title: Clinical characteristics and outcomes of critically ill patients with COVID-19 in a tertiary community hospital in upstate New York

text: Background: There are limited reports describing critically ill COVID-19 patients in New York. Methods: We conducted a retrospective analysis of 32 adult critically ill patients admitted to a tertiary community hospital in upstate NY, between March 14th and April 12th, 2020. We collected demographic, laboratory, ventilator, and treatment data, which were analyzed and clinical outcomes tabulated. Results: 32 patients admitted to the ICU were included, with mean ({+/-}SD) follow-up duration 21 {+/-} 7 days. Mean ({+/-}SD) age was 62.2 {+/-} 11.2 years, and 62.5% were men. 27 (84.4%) of patients had one or more medical co-morbidities and 50% of the patients were current or former smokers. The mean ({+/-}SD) duration of symptoms was 6.6 ({+/-}4.4) days before presentation, with cough (81.3%), dyspnea (68.7%), and fever (65.6%) being most common. 23 (71.9%) patients received invasive mechanical ventilation. 5 (15.6%) had died, 11 (34.4%) had been discharged home, and 16 (50%) remained hospitalized, 8 (25%) of which were still in ICU. Mean ({+/-}SD) length of ICU stay was 10.2 ({+/-}7.7) days, and mean ({+/-}SD) length of hospital stay was 14.8 ({+/-}7.7) days. Conclusion: Majority of patients were of older age and with medical co-morbidities. With adequate resource utilization, mortality of critically ill COVID-19 patients may not be as high as previously suggested.


title: ReCoNet: Multi-level Preprocessing of Chest X-rays for COVID-19 Detection Using Convolutional Neural Networks

text: Life-threatening COVID-19 detection from radiomic features has become a dire need of the present time for infection control and socio-economic crisis management around the world. In this paper, a novel convolutional neural network (CNN) architecture, ReCoNet (residual image-based COVID-19 detection network), is proposed for COVID-19 detection. This is achieved from chest X-ray (CXR) images shedding light on the preprocessing task considered to be very useful for enhancing the COVID-19 fingerprints. The proposed modular architecture consists of a CNN-based multi-level preprocessing filter block in cascade with a multi-layer CNN-based feature extractor and a classification block. A multi-task learning loss function is adopted for optimization of the preprocessing block trained end-to-end with the rest of the proposed network. Additionally, a data augmentation technique is applied for boosting the network performance. The whole network when pre-trained end-to-end on the CheXpert open source dataset, and trained and tested with the COVIDx dataset of 15,134 original CXR images yielded an overall benchmark accuracy, sensitivity, and specificity of 97.48%, 96.39%, and 97.53%, respectively. The immense potential of ReCoNet may be exploited in clinics for rapid and safe detection of COVID-19 globally, in particular in the low and middle income countries where RT-PCR labs and/or kits are in a serious crisis.


title: Assessing visible aerosol generation during vitrectomy in the era of Covid-19

text: Objective: To assess visible aerosol generation during simulated vitrectomy surgery. Methods: A model comprising a human cadaveric corneoscleral rim mounted on an artificial anterior chamber was used. Three-port 25 gauge vitrectomy simulated surgery was performed with any visible aerosol production recorded using high speed 4K camera. The following were assessed: (1) vitrector at maximum cut rate in static and dynamic conditions inside the model, (2) vitrector at air-fluid interface in physical model, (3) passive fluid-air exchange with a backflush hand piece, (4) valved cannulas under air, and (5) defective valved cannula under air. Results: No visible aerosol or droplets were identified when the vitrector was used within the model. In the physical model, no visible aerosol or droplets were seen when the vitrector was engaged at the air-fluid interface. Droplets were produced from the opening of backflush hand piece during passive fluid-air exchange. No visible aerosol was produced from the intact valved cannulas under air pressure, but droplets were seen at the beginning of fluid-air exchange when the valved cannula was defective. Conclusions: We found no evidence of visible aerosol generation during simulated vitrectomy surgery with competent valved cannulas. In the physical model, no visible aerosol was generated by the high-speed vitrector despite cutting at the air-fluid interface.


title: Keratin-Based Epidermal Green Autofluorescence is a Common Biomarker of Organ Injury

text: It is critical to discover biomarkers for non-invasive evaluation of inflammation and oxidative stress in human body - two key common pathological factors in numerous diseases. Our study has indicated keratin 1 (K1)-based epidermal autofluorescence (AF) as a novel biomarker of this type: Epidermal green AF intensity was significantly associated with both lipopolysaccharide (LPS) dosages and the serum levels of multiple cytokines in LPS-administered mice; and the green AF intensity of mouse’s skin or skin cell cultures was highly associated with the dosages of oxidative stress inducers. The epidermal AF had the characteristic polyhydral structure of the stratum spinosum. The polyhydral structure with highly increased green AF was also found in the Dorsal Index Finger’s skin of 45.59% of acute ischemic stroke (AIS) patients, which was profoundly decreased in the stroke patients’ skin during recovery phase. Our study has further obtained multiple lines of evidence indicating K1 as an origin of the pathological insult-induced AF, including the finding showing that K1 siRNA administration significantly attenuated the increase in the mice’ epidermal AF. Collectively, our study has indicated that K1-based epidermal AF is the first biomarker for non-invasive evaluation of inflammation and oxidative stress in the body. This finding forms a basis for novel keratin’s AF-based biomedical imaging technology for not only screening and diagnosis of inflammation- and oxidative stress-associated diseases including AIS and COVID-19, but also evaluations of the inflammation and oxidative stress in the body of natural populations.


title: Contacts in context: large-scale setting-specific social mixing matrices from the BBC Pandemic project

text: Social mixing patterns are crucial in driving transmission of infectious diseases and informing public health interventions to contain their spread. Age-specific social mixing is often inferred from surveys of self-recorded contacts which by design often have a very limited number of participants. In addition, such surveys are rare, so public health interventions are often evaluated by considering only one such study. Here we report detailed population contact patterns for United Kingdom based self-reported contact data from over 36,000 volunteers that participated in the massive citizen science project BBC Pandemic. The amount of data collected allows us generate fine-scale age-specific population contact matrices by context (home, work, school, other) and type (conversational or physical) of contact that took place. These matrices are highly relevant for informing prevention and control of new outbreaks, and evaluating strategies that reduce the amount of mixing in the population (such as school closures, social distancing, or working from home). In addition, they finally provide the possibility to use multiple sources of social mixing data to evaluate the uncertainty that stems from social mixing when designing public health interventions.


Covid-19 testing strategy of India - Current status and the way forward


title: treeheatr: an R package for interpretable decision tree visualizations

text: Summary treeheatr is an R package for creating interpretable decision tree visualizations with the data represented as a heatmap at the tree’s leaf nodes. The integrated presentation of the tree structure along with an overview of the data efficiently illustrates how the tree nodes split up the feature space and how well the tree model performs. This visualization can also be examined in depth to uncover the correlation structure in the data and importance of each feature in predicting the outcome. Implemented in an easily installed package with a detailed vignette, treeheatr can be a useful teaching tool to enhance students’ understanding of a simple decision tree model before diving into more complex tree-based machine learning methods. Availability The treeheatr package is freely available under the permissive MIT license at https://trang1618.github.io/treeheatr and https://cran.r-project.org/package=treeheatr. It comes with a detailed vignette that is automatically built with GitHub Actions continuous integration. Contact ttle@pennmedicine.upenn.edu


title: Chasing the origin of SARS-CoV-2 in Canada’s COVID-19 cases: A genomics study

text: The emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.


title: Characterising the epidemic spread of Influenza A/H3N2 within a city through phylogenetics

text: Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, it’s local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. We find trends in transmission dynamics correlated positively with trends in temperature, but not relative humidity nor school holidays. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network, while school children likely drove the spread within the remaining transmission network. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities. Author summary As shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be hugely important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what the drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct the how the transmission dynamics changed over the course of the season, which we correlate to changes, but not humidity or school holidays. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not pre-school aged children are important drivers of the local spread of influenza.


title: Data presented by the UK government as lockdown was eased shows the transmission of COVID-19 had already increased.

