title: Currently available intravenous immunoglobulin (Gamunex®-C and Flebogamma® DIF) contains antibodies reacting against SARS-CoV-2 antigens

text: Background There is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. In this study, we assessed currently marketed intravenous immunoglobulin (IVIG) products for antibodies against human common coronaviruses that may cross-react with the SARS-CoV-2 virus. Methods Gamunex®-C and Flebogamma® DIF (Grifols) IVIG were tested against several betacoronaviruses antigens using ELISA techniques: HCoV (undetermined antigen), HCoV-HKU1 (N protein), SARS-CoV (culture lysate), MERS-CoV (N protein; S1 protein/RBD; S protein), and SARS-CoV-2 (S1 protein). Results Both IVIG products showed consistent reactivity to components of the tested viruses. Positive cross-reactivity was seen in SARS-CoV, MERS-CoV, and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 μg/mL with Gamunex-C to 1 mg/mL with Flebogamma 5% DIF. Conclusion Gamunex-C and Flebogamma DIF IVIG contain antibodies reacting against SARS-CoV-2 antigens. These preparations may be useful for immediate treatment of COVID-19 disease.


title: Clinical and imaging manifestations of familial clustering corona virus disease 2019/ 家庭聚集性新型冠状病毒肺炎临床与影像学表现

text: Objective: To observe clinical and imaging manifestations of family clustering corona virus disease 2019 (COVID-19). Methods: Data of 16 COVID-19 patients from 7 groups of families were enrolled, and the family epidemiological history, onset time, clinical symptoms and imaging manifestations were retrospectively analyzed. Results: Positive findings of the first X-ray films existed in 9 cases, negative in 5 cases, while 2 cases were found with suspicious pneumonia. Positive CT findings were observed in 15 cases, including 12 with bilateral lung lesions and 3 with lesions in unilateral lung, while 1 case was found without abnormality. Pure ground glass opacities (GGO) were detected in 4 cases, pure small nodule in 1 case, coexisting of GGO, consolidation and nodule in 11 cases. Pericardial effusion was noticed in 1 case, pleural and interlobar pleural thickening in 4 cases, and small amount of pleural effusion in 1 case. After effective treatment, lesions were absorbed more than 50% in 12 (12/15,80.00%) patients, whereas residual lesions were still observed in 14 patients. Conclusion: Family clustering corona virus disease 2019 (COVID-19) has certain clinical characteristics. Combined with epidemiology and clinical symptoms, CT has important role in screening, early diagnosis, evaluation and follow-up of COVID-19.


Structural Heart Disease During a Pandemic


Coronavirus and Malta: weathering the storm


title: Collecting survey data among the 50+ population during the COVID-19 pandemic: The survey of health, (share)ageing and retirement in Europe

text: While the COVID-19 crisis resulted in a vast number of new research projects springing up like mushrooms everywhere, it had severe consequences for ongoing survey research and in particular for running data collections. The Survey of Health, Ageing and Retirement in Europe (SHARE) was hit by the virus in the middle of its Wave 8 data collection, which had to be suspended in all 28 participating countries. Responding to the evolving crisis situation and taking steps to resume fieldwork was especially challenging for SHARE, since (1) the 50+ population is more severely affected by COVID-19 than younger age groups and (2) the measures taken by governments in response to the outbreak differed across the countries. Against this background, we discuss possible solutions for adaptations regarding the mode of data collection, questionnaire content, sample design, and actual fieldwork.


title: Modelling interventions to control COVID-19 outbreaks in a refugee camp

text: Refugee camp populations are expected to be vulnerable to COVID-19 due to overcrowding, unsanitary conditions, and inadequate medical facilities. Because there has been no COVID-19 outbreak in a refugee camp to date, the potential for nonpharmaceutical interventions to slow the spread of COVID-19 in refugee camps remains untested. We used an agent-based model to simulate COVID-19 outbreaks in the Moria refugee camp, and we studied the effects of feasible interventions. Subdividing the camp ('sectoring') "flattened the curve," reducing peak infection by up to 70% and delaying peak infection by up to several months. The use of face masks coupled with efficient isolation of infected individuals reduced the overall incidence of infection and sometimes averted epidemics altogether. These interventions must be implemented quickly to be effective. Lockdowns had little effect on COVID-19 dynamics. Our findings provide an evidence base for camp managers planning intervention strategies against COVID-19 or future epidemics.


title: Mapping the Burden of COVID-19 in the United States

text: As of April 5th 2020, SARS-CoV-2 has resulted in over 273,000 confirmed infections in the United States of America. Incidence continues to rise. As the epidemic threatens to overwhelm health care systems, identifying regions where the expected disease burden is likely to be high relative to the rest of the country is critical for enabling prudent and effective distribution of emergency resources. Across all global regions affected by the pandemic, an elevated risk of severe outcomes has consistently been observed in older age groups. Using age-specific mortality patterns in tandem with demographic data, we map a projection of the cumulative burden of COVID-19 and the associated cumulative burden on the healthcare system at the county-scale in the United States for a scenario in which 20% of the population of each county acquires infection. We identify regions that may be particularly impacted relative to the rest of the country, and observe a general trend that per capita disease burden and relative healthcare system demand may be highest away from major population centers.


title: Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing

text: Corona Virus Disease 2019 (COVID-19) has spread rapidly to more than 70 countries and regions overseas and over 80000 cases have been infected, resulting in more than three thousand deaths. Rapid diagnosis of patients remains a bottleneck in containing the progress of the epidemic. We used automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to 2019-nCoV of 736 subjects. COVID-19 patients were becoming reactive(positive) for specific antibodies from 7-12 days after the onset of morbidity. Specific IgM and IgG increased with the progression of the disease. The areas under the ROC curves of IgM and IgG were 0.988 and 1.000, respectively. Specific antibody detection has good sensitivity and specificity. Detection of specific antibodies in patients with fever can be a good distinction between COVID-19 and other diseases, so as to be a complement to nucleic acid diagnosis to early diagnosis of suspected cases.


title: Outcomes of the 2019 Novel Coronavirus in patients with or without a history of cancer - a multi-centre North London experience

text: Background Four months after the first known case of the 2019 novel coronavirus disease (COVID-19), on the 11th March 2020, the WHO declared the outbreak a pandemic and acknowledged the potential to overwhelm national healthcare systems. The high prevalence and associated healthcare, social and economic challenges of COVID-19 suggest this pandemic is likely to have a major impact on cancer management, and has been shown to potentially have worse outcomes in this cohort of vulnerable patients (1). This study aims to compare the outcomes of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 positive disease in patients with or without a history of cancer. Method: We retrospectively collected clinical, pathological and radiological characteristics and outcomes of COVID-19 RT-PCR positive cancer patients treated consecutively in four different North London hospitals (cohort A). Outcomes recorded included morbidity, mortality and length of hospital stay. All clinically relevant outcomes were then compared to consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (12th March- 7th April 2020). Results: A total of 52 electronic patient records during the study time period were reviewed. Cohort A (median age 76 years, 56% males) and cohort B (median age 58 years, 62% male) comprised of 26 patients each. With the exclusion of cancer, both had a median of 2 comorbidities. Within cohort A, the most frequent underlying cancer was colorectal (5/26) and prostate cancer (5/26), and 77% of patients in Cohort A had received previous anti-cancer therapy. The most common presenting symptoms were cough and pyrexia in both cohorts. Frequent laboratory findings included lymphopenia, anaemia and elevated CRP in both cohorts, whilst hypokalaemia, hypoalbuminaemia and hypoproteinaemia was predominantly seen amongst patients with cancer. Median duration of admission was 7 days in both cohorts. The mortality rate was the same in both cohorts (23%), with median age of mortality of 80 years. Of cancer patients who died, all were advanced stage, had been treated with palliative intent and had received anti-cancer therapy within 13 days of admission. Conclusion: Old age, late stage of cancer diagnosis and multiple co-morbidities adversely influence the outcome of patients with COVID-19 positive patients. Whilst extra caution is warranted in the administration of anti-cancer therapies pertaining to the risk of immune-suppression, this data does not demonstrate a higher risk to cancer patients compared to their non-cancer counterparts.


title: Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Patients in Wuhan, China

text: Background With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. As such, data are urgently needed about risk factors associated with clinical outcomes. Methods A retrospective chart review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on their initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify factors associated with clinical outcomes, and logrank test was conducted for the association with clinical progression. Results Current standard treatments did not show significant improvement on patient outcomes in the study. By univariate logistic regression model, 27 risk factors were significantly associated with clinical outcomes. Further, multivariate regression indicated that age over 65 years, smoking, critical disease status, diabetes, high hypersensitive troponin I (>0.04 pg/mL), leukocytosis (>10 x 109/L) and neutrophilia (>75 x 109/L) predicted unfavorable clinical outcomes. By contrast, the use of hypnotics was significantly associated with favorable outcomes. Survival analysis also confirmed that patients receiving hypnotics had significantly better survival. Conclusions To our knowledge, this is the first indication that hypnotics could be an effective ancillary treatment for COVID-19. We also found that novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.


title: Unprecedented disruptions of lives and work: Health, distress and life satisfaction of working adults in China one month into the COVID-19 outbreak

text: We assess the health and wellbeing of normal adults living and working after one month of confinement to contain the COVID-19 outbreak in China. On Feb 20 and 21, 2020, we surveyed 369 adults in 64 cities in China that varied in their rates of confirmed coronavirus cases on their health conditions, distress and life satisfaction. 27% of the participants worked at the office, 38% resorted to working from home, and 25% stopped working due to the outbreak. Those who stopped working reported worse mental and physical health conditions as well as distress. The severity of COVID-19 in a location predicts life satisfaction, and this relationship is contingent upon the existing chronic health issues and hours of exercise of the individuals. Our evidence supports the need to pay attention to the health of people who were not affected by the virus epidemiologically, especially for people who stopped working during the outbreak. Our results highlight that physically active people might be more susceptible to wellbeing issues during the lockdown. Policymakers who are considering introducing restrictive measures to contain COVID-19 may benefit from understanding such health and wellbeing implications.


