title: Cardiovascular Impairment in COVID-19: Learning From Current Options for Cardiovascular Anti-Inflammatory Therapy

text: In December 2019, Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2, occurred in China and has currently led to a global pandemic. In addition to respiratory involvement, COVID-19 was also associated with significant multiple organ dysfunction syndrome (MODS). Cardiovascular impairment has been observed and is now drawing growing attention. Cardiovascular protective strategies are urgent and of great significance to the overall prognosis of COVID-19 patients. Direct viral infection, cytokine storm, and aggravation of existing cardiovascular diseases were recognized as possible mechanisms of cardiovascular impairment in COVID-19. Hyperactivated inflammation plays an important role in all three mechanisms and is considered to be fundamental in the development of cardiovascular impairment and MODS in COVID-19. Therefore, in addition to conventional cardiovascular treatment, anti-inflammatory therapy is a reasonable strategy for severe cases to further enhance cardiovascular protection and potentially mitigate MODS. We reviewed the inflammatory features and current promising treatments of COVID-19 as well as cardiovascular anti-inflammatory therapies that have been verified in previous clinical trials with positive outcomes. We believe that targeting the central pathway (IL-1β, TNF-α, IL-6), balancing the Th1 and Th2 response, and administering long-term anti-inflammatory therapy might be promising prospects to reduce cardiovascular impairment and even MODS during the acute and recovery phases of COVID-19. The cardiovascular anti-inflammatory therapies might be of great application value to the management of COVID-19 patients and we further propose an algorithm for the selection of anti-inflammatory therapy for COVID-19 patients with or at high risk of cardiovascular impairment. We recommend to take the experiences in cardiovascular anti-inflammatory therapy as references in the management of COVID-19 and conduct related clinical trials, while the clinical translation of novel treatments from preclinical studies or in vitro drug screening should proceed with caution due to unguaranteed efficacy and safety profiles.


title: Adaptations to a face-to-face initial teacher education course ‘forced’ online due to the COVID-19 pandemic

text: This report describes the adaptations made to one initial teacher education course at a Hong Kong university designed for face-to-face instruction that was required to be delivered exclusively on-line due to the suspension of face-to-face classes caused by the COVID-19 pandemic. It describes the adaptations the tutor made, and the challenges faced adapting to the new mode of delivery. It is hoped that others can learn from the author’s experience and be prepared for the suspension of face-to-face classes caused by the COVID-19 pandemic or other health emergencies.


title: What triggers online help-seeking retransmission during the COVID-19 period? Empirical evidence from Chinese social media

text: The past eight months witnessed COVID-19's fast-spreading at the global level. Limited by medical resources shortage and uneven facilities distribution, online help-seeking becomes an essential approach to cope with public health emergencies for many ordinaries. This study explored the driving forces behind the retransmission of online help-seeking posts. We built an analytical framework that emphasized content characteristics, including information completeness, proximity, support seeking type, disease severity, and emotion. Adopting the framework, a quantitative content analysis was conducted with a probability sample of 727 posts. The results illustrate the importance of individual information completeness, high proximity, instrumental support seeking. This study also reveals the severity principle and the power of anger in the dissemination of help-seeking messages. As one of the first online help-seeking diffusion analyses in the COVID-19 period, the theoretical and practical implications of this study are further discussed.


title: Wear behavior of additive manufactured zirconia

text: Abstract Complete consolidation of ceramic particles is feasible for SLA, but print directionality is well acknowledged to be a source of structural anisotropy. By varying build direction of SLA zirconia specimens, pin-on-disk tests were carried out to evaluate any differences in wear behavior and phase composition with respect to laminar architecture. All combinations of horizontal and vertical pin-disk combinations demonstrated equivalent wear coefficients and phase transformation from monoclinic to tetragonal zirconia but do exhibit a nominal trend in run-in wear. Given that microstructural consolidation of AM ceramics is highly dependent on debind and/or sintering rather than print parameters the absence of anisotropy introduce by print parameters could benefit the application and development around AM ceramics.


title: Paradigms about the COVID-2 pandemic: knowledge, attitudes and practices from medical students

text: Background: As the disease caused by the new coronavirus has spread globally, economic instability in healthcare systems has been significant, and the lack of knowledge, attitudes and practices among people has led the magnification of this disease. This reality is more accentuated especially in Ecuador, where, although many healthcare workers have been called to help in the regions most affected; the shortage of them combined with cultural and macroeconomic factors have led Ecuador to face the most aggressive outbreak in Latin America. In this context, the participation on the front line of the last year medical students are indispensable. For that reason, appropriate training on COVID-19 to last year medical students is an urgent need that universities and health systems must guarantee. We aimed to describe the knowledge, attitudes and practices in Ecuadorian last year medical students in order to identify the knowledge gaps, perceptions and behavior patterns, which could guide the design of better medical educational curricula on COVID-19. Methods: This was a cross-sectional 33-item online survey conducted between April 6 to April 20 assessing the knowledge, attitudes, and practices toward the diagnosis, treatment, prevention, and prognosis toward COVID-19 in Ecuadorian last year medical students. It was sent by email and by Facebook and WhatsApp. Results: A total of 309 students answered the survey. 88% (274/309) of students scored high about knowledge of the disease (more than 16 points). The majority of students were pessimistic about possible government actions, which is reflected in the negative attitude towards the control of the COVID-19 in Ecuador and volunteering during the outbreak in 77% (238/309) and 58% (179/309) of the students, respectively. Moreover 91% (280/309) of students said they did not have adequate protective equipment, neither training in their health facilities (49%, 152/309). Conclusions: The high level of students knowledge is an important opportunity to strengthen, improve and advance their training toward COVID-19. Creating a national curriculum may be one of the most effective ways for all students to be trained. Hopefully with this, negative attitudes will change and students will be better qualified. Keywords: Ecuador, medical students, COVID-19.