text: Background: Coronavirus disease 2019 (COVID-19) is an international emergency that has been addressed in many countries by changes in and restrictions on behaviour. These are often collectively labelled social distancing and lockdown. On the 23rd June 2020, Boris Johnson, the Prime Minister of the United Kingdom announced substantial easings of restrictions. This paper examines some of the data he presented. Methods: Generalised additive models, with negative binomial errors and cyclic term representing day-of-week effects, were fitted to data on the daily numbers of new confirmed cases of COVID-19. Exponential rates for the epidemic were estimated for different periods, and then used to calculate R, the reproduction number, for the disease in different periods. Results: After an initial stabilisation, the lockdown reduced R to around 0.81 (95% CI: 0.79, 0.82). This value increased to around 0.94 (95% CI 0.89, 0.996) for the fortnight from the 9th June 2020. Conclusions: Official UK data, presented as the easing of the lockdown was announced, shows that R was already more than half way back to 1 at that point. That suggests there was little scope for the announced changes to be implemented without restarting the spread of the disease.


title: Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital

text: Background: Health care workers (HCW) are a high-risk population to acquire SARS-CoV-2 infection from patients or other fellow HCW. At the same time, they can be contagious to highly vulnerable individuals seeking health care. This study aims at estimating the seroprevalence of antibodies against SARS-CoV-2 and associated factors in HCW from a large referral hospital in Barcelona, Spain, one of the countries hardest hit by COVID-19 in the world. Methods: From 28 March to 9 April 2020, we recruited a random sample of 578 HCW from the human resources database of Hospital Clinic in Barcelona. We collected a nasopharyngeal swab for direct SARS-CoV-2 detection through real time reverse-transcriptase polymerase chain reaction (rRT-PCR), as well as blood for plasma antibody quantification. IgM, IgG and IgA antibodies to the receptor-binding domain of the spike protein were measured by Luminex. The cumulative prevalence of infection (past or current) was defined by a positive SARS-CoV-2 rRT-PCR and/or antibody seropositivity. Results: Of the 578 total participants, 39 (6.7%, 95% CI: 4.8-9.1) had been previously diagnosed with COVID-19 by rRT-PCR, 14 (2.4%, 95% CI: 1.4-4.3) had a positive rRT-PCR at recruitment, and 54 (9.3%, 95% CI: 7.2-12.0) were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. Of the 54 seropositive HCW, 21 (38.9%) had not been previously diagnosed with COVID-19, although 10 of them (47.6%) reported past COVID-19-compatible symptoms. The cumulative prevalence of SARS-CoV-2 infection was 11.2% (65/578, 95% CI: 8.9-14.1). Among those with evidence of past or current infection, 40.0% (26/65) had not been previously diagnosed with COVID-19, of which 46.2% (12/26) had history of COVID-19-compatible symptoms. The odds of being seropositive was higher in participants who reported any COVID-19 symptom (OR: 8.84, 95% CI: 4.41-17.73). IgM levels positively correlated with age (rho=0.36, p-value=0.031) and were higher in participants with more than 10 days since onset of symptoms (p-value=0.022), and IgA levels were higher in symptomatic than asymptomatic subjects (p-value=0.041). Conclusions: The seroprevalence of antibodies against SARS-CoV-2 among HCW was lower than expected. Thus, being a high-risk population, we anticipate these estimates to be an upper limit to the seroprevalence of the general population. Forty per cent of those with past or present infection had not been previously diagnosed with COVID-19, which calls for active periodic rRT-PCR testing among all HCW to minimize potential risk of hospital-acquired SARS-CoV-2 infections.


title: CDC’s coronavirus test runs into early problems

text: Early batches of a kit developed by the US government to diagnose the novel coronavirus infection have been plagued by problems that initially limited their use and cast doubt on their accuracy The problems were first reported by the Washington Post, and C&EN learned soon after that the kits contained faulty reagents that led to inconclusive readouts The Centers for Disease Control and Prevention (CDC) has started an investigation into what exactly went wrong with the tests The CDC designed and manufactured the test kit, which detects the RNA genome of the virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) The US Food and Drug Administration has approved its use in public health departments nationwide As of March 5, SARS-CoV-2 has killed 10 people in the US and infected nearly 100 Several hundred people have been tested, but the CDC has now stopped reporting testing numbers in favor of [truncated]


title: Covid-19 prevalence estimation by random sampling in the wider population - Optimal sample pooling under varying assumptions about true prevalence

text: The number of confirmed Covid-19 cases in a population is used as a coarse measurement for the burden of disease. However, this number depends heavily on the sampling intensity and the various test criteria used in different jurisdictions. A wide range of sources indicate that a large fraction of cases go undetected. Estimates of the true prevalence of Covid-19 can be made by random sampling in the wider population. Here we use simulations to explore confidence intervals of prevalence estimates under different sampling intensities and degrees of sample pooling.


title: Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19

text: Background: COVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required. Methods: We developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots. Findings: The final model included age, lymphocyte count, lactate dehydrogenase and SpO2 as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0.89) and external (c=0.98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data. Interpretation: COVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate.


title: COVID-19 and Bangladesh: Challenges and How to Address Them

text: As the coronavirus outbreak quickly surges worldwide, many countries are adopting non-therapeutic preventive measures, which include travel bans, remote office activities, country lockdown, and most importantly, social distancing. However, these measures face challenges in Bangladesh, a lower-middle-income economy with one of the world's densest populations. Social distancing is difficult in many areas of the country, and with the minimal resources the country has, it would be extremely challenging to implement the mitigation measures. Mobile sanitization facilities and temporary quarantine sites and healthcare facilities could help mitigate the impact of the pandemic at a local level. A prompt, supportive, and empathic collaboration between the Government, citizens, and health experts, along with international assistance, can enable the country to minimize the impact of the pandemic.


title: Clinical and molecular characterization of COVID-19 hospitalized patients

text: Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.


title: Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December 2019, is a novel virus that causes a severe acute respiratory disease. The virus spike glycoproteins and nucleocapsid proteins are the main targets for the development of vaccines and antiviral drugs, to control the disease spread. We herein study the structural order-disorder propensity and the rates of evolution of these two proteins to characterize their B cell and T cell epitopes, previously suggested to contribute to immune response caused by SARS-CoV-2 infections. We first analyzed the rates of evolution along the sequences of spike and nucleocapsid proteins in relation to the spatial locations of their epitopes. For this purpose, we compared orthologs from seven human coronaviruses: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. We then focus on the local, structural order-disorder propensities of the protein regions where the SARS-CoV-2 epitopes are located. We show that the vast majority of nucleocapsid protein epitopes overlap the RNA-binding and dimerization domains and some of them are characterized by low rates of evolutions. Similarly, spike protein epitopes are preferentially located in regions that are predicted to be ordered and well-conserved, in correspondence of the heptad repeats 1 and 2. Interestingly, both the receptor-binding motif to ACE2 and the fusion peptide of spike protein are characterized by high rates of evolution, probably to overcome host immunity. In conclusion, our results provide evidence for conserved epitopes that may help to develop long-lasting, broad-spectrum SARS-CoV-2 vaccines.


title: Rapid in silico design of antibodies targeting SARS-CoV-2 using machine learning and supercomputing

text: Rapidly responding to novel pathogens, such as SARS-CoV-2, represents an extremely challenging and complex endeavor. Numerous promising therapeutic and vaccine research efforts to mitigate the catastrophic effects of COVID-19 pandemic are underway, yet an efficacious countermeasure is still not available. To support these global research efforts, we have used a novel computational pipeline combining machine learning, bioinformatics, and supercomputing to predict antibody structures capable of targeting the SARS-CoV-2 receptor binding domain (RBD). In 22 days, using just the SARS-CoV-2 sequence and previously published neutralizing antibody structures for SARS-CoV-1, we generated 20 initial antibody sequences predicted to target the SARS-CoV-2 RBD. As a first step in this process, we predicted (and publicly released) structures of the SARS-CoV-2 spike protein using homology-based structural modeling. The predicted structures proved to be accurate within the targeted RBD region when compared to experimentally derived structures published weeks later. Next we used our in silico design platform to iteratively propose mutations to SARS-CoV-1 neutralizing antibodies (known not to bind SARS-Cov-2) to enable and optimize binding within the RBD of SARS-CoV-2. Starting from a calculated baseline free energy of −48.1 kcal/mol (± 8.3), our 20 selected first round antibody structures are predicted to have improved interaction with the SARS-CoV-2 RBD with free energies as low as −82.0 kcal/mole. The baseline SARS-CoV-1 antibody in complex with the SARS-CoV-1 RBD has a calculated interaction energy of −52.2 kcal/mole and neutralizes the virus by preventing it from binding and entering the human ACE2 receptor. These results suggest that our predicted antibody mutants may bind the SARS-CoV-2 RBD and potentially neutralize the virus. Additionally, our selected antibody mutants score well according to multiple antibody developability metrics. These antibody designs are being expressed and experimentally tested for binding to COVID-19 viral proteins, which will provide invaluable feedback to further improve the machine learning–driven designs. This technical report is a high-level description of that effort; the Supplementary Materials includes the homology-based structural models we developed and 178,856 in silico free energy calculations for 89,263 mutant antibodies derived from known SARS-CoV-1 neutralizing antibodies.