title: The financing of SMEs in the Spanish tourism sector at the onset of the 2008 financial crisis: Lessons to learn?

text: Small and medium enterprises (SMEs) are a powerful economic engine in many European countries. Moreover, tourism SMEs are particularly important in the economies of countries in southern Europe due to the climate and sociodemographic situation, among other reasons. In Spain, specifically, these enterprises are a vital economic asset. Nonetheless, neither the importance of SMEs in the tourism industry nor the main factors that influence their capital structure have been sufficiently studied. We used panel data methodology with a regression model to analyse the capital structure of SMEs in the tourism sector at the onset of the 2008 financial crisis. Our results show the significance of SMEs within the tourism industry as well as the need to take into account the main factors that influence their capital, which are type (micro, small or medium enterprise), profitability, number of employees and size (logarithm of total assets). Furthermore, despite the robustness of these companies, they have been affected by the crisis. This study is of great interest as it provides indicators to understand the strength of tourist SMEs to confront potential crises.


Age-structured non-pharmaceutical interventions for optimal control of COVID-19 epidemic


title: Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box

text: New chemical matter is needed to target the divergent biology associated with the different life cycle stages of Plasmodium. Here, we report the parallel screening of the Medicines for Malaria Venture Pandemic Response Box to identify multistage-active and stage-specific compounds against various life cycle stages of Plasmodium parasites (asexual parasites, stage IV/V gametocytes, gametes, oocysts and liver stages) and for endectocidal activity. Hits displayed unique chemotypes and included two multistage-active compounds, 16 asexual-targeted, six with prophylactic potential and ten gametocyte-targeted compounds. Notably, four structurally diverse gametocyte-targeted compounds with potent transmission-blocking activity were identified: the JmjC inhibitor ML324, two azole antifungals including eberconazole, and the antitubercular clinical candidate SQ109. Besides ML324, none of these have previously attributed antiplasmodial activity, emphasizing the success of de novo parallel screening against different Plasmodium stages to deliver leads with novel modes-of-action. Importantly, the discovery of such transmission-blocking targeted compounds covers a previously unexplored base for delivery of compounds required for malaria elimination strategies.


title: Comparison of the Clinical Implications among Two Different Nutritional Indices in Hospitalized Patients with COVID-19

text: Background: Coronavirus disease 2019 (COVID 19) is an emerging infectious disease.It was first reported in Wuhan, China, and then broke out on a large scale around the world.This study aimed to assess the clinical significance of two different nutritional indices in 245 patients with COVID 19. Methods: In this retrospective single center study, we finally included 245 consecutive patients who confirmed COVID 19 in Wuhan University Zhongnan Hospital from January 1 to February 29. Cases were classified as either discharged or dead. Demographic, clinical and laboratory datas were registered, two different nutritional indices were calculated: (i)the Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI). We used univariate and multivariate logistic regression analysis to explore the relationship between nutritional indices and hospital death . Results: 212 of them were discharged and 33 of them died. In hospital mortality was signifcantly higher in the severe group of PNI than in the moderate and normal groups. It was also significantly worse in the severe CONUT group than in the moderate, mild , and normal CONUT groups. Multivariate logistic regression analysis showed the CONUT score (odds ratio3.371,95%CI (1.124 10.106), p = 0.030) and PNI(odds ratio 0.721,95% CI(0.581 0.896),P=0.003) were independent predictors of all cause death at an early stage; Multivariate logistic regression analysis also showed that the severe group of PNI was the independent risk predictor of in hospital death(odds ratio 24.225, 95% CI(2.147 273.327), p=0.010).The CONUT score cutoff value was 5.5 (56.00 and 80.81%; AUC 0.753; 95% CI(0.644 0.862);respectively).The PNI cutoff value was 40.58 (81.80 and 66.20%; AUC 0.778; 95% CI(0.686 0.809); respectively).We use PNI and the COUNT score to assess malnutrition, which can have a prognosis effect of COVID 19 patients. Conclusion:The CONUT score and PNI could be a reliable prognostic marker of all cause death in patients with COVID 19. Keywords: Coronavirus disease 2019; nutrition; indicies; prognosis


title: A Rapidly Deployable Negative Pressure Enclosure for Aerosol-Generating Medical Procedures

text: Abstract Background The coronavirus disease 2019 (COVID-19) pandemic presents significant safety challenges to healthcare professionals. In some jurisdictions, over 10% of confirmed cases of COVID-19 have been found among healthcare workers. Aerosol-generating medical procedures (AGMPs) may increase the risk of nosocomial transmission, exacerbated by present global shortages of personal protective equipment (PPE). Improved methods for mitigating risk during AGMPs are therefore urgently needed. Methods The Aerosol Containment Enclosure (ACE) was constructed from acrylic with silicone gaskets for arm port seals and completed with a thin plastic sheet. Hospital wall suction generated negative pressure within the ACE. To evaluate protective capability, differential pressures were recorded under static conditions and during simulated AGMPs. Smoke flow patterns, fluorescence aerosolization, and sodium saccharin aerosolization tests were also conducted. Results Negative pressures of up to -47.7 mmH2O were obtained using the enclosure with two wall suction units (combined outflow of 70 L min-1), with inflow of O2 of 15 L min-1. Negative pressures between -10 and -35 mmH2O were maintained during simulated AGMPs, including oxygen delivery by mask, airway suctioning, bag-mask manual ventilation and endotracheal intubation of a potential COVID-19 patient. The ACE effectively contained smoke, fluorescein aerosol, and sodium saccharin aerosol within the enclosure during use. Conclusions The ACE is capable of maintaining negative pressure during simulated AGMPs. In all cases, containment was improved relative to an identical enclosure with non-occluded ports at ambient pressure. During the current COVID-19 pandemic, the use of such a device may assist in reducing nosocomial infections among healthcare providers.


title: The psychological effects of quarantine during COVID-19 outbreak: Sentiment analysis of social media data

text: We rely on social distancing measures such as quarantine and isolation to contain the COVID-19. However, the negative psychological effects of these measures are non-negligible. To supplement previous research on psychological effects after quarantine, this research will investigate the effects of quarantine amid COVID-19. We adopt a sentiment analysis approach to analyze the psychological state changes of 1,278 quarantined persons with 214,874 tweets over four weeks spanning the period before, during, and after quarantine. We formed a control group of 1,278 unquarantined persons with 250,198 tweets. The tweets of both groups are analyzed by matching with a lexicon to measure the anxious depression level changes over time. We discovered a clear pattern of psychological changes for quarantined persons. Anxious depression levels significantly increased as quarantine starts, but gradually diminished as it progresses. However, anxious depression levels resurged after a 14-day quarantine. It was found that quarantine has a negative impact on the mental health of quarantined and unquarantined people. Whilst quarantine is deemed necessary, proper interventions such as emotion management should be introduced to mitigate its adverse psychological impacts.


title: Covid-19 Risk Among Airline Passengers: Should the Middle Seat Stay Empty?

text: Recent research results and data generate the approximation that, when all coach seats are full on a US jet aircraft, the risk of contracting Covid-19 from a nearby passenger is currently about 1 in 7,000. Under the middle seat empty policy, that risk falls to about 1 in 14,000. Risks are lower in flights that are not full. These estimates imply Covid-19 mortality risks to uninfected air travelers are higher than those associated with plane crashes but probably less than one in one million.


title: Estimating number of cases and spread of Coronavirus disease 2019 (COVID-19) in the United Kingdom using critical care admissions, February to March 2020

text: An exponential growth model was fitted to critical care admissions from multiple surveillance databases to determine likely COVID-19 case numbers and growth in the United Kingdom from 16 February - 23 March 2020, after which a national lockdown occurred. We estimate that on 23 March, there were 102,000 (median; 95% credible interval 54,000 - 155,000) new cases and 320 (211 - 412) new critical care reports, with 464,000 (266,000 - 628,000) cumulative cases since 16 February.


title: Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission

text: Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized.


title: Understanding the Role of Macrophages in Lung Inflammation Through Mathematical Modeling

text: Respiratory infections, such as the novel coronavirus (SARS-COV-2), and other lung injuries infect and damage the pulmonary epithelium. In the most severe cases this leads to acute respiratory distress syndrome (ARDS). Due to respiratory failure associated with ARDS, the clinical intervention is the use of mechanical ventilation. Despite the benefits of mechanical ventilators, pro-longed or misuse of these ventilators may lead to ventilation-induced lung injury (VILI). Damage caused to epithelial cells within the alveoli can lead to various types of complications and increased mortality rates. A key component of the immune response is recruitment of macrophages, immune cells that differentiate into phenotypes with unique pro- and/or anti-inflammatory roles based on the surrounding environment. An imbalance in pro- and anti-inflammatory responses can have deleterious effects on the individual’s health. To gain a greater understanding of the mechanisms of the immune response to VILI and post-ventilation outcomes, we develop a mathematical model of interactions between the immune system and site of damage while accounting for macrophage polarization. Through Latin Hypercube Sampling and available data, we generate a virtual cohort of patients with biologically feasible dynamics. We use a variety of methods to analyze the results, including a random forest decision tree algorithm and parameter sensitivity with eFAST. Analysis shows that parameters and properties of transients related to epithelial repair and M1 activation and de-activation best predicted outcome. Using this new information, we hypothesize interventions and use these treatment strategies to modulate damage in select virtual patients.