title: Early epidemiological and clinical manifestations of COVID-19 in Japan

text: Background: Severe acute respiratory syndrome coronaviruses -2 (SARS-COV2) named as COVID-19 had spread worldwide and leading to 1,210,956 confirmed cases and 67,594 deaths Methods: A data of 1192 confirmed cases and 43 deaths due to COVID-19 in Japan collected from the Ministry of Health, Labour and Welfare of Japan and analysed for different epidemiological parameters and their clinical manifestations. We used Clauset-Newman-Moore (CNM) clustering algorithm to develop web-network of confirmed cases to identified clusters of community transmission. Results: Out of 1192 confirmed cases, 90.60% were symptomatic and 9.39% were asymptomatic. The prevalence of COVID19 in males was 56.29% and 43.20 % in females. The mean interval (SD) from symptom onset to diagnosis was 6-22.6 days while mean interval (SD) from contact to onset of symptoms was 5-19.5 days. People of age range 40-79 were more infected and deaths median age was 80. The main symptoms were fever, dry cough, fatigue and pneumonia. The main infected cities were Tokyo (195/1192, 16.35%), Hokkaido (160/1192 13.42%), Aichi (150/1192, 12.58%) and Osaka (145/1192, 12.16%). Only 2.34% cases had travel history from Wuhan China and Osaka music concert was identify as main cluster for community transmission. While 556 (46.64%) cases were clinically diagnosed and 557 (46.72%) were confirmed by using RT-PCR. Conclusions: Other than, declare emergency Japan need to change their approach of diagnosing COVID-19, as asymptomatic cases prevalence is high and maybe it is reason for current sudden increase of cases. Screening centre should be establish away from hospitals, which are treating positive cases.


title: Exploring Epidemiological Behavior of Novel Coronavirus Outbreak through the Development and Analysis of COVID-19 Daily Dataset in Bangladesh

text: Globally, there is an obvious concern about the fact that the evolving 2019-nCoV coronavirus is a worldwide public health threat. The appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019 triggered a major global epidemic, which is now a major community health issue. As of April 17, 2020, according to Institute of Epidemiology, Disease Control and Research (IEDCR) Bangladesh has reported 1838 confirmed cases in between 8 March to 17 April 2020, with > 4.08% of mortality rate and >3.15% of recovery rate. COVID-19 outbreak is evolving so rapidly in Bangladesh; therefore, the availability of epidemiological data and its sensible analysis are essential to direct strategies for situational awareness and intervention. This article presents an exploratory data analysis approach to collect and analyze COVID-19 data on epidemiological outbreaks based on first publicly available COVID-19 Daily Dataset of Bangladesh. Various publicly open data sources on the outbreak of COVID-19 provided by the IEDCR, World Health Organization (WHO), Directorate General of Health Services (DGHS), and Ministry of Health and Family Welfare (MHFW) of Bangladesh have been used in this research. A Visual Exploratory Data Analysis (V-EDA) techniques have been followed in this research to understand the epidemiological characteristics of COVID-19 outbreak in different districts of Bangladesh in between 8 March 2020 to 12 April 2020 and these findings were compared with those of other countries. In all, this is extremely important to promptly spread information to understand the risks of this pandemic and begin containment activities in the country.


title: Comparison of the NeuMoDX, Diasorin Simplexa, Cepheid and Roche CDC SARS-CoV 2 EUA assays using nasopharyngeal/nasal swabs in universal transport media (UTM) and sputum and tracheal aspirates

text: In March 2019 the outbreak of SARS-CoV 2 was officially defined as a pandemic by the World Health Organization and shortly after, the United States Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to the Centers for Disease Control (CDC) for reverse transcription polymerase chain reaction (rtPCR) molecular testing for the detection of the SARS-CoV-2 virus from NP swabs. Since then, EUA with relaxed regulations were granted to numerous manufacturers and clinical microbiology laboratories to implement in-house testing assays with nasopharyngeal swabs (NP) and subsequently additional specimen types. Because of supply chain shortages leading to competition for reagents, sustaining any significant volume of testing soon became problematic. As a countermeasure, within several weeks the Henry Ford Microbiology Laboratory validated 4 different rtPCR assays and multiple specimen types using NeuMoDX, Diasorin Simplexa, Cepheid and Roche platforms. The purpose of this study was to analyze the analytic sensitivity of these rtPCR assays with NP/nasal swabs and sputum/tracheal aspirates. Qualitative analytic agreement between the 4 platforms for NP/nasal swabs ranged 95% - 100% overall with no statistically significant difference in threshold cT values. Similar results were obtained with the sputum/tracheal aspirates. These data demonstrate the high accuracy and reproducibility in detection of SARS-CoV 2 between the rtPCR assays performed on 4 different platforms with numerous specimen types.


title: The need to connect: Acute social isolation causes neural craving responses similar to hunger

text: When people are forced to be isolated from one another, do they crave social interactions in the same way a hungry person craves food? To address this question, we used functional magnetic resonance imaging (fMRI) to measure neural responses in participants (n=40) evoked by food and social cues after ten hours of mandated fasting or total social isolation. After isolation, people felt lonely and craved social interaction. Midbrain regions showed increased activation to food cues after fasting and to social cues after isolation; these responses were correlated with self-reported craving. Neural patterns in response to food cues when participants were hungry generalized to social cues after isolation. Our results support the intuitive idea that acute isolation causes social craving, similar to hunger.


title: LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2

text: C3A is a sub-clone of human hepatoblastoma HepG2 cell line with the strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and LY6E, three cellular proteins with known activity of interfering virus entry, expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-OC43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFITM3 restriction of human coronavirus entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a distinct mechanism. Importance Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control by host innate and adaptive immune responses. In the last decade, several interferon inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as host factors to facilitate the entry of several human pathogenic viruses, including human immunodeficiency virus, influenza A virus and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.


title: Management of common elective paediatric orthopaedic conditions during the COVID-19 pandemic: the Montreal experience

text: PURPOSE: To explore safe delays for the treatment of common paediatric orthopaedic conditions when faced with a life-threatening pandemic, COVID-19, and to propose a categorization system to address this question. METHODS: Review of the literature related to acceptable delays for treatment of common orthopaedic conditions, experience of healthcare professionals from low resource communities and expertise of experienced surgeons. RESULTS: Guidelines for the management of cancellations of elective surgeries during a period of resource reallocation are proposed. Elective cases must not be postponed indefinitely as adverse outcomes may result. Triage of waiting lists should include continuous monitoring of the patient and close communication with families despite social distancing and travel restrictions. Telehealth becomes a necessity. Common orthopaedic conditions are triaged into four groups according to urgency and safe and acceptable delay. Categories proposed are Emergent (life and limb threatening conditions), Urgent (within seven days), Semi-elective (postponed for three months) and Elective (postponed for three to 12 months). In total, 25 common orthopaedic conditions are reviewed and categorized. CONCLUSION: Given the uncertainty within healthcare during a pandemic, it is necessary to determine acceptable delays for elective conditions. We report our experience in developing guidelines and propose categorizing elective cases into four categories, based on the length of delay. Telemedicine plays a key role in determining the gravity of each situation and hence the amount of delay. These guidelines will assist others dealing with elective cases in the midst of a crisis. This paper initiates a coordinated effort to develop a consensus statement on safe delays. Published without peer review.