COVID-19: Plummeting Stroke Admissions and New Protocols


title: A meta-analysis of cocaine use disorder treatment effectiveness

text: Background: In both the U.S. and U.K., after a period of decline, prevalence of cocaine use has been increasing since 2012 and is now the second leading cause of overdose death from an illicit drug. However, psychosocial treatments for cocaine use disorders are limited, and no pharmacotherapy is approved by regulatory bodies in the U.S. or Europe. We performed a comprehensive meta-analysis to assess treatments impacts on cocaine use. Methods: We performed a meta-analysis of clinical trials that included the word "cocaine" in the title and were published between 31/12/1995 and 31/12/2017. All studies of outpatient adults with active cocaine use and reporting urinalysis results were included. Treatment approaches were clustered into 11 categories. Missing data were imputed using multiple imputation by chained equations. We calculated intention-to-treat log-odds ratios (OR) for the change in proportion of patients testing negative for cocaine at the end of each study and performed multivariate mixed-effects meta-regression. This study was prospectively registered on covidence.org on 31/12/2015, study 8731. Findings: One hundred fifty-seven studies with 15,842 participants were included. Only contingency management was significantly associated with increased odds of testing negative for cocaine (OR of 2.13, 95% CI 1.62-2.80) and remained significant after all sensitivity analyses. Interpretation: This meta-analysis is unique in its broad inclusivity of treatment types and trial designs over a two-decade period of investigation. Our results converge with focused meta-analyses on treatments for cocaine use disorders; thus, research efforts and policy changes that expanded implementation of contingency management programs are expected to reduce cocaine use in active users and the associated individual, community, and societal burdens associated.


title: Blood supply strategies facing a reference blood center in Brazil during the COVID-19 pandemic

text: Abstract Background The SARS-CoV-2 pandemic is having an impact on blood supply This situation has led to new strategies to minimize the impact on blood product availability Methods The Hemocentro UNICAMP, a regional reference center in Brazil, has established availability strategies, respecting national and local measures to decrease transmission of SARS-CoV-2 Measures include booking donation appointments, reorganization of areas to permit social distancing, a pre-reception to reinforce donor instructions, antisepsis of donors? hands with 70% gel alcohol at each step of the process, post-donation information (PDI) reinforcement, recruitment intensification using social media/mass media, rapid replacement of cancelled mobile collections, reinforcement of collection from army units Rational blood use was reinforced in hospitals, elective procedures were suspended and stricter blood distribution was adopted Results A median increase of 14 5% was obtained in weekly blood donations, versus pre-crises period (1338 vs 1169) and a 15 9% decrease in blood distribution (1312 vs 1103 red blood cell units) (P<0 0001, c2=28 8) Booked appointments corresponded to 42 2% of all donations made in the period, with a mean absence of 19% at bookings Mobile unit blood collections cancelled in the period were 8/25 per month (vs around 3/25 before) About 62% of the cancelled mobile collections could be replaced Mean PDI increased from 5/week vs 2/week in the previous period Conclusion The strategy proved successful, although questions about the best approach to maintain blood supply during the COVID-19 pandemic remain Such experiences may help Blood Centers to design strategies to maintain blood stores during pandemic situations in the future


title: A generalized overview of SARS-COV-2: Where does the current knowledge stand?

text: The novel coronavirus known to have brought the world to a standstill is responsible for many deaths throughout the globe as of now. The causative agent (SARS-CoV-2) for coronavirus disease 2019 (COVID-19) has been recognized as a zoonotic transfer. Although, the medium of animal-human transmission is still unknown, bats maybe a potential reservoir of this novel strain. Due to its high rate of transmission the most favorable way of limiting the outbreak’s extent is by early diagnosis followed by isolation of the infected individuals. So far, the most widely used diagnosis methods are RT-qPCR which detects specific sequences of the viral RNA. Some other methods include serological tests and the recently introduced CRISPR-CAS-12 based assays. As of now, no specific therapeutic treatments are known for COVID-19 however the use of some broad-spectrum antiviral drugs and convalescent plasma therapy have demonstrated positive outcomes. Apart from these treatments, vaccine development for SARS-CoV-2 is also in progress by 17 known companies. This article provides a comprehensive insight on the recently emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) including its origin, transmission mechanism, pathophysiology and updated treatment methods.


title: The impact of temperature and absolute humidity on the coronavirus disease 2019 (COVID-19) outbreak - evidence from China

text: OBJECTIVE To investigate the impact of temperature and absolute humidity on the coronavirus disease 2019 (COVID-19) outbreak. DESIGN Ecological study. SETTING 31 provincial-level regions in mainland China. MAIN OUTCOME MEASURES Data on COVID-19 incidence and climate between Jan 20 and Feb 29, 2020. RESULTS The number of new confirm COVID-19 cases in mainland China peaked on Feb 1, 2020. COVID-19 daily incidence were lowest at -10 and highest at 10 ,while the maximum incidence was observed at the absolute humidity of approximately 7 g/m3. COVID-19 incidence changed with temperature as daily incidence decreased when the temperature rose. No significant association between COVID-19 incidence and absolute humidity was observed in distributed lag nonlinear models. Additionally, A modified susceptible-exposed-infectious-recovered (M-SEIR) model confirmed that transmission rate decreased with the increase of temperature, leading to further decrease of infection rate and outbreak scale. CONCLUSION Temperature is an environmental driver of the COVID-19 outbreak in China. Lower and higher temperatures might be positive to decrease the COVID-19 incidence. M-SEIR models help to better evaluate environmental and social impacts on COVID-19.


title: Power Laws in Superspreading Events: Evidence from Coronavirus Outbreaks and Implications for SIR Models

text: While they are rare, superspreading events (SSEs), wherein a few primary cases infect an extraordinarily large number of secondary cases, are recognized as a prominent determinant of aggregate infection rates (R0). Existing stochastic SIR models incorporate SSEs by fitting distributions with thin tails, or finite variance, and therefore predicting almost deterministic epidemiological outcomes in large populations. This paper documents evidence from recent coronavirus outbreaks, including SARS, MERS, and COVID-19, that SSEs follow a power law distribution with fat tails, or infinite variance. We then extend an otherwise standard SIR model with estimated power law distributions, and show that idiosyncratic uncertainties in SSEs will lead to large aggregate uncertainties in infection dynamics, even with large populations. That is, the timing and magnitude of outbreaks will be unpredictable. While such uncertainties have social costs, we also find that they on average decrease the herd immunity thresholds and the cumulative infections because per-period infection rates have decreasing marginal effects. Our findings have implications for social distancing interventions: targeting SSEs reduce not only the average rate of infection (R0) but also its uncertainty. To understand this effect, and to improve inference of the average reproduction numbers under fat tails, estimating the tail distribution of SSEs is vital.


title: The date predicted 200.000 cases of Covid-19 in Spain using SutteARIMA

text: The aim of this study is predicted 200.000 cases of Covid-19 in Spain. Covid-19 Spanish confirmed data obtained from Worldometer from 01 March 2020 - 17 April 2020. The data from 01 March 2020 - 10 April 2020 using to fitting with data from 11 April - 17 April 2020. For the evaluation of the forecasting accuracy measures, we use mean absolute percentage error (MAPE). Based on the results of SutteARIMA fitting data, the accuracy of SutteARIMA for the period 11 April 2020 - 17 April 2020 is 0.61% and we forecast 20.000 confirmed cases of Spain by the WHO situation report day 90/91 which is 19 April 2020 / 20 April 2020.


