFT) significantly shorter in COVID-19 patients compared with healthy controls. Our results suggest that hypercoagulopathy is present in hospitalized patients with mild to severe COVID-19 pneumonia. Conclusion ROTEM variables (EXTEM-MCF, FIBTEM-MCF, EXTEM-CT, EXTEM-CFT) were significantly different in COVID-19 patients early after admission compared with healthy controls. This pattern was more pronounced in patients with increased disease severity, suggesting that ROTEM-analysis could be a potentially useful predictor of thromboembolic complications and mortality in these patients.


title: Genes associated with liver damage signalling pathways may impact the severity of COVID-19 symptoms in Spanish and Italian populations

text: Aim The novel SARS-CoV-2 virus, which causes the COVID-19 disease, has infected more than 10 million people and caused 500K deaths worldwide. In Europe, over 2 million confirmed cases have been reported, while nearly 200K people have died from the disease. Despite strict containment measures in Spain and Italy after the first reported COVID-19 patient, these two countries have remained in the top five European nations with the highest mortality rate for over two months. We hypothesised that a genetic mechanism could partially explain the poor survival outcome observed in these two countries. Methods An extensive literature search to identify human candidate genes linked to SARS-CoV infection, host immune evasion and disease aggressiveness was carried out. Pathway analysis (IPA) was performed to select the most significantly associated canonical signalling pathways with the genes of interest. The genetic variants’ at these genes with ±1Mb flanking region was extracted (GRCh37/hg19 built). Over 80 million single nucleotide polymorphisms (SNPs) were analysed in genome-wide data of 2,504 individuals (1000 genomes, phase III, https://www.internationalgenome.org/). Principal component (PC) analysis was performed, ancestry by the whole genome was inferred and subsets of the regions of interest were extracted (PLINK v1.9b, http://pngu.mgh.harvard.edu/purcell/plink/). PC1 to PC20 values from five European ancestries, including the Spanish and Italian populations, were used for PC analysis. Gene function predictions were run with our genes of interest as a query to the GeneMANIA Cytoscape plugin (https://genemania.org/). Results A total of 437 candidate genes associated with SARS were identified, including 21 correlated with COVID-19 aggressiveness. The two most significant pathways associated with all 437 genes (Caveolar-mediated Endocytosis and MSP-RON Signalling) did not show any segregation at the population level. However, the most significant canonical pathway associated with genes linked to COVID-19 aggressiveness, the Hepatic Fibrosis and Hepatic Stellate Cell Activation, showed population-specific segregation. Both the Spanish and Italian populations clustered together from the rest of Europe. This was also observed for the Finnish population but in the opposite direction. These results suggest some of the severe COVID-19 cases reported in Spain and Italy could be partially explained by a pre-existing liver condition (especially liver cancer) and/or may lead to further COVID-19 related liver complications.


title: A simple mathematical model for Coronavirus (COVID-19)

text: A novel coronavirus (COVID-19) was identified in Wuhan, China in the end of 2019, it causing an outbreak of viral pneumonia. It caused to the death rate of 4:63% among 571; 678 confirmed cases around the world to the March 28th, 2020. In this brief current study, we will present a simple mathematical model where we show how the probability of successfully getting infected when coming into contact with an infected individual and the per capita contact rate affect the healthy and infected population with time. The proposed model is used to offer predictions about the behavior of COVID-19 for a shorter period of time.


title: Clinical characteristics of Coronavirus Disease 2019 (COVID-19) patients in Kuwait

text: Abstract Background: In early December 2019, the first clusters of Coronavirus Disease 2019 (COVID-19) were identified in Wuhan, China and attributed to a novel coronavirus, now known as Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV2). Kuwait reported its first cases of COVID-19 on February 24th 2020 and since then the number of cases has been increasing rapidly. Methods and Findings: This is a retrospective single-center study of consecutive 417 COVID-19 patients admitted to Jaber Al-Ahmad hospital between 24/2/2020 and 24/5/2020. The mean age of cohort was 45.35 years (S.D. 17.16) and 62.8% of cases were males. Patients were divided into four groups; Asymptomatic group, symptomatic group with mild form of the disease, ICU survivors and ICU death. In total, 39.3% of patients were asymptomatic, 41% were symptomatic with mild symptoms, 5.3% were admitted to ICU and recovered and 14.4% died. Mean age of ICU patients was 53.61 years (S.D. 13.43). Comorbidities were more prevalent in ICU death group when compared to other groups (p<0.05) including Diabetes (40%), Hypertension (46.7%), Asthma (20.3%) and cardiovascular disease (21.7%). Blood biochemistry analysis showed that ICU death group had a characteristic abnormal pattern of certain markers upon admission in the ICU. Including significantly high WBC and neutrophil counts (P<0.05) and prolonged Prothrombin Time (PT) and activated partial thromboplastin time (APTT) (P<0.05). D-dimer, C-reactive protein and Procalcitonin (PCT) showed significantly high levels in ICU admissions and in ICU death group in particular (P<0.05). Kidney injury complications were reported in 65% of ICU death group (P<0.05) which also showed significantly elevated urea levels (P<0.05). We also reported rapid deteriorating kidney function (eGFR) in ICU death cases during ICU stay until the outcome was reached. Conclusions: In this single-center study of 417 COVID19 patients in Kuwait. The disease showed varying degree of severity ranging from asymptomatic status to death. Our comprehensive laboratory analysis revealed distinct abnormal patterns of markers that are associated with poor prognosis. Our dynamic profiling of eGFR in COVID-19 ICU patients highlight potential role of renal markers in forecasting disease outcome and perhaps identify patients at risk of poor outcome.


title: Dimensions and modulators of behavioural and mental-health changes during the Covid-19 pandemic: an N=343,017 study

text: BACKGROUND The effects of the Covid-19 pandemic on mental health remain unclear. To mitigate the risks and capitalise on opportunities for positive change, we must understand how the impact has been mediated by sociodemographics, mental disorders, personality traits, life circumstances and the coping measures people choose to take. METHODS Data were collected from 376,987 members of the general public, predominantly in the UK, between late December 2019 and May 2020. Interaction models examined differences in sociodemographic distributions of mood and anxiety for 233,268 people in January vs. 109,749 in May. Factor analysis of a comprehensive instrument determined the dimensionality of self-perceived pandemic-driven change in wellbeing, outlook and behaviour for 74,830 participants in May. Linear modelling identified demographic, contextual, clinical, and trait predictors of pandemic impact. Topic modelling distilled prevalent advice from free-text responses. RESULTS Anxiety, depression and insomnia changed markedly in demographically-mediated ways. Untoward changes were larger for older adults. Benefits were greater for younger adults. Social connectedness was negatively affected across most mental and neurological conditions. There were disorder-specific changes in other domains, e.g., heightened conflict at home for attention-deficit hyperactivity disorder and heightened anxiety for obsessive-compulsive disorder. Psychiatric symptoms, personality traits, occupational variables and living conditions were amongst the strongest predictors of pandemic impact. Frontline health workers, carers of vulnerable older adults, and disabled or sheltered adults were disproportionately affected. Fifty advice topics were identified from free-text, the prevalence of which covaried with subpopulation, context and traits. CONCLUSIONS The general public report positive and negative consequences of the pandemic. Particular subsets of people have heightened risk of untoward effects whereas other groups appear resilient. To be valid and effective, studies seeking to quantify, predict or mitigate the impact of pandemics on mental health should apply holistic approaches, combining multiple psycho-socio-economic factors.