title: A municipality-based approach using commuting census data to characterise the vulnerability to influenza-like epidemic: the COVID-19 application in Italy.

text: In February 2020, Italy became the epicentre for COVID-19 in Europe and at the beginning of March, in response to the growing epidemic, the Italian Government put in place emergency measures to restrict the movement of the population. Human mobility represents a crucial element to be considered in modelling human infectious diseases. In this paper, we examined the mechanisms underlying COVID-19 propagation using a Susceptible-Infected stochastic model (SI) driven mainly by commuting network in Italy. We modelled a municipality-specific contact rate to capture the disease permeability of each municipality, considering the population at different times of the day and describing the characteristic of the municipalities as attractors of commuters or places that make their workforce available elsewhere. The purpose of our analysis is to provide a better understanding of the epidemiological context of COVID-19 in Italy and to characterize the territory in terms of vulnerability at local or national level. The use of data at such a high spatial resolution allows highlighting particular situations on which the health authorities can promptly intervene to control the disease spread. Our approach provides decision-makers with useful geographically detailed metrics to evaluate those areas at major risk for infection spreading and for which restrictions of human mobility would give the greatest benefits, not only at the beginning of the epidemic but also in the last phase, when the risks deriving from the gradual lockdown exit strategies must be carefully evaluated.


title: Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis

text: Substance use disorders (SUDs) are characterized by a compulsion to seek and consume one or more substances of abuse, with a perceived loss of control and negative emotional state. Repeated use of a substance results in synaptic and morphological changes, secondary to toxicity and SUD pathology in the dopamine striato-thalamo-cortical and limbic pathways. These neuroadaptations seem to vary between studies, which could be related to divergent effects of substances, consumption severity or other unknown factors. We therefore identified studies investigating the effects of SUDs using volumetric whole-brain voxel-based morphometry (VBM) in gray (GM) and white matter (WM). We performed a systematic review and meta-analysis of VBM studies using the anatomic likelihood estimation (ALE) method implemented in GingerALE (PROSPERO pre-registration CRD42017071222). Fifty studies met inclusion criteria and were included in the final quantitative meta-analysis, with a total of 538 foci, 88 experiments and 4370 participants. We found convergence and divergence in brain regions and volume effects (higher vs lower volume) in GM and WM depending on the severity of consumption pattern and type of substance. Convergent pathology was evident across substances in GM of the insula, anterior cingulate cortex, putamen, and thalamus, and in WM of the thalamic radiation and internal capsule bundle. Divergent pathology between occasional use (cortical pathology) and addiction (cortical-subcortical pathology) provides evidence of a possible top-down neuroadaptation. Our findings indicate distinctive brain morphometry alterations in SUDs, which may inform our understanding of disease progression and ultimately therapeutic approaches.


title: Feasibility of controlling 2019-nCoV outbreaks by isolation of cases and contacts

text: Background: To assess the viability of isolation and contact tracing to control onwards transmission from imported cases of 2019-nCoV. Methods: We developed a stochastic transmission model, parameterised to the 2019-nCoV outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a 2019 nCoV-like pathogen. We considered scenarios that varied in: the number of initial cases; the basic reproduction number R0; the delay from symptom onset to isolation; the probability contacts were traced; the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. Findings: While simulated outbreaks starting with only 5 initial cases, R0 of 1.5 and little transmission before symptom onset could be controlled even with low contact tracing probability, the prospects of controlling an outbreak dramatically dropped with the number of initial cases, with higher R0, and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1.5 were controllable with under 50% of contacts successfully traced. For R0 of 2.5 and 3.5, more than 70% and 90% of contacts respectively had to be traced to control the majority of outbreaks. The delay between symptom onset and isolation played the largest role in determining whether an outbreak was controllable for lower values of R0. For higher values of R0 and a large initial number of cases, contact tracing and isolation was only potentially feasible when less than 1% of transmission occurred before symptom onset. Interpretation: We found that in most scenarios contact tracing and case isolation alone is unlikely to control a new outbreak of 2019-nCov within three months. The probability of control decreases with longer delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.


title: Modeling COVID-19 epidemics in an Excel spreadsheet: Democratizing the access to first-hand accurate predictions of epidemic outbreaks

text: COVID-19, the first pandemic of this decade and the second in less than 15 years, has harshly taught us that viral diseases do not recognize boundaries; however, they truly do discriminate between aggressive and mediocre containment responses. We present a simple epidemiological model that is amenable to implementation in Excel spreadsheets and sufficiently accurate to reproduce observed data on the evolution of the COVID-19 pandemics in different regions (i.e., Italy, Spain, and New York City (NYC)). We also show that the model can be adapted to closely follow the evolution of COVID-19 in any large city by simply adjusting two parameters related to (a) population density and (b) aggressiveness of the response from a society/government to epidemics. Moreover, we show that this simple epidemiological simulator can be used to assess the efficacy of the response of a government/society to an outbreak.


News: One Italian Hospital's Response to the COVID-19 Crisis


title: Deep Learning-based Detection for COVID-19 from Chest CT using Weak Label

text: Accurate and rapid diagnosis of COVID-19 suspected cases plays a crucial role in timely quarantine and medical treatment. Developing a deep learning-based model for automatic COVID-19 detection on chest CT is helpful to counter the outbreak of SARS-CoV-2. A weakly-supervised deep learning-based software system was developed using 3D CT volumes to detect COVID-19. For each patient, the lung region was segmented using a pre-trained UNet; then the segmented 3D lung region was fed into a 3D deep neural network to predict the probability of COVID-19 infectious. 499 CT volumes collected from Dec. 13, 2019, to Jan. 23, 2020, were used for training and 131 CT volumes collected from Jan 24, 2020, to Feb 6, 2020, were used for testing. The deep learning algorithm obtained 0.959 ROC AUC and 0.976 PR AUC. There was an operating point with 0.907 sensitivity and 0.911 specificity in the ROC curve. When using a probability threshold of 0.5 to classify COVID-positive and COVID-negative, the algorithm obtained an accuracy of 0.901, a positive predictive value of 0.840 and a very high negative predictive value of 0.982. The algorithm took only 1.93 seconds to process a single patient's CT volume using a dedicated GPU. Our weakly-supervised deep learning model can accurately predict the COVID-19 infectious probability in chest CT volumes without the need for annotating the lesions for training. The easily-trained and high-performance deep learning algorithm provides a fast way to identify COVID-19 patients, which is beneficial to control the outbreak of SARS-CoV-2. The developed deep learning software is available at \url{https://github.com/sydney0zq/covid-19-detection}.