title: Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis.

text: RT-qPCR utilising upper respiratory swabs are the diagnostic gold standard for SARS-CoV-2 despite reported low sensitivity and limited scale up due to global shortages. Saliva is a non-invasive, equipment independent alternative to swabs. We collected 145 paired saliva and nasal/throat (NT) swabs at diagnosis (day 0) and repeated on day 2 and day 7 dependent on inpatient care and day 28 for study follow up. Laboratory cultured virus was used to determine the analytical sensitivity of spiked saliva and swabs containing amies preservation media. Self-collected saliva samples were found to be consistent, and in some cases superior when compared to healthcare worker collected NT swabs from COVID-19 suspected participants. We report for the first time the analytical limit of detection of 10-2 and 100 pfu/ml for saliva and swabs respectively. Saliva is a easily self-collected, highly sensitive specimen for the detection of SARS-CoV-2.


title: Can medication mitigate the need for a strict lock down?: A mathematical study of control strategies for COVID-19 infection

text: We formulate a deterministic epidemic model to study the effects of medication on the transmission dynamics of Corona Virus Disease (COVID-19). We are especially interested in how the availability of medication could change the necessary quarantine measures for effective control of the disease. We model the transmission by extending the SEIR model to include asymptomatic, quarantined, isolated and medicated population compartments. We calculate the basic reproduction number R_0 and show that for R_0<1 the disease dies out and for R_0>1 the disease is endemic. Using sensitivity analysis we establish that R_0 is most sensitive to the rates of quarantine and medication. We also study how the effectiveness and the rate of medication along with the quarantine rate affect R_0. We devise optimal quarantine, medication and isolation strategies, noting that availability of medication reduces the duration and severity of the lock-down needed for effective disease control. Our study also reinforces the idea that with the availability of medication, while the severity of the lock downs can be eased over time some social distancing protocols need to be observed, at least till a vaccine is found. We also analyze the COVID-109 outbreak data for four different countries, in two of these, India and Pakistan the curve is still rising, and in he other two, Italy and Spain, the epidemic curve is now falling due to effective quarantine measures. We provide estimates of R_0 and the proportion of asymptomatic individuals in the population for these countries.


title: Performance of progressive and adaptive COVID-19 exit strategies: a stress test analysis for managing intensive care unit rates

text: Background: In May 2020, many European countries have begun to introduce an exit strategy for the coronavirus disease 2019 (COVID-19) pandemic which involves relaxing social distancing measures. Predictive epidemiological modeling indicates that chances for resurgence are high. However, parametrization of the epidemiological nature of COVID-19 and the effect of relaxing social distancing is not well constrained, resulting in highly uncertain outcomes in view of managing future intensive care unit (ICU) needs. Methods and findings: For performance analysis of exit strategies we developed an open-source ensemble-based Susceptible-Exposed-Infectious-Removed (SEIR) model. It takes into account uncertainties for the COVID-19 parametrization and social distancing measures. The model is calibrated to data of the outbreak and lockdown phase. For the exit phase, the model includes the capability to activate an emergency brake, reinstating lockdown conditions. Alternatively, the model uses an adaptive COVID-19 cruise control (ACCC) capable to retain a targeted ICU level. The model is demonstrated for the Netherlands and we analyzed progressive and adaptive exit strategies through a stress test of managing ICU rates. The progressive strategy reflects the outcome of social and economic pressure to use one-way steering toward progressively relaxing measures at an early stage. It is marked by a high probability for the activation of the emergency brake due to an unsolicited growth of ICU needs in the following months. Alternatively, the two-way steering ACCC can flatten ICU needs in a more gradual way and avoids activation of the emergency brake. It also performs well for seasonal variation in the reproduction number of severe acute respiratory syndrome-coronavirus. Conclusions: The adaptive strategy (ACCC) is favored, as it avoids the use of the emergency brake at the expense of small steps of restrictive measures and allows the exploration of riskier and potentially rewarding measures in the future pathways of the exit strategy.


Covert coronavirus, chaos prize and the cost of contact-tracing.


title: Hydroxychloroquine alone or in combination with azithromycin to prevent major clinical events in hospitalised patients with coronavirus infection (COVID-19): rationale and design of a randomised, controlled clinical trial

text: Introduction: Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral clearance in patients with COVID-19, but its effect on clinical outcomes remains uncertain. Methods and analysis: We describe the rationale and design of an open-label pragmatic multicentre randomised (concealed) clinical trial of 7 days of hydroxychloroquine (400 mg BID) plus azithromycin (500 mg once daily), hydroxychloroquine 400 mg BID, or standard of care for moderately severe hospitalised patients with suspected or confirmed COVID-19 (in-patients with up to 4L/minute oxygen supply through nasal catheter). Patients are randomised in around 50 recruiting sites and we plan to enrol 630 patients with COVID-19. The primary endpoint is a 7-level ordinal scale measured at 15-days: 1)not hospitalised, without limitations on activities; 2)not hospitalised, with limitations on activities; 3)hospitalised, not using supplementary oxygen; 4)hospitalised, using supplementary oxygen; 5)hospitalised, using high-flow nasal cannula or non-invasive ventilation; 6)hospitalised, on mechanical ventilation; 7)death. Secondary endpoints are the ordinal scale at 7 days, need for mechanical ventilation and rescue therapies during 15 days, need of high-flow nasal cannula or non-invasive ventilation during 15 days, length of hospital stay, in-hospital mortality, thromboembolic events, occurrence of acute kidney injury, and number of days free of respiratory support at 15 days. Secondary safety outcomes include prolongation of QT interval on electrocardiogram, ventricular arrhythmias, and liver toxicity. The main analysis will consider all patients with confirmed COVID-19 in the groups they were randomly assigned. Ethics and dissemination: This study has been approved by Brazil's National Ethic Committee (CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete, as well as presented and reported to local health agencies. ClinicalTrials.gov identifier: NCT04322123


title: Distinguishing between COVID-19 and the common cold in a primary care setting - comparison of patients with positive and negative SARS-CoV-2 PCR results.

text: Background: Combating the COVID-19 pandemic is a major challenge for health systems, citizens and policy makers worldwide. Early detection of affected patients within the huge population of patients with common cold symptoms is an important element of this effort but often hindered by limited testing resources. We aimed to identify predictive risk profiles for a positive PCR result in primary care. Methods: Multi-center cross-sectional cohort study on predictive characteristics over a period of 4 weeks in primary care patients in Germany. We evaluated age, sex, reason for testing, risk factors, symptoms, and expected PCR result for their impact on the test result. Results: In total, 374 patients in 14 primary care centers received SARS-CoV-2 PCR swab testing and were included in this analysis. A fraction of 10.7% (n=40) tested positive for COVID-19. Patients who reported anosmia had a higher odds ratio (OR: 4.54; 95%-CI: 1.51-13.67) for a positive test result while patients with a sore throat had a lower OR (OR: 0.33; 95%-CI: 0.11-0.97). Patients who had a first grade contact with an infected persons and showed symptoms themselves also had an increased OR for positive testing (OR: 5.16; 95% CI: 1.72-15.51). This correlation was also present when they themselves were still asymptomatic (OR: 12.55; 95% CI: 3.97-39.67). Conclusion: The reported contact to an infected person is the most important factor for a positive PCR result, independent of any symptoms of illness in the tested patient. Those persons with contact to an infected person should always get a PCR test. If no contact is reported and testing material is scarce, anosmia should increase the likelihood of performing a test, while a sore throat should decrease it.


title: The self and its world: A neuro-ecological and temporo-spatial account of existential fear

text: The current international crisis situation caused by the COVID-19 pandemic is having a strong psychological impact on our subjectivities. We are constantly threatened by the danger of i) being infected, ii) infecting other people, and (iii) by the loss of social relation. Departing from these premises, we here aim to investigate the psychological and neurodynamics of this complex phenomenon. First, we discuss about recent psychological and neuronal findings on fear and its disorders, related to an unbalanced intero-exteroceptive processing and emotional regulation. Secondly we move to the psychological and neuronal dynamics of self and others characterized by a temporo-spatial alignment with the world. Due to the neural overlap of emotion and self and the deep-reaching neuro-ecological layers of self, emotional feelings like fear and anxiety cannot be detached and dissociated from the world; they signify the world–brain relation, and, more specifically, our self-other relation. The deepest neuro-ecological and neuro-social layers of self are threatened by the loss of subjectivity, which is manifest in our loss of body and thus the fear of dying, and the loss of intersubjectivity that surfaces in our fear of infecting others, which reflect the intimate anchorage of the self with the world. In our opinion the pandemic of COVID-19 deeply affect our sense of self and its spatio-temporal neuronal dynamics providing the prerequisites for the manifestation of fear and existential anxiety, thus disrupting the brain-world relation with significant repercussions on our psyche and on our daily lives.