title: Geographical surveillance of COVID-19: Diagnosed cases and death in the United States

text: Abstract Background COVID-19 is a new coronavirus that has spread from person to person throughout the world. Geographical disease surveillance is a powerful tool to monitor the spread of epidemics and pandemic, providing important information on the location of new hot-spots, assisting public health agencies to implement targeted approaches to minimize mortality. Methods County level data from January 22-April 28 was downloaded from USAfacts.org to create heat maps with ArcMapTM for diagnosed COVID-19 cases and mortality. The data was analyzed using spatial and space-time scan statistics and the SaTScanTM software, to detect geographical cluster with high incidence and mortality, adjusting for multiple testing. Analyses were adjusted for age. While the spatial clusters represent counties with unusually high counts of COVID-19 when averaged over the time period January 22-April 20, the space-time clusters allow us to identify groups of counties in which there exists a significant change over time. Results There were several statistically significant COVID-19 clusters for both incidence and mortality. Top clusters with high rates included the areas in and around New York City, New Orleans and Chicago, but there were also several small rural clusters. Top clusters for a recent surge in incidence and mortality included large parts of the Midwest, the Mid-Atlantic Region, and several smaller areas in and around New York and New England. Conclusions Spatial and space-time surveillance of COVID-19 can be useful for public health departments in their efforts to minimize mortality from the disease. It can also be applied to smaller regions with more granular data. Keywords: Clusters, prospective space-time analysis, spatial analysis, COVID-19.


title: Treatment of patients with COVID-19 and concomitant cardiovascular diseases: Do not Forget about the Principles of Evidence-based Medicine/ Лечение больных с COVID-19 и сопутствующими сердечно-сосудистыми заболеваниями: не забывать о принципах доказательной медицины

text: The recent discussion about the dangers of using angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA) in patients with COVID-19 is analyzed in the article. There is controversy over the hypothesis that these drugs can be factors contributing to an unfavorable outcome of a viral disease, as well as the absence of any clinical evidence for this hypothesis. The opinion that withdrawal of ACE inhibitors and ARA in patients with COVID-19 may increase the risk of adverse outcomes is presented.


COVID-19 Pandemic: Public Health Implications in Nepal


title: Containing Covid-19 outbreaks with spatiallytargeted short-term lockdowns and mass-testing

text: We assess the efficacy of spatially targeted lockdown or mass-testing and case-isolation in individual communities, as a compliment to contact-tracing and social-distancing, for containing SARS-CoV-2 outbreaks. Using the UK as a case study,we construct a stochastic branching process model for the virus transmission, embedded on a network interaction model encoding mobility patterns in the UK. The network model is based on commuter data from the 2011 census, a catchment area model for schools, and a phenomenological model for mobility and interactions outside of work, school, and the home.We show that for outbreak scenarios where contact-tracing and moderate social distancing alone provide suppression but do not contain the spread, targeted lockdowns or mass-testing interventions at the level of individual communities (with just a few thousand inhabitants) can be effective at containing outbreaks. For spatially targeted mass-testing, a moderate increase in testing capacity would be required (typically<40000 additional tests per day), while for local lockdowns we find that only a small fraction (typically<0.1%) of the population needs to be locked down at any one time (assuming that one third of transmission occurs in the home, at work or school, and out in the wider community respectively). The efficacy of spatially targeted interventions is contingent on an appreciable fraction of transmission events occurring within (relative to across)communities. Confirming the efficacy of community-level interventions therefore calls for detailed investigation of spatial transmission patterns for SARS-CoV-2, accounting for sub-community-scale transmission dynamics, and changes in mobility patterns due to the presence of other containment measures (such as social distancing and travel restrictions).


title: Exponential phase of covid19 expansion is not driven by climate at global scale

text: The pandemic state of COVID-19 caused by the SARS CoV-2 put the world in quarantine and is causing an unprecedented economic crisis. However, COVID-19 is spreading in different rates at different countries. Here, we tested the effect of three classes of predictors, i.e., socioeconomic, climatic and transport, on the rate of daily increase of COVID-19. We found that global connections, represented by countries importance in the global air transportation network, is the main explanation for the growth rate of COVID-19 in different countries. Climate, geographic distance and socioeconomics did not affect this big picture analysis. Geographic distance and climate were significant barriers in the past but were surpassed by the human engine that allowed us to colonize almost every corner on Earth. Based on our global analysis, the global network of air transportation could lead to a worst-case scenario of synchronous global pandemic if board control measures in international airports were not taken and are not sustained during this pandemic. Despite all limitations of a global analysis, our results indicate that the current claims that the growth rate of COVID-19 may be lower in tropical countries should be taken very carefully, at risk to disturb well-established and effective policy of social isolation that may help to avoid higher mortality rates due to collapse of national health systems. This is the case of Brazil, a well-connected tropical country that presents the second highest increase rate of COVID-19 and might experience a serious case of human-induced disasters if decision makers take into consideration unsupported claims of the growth rate of COVID-19 might be lower in tropical countries.


Hohes Mortalitätsrisiko bei Diabetespatienten mit COVID-19


title: A Droplet Digital PCR Assay to Detect SARS-CoV-2 RNA

text: We describe a quantitative droplet digital PCR (ddPCR) assay for detection of SARS-CoV-2 viral ribonucleic acid (RNA) in total RNA extracted from human sputum. This method was validated using the guidance of the United States Food and Drug Administration Accelerated Emergency Use Authorization (EUA) Template for SARS-CoV-2 that Causes Coronavirus Disease (COVID-19) Molecular Testing of Respiratory Speciment in CLIA Certified High-Complexity Laboratories. Though our laboratory is not CLIA certified, this method met all criteria specified by the guidance document with a Limit of Detection (LOD) of 0.25 copies/microliter in the final ddPCR (at least 19/20 replicates reactive), which we consider to be a Lower Limit of Quantification (LLOQ); inclusivity of all known annotated SARS-CoV-2 genomes; no cross-reactivity with other respiratory pathogens; and reactivity of all contrived positives at or above the LOD.


title: A New Predictor of Disease Severity in Patients with COVID-19 in Wuhan, China

text: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, Hubei, China. This study sought to elucidate a novel predictor of disease severity in patients with coronavirus disease-19 (COVID-19) cased by SARS-CoV-2. Methods: Patients enrolled in this study were all hospitalized with COVID-19 in the Central Hospital of Wuhan, China. Clinical features, chronic comorbidities, demographic data, and laboratory and radiological data were reviewed. The outcomes of patients with severe pneumonia and those with non-severe pneumonia were compared using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) to explore clinical characteristics and risk factors. The receiver operating characteristic curve was used to screen optimal predictors from the risk factors and the predictive power was verified by internal validation. Results: A total of 377 patients diagnosed with COVID-19 were enrolled in this study, including 117 with severe pneumonia and 260 with non-severe pneumonia. The independent risk factors for severe pneumonia were age [odds ratio (OR): 1.059, 95% confidence interval (CI): 1.036-1.082; p < 0.001], N/L (OR: 1.322, 95% CI: 1.180-1.481; p < 0.001), CRP (OR: 1.231, 95% CI: 1.129-1.341; p = 0.002), and D-dimer (OR: 1.059, 95% CI: 1.013-1.107; p = 0.011). We identified a product of N/L*CRP*D-dimer as having an important predictive value for the severity of COVID-19. The cutoff value was 5.32. The negative predictive value of less than 5.32 for the N/L*CRP*D-dimer was 93.75%, while the positive predictive value was 46.03% in the test sets. The sensitivity and specificity were 89.47% and 67.42%. In the training sets, the negative and positive predictive values were 93.80% and 41.32%, respectively, with a specificity of 70.76% and a sensitivity of 89.87%. Conclusions: A product of N/L*CRP*D-dimer may be an important predictor of disease severity in patients with COVID-19.


title: Identifying the Real Effects of Zombie Lending

text: The policy response to COVID-19 includes the provision of credit guarantees to firms, a provision that may generate zombie lending According to the recent literature, the relative performance of healthy firms deteriorates as the fraction of zombies increases We argue that this literature faces a serious identification problem, because firm performance is often used to define zombies (sometimes implicitly) We show that, under general conditions for the distribution of firm performance, the correlation between healthy firm performance and zombies is a mechanical consequence of an increase in the fraction of zombies with no causal meaning


title: Coronavirus disease-19: The First 7,755 Cases in the Republic of Korea

text: We report the first 7,755 patients with confirmed COVID19 in Korea as of March 13, 2020. A total of 66 deaths were identified, resulting case fatality proportion of 0.9%. Older people, and those with coexisting medical conditions were at risk for fatal outcomes. The highest number of cases were from Daegu, followed by Gyeongbuk, with elevated age-stratified case fatality. This summary may help to understand the disease dynamics in the early phase of COVID19 outbreak, therefore, to guide future public health measures.


title: Perceptions of students regarding E-learning during Covid-19 at a private medical college

text: OBJECTIVE: The purpose of this study was to determine the perceptions of students towards e-learning during the lock down. METHODS: A descriptive cross-sectional study was conducted at Liaquat College of Medicine and Dentistry. MBBS and BDS students of all levels participated in the study with a sample size calculated as 377. A self-administered questionnaire was developed. After validation from the Medical Education Experts, pilot test was run on 30 participants before the administration of the questionnaire. The questionnaire was emailed to the participants for data collection. Reliability of the questionnaire was determined. Independent T-test was applied for determining the perceptions of students towards e-learning. Frequencies and percentages were also computed for demographics. RESULTS: Total 382 responses were received.137 males and 245 females participated in the study. 0.851 was calculated as Cronbach’s alpha of the questionnaire. Overall, 77% students have negative perceptions towards e-learning. 76% of the students use mobile device for their e-learning. CONCLUSION: Students did not prefer e-teaching over face-to-face teaching during the lock down situation. Administration and faculty members should take necessary measures for improving e-teaching for better learning during lock down.