title: Daily growth rate of scientific production on Covid-19. Analysis in databases and open access repositories

text: The scientific community is facing one of its greatest challenges in solving a global health problem: COVID-19 pandemic. This situation has generated an unprecedented volume of publications. What is the volume, in terms of publications, of research on COVID-19? The general objective of this research work is to obtain a global vision of the daily growth of scientific production on COVID-19 in different databases (Dimensions, Web of Science Core Collection, Scopus-Elsevier, Pubmed and eight repositories). In relation to the results obtained, Dimensions indexes a total of 9435 publications (69% with peer review and 2677 preprints) well above Scopus (1568) and WoS (718). This is a classic biliometric phenomenon of exponential growth (R2 = 0.92). The global growth rate is 500 publications and the production doubles every 15 days. In the case of Pubmed the weekly growth is around 1000 publications. Of the eight repositories analysed, Pubmed Central, Medrxiv and SSRN are the leaders. Despite their enormous contribution, the journals continue to be the core of scientific communication. Finally, it has been established that three out of every four publications on the COVID-19 are available in open access. The information explosion demands a serious and coordinated response from information professionals, which places us at the centre of the information pandemic.


title: Assessing the community risk perception toward COVID-19 outbreak in South Korea: evidence from Google and NAVER relative search volume

text: This study aimed to explore the patterns of community health risk perception of coronavirus disease 2019 (COVID-19) in South Korea using Internet search data. Google and NAVER relative search volume data were collected using COVID-19-related terms in Korean language. Online queries were compared with the number of new COVID-19 cases and tests. Time series trends and Spearmans rank correlation coefficients showed that the number of COVID-19-related queries in South Korea increased during the local and international events; higher in women, certain age groups; and higher in affected areas, which represented the community health risk perception. Greater correlations were found in mobile searches compared to that of desktop searches, indicating the changing behavior in searching health online information. The use of both Google and NAVER RSV to explore the patterns of community health risk perception could be beneficial for targeting risk communication in several perspectives including time, population characteristics, and location.


title: How effective can homemade face masks be?

text: With cases of COVID-19 growing rapidly in the US and evidence mounting that the virus responsible, SARS-CoV-2, can be spread by infected people before they develop symptoms, the US Centers for Disease Control and Prevention recommended April 3 that people wear cloth face coverings in public places This guidance is a shift from the center’s previous position that healthy people needed to wear masks only when caring for a sick person The recommendation also follows recent calls by experts on social media and other platforms for the general public to don nonmedical, cloth masks to help reduce the transmission of the novel coronavirus “Members of the general public should wear non-medical fabric face masks when going out in public in one additional societal effort to slow the spread of the virus down,” Tom Inglesby, director of the Johns Hopkins Center for Health Security, tweeted March 29 These experts hope the View: PDF ;Full Text HTML


title: Association between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers use and the risk of infection and clinical outcome of COVID-19: a comprehensive systematic review and meta-analysis.

text: Background The effect of using Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin-receptor blockers (ARBs) on the risk of coronavirus disease 2019 (COVID-19) is a topic of recent debate. Although studies have examined the potential association between them, the results remain controversial. This study aims to determine the true effect of ACEI/ARBs use on the risk of infection and clinical outcome of COVID-19. Methods Five electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) were retrieved to find eligible studies. Meta-analysis was performed to examine the association between ACEI/ARBs use and the risk of infection and clinical outcome of COVID-19. Results 22 articles containing 157,328 patients were included. Use of ACEI/ARBs was not associated with increased risk of infection (Adjusted OR: 0.96, 95% CI: 0.91-1.01, I2=5.8%) or increased severity (Adjusted OR: 0.90, 95% CI: 0.77-1.05, I2=27.6%) of COVID-19. The use of ACEI/ARBs was associated with lower risk of death from COVID-19 (Adjusted OR: 0.66, 95% CI: 0.44-0.99, I2=57.9%). Similar results of reduced risk of death were also found for ACEI/ARB use in COVID-19 patients with hypertension (Adjusted OR: 0.36, 95% CI: 0.17-0.77, I2=0). Conclusion This study provides evidence that ACEI/ARBs use for COVID-19 patients does not lead to harmful outcomes and may even provide a beneficial role and decrease mortality from COVID-19. Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents. Keywords: COVID-19; Angiotensin-converting enzyme inhibitor; Angiotensin-receptor blockers; risk; systematic review; meta-analysis


title: Updates of Cardiovascular Manifestations in COVID-19: Korean Experience to Broaden Worldwide Perspectives

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Not just respiratory complications such as pneumonia and acute respiratory distress syndrome, cardiac manifestations have drawn attention due to the increased risk of mortality and morbidity related to SARS-CoV-2 infections. The mechanisms of the cardiac injury related to SARS-CoV-2 infections have been direct cardiac injury caused by angiotensin converting enzyme 2, hypoxemia, microvascular damage, and a systemic inflammatory response. Stress induced cardiomyopathy in a critically ill condition and acute coronary syndrome due to a vulnerable plaque rupture with coagulopathy can finally lead to acute heart failure with further cardiac manifestations. When dealing with the highly contagious viral disease-related cardiac manifestations, we should carefully apply the diagnostic and therapeutic methods to achieve the best therapeutic results without adding any risk of disease transmission.


title: The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach

text: Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=-0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= -0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= -0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= -0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= -0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= -1.000) and mortality (r= -1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.


title: In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges

text: The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 Ångstrom, and is publicly available at EMPIAR-10453.


title: Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study.

text: Background The potential benefit of a combination therapy with lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) on COVID-19 has been speculated. We explored the effect of the timing of LPV/r + HCQ initiation on the outcome of patients with COVID-19. Methods A retrospective cohort study was conducted on patients with COVID-19 who started treatment with LPV/r plus HCQ between February 21 and March 20, 2020, at Luigi Sacco Hospital in Milan, Italy. Over time cumulative incidence of clinical improvement was compared between patients who started treatment less than 5 days from the onset of symptoms [early treatment group (ET)] and those who initiated it later [delayed treatment group (DT)]. The association of LPV/r plus HCQ initiation timing on 30-day mortality was also assessed by univariate and multivariate logistic models. Results The study included 172 patients, prevalently males (72%) in their sixties, with a moderate (53.4%) or severe (34.9%) disease. Fourty-three (25%) patients were included in the ET group and and 129 (75%) in the DT group. Severity of disease did not significantly differ between the two groups. Conclusion Timing of LPV/r + HCQ initiation seems to have no impact on COVID-19 clinical course in terms of improvement and 30-day mortality. These findings rise doubts on the clincial efficacy of this regimen.