title: Temporal dynamics in viral shedding and transmissibility of COVID-19

text: We report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.


title: COVID-19 data analysis and modeling in Palestine

text: We estimate an actual number of infected cases in Palestine based on the 18-day effect from infection to death. We find that the number of cases in April 22 varies between 506 and 2 026 infected cases. We also focus on the reproductive number in Palestine based on population dynamics with two SEIR models. Dataset is from 5 March to 22 April 2020. With a transmission rate equal to 4.55 106, on May 22, the simulations predict 11 014 total infected cases in the optimistic scenario and 113 171 in the worst one. The crest of the pandemic is from 22 to 27 May 2020. The reproductive number R0 is equal to 1.54 for a fixed fraction of 0.6 of symptomatic cases that are reported and for a removal rate of 7. Palestinian COVID-19 mortality number is equal to 6 per million. It is small compared to countries neighboring Palestine. The infected number is equal to 88.4 per million, which is less than most of its neighbors. The basic reproduction number is still greater than 1. Changes to the transmission rate (over time) would be advisable, to fall R0 below the critical threshold.


title: Modelling the impact of Plasma Therapy and Immunotherapy for Recovery of COVID-19 Infected Individuals

text: Since the first case of COVID-19 was detected in Wuhan, China in December 2019, COVID-19 has become a pandemic causing a global economic and public health emergency. There is no known treatment or vaccine available for COVID-19 to date. Immunotherapy and plasma therapy has been used with satisfactory efficacy over the past two decades in many viral infections like SARS (Systemic Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome), and H1N1. Limited data from China show clinical benefit, radiological resolution, reduction in viral loads, and improved survival. Our aim is to create a mathematical model for COVID-19 transmission and then apply various control parameters to see their effects on recovery from COVID-19 disease. We have formulated a system of non-linear ordinary differential equations, calculated basic reproduction R0, and applied five different controls (self-isolation, quarantine, herd immunity, immunotherapy, plasma therapy) to test the effectiveness of control strategy. Control optimality was checked by Lagrangian functions. Numerical simulations and bifurcation analyses were carried out. The study concludes that the COVID-19 outbreak can be controlled up to a significant level three weeks after applying all the control strategies together. These strategies lead to a reduction in hospitalization and a rise in recovery from infection. Immunotherapy is highly effective initially in hospitalized infected individuals however better results were seen in the long term with plasma therapy.


title: Telesimulation for COVID-19 Ventilator Management Training With Social-Distancing Restrictions During the Coronavirus Pandemic

text: Background. In early 2020, the novel coronavirus pandemic forced communities around the globe to shut down and isolate. Routine graduate medical education activities have also been suspended as resident and fellow physicians-in-training have been re-deployed to support critical patient care services. Innovation. We developed a two-part hybrid telesimulation model to teach COVID-19 ventilator management strategies while physically separating a group of learners and an instructor from one another. Learners consisted of non-ICU health care providers with limited experience in ventilator management being redeployed to manage ICU level COVID-19 infected patients. In the first week, the video tutorial has been viewed over 500 times and we have facilitated 14 telesimulation sessions, including 48 participants comprised of hospitalists, emergency medicine physicians and physician assistants, pediatric residents, nurses, and a nurse educator. Conclusion. We believe that the combination of a video tutorial followed by an interactive telesimulation was successful in providing timely education during a coronavirus pandemic. Furthermore, it reinforced the value and flexibility in which simulation education could continue conveniently for learners despite significant restrictions in place during the coronavirus pandemic. Research is needed to assess the efficacy of this hybrid intervention in preparing healthcare workers and to determine if the knowledge is successfully transferred to the clinical setting.


title: Literature Listing

text: Abstract The quarterly Literature Listing is intended as a current awareness service for readers indicating newly published books, journal and conference articles on: patent search techniques, databases, analysis and classifications; patent searcher certification; patents relating to a) life sciences and pharmaceuticals and b) software; patent policy and strategic issues; trade marks; designs; domain names; and articles reviewing historical aspects of intellectual property or reviewing specific topics/persons. The current Literature Listing was compiled end-May 2020. Key resources used are Scopus, Digital Commons, publishers’ RSS feeds, and serendipity! Please feel free to send the author details of newly published reports/monographs/books for potential inclusion.


title: Emotional distress and associated sociodemographic risk factors during the COVID-19 outbreak in Spain

text: Background Spain is one of the countries that has been most affected by COVID-19 disease. However, the emotional distress on the Spanish population remains poorly understood. The aim of this study was to determine the presence of emotional disorders and related symptoms and to assess the influence of sociodemographic characteristics on this population. Methods We conducted a cross-sectional survey using an online platform. Participation was completely voluntary. Sociodemographic variables were collected and symptoms of anxiety, depression, and panic were assessed through three questionnaires: Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and the Patient Health Questionnaire-Panic Disorder (PHQ-PD). Chi-squared statistics were applied to determine the influence of sociodemographic variables on symptom severity and diagnosis. Results Most respondents (n=1753) were female (76.8%), with a mean (SD) age of 40.4 (12.9) years; 39.1% were married and 39.5% held a high school degree. Severe and moderate symptoms of anxiety and depression were high (6.5% and 14.3%; 9.9% and 12.9%, respectively) and more than one in four participants (25.7%) experienced a panic attack. A high proportion of participants met diagnostic criteria for emotional disorders: 15.3% for GAD; 12.2% for MDD; and 17.2% for PD. Significant risk factors were as follows: female, young adult, single, unemployed, and low income. Conclusion Due to limitations related to the study design (convenience sample), the findings of these study may not be applicable to the general population. Nonetheless, the high prevalence of emotional symptoms and disorders in this sample suggests that mental health interventions are urgently needed in Spain.


title: SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts

text: Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-grade 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) co-registered with computed tomography (CT) revealed pulmonary lesions at 4 days post-infection (dpi) that resolved over time. Infectious virus was shed from both respiratory and gastrointestinal (GI) tracts in all animals in a biphasic manner, first between 2-7 dpi followed by a recrudescence at 14-21 dpi. Viral RNA (vRNA) was found throughout both respiratory and gastrointestinal systems at necropsy with higher levels of vRNA found within the GI tract tissues. All animals seroconverted simultaneously for IgM and IgG, which has also been documented in human COVID-19 cases. Young AGM represent an excellent species to study mild/subclinical COVID-19 disease and have shed light on unknown aspects of long-term virus shedding. They are ideally suited for preclinical evaluation of candidate vaccines and therapeutic interventions. One Sentence Summary Subclinical infection of African green monkeys infected with SARS-CoV-2 results in prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts.


title: Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR

text: Background COVID-19 pandemic is underway. Some COVID-19 cases re-tested positive for SARS-CoV-2 RNA after discharge raising the public concern on their infectivity. Characterization of re-positive cases are urgently needed for designing intervention strategies. Methods Clinical data were obtained through Guangdong COVID-19 surveillance network. Neutralization antibody titre was determined using a microneutralization assay. Potential infectivity of clinical samples was evaluated after the cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing. Results Among 619 discharged COVID-19 cases, 87 were re-tested as SARS-CoV-2 positive in circumstance of social isolation. All re-positive cases had mild or moderate symptoms in initial diagnosis and a younger age distribution (mean, 30.4). Re-positive cases (n=59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n=150) parallel-tested in this study. No infective viral strain could be obtained by culture and none full-length viral genomes could be sequenced for all re-positive cases. Conclusions Re-positive SARS-CoV-2 was not caused by the secondary infection and was identified in around 14% of discharged cases. A robust Nabs response and a potential virus genome degradation were detected from nearly all re-positive cases suggesting a lower transmission risk, especially through a respiratory route.