title: Estimating the last day for COVID-19 outbreak in mainland China

text: Our main aim is to estimate the last day for COVID-19 outbreak in mainland China. We developed mathematical models to predict reasonable bounds on the date of end of the COVID-19 epidemics in mainland China with strong quarantine and testing measures for a sufficiently long time. We used reported data in China from January 20, 2020 to April 9, 2020. We firstly used a deterministic approach to obtain a formula to compute the probability distribution of the extinction date by combining the models and continuous-time Markov processes. Then we present the individual based model (IMB) simulations to compare the result by deterministic approach and show the absolute difference between the estimated cumulative probability distribution computed by simulations and formula. We provide the predictions of the last day of epidemic for different fractions f of asymptomatic infectious that become reported symptomatic infectious.


title: Internet Search Patterns Reveal Clinical Course of Disease Progression for COVID-19 and Predict Pandemic Spread in 32 Countries

text: Effective public health response to COVID-19 relies on accurate and timely surveillance of local pandemic spread, as well as rapid characterization of the clinical course of disease in affected individuals. De novo diagnostic testing methods developed for emergent pandemics are subject to significant development delays and capacity limitations. There is a critical need for complementary surveillance approaches that can function at population-scale to inform public health decisions in real-time. Internet search patterns provide a number of important advantages relative to laboratory testing. We conducted a detailed global study of Internet search patterns related to COVID-19 symptoms in multiple languages across 32 countries on six continents. We found that Internet search patterns reveal a robust temporal pattern of disease progression for COVID-19: Initial symptoms of fever, dry cough, sore throat and chills are followed by shortness of breath an average of 5.22 days [95% CI 3.30-7.14] after symptom onset, matching the precise clinical course reported in the medical literature. Furthermore, we found that increases in COVID-19-symptom-related searches predict increases in reported COVID-19 cases and deaths 18.53 days [95% CI 15.98-21.08] and 22.16 days [95% CI 20.33-23.99] in advance, respectively. This is the first study to show that Internet search patterns can be used to reveal the detailed clinical course of a disease. These data can be used to track and predict the local spread of COVID-19 before widespread laboratory testing becomes available in each country, helping to guide the current public health response.


title: Impact of Superspreaders on dissemination and mitigation of COVID-19

text: Background: The emerging SARS-CoV-2 virus has caused a global pandemic characterized by superspreader events. Heterogeneity in transmission risk is a known phenomenon in infectious diseases and was also seen in SARS and MERS outbreaks since 2003. The pandemic has led countries to control the pandemic spread using unprecedented severe mitigation strategies that include quarantine and lock-down. This has has been highly successful in terms of halting the spread, but had enormous socioeconomic cost. We set out to theoretically explore whether a model that includes the phenomenon of superspreaders may guide us towards a cost-effective mitigation strategy. Methods: We developed an agent-based model that includes persons that spread the disease far more readily than other persons. This allow us to investigate effect of containment strategies in both a random SEIR like scenario, and in a transmission model that work with structured society. Our model considered even contact patterns in three settings: home, work and a category of "other" settings representing diffuse social contacts. We introduced superspreaders either as a fixed proportion of the population, or as a broad spectrum of infectivity. For each choice, the model was then calibrated to an overall realistic daily growth rate of 23 percentage. As sensitivity analyses we varied the fraction of superspreaders as well the distribution of their infectivity. To compare the simulation findings for each mitigation scenario we considered the maximum daily ICU utility. Results: As expected, without mitigation imposed, the inclusion of superspreaders does not meaningfully change the epidemic trajectory. However when introducing mitigation strategies imposed on each of the three settings, we find that the presence of superspreaders made a substantial difference. The simulations demonstrate that the best strategy is to focus on limiting contacts in the other category. This in particular suggests that limiting diffuse social contacts in settings such as bars, transportation, restaurants, parties, concerts and lecture halls is far more effective than limiting the same amount of contact events in the home and work setting. Conclusions: To appreciate effect of heterogeneity in various social spheres we need to rethink disease transmission models. Doing so, we found that wide distribution of infectivity favours strategies that reduces the max, while leaving the typical behaviour undisturbed. We found that most workplaces may be opened without much influence on the epidemic, while one could snuff out transmission with an effective avoidance of other contacts. Interestingly, including a consideration of superspreaders can help explain the dramatic success of even moderate lock-down strategies as that practiced in Denmark and Sweden. And it points to the need to avoid mass gatherings until either flock immunity has been achieved or an effective vaccine is available.


title: Suppression of Groups Intermingling as Appealing Option For Flattening and Delaying the Epidemiologic Curve While Allowing Economic and Social Life at Bearable Level During COVID-19 Pandemic

text: In this work, we simulate the COVID-19 pandemic dynamics in a population modeled as a network of groups wherein infection can propagate both via intra-group and via inter-group interactions. Our results emphasize the importance of diminishing the inter-group infections in the effort of substantial flattening and delaying of the epi(demiologic) curve with concomitant mitigation of disastrous economy and social consequences. To exemplify with a limiting case, splitting a population into m (say, 5 or 10) noninteracting groups while keeping intra-group interaction unchanged yields a stretched epidemiologic curve having the maximum number of daily infections reduced and postponed in time by the same factor m (5 or 10). More generally, our study suggests a practical approach to fight against SARS-CoV-2 virus spread based on population splitting into groups and minimizing intermingling between them. This strategy can be pursued by large-scale infrastructure reorganization of activity at different levels in big logistic units (e.g., large productive networks, factories, enterprises, warehouses, schools, (seasonal) harvest work). Importantly, unlike total lockdwon strategy, the proposed approach prevents economic ruin and keeps social life at a more bearable level than distancing everyone from anyone.


title: Prediction of COVID-19 Active and Total Cases After a Fall and Rise of Cases

text: During the progress of the COVID-19, many countries have observed that their active cases tend to rise again after falling for some time. This may cause some mathematical models like the one discussed in [2] tend to make errors in the future prediction. We discuss a simple method to better the future prediction in such cases. This method is applied on the active and total cases data for the countries USA and Canada. In the case of Canada, the method succeeded in predicting the date when the active cases began to decrease. In the case of USA, a major improvement in prediction was observed when the method was applied: the predicted active and total cases are 1465602 and 2729015 for June 30; whereas the actual values are 1455400 and 2728856. We also give the active and total cases prediction for Canada and the USA for the first week of July 2020.


title: Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide

text: The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.


title: Response and role of palliative care during the COVID-19 pandemic: a national telephone survey of hospices in Italy

text: Background Palliative care is an essential component of healthcare in pandemics, contributing to symptom control, psychological support, and supporting triage and complex decision making. Aim To examine preparedness for, and impact of, the COVID-19 pandemic on hospices in Italy to inform the response in other countries. Design Cross-sectional telephone survey, carried out in March 2020. Setting Sixteen Italian hospices, purposively sampled according to COVID-19 risk into high (more than 25 COVID-19 cases per 100,000 inhabitants), medium (15-25 cases per 100,000), and low risk (fewer than 15 cases per 100,000) regions. A brief questionnaire was developed to guide the interviews. Descriptive analysis was undertaken. Results Seven high risk, five medium risk and four low risk hospices provided data. Two high risk hospices had experienced COVID-19 cases among both patients and staff. All hospices had implemented policy changes, and several had rapidly implemented changes in practice including transfer of staff from inpatient to community settings, change in admission criteria, and daily telephone support for families. Concerns included scarcity of personal protective equipment, a lack of hospice-specific guidance on COVID-19, anxiety about needing to care for children and other relatives, and poor integration of palliative care in the acute setting. Conclusion The hospice sector is capable of responding flexibly and rapidly to the COVID-19 pandemic. Governments must urgently recognise the essential contribution of hospice and palliative care to the COVID-19 pandemic, and ensure these services are integrated into the health care system response. Availability of personal protective equipment and setting-specific guidance is essential.


title: A mathematical modelling approach in the spread of the novel 2019 coronavirus SARS-COV-2 (COVID-19) pandemic

text: The novel 2019 coronavirus, SARS-CoV-2 (COVID-19), emerged towards the end of 2019 in the city of Wuhan in the province of Hubei in the People’s Republic of China, and it has spread to the entire world very fast and in a very short time. This study aimed to investigate the course of the pandemic by mathematical modelling based on the information that the time-dependent change (spreading) rate of the H number of individuals who have caught a contagious disease is proportional to the multiplication of the numbers of those who have caught the disease and those who have not. According to the results of the mathematical modelling in our study, in the case that sufficient precautions are not taken, or precautions are reduced, the course of the pandemic may show a very fast change in the negative direction. For this reason, every precaution, individual or social, will be significant in terms of the course of the COVID-19 pandemic.