title: Survival analysis of hospital length of stay of novel coronavirus (COVID-19) pneumonia patients in Sichuan, China

text: Objective Allocation of medical resource is essential to a strong public health system in response to COVID-19. Analysis of confirmed COVID-19 patients' hospital length of stay in Sichuan can be informative to decision-making in other regions of the world. Design A retrospective cross-sectional study. Data and Method Data from confirmed COVID-19 cases in Sichuan Province were obtained from the National Notifiable Diseases Reporting System (NNDRS) and field survey. We collected information on demographic, epidemiological, clinical characteristics, and the length of hospital stay for confirmed patients. We conducted an exploratory analysis using adjusted multivariate cox-proportional models. Participants A total of 538 confirmed patients of COVID-19 infection in Sichuan Province from January to March 2020. Outcome measure The length of hospital stay after admissions for confirmed patients. Results From January 16, 2020 to March 4, 2020, 538 human cases of COVID-19 infection were laboratory-confirmed, and were hospitalized for treatment. Among these, 271 (50%) were 45 years of age or above, 285 (53%) were male, 450 (84%) were considered as having mild symptoms. The median hospital length of stay was 19 days (interquartile range (IQR): 14-23, Range: 3-41). Adjusted multivariate analysis showed that longer hospital length of stay was associated with factors aged 45 and over (HR: 0.74, 95% CI: 0.60-0.91), those admitted to provincial hospital (HR: 0.73, 95% CI: 0.54-0.99), and those with serious illness (HR: 0.66, 95% CI: 0.48-0.90); living in areas with more than 5.5 healthcare workers per 1000 population (HR: 1.32, 95% CI: 1.05-1.65) was associated with shorter hospital length of stay. There was no gender difference. Conclusions Preparation control measures of COVID-19 should involve the allocation of sufficient medical resources, especially in areas with older vulnerable populations and in areas that lack basic medical resources.


title: J.L. Anderson Capitalist Pigs: Pigs, Pork, and Power in America 2019 West Virginia University Press Morgantown 285 pages, US$99.99 hardcover

text: Unknown


title: Laparoscopy during the COVID-19 pandemic: Absence of evidence is not evidence of absence

text: From a local outbreak to a global pandemic, the severe acute respiratory syndrome-coronavirus-2 infection has spread across 210 borders to infect 2 5 million humans There is an organized disruption in the routine hospital functioning to divert the available resources for effective crisis management;most of the departments have been split to carve out a “COVID task force ” The recommended indications for treatment of various medical conditions, medical procedures, and protocols have regressed on the evolutionary timeline Newer recommendations are being released and updated regularly based on emerging evidence and experts' opinions In view of exponential spread of the virus through routes already identified or those still elusive, the shedding of the virus during the incubation period, and lack of scientific evidence, the questions of “laparoscopy” or “no laparoscopy” assume importance Herein, the evidence in literature pertaining to patient safety, efficient and effective utilization of hospital resources, and safety of health-care workers (HCWs) during the pandemic have been reviewed from the perspective of laparoscopy The pathobiology of the virus including its survival properties and the different modes of transmission has been highlighted, and the relative risk to the HCWs between open and laparoscopic surgery dwelt upon The recommendations from various international bodies have been discussed Notwithstanding the absence of concrete evidence to exclude the possibility of bioaerosol-based transmission of the disease to the operating room staff, there is a multitude of other concerns which are addressed by avoiding the use of the laparoscope in the current scenario Moreover, the absence of evidence is not evidence of absence;considering the high contagion and a long latent period associated with this virus, the onus is upon each individual surgeon to decide if one needs evidence of bioaerosol-based transmission or evidence in favor of safety before taking up 'laparoscopy' against 'open surgery'


title: Investigations on machinability aspects of AISI 52100 with minimum quantity solid lubrication

text: Abstract Sustainability has been a major concern of today’s manufacturing industries. Various efforts have been made to improve the productivity and performance of machining. It is always aimed to reduce the heat generated during machining by various cooling and lubrication approaches. In the present work, efforts have been made to assess the effectiveness of minimum quantity lubrication and solid lubricants in machining. Experiments have been performed under MQL and MQSL environment with selected flow rate (300 ml/hr), 20 wt% of calcium fluoride (CaF2) and 10µm particle size of solid lubricant and results are compared with dry and flood cooling environment. The process performance is observed by measuring surface roughness produced, tool flank wear, the microhardness of machined workpiece, and forms of the chip produced. Results revealed the superiority of lubricant mixture applied in form of MQSL due to enhanced lubricating properties imparted by solid lubricant added with MQL.


title: ai-corona: Radiologist-Assistant Deep Learning Framework for COVID-19 Diagnosis in Chest CT Scans

text: Background: With the global outbreak of COVID-19 epidemic since early 2020, there has been considerable attention on CT-based diagnosis as an effective and reliable method. Recently, the advent of deep learning in medical diagnosis has been well proven. Convolutional Neural Networks (CNN) can be used to detect the COVID-19 infection imaging features in a chest CT scan. We introduce ai-corona, a radiologist-assistant deep learning framework for COVID-19 infection diagnosis using the chest CT scans. Method: Our dataset comprises 2121 cases of axial spiral chest CT scans in three classes; COVID-19 abnormal, non COVID-19 abnormal, and normal, from which 1764 cases were used for training and 357 cases for validation. The training set was annotated using the reports of two experienced radiologists. The COVID-19 abnormal class validation set was annotated using the general consensus of a collective of criteria that indicate COVID-19 infection. Moreover, the validation sets for the non COVID-19 abnormal and the normal classes were annotated by a different experienced radiologist. ai-corona constitutes a CNN-based feature extractor conjoined with an average pooling and a fully-connected layer to classify a given chest CT scan into the three aforementioned classes. Results: We compare the diagnosis performance of ai-corona, radiologists, and model-assisted radiologists for six combinations of distinguishing between the three mentioned classes, including COVID-19 abnormal vs. others, COVID-19 abnormal vs. normal, COVID-19 abnormal vs. non COVID-19 abnormal, non COVID-19 abnormal vs. others, normal vs. others, and normal vs. abnormal. ai-corona achieves an AUC score of 0.989 (95% CI: 0.984, 0.994), 0.997 (95% CI: 0.995, 0.999), 0.986 (95% CI: 0.981, 0.991), 0.959 (95% CI: 0.944, 0.974), 0.978 (95% CI: 0.968, 0.988), and 0.961 (95% CI: 0.951, 0.971) in each combination, respectively. By employing Bayesian statistics to calculate the accuracies at a 95% confidence interval, ai-corona surpasses the radiologists in distinguishing between the COVID-19 abnormal class and the other two classes (especially the non COVID-19 abnormal class). Our results show that radiologists diagnostic performance improves when incorporating ai-coronas prediction. In addition, we also show that RT-PCRs diagnosis has a much lower sensitivity compared to all the other methods. Conclusion: ai-corona is a radiologist-assistant deep learning framework for fast and accurate COVID19 diagnosis in chest CT scans. Our results ascertain that our framework, as a reliable detection tool, also improves experts diagnosis performance and helps especially in diagnosing non-typical COVID-19 cases or non COVID-19 abnormal cases that manifest COVID-19 imaging features in chest CT scan. Our framework is available at: ai-corona.com