title: Investigating the likely association between genetic ancestry and COVID-19 manifestation

text: The novel coronavirus 2019-nCoV/SARS-CoV-2 infection has shown discernible variability across the globe. While in some countries people are recovering relatively quicker, in others, recovery times have been comparatively longer and numbers of those succumbing to it high. In this study, we aimed to evaluate the likely association between an individual's ancestry and the extent of COVID-19 manifestation employing Europeans as the case study. We employed 10,215 ancient and modern genomes across the globe assessing 597,573 single nucleotide polymorphisms (SNPs). Pearson's correlation coefficient (r) between various ancestry proportions of European genomes and COVID-19 death/recovery ratio was calculated and its significance was statistically evaluated. We found significant positive correlation (p=0.03) between European Mesolithic hunter gatherers (WHG) ancestral fractions and COVID-19 death/recovery ratio and a marginally significant negative correlation (p=0.06) between Neolithic Iranian ancestry fractions and COVID-19 death/recovery ratio. We further identified 404 immune response related single nucleotide polymorphisms (SNPs) by comparing publicly available 753 genomes from various European countries against 838 genomes from various Eastern Asian countries in a genome wide association study (GWAS). Prominently we identified that SNPs associated with Interferon stimulated antiviral response, Interferon-stimulated gene 15 mediated antiviral mechanism and 2'-5' oligoadenylate synthase mediated antiviral response show large differences in allele frequencies between Europeans and East Asians. Overall, to the best of our knowledge, this is the first study evaluating the likely association between genetic ancestry and COVID-19 manifestation. While our current findings improve our overall understanding of the COVID-19, we note that the development of effective therapeutics will benefit immensely from a more detailed analyses of individual genomic sequence data from COVID-19 patients of varied ancestries.


title: Application of traditional Chinese medicine in prevention and treatment of COVID-19/ 基于中医药防治新型冠状病毒肺炎的用药探析

text: The outbreak of COVID-19 in Wuhan Province of China is highly contagious, rapid transmission and widespread, which has aroused great concern at home and abroad. WHO declared COVID-19 as an international public health emergency of concern. In the face of major epidemic situation, our hospital has carried out investigation and analysis on the use of traditional Chinese medicine in the prevention and treatment of COVID-19, and summarized the direction of diagnosis and treatment of traditional Chinese medicine and the main points of use of antiviral traditional Chinese medicine, classic prescriptions and Chinese patent medicine, in order to provide reference for diagnosis and treatment of COVID-19 and rational drug selection in medical institutions.


title: Effect of large-scale testing platform in prevention and control of the COVID-19 pandemic: an empirical study with a novel numerical model

text: Background: China adopted an unprecedented province-scale quarantine since January 23rd 2020, after the novel coronavirus (COVID-19) broke out in Wuhan in December 2019. Responding to the challenge of limited testing capacity, large-scale standardized and fully-automated laboratory (Huo-Yan) was built as an ad-hoc measure. There was so far no empirical data or mathematical model to reveal the impact of the testing capacity improvement since the quarantine. Methods: We integrated public data released by the Health Commission of Hubei Province and Huo-Yan Laboratory testing data into a novel differential model with non-linear transfer coefficients and competitive compartments, to evaluate the trends of suspected cases under different nucleic acid testing capacities. Results: Without the establishment of Huo-Yan, the suspected cases would increased by 47% to 33,700, the corresponding cost of the quarantine would be doubled, and the turning point of the increment of suspected cases and the achievement of "daily settlement" (all daily new discovered suspected cases were diagnosed according to the nucleic acid testing results) would be delayed for a whole week and 11 days. If the Huo-Yan Laboratory could ran at its full capacity, the number of suspected cases could started to decrease at least a week earlier, the peak of suspected cases would be reduced by at least 44% and the quarantine cost could be reduced by more than 72%. Ideally, if a daily testing capacity of 10,500 could achieved immediately after the Hubei lockdown, "daily settlement" for all suspected cases would be achieved immediately. Conclusions: Large-scale and standardized clinical testing platform with nucleic acid testing, high-throughput sequencing and immunoprotein assessment capabilities need to be implemented simultaneously in order to maximize the effect of quarantine and minimize the duration and cost. Such infrastructure like Huo-Yan, is of great significance for the early prevention and control of infectious diseases for both common times and emergencies.


Visit to singapore medical journal during covid-19 outbreak: Learning “beyond” the expectation


title: Analysis of the effect of proton pump inhibitors on the course of common COVID-19

text: Background/aims: To evaluate the effect of proton pump inhibitors on the course of common COVID-19. Methods: Clinical data of common COVID-19 patients admitted to the Shanghai public health clinical center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses. Results: A total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of SARS-CoV-2 clearance and the cumulative incidence of discharge, and the same after Propensity Score Match, all P > 0.05. Multivariate analysis suggested that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of hospital stay in COVID-19 patients was shortened by SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05. Conclusion: Proton pump inhibitors use have no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.


title: Classification of Covid-19 coronavirus, pneumonia and healthy lungs in CT scans using Q-deformed entropy and deep learning features

text: Many health systems over the world have collapsed due to limited capacity and a dramatic increase of suspected COVID-19 cases. What has emerged is the need for finding an efficient, quick and accurate method to mitigate the overloading of radiologists' efforts to diagnose the suspected cases. This study presents the combination of deep learning of extracted features with the Q-deformed entropy handcrafted features for discriminating between COVID-19 coronavirus, pneumonia and healthy computed tomography (CT) lung scans. In this study, pre-processing is used to reduce the effect of intensity variations between CT slices. Then histogram thresholding is used to isolate the background of the CT lung scan. Each CT lung scan undergoes a feature extraction which involves deep learning and a Q-deformed entropy algorithm. The obtained features are classified using a long short-term memory (LSTM) neural network classifier. Subsequently, combining all extracted features significantly improves the performance of the LSTM network to precisely discriminate between COVID-19, pneumonia and healthy cases. The maximum achieved accuracy for classifying the collected dataset comprising 321 patients is 99.68%.


title: The need for household panelsoep-covsurveys in times of crisis: The case of SOEP-CoV

text: The spread of the novel coronavirus, SARS-CoV-2, poses major challenges for individuals and societies at large. The question now is how individuals and society are dealing with these challenges, and what health, psychological, social, and economic effects they will have to bear. Meaningful answers can only be provided using a generalizable database that contains contex-tual information such as family characteristics and offers a life-course perspective. We argue that these criteria are best met by household panel survey data. In this paper, we illustrate the importance of such data and show how they can aid in explaining the current and future effects of the pandemic on individuals, households, and society. Furthermore, we describe the survey design of SOEP-CoV, a supplementary telephone survey to the German Socio-Economic Panel (SOEP) study.


title: Outbreak analysis with a logistic growth model shows COVID-19 suppression dynamics in China

text: China experienced an outbreak of a novel coronavirus, SARS-CoV2, from mid-January till mid-March 2020. Here we review the curves of epidemic growth and decline of the virus in China using a phenomenological logistic growth model to summarize the dynamics of the outbreak using three parameters that characterize the epidemic's timing, rate and peak. During the initial phase, the number of cases doubled every 2.7 (range 2.2 - 4.4) days. The rate of increase in the number of reported cases peaked approximately 10 days after suppression measures were started on 23-25 January 2020. The peak in the number of reported sick cases occurred on average 18 days after the start of measures. From the time of starting measures till the peak, the number of cases increased by a factor 38.5 in the province Hubei, and by a factor 9.5 for all of China (range: 6.2-20.4 in the other provinces). Complete suppression took up to 2 months (range: 23-57d.), during which period severe restrictions, social distancing measures, testing and isolation of cases were in place. The suppression of the disease in China has been successful, acting as a beacon of hope for countries outside China where the epidemic is still in a phase of increase and authorities need to decide their course of action.