title: Study of Morphological Nature of Coronavirus: Causes and Prevention

text: The emergence of an unusual Corona virus (COVID-19) flu pandemic starting in China in December 2019, spreading all around the globe is a major threat to public health The investigations have shown this virus originated from a seafood market in Wuhan However, the unavailability of medicines for the new disease is a big challenge all around An attempt has been made in the present article to familiarise about the morphology of the virus The study of effect of pH, temperature and relative humidity is also depicted Various preventive measures have also been discussed The natural dietary measures suggested in the paper would be very beneficial to improve and boost the immunity of the mankind


title: Stochastic discrete epidemic modeling of COVID-19 transmission in the Province of Shaanxi incorporating public health intervention and case importation

text: Before the lock-down of Wuhan/Hubei/China, on January 23rd 2020, a large number of individuals infected by COVID-19 moved from the epicenter Wuhan and the Hubei province due to the Spring Festival, resulting in an epidemic in the other provinces including the Shaanxi province. The epidemic scale in Shaanxi was comparatively small and with half of cases being imported from the epicenter. Based on the complete epidemic data including the symptom onset time and transmission chains, we calculate the control reproduction number (1.48-1.69) in Xian. We could also compute the time transition, for each imported or local case, from the latent, to infected, to hospitalized compartment, as well as the effective reproduction number. This calculation enables us to revise our early deterministic transmission model to a stochastic discrete epidemic model with case importation and parameterize it. Our model-based analyses reveal that the newly generated infections decay to zero quickly; the cumulative number of case-driven quarantined individuals via contact tracing stabilize at a manageable level, indicating that the intervention strategies implemented in the Shaanxi province have been effective. Risk analyses, important for the consideration of resumption of work, show that a large second outbreak is expected if the level of case importation remains at the same level as between January 10th and February 4th 2020. However, if the case importation decreases by 30%, 60% and 90%, the second outbreak if happening will be of small-scale assuming contact tracing and quarantine/isolation remain as effective as before. Finally, we consider the effects of intermittent inflow with a Poisson distribution on the likelihood of multiple outbreaks. We believe the developed methodology and stochastic model provide an important model framework for the evaluation of revising travel restriction rules in the consideration of resuming social-economic activities while managing the disease control with potential case importation.


title: Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 1 - Face masks, eye protection and person distancing: systematic review and meta-analysis

text: Abstract OBJECTIVE: To examine the effectiveness of eye protection, face masks, or person distancing on interrupting or reducing the spread of respiratory viruses. DESIGN: Update of a Cochrane review that included a meta-analysis of observational studies during the SARS outbreak of 2003. DATA SOURCES: Eligible trials from the previous review; search of Cochrane Central Register of Controlled Trials, PubMed, Embase and CINAHL from October 2010 up to 1 April 2020; and forward and backward citation analysis. DATA SELECTION: Randomised and cluster-randomised trials of people of any age, testing the use of eye protection, face masks, or person distancing against standard practice, or a similar physical barrier. Outcomes included any acute respiratory illness and its related consequences. DATA EXTRACTION AND ANALYSIS: Six authors independently assessed risk of bias using the Cochrane tool and extracted data. We used a generalised inverse variance method for pooling using a random-effects model and reported results with risk ratios and 95% Confidence Intervals (CI). RESULTS: We included 15 randomised trials investigating the effect of masks (14 trials) in healthcare workers and the general population and of quarantine (1 trial). We found no trials testing eye protection. Compared to no masks there was no reduction of influenza-like illness (ILI) cases (Risk Ratio 0.93, 95%CI 0.83 to 1.05) or influenza (Risk Ratio 0.84, 95%CI 0.61-1.17) for masks in the general population, nor in healthcare workers (Risk Ratio 0.37, 95%CI 0.05 to 2.50). There was no difference between surgical masks and N95 respirators: for ILI (Risk Ratio 0.83, 95%CI 0.63 to 1.08), for influenza (Risk Ratio 1.02, 95%CI 0.73 to 1.43). Harms were poorly reported and limited to discomfort with lower compliance. The only trial testing quarantining workers with household ILI contacts found a reduction in ILI cases, but increased risk of quarantined workers contracting influenza. All trials were conducted during seasonal ILI activity. CONCLUSIONS: Most included trials had poor design, reporting and sparse events. There was insufficient evidence to provide a recommendation on the use of facial barriers without other measures. We found insufficient evidence for a difference between surgical masks and N95 respirators and limited evidence to support effectiveness of quarantine. Based on observational evidence from the previous SARS epidemic included in the previous version of our Cochrane review we recommend the use of masks combined with other measures.


title: Quantifying the success of measles vaccination campaigns in the Rohingya refugee camps

text: In the wake of the Rohingya population's mass migration from Myanmar, one of the world's largest refugee settlements was constructed in Cox's Bazar, Bangladesh to accommodate nearly 900,000 new refugees. Refugee populations are particularly vulnerable to infectious disease outbreaks due to many population and environmental factors. A large measles outbreak, with over 2,500 cases, occurred among the Rohingya population between September and December 2017. Here, we estimate key epidemiological parameters and use a dynamic mathematical model of measles transmission to evaluate the effectiveness of the reactive vaccination campaigns in the refugee camps. We also estimate the potential for subsequent outbreaks under different vaccination coverage scenarios. Our modeling results highlight the success of the vaccination campaigns in rapidly curbing transmission and emphasize the public health importance of maintaining high levels of vaccination in this population, where high birth rates and historically low vaccination coverage rates create suitable conditions for future measles outbreaks.


title: Augmenting contact matrices with time-use data for fine-grained intervention modelling of disease dynamics: A modelling analysis

text: Background: Social distancing is an important public health intervention to reduce or interrupt the sustained community transmission of emerging infectious pathogens, such as SARS-CoV-2 during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to explore the impact on the epidemic curve of fewer contacts when individuals reduce the time they spend on selected daily activities. Methods: We combined the large-scale empirical data of a social contact survey and a time-use survey to estimate contact matrices by age group (0-15, 16-24, 25-44, 45-64, 65+) and daily activity (work, schooling, transportation, and four leisure activities: social visits, bar/cafe/restaurant visits, park visits, and non-essential shopping). We assumed that reductions in time are proportional to reductions in contacts. The derived matrices were then applied in an age-structured dynamic-transmission model of COVID-19 to explore the effects. Findings: The relative reductions in the derived contact matrices were highest when closing schools (in ages 0-14 years), workplaces (15-64 years), and stopping social visits (65+ years). For COVID-19, the closure of workplaces, schools, and stopping social visits had the largest impact on reducing the epidemic curve and delaying its peak, while the predicted impact of fewer contacts in parks, bars/cafes/restaurants, and non-essential shopping were minimal. Interpretation: We successfully augmented contact matrices with time-use data to predict the highest impact of social distancing measures from reduced contacts when spending less time at work, school, and on social visits. Although the predicted impact from other leisure activities with potential for close physical contact were minimal, changes in mixing patterns and time-use immediately after re-allowing social activities may pose increased short-term transmission risks, especially in potentially crowded environments indoors.


Breaking News: EDs Should Hoard Every Gown and Surgical Mask and Lock Up N95s


title: The impact of isolation measures due to COVID-19 on energy intake and physical activity levels in Australian university students

text: Background: The pandemic inflicted by coronavirus disease 2019 (COVID-19) resulted in physical isolation measures in many parts of the world. In Australia, nationwide restrictions included staying at home, unless seeking medical care, providing care, purchasing food, undertaking exercise, or attending work in an essential service. All undergraduate university classes transitioned to online, mostly home-based learning. This disruption to daily life may have consequences for eating and physical activity patterns. Methods: In this observational study, we examined the effect of isolation measures, during the early phase of the COVID-19 pandemic in Australia (March/April), on diet (24-hour diet recall, ASA-24) and physical activity (Active Australia Survey) patterns among third-year biomedical students in Brisbane, Australia. Findings were compared to students enrolled in the same course in the previous two years. Results: In females, energy intake was ~20% greater in 2020 compared with 2018 and 2019, and the frequency of snacking and energy density of consumed snacks were also increased. In males, there was no difference in energy intake or snacking behaviour. Physical activity was impacted for both sexes, whereby fewer students undertook any walking activity and, of those that did, time spent doing so was less compared with 2018 and 2019. The proportion of students reporting any vigorous activity was not different for males or females but, among males who participated in this level of activity, the duration was less in 2020 compared with previous years. The proportion of male and female students achieving sufficient levels of activity, defined by at least 150 mins over at least 5 sessions, was ~30% less in 2020. Indeed, the majority of students reported as having undertaken less physical activity than usual. Conclusions: Increased energy intake for females and reduced physical activity for males and females demonstrate impacts of isolation measures that may have deleterious consequences for physical and mental wellbeing, with the potential to affect long-term nutrition and activity patterns.


title: Virus on the Brain

text: Far from just affecting the lungs, covid-19 seems to cause a host of neurological problems. Jessica Hamzelou investigates


title: What does simple power law kinetics tell about our response to coronavirus pandemic?

text: Coronavirus pandemic of 2019-2020 has already affected over a million people and caused over 50,000 deaths worldwide (as on April 3, 2020). Roughly half of the world population has been asked to work from home and practice social distancing as the search for a vaccine continues. Though government interventions such as lockdown and social distancing are theoretically useful, its debatable whether such interventions are effective in flattening the curve, which is ceasing or reducing the growth of infection in control populations. In this article, I present a simple power law model that enables a comparison of countries in time windows of 14 days since first coronavirus related death is reported in that country. It therefore provides means to access the efficacy of above interventions.