Ready, steady... go?


title: Effects of Tocilizumab on Mortality in Hospitalized Patients with COVID-19: A Multicenter Cohort Study

text: Background While there are no treatments with proven efficacy for patients with severe coronavirus disease 2019 (COVID 19), tocilizumab has been proposed as a candidate therapy, especially among patients with higher systemic inflammation. Methods We conducted a cohort study of patients hospitalized with COVID 19 in Spain. The primary outcome was time to death and the secondary outcome time to intensive care unit admission (ICU) or death. We used inverse probability weighting to fit marginal structural models adjusted for time varying covariates to determine the causal relationship between tocilizumab use and the outcomes. Results A total of 1,229 and 10,673 person/days were analyzed. In the adjusted marginal structural models, a significant interaction between tocilizumab use and high C reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (aHR 0.34, 95% CI 0.16 to 0.72, p=0.005) and ICU admission or death (aHR 0.38, 95% CI 0.19 to 0.81, p=0.011) among patients with baseline CRP >150 mg/L, but not among those with CRP [≤]150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings. Conclusions In this large observational study, tocilizumab was associated with a lower risk of death or ICU or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID 19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials and support the use of tocilizumab among subjects with higher CRP levels.


title: Self-reported changes in energy balance behaviors during COVID-19 related home confinement: A Cross-Sectional Study

text: Background: The COVID-19 pandemic has caused people to shelter-at-home for an extended period, resulting in a sudden rise in unstructured time. This unexpected disruption in everyday life has raised concerns about weight management, especially in high-risk populations of women and individuals with overweight and obesity. This study aimed to investigate the changes in behaviors that may impact energy intake and/or energy expenditure in U.S. adults during the home confinement. Methods: Cross-sectional data from 1,779 adults were collected using an online Qualtrics survey between April 24th and May 4th, 2020. Self-reported data on demographics, eating behaviors, physical activity, sleep, screen time, takeout food intake, and food purchasing behaviors were collected. Chi-Square analyses were conducted to evaluate differences in the percent of participants reporting increasing, decreasing, or staying the same in each health behavior since the COVID-19 outbreak in their area. Each analysis was followed by comparing whether increases or decreases were more likely for each health behavior. Similar comparisons were made between male and female participants and between body mass index (BMI) categories. Results: We observed an increase in the intake of both healthy and energy-dense unhealthy foods and snacks during the home confinement. Participants also reported increases in sedentary activities and decrease in physical activity, alcohol intake, and consumption of takeout meals during this time. In women, several behavioral changes support greater energy intake and less energy expenditure than men. No clear difference in patterns was observed across BMI status. Conclusion: Acute changes in behaviors underscore the significance of a sudden increase in unstructured time at home on potential weight gain. Our findings support the need to implement and support measures that promote strategies to maintain body weight and establish a methodology to collect body weight data at multiple time points to longitudinally assess the dynamic relationship between behaviors and body weight change.


title: Ayurveda’s holistic lifestyle approach for the management of coronavirus disease (COVID-19): Possible role of Tulsi

text: Coronavirus disease COVID-19 is caused by the recently discovered corona virus that can spread between animals and humans. The outbreak of the corona virus was begun in Wuhan, China, in December 2019. The most com-mon symptoms are fever, tiredness, and dry cough. Some individuals also develop aches and pains, nasal congestion, runny nose, sore throat, or diar-rhea. It was reported that traditional remedies may alleviate the symptoms of COVID-19. Ayurveda is the world’s oldest medical system that can manage any disease without side effects. Ayurveda is equipped with varieties of treatment modalities to handle with any type of deadly diseases. However, a major drawback is a lack of adequate scientific basis. Tulsi has multi-modal therapeutic effects, we hypothesize that tulsi may be effective in the prevention and management of COVID-19. Though the existing literature supports the management of symptoms of COVID-19 using tulsi, a lack of standard formulation limits its use. This is the need of time to start with translational research to provide scientific evidence for the efficacy and to establish the standard formulation of tulsi in the management of COVID-19.


title: Decline of humoral responses against SARS-CoV-2 Spike in convalescent individuals

text: In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to COVID-19 patients. The therapy has been deemed safe and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here we performed repeated analyses at one-month interval on 31 convalescent individuals to evaluate how the humoral responses against the SARS-CoV-2 Spike, including neutralization, evolve over time. We observed that receptor-binding domain (RBD)-specific IgG slightly decreased between six and ten weeks after symptoms onset but RBD-specific IgM decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing SARS-CoV-2 S wild-type or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after symptoms resolution.


title: A model for COVID-19 prediction in Iran based on China parameters

text: Background: The rapid spread of COVID-19 virus from China to other countries and outbreaks of disease require an epidemiological analysis of the disease in the shortest time and an increased awareness of effective interventions. The purpose of this study was to estimate the COVID-19 epidemic in Iran based on the SIR model. The results of the analysis of the epidemiological data of Iran from January 22 to March 8, 2020 were investigated and the prediction was made until March 29, 2020. Methods: By estimating the three parameters of time-dependent transmission rate, time-dependent recovery rate, and time-dependent mortality rate from Covid-19 outbreak in China, and using the number of Covid-19 infections in Iran, we predicted the number of patients for the next month in Iran. Each of these parameters was estimated using GAM models. All analyses were conducted in R software using the mgcv package. Findings: On average, 925 people with COVID-19 are expected to be infected daily in Iran. The epidemic peaks within one week (15.03.2020 to 03.21.2020) and reaches its highest point on 03.18.2020 with 1126 infected cases. Conclusion: The most important point is to emphasize the timing of the epidemic peak, hospital readiness, government measures and public readiness to reduce social contact.