title: Sulforhodamine B and exogenous surfactant effects on alveolar surface tension in acute respiratory distress syndrome models

text: BACKGROUND In the acute respiratory distress syndrome (ARDS), elevated alveolar surface tension, T, may increase ventilation-induced lung injury. Exogenous surfactant therapy has not reduced ARDS mortality. Sulforhodamine B (SRB), which acts with albumin to improve native lung surfactant efficacy, could be an alternative T-lowering therapeutic. We test whether substances suspected of elevating T in ARDS raise T in the lungs – where, unlike in most in vitro tests, the surfactant monolayer is intact – and test the abilities of exogenous surfactant and SRB to reduce T. METHODS In isolated rat lungs, we micropuncture a surface alveolus and instill a solution containing a substance purported to raise T in ARDS: control saline, cell debris, secretory phospholipase A2 (sPLA2), acid or mucins. We test each substance alone; with albumin, to model proteinaceous edema liquid; with albumin and subsequent exogenous surfactant; or with albumin and SRB. We determine T by combining servo-nulling pressure measurement with confocal microscopy, and applying the Laplace relation. RESULTS In the control group, saline, albumin and Infasurf do not alter T; SRB reduces T below normal. With albumin, the experimental substances raise T. With cell debris, surfactant does not alter T; SRB normalizes T. With sPLA2, surfactant normalizes T; SRB reduces T. With acid or mucins, neither surfactant nor SRB alters T. CONCLUSIONS The inability of surfactant to counter cell debris may contribute to the failure of surfactant therapy for ARDS. For non-aspiration ARDS, SRB, which can be delivered intravascularly to target injured lung regions, holds promise as a treatment. Summary In the acute respiratory distress syndrome (ARDS), surface tension, T, is believed to be elevated and surfactant therapy has failed to reduce mortality. Here, we test whether various substances suggested to contribute to elevated T in ARDS in fact raise T in the lungs. And we test the ability of exogenous surfactant and of a potential alternative therapeutic, sulforhodamine B (SRB), to reduce T. We find exogenous surfactant unable to lower T in the presence of cell debris but SRB, which can be administered intravascularly, a candidate for lowering T in non-aspiration ARDS.


title: Anomalous atmospheric circulation favored the spread of COVID-19 in Europe

text: The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in terms of air temperature and humidity, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus's propagation, by short-range droplet transmission as well as likely by long-range aerosol (airborne) transmission.


title: Predicting COVID-19 Peaks Around the World

text: The official data for the time evolution of active cases of COVID-19 pandemics around the world are available online For all countries, a peak has been either observed (China and South Korea) or is expected in the near future The approximate dates and heights of those peaks have important epidemiological implications Inspired by similar complex behavior of volumes of transactions of stocks at the NYSE and NASDAQ, we propose aq-statistical functional form that appears to describe satisfactorily the available data for all countries Consistently, predictions of the dates and heights of those peaks in severely affected countries become possible unless efficient treatments or vaccines, or sensible modifications of the adopted epidemiological strategies, emerge


title: Data-Based Analysis, Modelling and Forecasting of the COVID-19 outbreak

text: Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infected-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R0), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R0 as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ~4.6, while the one computed under the second scenario was found to be ~3.2. Thus, based on the SIRD simulations, the estimated average value of R0 was found to be ~2.6 based on confirmed cases and ~2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around 0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.


Ibuprofen has synergism with SARS-CoV-2 infection


title: A Noncooperative Game Analysis for Controlling COVID-19 Outbreak

text: COVID-19 is a global epidemic. Till now, there is no remedy for this epidemic. However, isolation and social distancing are seemed to be effective to control this pandemic. In this paper, we provide an analytical model on the effectiveness of the sustainable lockdown policy that accommodates both isolation and social distancing features of the individuals. To promote social distancing, we analyze a noncooperative game environment that provides an incentive for maintaining social distancing. Furthermore, the sustainability of the lockdown policy is also interpreted with the help of a game-theoretic incentive model for maintaining social distancing. Finally, an extensive numerical analysis is provided to study the impact of maintaining a social-distancing measure to prevent the Covid-19 outbreak. Numerical results show that the individual incentive increases more than 85% with an increasing percentage of home isolation from 25% to 100% for all considered scenarios. The numerical results also demonstrate that in a particular percentage of home isolation, the individual incentive decreases with an increasing number of individuals.


title: Modelling the epidemiological trend and behavior of COVID-19 in Italy

text: As of March 16, 2020, over 185,000 across the world, Italy became the red hotspot for the COVID-19 pandemic after China. With over 35,000 cases and 2900 deaths reported in the month of March in Italy, it is necessary to stimulate epidemic trend to understand the behavior of COVID-19 in Italy. By S.E.I.R. simulation, we estimated the most representative epidemic parameters occurred from March 1 to 14, 2020, thus being able to evaluate the consistency of the containment rules and identify possible Sars-Cov-2 local mutations. Our estimations are based on some assumptions and limitations exited.


title: Assessing the influence of parental anxiety on childhood anxiety during the COVID-19 pandemic in the United Arab Emirates

text: The COVID-19 pandemic originated in Wuhan, China on December 31st and spread into international borders, leading to a public health crisis and complete shutdown of countries. The strict quarantine measures taken by governments kept a large number of people, around the world, in isolation and affected many aspects of people's lives. These unprecedented changes triggered a wide variety of psychological problems ranging from panic disorders, anxiety and depression. In this study, we aim to explore anxiety levels among parents, teachers and the general community amid the COVID-19 pandemic in the UAE, as well as identify emotional and anxiety disorders in children. Using a web-based cross-sectional survey we collected data from 2,200 self-selected assessed volunteers. Demographic information, knowledge and beliefs about COVID-19, generalized anxiety disorder (GAD) using the (GAD-7) scale , emotional problems in children using the strengths and difficulties questionnaire (SDQ), worry and fear about COVID-19, coping mechanisms and general health information were collected. The overall prevalence of GAD in the general population was 71% with younger people (59.8%) and females (51.7%) reporting the highest levels of anxiety. Parents who were teachers reported the highest percentage of emotional problems in children (26.7%) compared to parents only (14.6%) or teachers only (4.7%). Multivariate logistic regression for GAD-7 score showed that females, participants who felt public fear was justifiable, persons who worried about COVID-19, persons who intended to take the COVID-19 vaccine and smokers were all associated with anxiety. Multivariate logistic regression for SDQ showed parents who had severe anxiety levels were 7 times more likely to report more emotional problems in their children (OR=7.00, 95% CI, 3.45 to 14.0) than less anxious parents. Findings suggest the urgency of policy makers to develop effective screening and coping strategies for parents and teachers and more specifically for vulnerable children.


title: FliI6-FliJ molecular motor assists with unfolding in the type III secretion export apparatus

text: The role of rotational molecular motors of the ATP synthase class is integral to the metabolism of cells. Yet the function of FliI6-FliJ complex - a homolog of the F1 ATPase motor - within the flagellar export apparatus remains unclear. We use a simple two-state model adapted from studies of linear molecular motors to identify key features of this motor. The two states are the ‘locked’ ground state where the FliJ coiled coil filament experiences fluctuations in an asymmetric torsional potential, and a ‘free’ excited state in which FliJ undergoes rotational diffusion. Michaelis-Menten kinetics was used to treat transitions between these two states, and obtain the average angular velocity of the FliJ filament within the FliI6 stator: ωmax ≈ 9.0 rps. The motor was then studied under external counter torque conditions in order to ascertain its maximal power output: Pmax ≈ 42 kBT/s, and the stall torque: Gstall ≈ 3 kBT/rad. Two modes of action within the flagellar export apparatus are proposed, in which the motor performs useful work either by continuously ‘grinding’ through the resistive environment, or by exerting equal and opposite stall force on it. In both cases, the resistance is provided by flagellin subunits entering the flagellar export channel prior to their unfolding. We therefore propose that the function of the FliI6-FliJ complex is to lower the energy barrier and therefore assist in unfolding of the flagellar proteins before feeding them into the transport channel.


title: Spread of COVID-19: Investigation of universal features in real data

text: We present results on the existence of various common patterns in the growth of the total number of patients affected by COVID-19, a disease acquired through infection by a novel coronavirus, in different countries. For this purpose we propose a scaling model that can have general applicability in the understanding of real data of epidemics. This is analogous to the finite-size scaling, a technique used in the literature of phase transition to identify universality classes. In the disease model, the size of a system is proportional to the volume of the population, within a geographical region, that have been infected at the death of the epidemic or are eventually going to be infected when an epidemic ends. Outcome of our study, for COVID-19, via application of this model, suggests that in most of the countries, after the `onset' of spread, the growths are described by rapid exponential function, for significantly long periods. In addition to accurately identifying this superuniversal feature, we point out that the model is helpful in grouping countries into universality classes, based on the late time behavior, characterized by physical distancing practices, in a natural way. This feature of the model can provide direct comparative understanding of the effectiveness of lockdown-like social measures adopted in different places.