title: GRANDMA Observations of Advanced LIGO's and Advanced Virgo's Third Observational Campaign

text: GRANDMA is a network of 25 telescopes of different sizes, including both photometric and spectroscopic facilities. The network aims to coordinate follow-up observations of gravitational-wave candidate alerts, especially those with large localisation uncertainties, to reduce the delay between the initial detection and the optical confirmation. In this paper, we detail GRANDMA's observational performance during Advanced LIGO/Advanced Virgo Observing Run 3 (O3), focusing on the second part of O3; this includes summary statistics pertaining to coverage and possible astrophysical origin of the candidates. To do so, we quantify our observation efficiency in terms of delay between gravitational-wave candidate trigger time, observations, and the total coverage. Using an optimised and robust coordination system, GRANDMA followed-up about 90 % of the gravitational-wave candidate alerts, i.e. 49 out of 56 candidates. This led to coverage of over 9000 deg2 during O3. The delay between the gravitational-wave candidate trigger and the first observation was below 1.5 hour for 50 % of the alerts. We did not detect any electromagnetic counterparts to the gravitational-wave candidates during O3, likely due to the very large localisation areas (on average thousands of degrees squares) and relatively large distance of the candidates (above 200 Mpc for 60 % of BNS candidates). We derive constraints on potential kilonova properties for two potential binary neutron star coalescences (GW190425 and S200213t), assuming that the events' locations were imaged.


title: Addition of Tocilizumab to the standard of care reduces mortality in severe COVID-19: A systematic review and meta-analysis

text: Introduction: Tocilizumab is an anti-interleukin-6 antibody that has been used for the treatment of severe coronavirus disease 2019 (COVID-19). However, the concrete evidence of its benefit in reducing the mortality in severe COVID-19 is lacking. Therefore, we performed a systematic review and meta-analysis of relevant studies that compared the efficacy of Tocilizumab in severe COVID-19 vs. standard of care alone. Methods: Literature search for studies that compared Tocilizumab and Standard of care in the treatment of COVID-19 was done using major online databases from December 2019 to June 14th, 2020. Search words Tocilizumab, anti-interleukin-6 antibody, and COVID-19 or coronavirus 2019 in various combinations were used. Articles in the form of abstracts, letters without original data, case reports, and reviews were excluded. Data was gathered on an excel sheet, and statistical analysis was performed using Review Manager 5.3. Results: Five studies were eligible from 693 initial studies, including 3,641 patients (>2283 males). There were thirteen retrospective studies and three prospective studies. There were 2,488 patients in the standard of care group and 1,153 patients in the Tocilizumab group. The death rate in the tocilizumab group, 22.4% (258/1153), was lower than the standard of care group, 26.21% (652/2,488) (Pooled odds ratio 0.57 [95% CI 0.36-0.92] p=0.02). There was a significant heterogeneity (Inconsistency index= 80%) among the included studies. Conclusion: The addition of Tocilizumab to the standard of care reduces mortality in severe COVID-19. Larger randomized clinical trials are needed to validate these findings.


title: Parametric analysis of early data on COVID-19 expansion in selected European countries

text: We analyze the early data on COVID-19 expansion in selected European countries using an analytical parametric model. A description of the time dependence of the disease expansion and a method to evaluate trends of the expansion are proposed. Several features are observed in the data, namely a high predictability of the expansion of disease in Italy and a convergence of the “pushback” parameter towards a limiting value in all the countries where restrictive measures have been adopted. Basic predictions for the evolution of the disease expansion are made for selected countries with a stable evolution in the parametric space of the model. The findings presented here should contribute to the understanding of the behavior of the disease expansion and the role of the restrictive measures on the evolution of the expansion.


title: [Can we manage prophylactic therapy in COVID-19 patients to prevent severe illness complications? ]/ Podemos atuar preventivamente para evitar que os pacientes portadores de COVID-19 evoluam de forma mais grave?

text: Abstract Many patients with COVID-19 have thromboembolic complications that worsen their prognosis Herein, the authors propose a modified version of the CHA2DS2-VASc score, including 1 point for COVID-19, so that prophylaxis to protect against thromboembolic events would be indicated before the condition becomes severe The advantages of this modification would be prevention of the patient’s condition worsening due to thromboembolic problems and reduction of the likelihood of a need for intensive care and mechanical ventilation, reducing mortality


Community supervision and COVID


title: Human IgG neutralizing monoclonal antibodies block SARS-CoV-2 infection

text: The coronavirus induced disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide threat to human lives, and neutralizing antibodies present a great therapeutic potential in curing affected patients. We purified more than one thousand memory B cells specific to SARS-CoV-2 S1 or RBD (receptor binding domain) antigens from 11 convalescent COVID-19 patients, and a total of 729 naturally paired heavy and light chain fragments were obtained by single B cell cloning technology. Among these, 178 recombinant monoclonal antibodies were tested positive for antigen binding, and the top 13 binders with Kd below 0.5 nM are all RBD binders. Importantly, all these 13 antibodies could block pseudoviral entry into HEK293T cells overexpressing ACE2, with the best ones showing IC50s around 2-3 nM. We further identified 8 neutralizing antibodies against authentic virus with IC50s within 10 nM. Among these, 414-1 blocked authentic viral entry at IC50 of 1.75 nM and in combination with 105-38 could achieve IC50 as low as 0.45 nM. Meanwhile, we also found that 3 antibodies could cross-react with the SARS-CoV spike protein. Altogether, our study provided a panel of potent human neutralizing antibodies for COVID19 as therapeutics candidates for further development.


title: Severe obesity is associated with higher in-hospital mortality in a cohort of patientswith COVID-19 in the Bronx, New York

text: Background & Aims: New York is the current epicenter of Coronavirus disease 2019 (COVID-19) pandemic. The underrepresented minorities, where the prevalence of obesity is higher, appear to be affected disproportionately. Our objectives were to assess the characteristics and early outcomes of patients hospitalized with COVID-19 in the Bronx and investigate whether obesity is associated with worse outcomes. Methods: This retrospective study included the first 200 patients admitted to a tertiary medical center with COVID-19. The electronic medical records were reviewed at least three weeks after admission. The primary endpoint was in-hospital mortality. Results: 200 patients were included (female sex: 102, African American: 102). The median BMI was 30 kg/m2. The median age was 64 years. Hypertension (76%), hyperlipemia (46.2%), and diabetes (39.5%) were the three most common comorbidities. Fever (86%), cough (76.5%), and dyspnea (68%) were the three most common symptoms. 24% died during hospitalization (BMI <25 kg/m2: 31.6%, BMI 25-34 kg/m2: 17.2%, BMI[≥]35 kg/m2: 34.8%, p= 0.03). The multivariate analysis for mortality, demonstrates that BMI[≥]35 kg/m2 (OR: 3.78; 95% CI: 1.45 - 9.83; p=0.006), male sex (OR: 2.74; 95% CI: 1.25 - 5.98; p=0.011) and increasing age (OR: 1.73; 95% CI: 1.13 - 2.63; p=0.011) were independently associated with higher inhospital mortality. Similar results were obtained for the outcomes of increasing oxygen requirement and intubation. Conclusions: In this cohort of hospitalized patients with COVID-19 in a minority-predominant population, severe obesity, increasing age, and male sex were associated with higher in-hospital mortality and in general worse in-hospital outcomes.


COVID-19: How Neurologists Are Defining Those ‘Essential’ Visits in Migraine, Stroke, Epilepsy, and Multiple Sclerosis


title: Validation of reported risk factors for disease classification and prognosis in COVID-19: a descriptive and retrospective study

text: Risk indicators viral load (ORF1ab Ct), lymphocyte percentage (LYM%), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and lactic acid (LA) in COVID-19 patients have been proposed in recent studies. However, the predictive effects of those indicators on disease classification and prognosis remains largely unknown. We dynamically measured those reported indicators in 132 cases of COVID-19 patients including the moderate-cured (moderated and cured), severe-cured (severe and cured) and critically ill (died). Our data showed that CRP, PCT, IL-6, LYM%, lactic acid and viral load could predict prognosis and guide classification of COVID-19 patients in different degrees. CRP, IL-6 and LYM% were more effective than other three factors in predicting prognosis. For disease classification, CRP and LYM% were sensitive in identifying the types between critically ill and severe (or moderate). Notably, among the investigated factors, LYM% was the only one that could distinguish between the severe and moderate types. Collectively, we concluded that LYM% was the most sensitive and reliable predictor for disease typing and prognosis. During the COVID-19 pandemic, the precise classification and prognosis prediction are critical for saving the insufficient medical resources, stratified treatment and improving the survival rate of critically ill patients. We recommend that LYM% be used independently or in combination with other indicators in the management of COVID-19.


title: Two Wolf-Rayet stars at the heart of colliding-wind binary Apep

text: Infrared imaging of the colliding-wind binary Apep has revealed a spectacular dust plume with complicated internal dynamics that challenges standard colliding-wind binary physics. Such challenges can be potentially resolved if a rapidly-rotating Wolf-Rayet star is located at the heart of the system, implicating Apep as a Galactic progenitor system to long-duration gamma-ray bursts. One of the difficulties in interpreting the dynamics of Apep is that the spectral composition of the stars in the system was unclear. Here we present visual to near-infrared spectra that demonstrate that the central component of Apep is composed of two classical Wolf-Rayet stars of carbon- (WC8) and nitrogen-sequence (WN4-6b) subtypes. We argue that such an assignment represents the strongest case of a classical WR+WR binary system in the Milky Way. The terminal line-of-sight wind velocities of the WC8 and WN4-6b stars are measured to be $2100 \pm 200$ and $3500 \pm 100$ km s$^{-1}$, respectively. If the mass-loss rate of the two stars are typical for their spectral class, the momentum ratio of the colliding winds is expected to be $\approx$ 0.4. Since the expansion velocity of the dust plume is significantly smaller than either of the measured terminal velocities, we explore the suggestion that one of the Wolf-Rayet winds is anisotropic. We can recover a shock-compressed wind velocity consistent with the observed dust expansion velocity if the WC8 star produces a significantly slow equatorial wind with a velocity of $\approx$530 km s$^{-1}$. Such slow wind speeds can be driven by near-critical rotation of a Wolf-Rayet star.