title: Responsibility for vitamin D supplementation of elderly care home residents in England: falling through the gap between medicine and food

text: Abstract Introduction: Vitamin D supplements are recommended for elderly care home residents with little sunlight exposure. However, their use in care homes is limited and vitamin D deficiency in residents is widespread. This study aimed to understand perceived responsibility for the vitamin D status of residents and the determinants of current practice around supplementation. Methods: Thirteen semi-structured interviews were conducted with key informants in two areas of Southern England including care home managers, general practitioners (GPs) and public health professionals. Interviews were audio recorded and transcribed verbatim. Results: Inductive thematic analysis identified four themes: medical framing; professional and sector boundaries; awareness of national guidance; and ethical and practical issues. Vitamin D supplements were not routinely given to residents, and most participants, including the GPs, believed the vitamin D status of residents was the responsibility of the GP. Care home managers felt unable to make decisions about vitamin D and vulnerable to suggestions of wrongdoing in administering over-the-counter vitamin tablets. This results in vitamin D requiring prescription by medical professionals and few care home residents receiving vitamin D supplements. Conclusion: The medical framing of vitamin D supplements in care homes is a practical barrier to residents receiving them and is out of step with public health recommendations. Vitamin D levels in care home residents could be improved through universal supplementation. This requires a paradigm shift so that vitamin D is understood as a protective nutrient as well as a medicine, and a public health as well as a medical responsibility. The failure to ensure vitamin D adequacy of residents may emerge as a factor in the spread and severity of COVID-19 in care homes and gives increased urgency to addressing this issue.


title: Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients

text: As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.


title: Appendix A Emergency Preparedness, Response & Recovery Checklist Beyond the Emergency Management Plan

text: Unknown


title: A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19

text: Abstract Background Novaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19. Methods In laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patients Results Novaferon inhibited the viral replication in infected cells (EC50=1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC50=0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group. Conclusions Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon. Key words: COVID-19, SARS-CoV-2, Novaferon, Antiviral drug, Lopinavir/Ritonavir


title: The Social and Economic Factors Underlying the Impact of COVID-19 Cases and Deaths in US Counties

text: This paper uncovers the socioeconomic and health/lifestyle factors that can explain the differential impact of the coronavirus pandemic on different parts of the United States. Using a dynamic panel model with daily reported number of cases for US counties over a 20-day period, the paper develops a Vulnerability Index for each county from an epidemiological model of disease spread. County-level economic, demographic, and health factors are used to explain the differences in the values of this index and thereby the transmission and concentration of the disease across the country. These factors are also used in a zero-inflated negative binomial pooled model to examine the number of reported deaths. The paper finds that counties with high per capita personal income have high incidence of both reported cases and deaths. The unemployment rate is negative for deaths implying that places with low unemployment rates or higher economic activity have higher reported deaths. Counties with higher income inequality as measured by the Gini coefficient experienced more deaths and reported more cases. There is a remarkable similarity in the distribution of cases across the country and the distribution of distance-weighted international passengers served by the top international airports. Counties with high concentrations of non-Hispanic Blacks, Native Americans, and immigrant populations have higher incidence of both cases and deaths. The distribution of health risk factors such as obesity, diabetes, smoking are found to be particularly significant factors in explaining the differences in mortality across counties. Counties with higher numbers of primary care physicians have lower deaths and so do places with lower hospital stays for preventable causes. The stay-at-home orders are found to be associated with places of higher cases and deaths implying that they were perhaps imposed far too late to have contained the virus in the places with high-risk populations. It is hoped that research such as these will help policymakers to develop risk factors for each region of the country to better contain the spread of infectious diseases in the future.


title: SARS-CoV-2 entry related genes are comparably expressed in children's lung as adults

text: To explore whether the expression levels of viral-entry associated genes might contribute to the milder symptoms in children, we analysed the expression of these genes in both children and adults' lung tissues by single cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC). Both scRNA-seq and IHC analyses showed comparable expression of the key genes for SARS-CoV-2 entry in children and adults, including ACE2, TMPRSS2 and FURIN, suggesting that instead of lower virus intrusion rate, other factors are more likely to be the key reasons for the milder symptoms of SARS-CoV-2 infected children.


title: Medical Management of COVID-19: Evidence and Experience

text: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this infectious disease is termed COVID-19 in short. On a global scale, as of June 1, 2020, the World Health Organization (WHO) published statistics of 6,057,853 infected patients and 371,166 deaths worldwide. Despite reported observational data about the experimental use of certain drugs, there is no conclusively proven curative therapy for COVID-19 as of now; however, remdesivir received emergency use authorization (EUA) by the Food and Drug Administration (FDA) recently for use in patients hospitalized with COVID-19. There are several ongoing clinical trials related to the pharmacological choices of therapy for COVID-19 patients; however, drug trials related to observational studies so far have yielded mixed results and therefore have created a sense of confusion among healthcare professionals (HCPs). In this review article, we seek to collate and provide a summary of treatment strategies for COVID-19 patients with a variable degree of illness and discuss pharmacologic and other therapies intended to be used either as experimental medicine/therapy or as part of supportive care in complicated cases of COVID-19.


title: Investigation of subsequent and co-infections associated with SARS-CoV-2 (COVID-19) in hospitalized patients

text: Background SARS-CoV-2 has drastically affected healthcare globally and causes COVID-19, a disease that is associated with substantial morbidity and mortality. We aim to describe rates and pathogens involved in co-infection or subsequent infections and their impact on clinical outcomes among hospitalized patients with COVID-19. Methods Incidence of and pathogens associated with co-infections, or subsequent infections, were analyzed in a multicenter observational cohort. Clinical outcomes were compared between patients with a bacterial respiratory co-infection (BRC) and those without. A multivariable Cox regression analysis was performed evaluating survival. Results A total of 289 patients were included, 48 (16.6%) had any co-infection and 25 (8.7%) had a BRC. No significant differences in comorbidities were observed between patients with co-infection and those without. Compared to those without, patients with a BRC had significantly higher white blood cell counts, lactate dehydrogenase, C-reactive protein, procalcitonin and interleukin-6 levels. ICU admission (84.0 vs 31.8%), mechanical ventilation (72.0 vs 23.9%) and in-hospital mortality (45.0 vs 9.8%) were more common in patients with BRC compared to those without a co-infection. In Cox proportional hazards regression, following adjustment for age, ICU admission, mechanical ventilation, corticosteroid administration, and pre-existing comorbidities, patients with BRC had an increased risk for in-hospital mortality (adjusted HR, 3.37; 95% CI, 1.39 to 8.16; P = 0.007). Subsequent infections were uncommon, with 21 infections occurring in 16 (5.5%) patients. Conclusions Co-infections are uncommon among hospitalized patients with COVID-19, however, when BRC occurs it is associated with worse clinical outcomes including higher mortality.