title: SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface

text: COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a novel betacoronavirus discovered in December 2019 and closely related to the SARS coronavirus (CoV). Both viruses use the human ACE2 receptor for cell entry, recognizing it with the Receptor Binding Domain (RBD) of the S1 subunit of the viral spike (S) protein. The S2 domain mediates viral fusion with the host cell membrane. Experience with SARS and MERS coronavirus has shown that potent monoclonal neutralizing antibodies against the RBD can inhibit the interaction with the virus cellular receptor (ACE2 for SARS) and block the virus cell entry. Assuming that a similar strategy would be successful against SARS-CoV-2, we used phage display to select from the human naïve universal antibody gene libraries HAL9/10 anti SARS2 spike antibodies capable of inhibiting interaction with ACE2. 309 unique fully human antibodies against S1 were identified. 17 showed more than 75% inhibition of spike binding to cells expressing ACE2, assessed by flow cytometry and several antibodies showed even an 50% inhibition at a molar ratio of the antibody to spike protein or RBD of 1:1. Furthermore, these antibodies neutralized active SARS-Cov-2 virus infection of VeroE6 cells. All 17 were all able to bind the isolated RBD, four of them with sub-nanomolar EC50. Epitope analysis of the antibodies revealed that six bind at the RBD-ACE2 interface and two on the opposite side of the domain. Universal libraries from healthy donors offer the advantage that antibodies can be generated quickly and independent from the availability of material from recovered patients in a pandemic situation.


title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates

text: We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL (pro)) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart. With the 3CL (pro) molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.


title: Downgrading disease transmission risk estimates using terminal importations

text: As emerging and re-emerging infectious diseases like dengue, Ebola, chikungunya, and Zika threaten new populations worldwide, officials scramble to assess local severity and transmissibility, with little to no epidemiological history to draw upon. Standard methods for assessing autochthonous (local) transmission risk make either indirect estimates based on ecological suitability or direct estimates only after local cases accumulate. However, an overlooked source of epidemiological data that can meaningfully inform risk assessments prior to outbreak emergence is the absence of transmission by imported cases. Here, we present a method for updating a priori ecological estimates of transmission risk using real-time importation data. We demonstrate our method using Zika importation and transmission data from Texas in 2016, a high-risk region in the southern United States. Our updated risk estimates are lower than previously reported, with only six counties in Texas likely to sustain a Zika epidemic, and consistent with the number of autochthonous cases detected in 2017. Importation events can thereby provide critical, early insight into local transmission risks as infectious diseases expand their global reach.


Successful Heart Transplantation to a Fulminant Myocarditis Patient during COVID-19 Outbreak – Lessons Learned


title: Genomic epidemiology of a densely sampled COVID19 outbreak in China

text: Analysis of genetic sequence data from the pandemic SARS Coronavirus 2 can provide insights into epidemic origins, worldwide dispersal, and epidemiological history. With few exceptions, genomic epidemiological analysis has focused on geographically distributed data sets with few isolates in any given location. Here we report an analysis of 20 whole SARS-CoV 2 genomes from a single relatively small and geographically constrained outbreak in Weifang, People's Republic of China. Using Bayesian model-based phylodynamic methods, we estimate the reproduction number for the outbreak to be 1.99(95% CI:1.48-3.14). We further estimate the number of infections through time and compare these estimates to confirmed diagnoses by the Weifang Centers for Disease Control. We find that these estimates are consistent with reported cases and there is unlikely to be a large undiagnosed burden of infection over the period we studied.


title: Divide and conquer – machine-learning integrates mammalian, viral, and network traits to predict unknown virus-mammal associations

text: Our knowledge of viral host ranges remains limited. Completing this picture by identifying unknown hosts of known viruses is an important research aim that can help identify zoonotic and animal-disease risks. Furthermore, such understanding can be used to mitigate against viral spill-over from animal reservoirs into human population. To address this knowledge-gap we apply a divide-and-conquer approach which separates viral, mammalian and network features into three unique perspectives, each predicting associations independently to enhance predictive power. Our approach predicts over 20,000 unknown associations between known viruses and mammalian hosts, suggesting that current knowledge underestimates the number of associations in wild and semi-domesticated mammals by a factor of 4.3, and the average mammalian host-range of viruses by a factor of 3.2. In particular, our results highlight a significant knowledge gap in the wild reservoirs of important zoonotic and domesticated mammals’ viruses: specifically, lyssaviruses, bornaviruses and rotaviruses.


title: Guidance for the Treatment and Management of COVID‐19 Among People with Intellectual Disabilities

text: The current COVID‐19 pandemic is a pressing world crisis and people with intellectual disabilities (IDs) are vulnerable due to disparity in healthcare provision and physical and mental health multimorbidity. While most people will develop mild symptoms upon contracting severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), some will develop serious complications. The aim of this study is to present guidelines for the care and treatment of people with IDs during the COVID‐19 pandemic for both community teams providing care to people with IDs and inpatient psychiatric settings. The guidelines cover specific issues associated with hospital passports, individual COVID‐19 care plans, the important role of families and carers, capacity to make decisions, issues associated with social distancing, ceiling of care/treatment escalation plans, mental health and challenging behavior, and caring for someone suspected of contracting or who has contracted SARS‐CoV‐2 within community or inpatient psychiatric settings. We have proposed that the included conditions recommended by Public Health England to categorize someone as high risk of severe illness due to COVID‐19 should also include mental health and challenging behavior. There are specific issues associated with providing care to people with IDs and appropriate action must be taken by care providers to ensure that disparity of healthcare is addressed during the COVID‐19 pandemic. We recognize that our guidance is focused upon healthcare delivery in England and invite others to augment our guidance for use in other jurisdictions.


COVID-19 & Multiple Myeloma: Delay ASCT


title: IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY

text: Objective: We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality. Design: We performed a single-centre retrospective cohort study. Setting: A University hospital in Madrid, Spain, during March 2020. Participants: Patients admitted with SARS-CoV-2 pneumonia. Exposures: Patients treated with steroids were compared to patients not treated with steroids. A propensity-score for steroid treatment was developed. Different steroid regimens were also compared, and adjusted with a second propensity score. Main Outcomes and Measures: To determine the role of steroids in in-hospital mortality, univariable and multivariable analyses were performed, and adjusted including the propensity score as a covariate. Survival times were compared using a log-rank test. Results: During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) consecutive patients were treated with steroids and 67 patients were assigned to the control cohort. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8 to13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], OR 0.51 [0.27 to 0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048 to 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone (or equivalent) versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710). Conclusions: Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone or equivalent and glucocorticoid pulses. These results support the use of glucocorticoids in SARS-CoV2 infection.


title: Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment

text: Background Coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. Methods Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. Findings Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52.2% (24/46) had severe thrombocytopenia, compared to 6.7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81.3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. Interpretation Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.


title: Will novel coronavirus (COVID-19) pandemic impact agriculture, food security and animal sectors?/ Qual será o impacto da pandemia do novo coronavirus (COVID-19) na agricultura, segurança alimentar e setores de produção animal

text: The whole world is in a great danger due to the novel coronavirus (COVID-19) pandemic. In December 2019, the outbreak of COVID-19 took place in Wuhan, China and then rapidly spread all over the world. The current study provides potential expectations for the adverse impact of (COVID-19). The global infection affected globe on agricultural level such as agriculture, food supplies and animal production sectors. Till today, 29thApril 2020, there is no vaccine available for treating novel coronavirus, consequently, the outbreak resulted in closing borders and reducing production following social distancing measures. This short communication illustrates the possible implications and expected outcomes of the outbreak of coronavirus (COVID-19) on agricultural, food security, integrated pest management (IPM), animal productivity; and it predicts, as well, the possible adverse impacts on the economy worldwide. Brazil has one of the most important tropical agriculture in the world, being a leader in soybean production in the world. This chain impacts others such as meat and eggs. The impact of COVID-19 will be positive, encouraging the country to consolidate its leadership in the world market, stimulating exports, the machinery, inputs and fertilizers market, as well as generating employment and income in the country.