title: Comorbidities and Disparities in Outcomes of COVID-19 Among African American and White Patients

text: Initial surveillance data suggests a disproportionately high number of deaths among Black patients with COVID-19. However, high-risk comorbidities are often over-represented in the Black population, and understanding whether the disparity is entirely secondary to them is essential. We performed a retrospective cohort study using real-time analysis of electronic medical records (EMR) of patients from multiple healthcare organizations in the United States. Our results showed that Black patients with COVID-19 have a significantly higher risk of mortality, hospitalization, and invasive mechanical ventilation compared to White patients. The incremental risk of poor outcomes in Blacks persists despite accounting for a higher prevalence of comorbidities. This may point to the disparities in socioeconomic determinants of health affecting Blacks and the need for an improvement in the care of this vulnerable population.


title: Beyond the Spike: identification of viral targets of the antibody response to SARS-CoV-2 in COVID-19 patients

text: Background: The SARS-CoV-2 virus emerged in December 2019 and caused a pandemic associated with a spectrum of COVID-19 disease ranging from asymptomatic to lethal infection. Serology testing is important for diagnosis of infection, determining infection attack rates and immunity in the population. It also informs vaccine development. Although several serology tests are in use, improving their specificity and sensitivity for early diagnosis on the one hand and for detecting past infection for population-based studies, are priorities. Methods: We evaluated the anti-SARS-CoV-2 antibody profiles to 15 SARS-CoV-2 antigens by cloning and expressing 15 open reading frames (ORFs) in mammalian cells and screened antibody responses to them in COVID-19 patients using the Luciferase Immunoprecipitation System (LIPS). Results: The LIPS technique allowed us to detect antibody responses in COVID-19 patients to 11 of the 15 SARS-CoV-2 antigens tested, identifying novel immunogenic targets. This technique shows that antigens ORF3b and ORF8 allow detection of antibody early in infection in a specific manner and reveals the immuno-dominance of the N antigen in COVID-19 patients. Conclusion: Our report provides an unbiased characterization of antibody responses to a range of SARS-CoV-2 antigens. The combination of 3 SARS-CoV-2 antibody LIPS assays, i.e. N, ORF3b, and ORF8, is sufficient to identify all COVID-19 patients of our cohort even at early time-points of illness, whilst Spike alone fails to do so. Furthermore, our study highlights the importance of investigating new immunogens NSP1, ORF3b, ORF7a and ORF8 which may mediate immune functions other than neutralization which may be beneficial or harmful to the patient.


title: COVID-19 in India: Predictions, Reproduction Number and Public Health Preparedness

text: Abstract Introduction: The COVID-19 has emerged as a global concern for public health due to large scale outbreak. The number of confirmed cases has also been increased in India in the past few weeks. The predictions for the COVID-19 can provide insights into the epidemiology of the disease, which helps policymakers to check health system capacities. Methods: We obtained data on daily confirmed, recovered and death cases for a period of 21 days and have implemented the exponential growth model to predict future cases for all the three components. The mathematical model was used to calculate the average reproduction number and herd immunity. We estimated the number of active cases till the 30th of April. We have also tried to analyze the public health capacity to combat COVID-19 in India. Results: If the exponential growth in the number of cases continues then the total number of active cases will be 2,49,635 until the end of April. The reproduction number for COVID-19 in India was found to be 2.56 and herd immunity as 61%. The cumulative cases predicted by the mathematical model was 1,20,203. Discussion: This prediction provides an alarming situation for India in terms of public health preparedness. The number of tests is needed to increase to detect all the cases of COVID-19 in India. Though some serious preventive measures have been implemented, but India should be ready to face any sudden community outbreak. Keywords: COVID-19, India, predictions, reproduction number, public health capacity


title: Clinical outcomes of SARS-CoV-2 pandemic in long-term care facilities for people with epilepsy: observational study

text: Objectives: COVID-19 is spreading in long-term care facilities with devastating outcomes worldwide, especially for people with chronic health conditions. There is a pressing need to adopt effective measures prevention and containment of in such settings. Design: Retrospective cohort study assessing the effect of enhanced surveillance and early preventative strategies and comparing outcomes for people with severe epilepsy and other comorbidities Setting: Three long-term care facilities: Chalfont Centre for Epilepsy (CCE), St. Elisabeth (STE), and The Meath (TM) with different models of primary and specialist care involvement, in the United Kingdom Participants: 286 long-term residents (age range 19-91 years), 740 carers who had been in contact with the residents during the observation period between 16 March and 05 June 2020. Interventions: Early preventative and infection control measures with identification and isolation of symptomatic cases, with additional enhanced surveillance and isolation of asymptomatic residents and carers at one site (CCE) Main outcome measures: Infection rate for SARS-CoV-2 among residents and carers, asymptomatic rate and case fatality rate, if available. Results: During a 12-week observation period, we identified 29 people (13 residents) who were SARS-CoV-2 positive with confirmed outbreaks amongst residents in two long-term care facilities (CCE, STE). At CCE, two out of 98 residents were symptomatic and tested positive, one of whom died. A further seven individuals testing positive on weekly enhanced surveillance had a completely asymptomatic course. One asymptomatic carer tested positive after contact with confirmed COVID-19 patients in another institution. Since 30 April 2020, during on-site weekly enhanced surveillance all 275 caregivers tested repeatedly negative. At STE, three out of 146 residents were symptomatic and tested positive, a fourth tested positive during hospital admission for symptoms not related to COVID-19. Since April 6, 2020, 105/215 carers presenting with typical symptoms for COVID-19 were tested, of whom 15 tested positive. At TM, testing of symptomatic carers only started from early/mid-April, whilst on-site testing, even of symptomatic residents, was not available until recently. During the observation period, eight of 80 residents were symptomatic but none was tested. Twenty-six of 250 carers were symptomatic and were tested, of whom two tested positive. Conclusions: Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic cases are identified through enhanced surveillance at individual and care staff level. We observed a low rate of morbidity and mortality which confirmed that preventative measures with isolation of suspected and confirmed cases of COVID-19 can reduce resident-to-resident and reverse resident-to-carer transmission.


title: Updated estimates of comorbidities associated with risk for COVID-19 complications based on US data

text: We updated previous estimates (wwwnc.cdc.gov/eid/article/26/8/20-0679_article) of adults with any underlying condition increasing risk of complications from COVID-19 using recent US hospitalization data instead of mortality data from China. This substitutes obesity for cancer in the definition and increased the percentage of adults reporting more than 1 condition to 56.0% (95% CI 55.7-56.4). When controlled for all measures listed, factors increasing odds of reporting any of the underlying conditions include being male, older, African American, American Indian, household income <$25,000, < high school education, underinsurance, living in the South or Midwest (vs. West), plus the risk factors of ever smoking, sedentary lifestyle, and inadequate fruit and vegetable consumption. Population-attributable risk for the listed risk factors was 13.0%, 12.6%, and 15.0% respectively. Results have potential implications for policies based on risk-stratification of the population and for improvement of risk status through lifestyle change. National support for a health promotion campaign would be timely.


title: In this issue of Occupational Medicine

text: The recent COVID-19 outbreak in Wuhan city (Hubei Province of central China), presents significant public health challenges not only in china but across all affected countries worldwide. Koh [1] succinctly describes what coronaviruses are, and outlines six known species associated with human illnesses. The article also describes countries of origin of previous coronavirus disease outbreaks and reports number of known fatalities with associated case-fatality rates. Occupations implicated in the current COVID-19 outbreak are detailed and groups at high risk of contracting the infection e.g. healthcare workers highlighted. Social stigmatisation associated with COVID-19 is explored and suggested measures to contain the infection discussed.


title: An overview and evaluation of alternative forming processes for complex aluminium products

text: Abstract Many industries are facing new forces that cause upheaval in the way products are designed, engineered, produced and used. Consumer preferences in terms of personalization and customization, sustainability criteria and the availability of digital technology together create a new paradigm for integrated product and process development. This paper unfolds from this macro perspective and makes a trajectory towards how this view influence existing and emerging metal forming processes. Knowing that design spaces in many applications are compressed, we hypothesize that characteristics such as die cost, formability, dimensional accuracy, production volume, cycle time, change-over-time, and value stream synergies become ever more important in the future. This paper outlines opportunities and limitations of several alternative forming processes due to these characteristics, and provides advice on how to select an appropriate process in relation to problem at hand, and shortfalls on industrial maturity and applicability of the following processes, viz., single point incremental forming, hydroforming, stretch-bending, and press form hardening.


title: A study on control of novel corona-virus (2019-nCoV) disease process by using PID controller

text: In this paper, the SEIR dynamic model will be used to model the epidemic of coronvirus (2019-nCoV)disease. The SEIR model has been used to model infectious diseases in Malaysia.Then, the spread and control of the disease is simulated applying a PID controller. The results of this study show that the implementation of strict restrictions such as quarantine, social distancing and closure of gathering centers is effective in controlling the disease. Using the results and analyzing them, it was found that early and strict implementation of strict restrictions such as quarantine, social distance and closure of centers with a high percentage of community is very important to control this disease and prevent irreparable economic losses and depreciation of medical staff


title: Mathematical model of COVID-19 spread in Turkey and South Africa

text: A comprehensive study about the spread of COVID-19 cases in Turkey and South Africa has been presented in this paper . An exhaustive statistical analysis encompassing arithmetic, geometric, harmonic means, standard deviation, skewness, variance, Pearson and Spearman correlation was derived from the data collected from Turkey and South Africa within the period of 11 March 2020 to 3 May 2020 and 05 March and 3 of May respectively. It was observed that in the case of Turkey, a negative Spearman correlation for the number of infected class and a positive Spearman correlation for both the number of deaths and recoveries were obtained. This implied that the daily infections could decrease, while the daily deaths and number of recovered people could increase under current conditions. In the case of South Africa, a negative Spearman correlation for both daily deaths and daily infected people was obtained, indicating that these numbers may decrease if the current conditions are maintained. The utilization of a statistical technique predicted the daily number of infected, recovered and dead people for each country; and three results were obtained for Turkey, namely an upper boundary, a prediction from current situation and lower boundary. The prediction shows that Turkey may register in the near future approximately more than 6000 new infections in a day as worst case scenario; and less than 300 cases in the perfect scenario. However, the country could register in the near future a daily number of 27000 people recovered from COVID-19 in the perfect scenario; and less than 5000 people in a worst scenario. Moreover, Turkey in a worst-case scenario could record a high number of approximately 200 deaths per day; and less than 150 deaths in a perfect scenario. Similarly, in the case of South Africa, the prediction results show that in the near future the country could register about 500 new infected cases daily and more than 25 deaths in the worst scenario; while in a perfect scenario less than 50 new infected and zero death cases could be recorded. The histograms of the daily number of newly infected, recovered and death showed a sign of lognormal and normal distribution, which is presented using the Bell curving method parameters estimation. A new mathematical model COVID-19 comprised of nine classes was suggested; of which a formula of the reproductive number, well-poseness of the solutions and the stability analysis were presented in details. The suggested model was further extended to the scope of nonlocal operators for each case; whereby the Atangana-Seda numerical method was used to provide numerical solutions, and simulations were performed for different non-integer numbers. Additionally, sections devoted to control optimal and others dedicated to compare cases between Turkey and South Africa with the aim to comprehend why there are less numbers of deaths and infected people in South Africa than Turkey were presented in details.


title: Fear, Access, and the Real-Time Estimation of Etiological Parameters for Outbreaks of Novel Pathogens

text: Early analysis of outbreaks of novel pathogens to evaluate their likely public health impact depends on fitting predictive models to data gathered and updated in real-time. Both transmission rates and the critical threshold (i.e. the pathogen's 'reproductive number') are inferred by finding the values that provide the best model fit to reported case incidence. These models and inferred results are then the basic tools used for public health planning: how many people expected to be infected, at what scales of time and space, and whether potential intervention strategies impact disease transmission and spread. An underlying assumption, however, is that the ability to observe new cases is either constant, or at least constant relative to diagnostic test availability. We present a demonstration, discussion, and mathematical analysis of how this assumption of predictable observability in disease incidence can drastically impact model accuracy. We also demonstrate how to tailor estimations of these parameters to a few examples of different types of shifting influences acting on detection, depending on the likely sensitivity of surveillance systems to errors from sources such as clinical testing rates and differences in healthcare-seeking behavior from the public over time. Finally, we discuss the implications of these corrections for both historical and current outbreaks.


title: COVID-19, Modern Pandemic: A Systematic Review From Front-Line Health Care Providers’ Perspective

text: Coronavirus disease 2019 (COVID-19) caused infection in 168,000 cases worldwide in about 148 countries and killed more than 6,610 people around the world as of March 16, 2020, as per the World Health Organization (WHO). Compared to severe acute respiratory syndrome and Middle East respiratory syndrome, there is the rapid transmission, long incubation period, and disease containment is becoming extremely difficult. The main aim of this systematic review is to provide a comprehensive clinical summary of all the available data from high-quality research articles relevant to the epidemiology, demographics, trends in hospitalization and outcomes, clinical signs and symptoms, diagnostic methods and treatment methods of COVID-19, thus increasing awareness in health care providers. We also discussed various preventive measures to combat COVID-19 effectively. A systematic and protocol-driven approach is needed to contain this disease, which was declared as a global pandemic on March 11, 2020, by the WHO.


title: COVID-19 and Older Adults. Lessons Learned from the Italian Epicenter

text: On March 13th, 2020, The World Health Organization effectively established that Europe is the new the COVID-19 pandemic world epicenter, as cases in Italy and other European nations soared. The numbers in Italy have climbed with over 80,000 cases as of March 25th, 2020 and with over 8000 deaths, placing Italy now as the country with the highest mortality rate. Importantly, older adults are particularly vulnerable to get severe illness, complications, and to have a higher mortality rate than any other age group. The clinical presentation in older adults with severe illness, in the experience from geriatricians in Lombardy, is described as quite sudden; patients can develop severe hypoxemia with the need of ventilation support in few hours. Geriatric syndromes are not a common form of presentation for COVID-19 in severe illness. It is suggested that stratification by frailty level may help to detect the most vulnerable, and decisions about healthcare resource prioritization should not be taken based only on age itself or previous diagnosis, such as having dementia.


title: Chloroquine and hydroxychloroquine effectiveness in human subjects during coronavirus: a systematic review

text: In a search to find effective treatments for COVID-19, chloroquine and hydroxychloroquine have gained attention. We aim to provide evidence to support clinical decision-making regarding medication for the treatment of COVID-19 by carrying out a systematic review of the literature. The electronic databases MEDLINE, EMBASE, Global Health, and HMIC were searched up to April 2020. Eligible study outcomes included: extubation or patient recovery. Relevant data were extracted and analysed by narrative synthesis. Our results included six studies in the review of which four studies were of good or fair quality. All eligible studies included were for coronavirus involving the use of either chloroquine or hydroxychloroquine to treat common symptoms such as fever, cough, shortness of breath and fatigue. Outcomes most commonly reported were improved lung function, viral clearance, and hospital discharge. Strong evidence to support the use of chloroquine and hydroxychloroquine in the treatment of COVID-19 is lacking. Fast track trials are riddled with bias and may not conform to rigorous guidelines which may lead to inadequate data being reported. The use of these drugs in combination with other medications may be useful but without knowing which groups they are suited for and when they may cause more harm than good.


Recognizing and controlling airborne transmission of SARS‐CoV‐2 in indoor environments


title: Tocilizumab in Severe COVID-19 Pneumonia and Concomitant Cytokine Release Syndrome

text: Younger patients with COVID-19 may experience an exaggerated immune response to SARS-CoV-2 infection and develop cytokine release syndrome (CRS), which may be life threatening. There is no proven antiviral therapy for COVID-19 so far, but profound immunosuppression has recently been suggested as a treatment for COVID-19-associated CRS. We present a case of life-threatening CRS caused by COVID-19 infection with a favourable response to immunosuppressive therapy with tocilizumab (TCZ). The rapid clinical and biochemical improvement following TCZ administration suggests that treatment with immunotherapy can be life-saving in selected patients with COVID-19-induced CRS. LEARNING POINTS: Cytokine release syndrome may cause sudden and potentially life-threatening clinical deterioration in COVID-19 pneumonia, particularly in younger patients. Immunosuppressive therapy may provide important additional therapeutic benefit in these patients. Tocilizumab, a specific IL-6 inhibitor, led to dramatic clinical improvement in a young patient with severe COVID-19-associated cytokine release syndrome.


title: Preprinting a pandemic: the role of preprints in the COVID-19 pandemic

text: The world continues to face an ongoing viral pandemic that presents a serious threat to human health. The virus underlying the COVID-19 disease, SARS-CoV-2, has caused over 3.2 million confirmed cases and 220,000 deaths between January and April 2020. Although the last pandemic of respiratory disease of viral origin swept the globe only a decade ago, the way science operates and responds to current events has experienced a paradigm shift in the interim. The scientific community has responded rapidly to the COVID-19 pandemic, releasing over 16,000 COVID-19 related scientific articles within 4 months of the first confirmed case, of which at least 6,000 were hosted by preprint servers. We focused our analysis on bioRxiv and medRxiv, two growing preprint servers for biomedical research, investigating the attributes of COVID-19 preprints, their access and usage rates, characteristics of their sharing on online platforms, and the relationship between preprints and their published articles. Our data provides evidence for increased scientific and public engagement (COVID-19 preprints are accessed and distributed at least 15 times more than non-COVID-19 preprints) and changes in journalistic practice with reference to preprints. We also find evidence for changes in preprinting and publishing behaviour: COVID-19 preprints are shorter, with fewer panels and tables, and reviewed faster. Our results highlight the unprecedented role of preprints and preprint servers in the dissemination of COVID-19 science, and the likely long-term impact of the pandemic on the scientific publishing landscape.


title: Single Nucleus Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection

text: Respiratory failure is the leading cause of COVID-19 death and disproportionately impacts adults more than children. Here, we present a large-scale snATAC-seq dataset (90,980 nuclei) of the human lung, generated in parallel with snRNA-seq (46,500 nuclei), from healthy donors of ~30 weeks, ~3 years and ~30 years of age. Focusing on genes implicated in SARS-CoV-2 cell entry, we observed an increase in the proportion of alveolar epithelial cells expressing ACE2 and TMPRSS2 in adult compared to young lungs. Consistent with expression dynamics, 10 chromatin peaks linked to TMPRSS2 exhibited significantly increased activity with age and harbored IRF and STAT binding sites. Furthermore, we identified 14 common sequence variants in age-increasing peaks with predicted regulatory function, including several associated with respiratory traits and TMPRSS2 expression. Our findings reveal a plausible contributor to why children are more resistant to COVID-19 and provide an epigenomic basis for transferring this resistance to older populations.