title: Observation on clinical effect of Shufeng Jiedu Capsule combined with Arbidol Hydrochloride Capsule in treatment of COVID-19/ 疏风解毒胶囊联合阿比多尔治疗新型冠状病毒肺炎的回顾性研究

text: Objective: To observe the clinical effect of Shufeng Jiedu Capsule combined with Arbidol Hydrochloride Capsule in the treatment of COVID-19. Methods： From January 31, 2020 to February 11, 2020, 70 patients with COVID-19 diagnosed and treated in Bozhou people's hospital were selected. According to the different treatments, they were divided into two groups: 40 patients in combination group and 30 patients in Arbidol Hydrochloride Capsule group. Patients in both groups were given routine Arbidol Hydrochloride Capsule orally. On this basis, the combination group was given oral Shufeng Jiedu Capsule for 10 d. The antipyretic time and the disappearance time of dry cough, nasal congestion, runny nose, sore throat, fatigue, diarrhea and other symptoms of patients in two groups were compared. The negative conversion ratio and negative conversion time of novel coronavirus (SARS-CoV-2) were also compared between two groups of patients. Results： There were significant differences in antipyretic time, the disappearance time of dry cough, nasal congestion, runny nose, pharyngeal pain, fatigue, diarrhea, and novel coronavirus negative conversion time in the combination treatment group compared with the control group (P < 0.05). The negative conversion time of combination treatment group was significantly shorter than Arbidol Hydrochloride Capsule group (P < 0.05). Conclusion: The combination of Shufeng Jiedu Capsule and Arbidol Hydrochloride Capsule was better than Arbidol Hydrochloride Capsule alone in the treatment of COVID-19, which could significantly shorten the symptoms improvement time and negative conversion time of the clinical patients.


title: Global academic response to COVID-19: Cross-sectional study

text: Objective: To describe the global academic response to COVID-19 during its early stages. The responsiveness of investigators, editorial teams, and publishers was explored. Design: Cross-sectional bibliometric review of COVID-19 literature. A parallel search of Middle East Respiratory Syndrome (MERS) literature was performed for comparison of outcomes. Data sources: MEDLINE and EMBASE databases. The search for COVID-19 studies was performed between 1st November 2019 and 24th March 2020. The search for MERS studies was performed one year earlier between 1st November 2018 and 24th March 2019. Main outcome measures: Investigator-responsiveness was assessed by measuring the volume and type of published research. Editorial-responsiveness was assessed by measuring the time from manuscript submission to acceptance and the availability of original data to support the study results. Publisher-responsiveness was assessed by measuring the time from manuscript acceptance to first publication and the provision of open access. Results: In total, 398 of 2835 COVID-19 and 55 of 1513 MERS search results were eligible. Most COVID-19 studies were clinical reports (n=242; 60.8%) and the majority of these were case series (n=105; 43.4%) and single cases (n=65; 26.9%). The times from manuscript submission to acceptance (median: 5 days (IQR: 3-11) vs 71.5 days (38-106); P<0.001) and acceptance to publication (median: 5 days (IQR: 2-8) vs. 22.5 days (4-48.5-; P<0.001) were strikingly shorter for COVID-19. Almost all COVID-19 (n=396; 99.5%) and MERS (n=55; 100%) studies were available with open-access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID-19 and 10 (18.2%) MERS studies (P=0.203). Conclusions: The early academic response to COVID-19 was characterised by investigators aiming to define the disease. These studies were made rapidly and openly available by editorial and publishing teams. Data sharing practises are an essential target for improvement as the pandemic progresses.


title: Monitoring social distancing and SARS-CoV-2 transmission in Brazil using cell phone mobility data

text: Social distancing measures have emerged as the predominant intervention for containing the spread of COVID-19, but evaluating adherence and effectiveness remains a challenge. We assessed the relationship between aggregated mobility data collected from mobile phone users and the time-dependent reproduction number R(t), using severe acute respiratory illness (SARI) cases reported by Sao Paulo and Rio de Janeiro. We found that the proportion of individuals staying home all day (isolation index) had a strong inverse correlation with R(t) (rho<-0.7) and was predictive of COVID-19 transmissibility (p<0.0001). Furthermore, indexs of 46.7% had the highest accuracy (93.9%) to predict R(t) below one. This metric can be monitored in real time to assess adherence to social distancing measures and predict their effectiveness for controlling SARS-CoV-2 transmission.


title: SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium

text: Various reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.


title: Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses

text: Purpose The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these. Methods We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach. Results We found 872 eligible sources from 29 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future. Conclusion Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research.


title: Monocyte CD169 expression as a biomarker in the early diagnosis of COVID-19

text: We assessed the expression of the cell adhesion molecule Sialoadhesin (CD169), a type I interferon-inducible receptor, on monocytes (mCD169) in 53 adult patients admitted to the hospital during the COVID-19 outbreak for a suspicion of SARS-CoV-2 infection. mCD169 was strongly overexpressed in 30 out of 32 (93.7%) confirmed COVID-19 cases, compared to three out of 21 (14.3%) patients for whom the diagnosis of COVID-19 was finally ruled out. mCD169 was associated with the plasma interferon alpha level and thrombocytopenia. mCD169 testing may be helpful for the rapid triage of suspected COVID-19 patients during an outbreak.


title: High Resolution CT Imaging Dynamic Follow-Up Study of Novel Coronavirus Pneumonia

text: Objective: To explore the clinical characteristics and dynamic follow-up changes of high resolution CT (HRCT) in 270 patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods: Two hundred seventy COVID-19 pneumonia patients were retrospectively analyzed, including 146 males and 124 females, with median age of 51 (9,89). The clinical features, laboratory examination indexes and HRCT evolution findings of 270 COVID-19 pneumonia patients were analyzed. Results: 264 cases (95.74%) were positive at the first time nucleic acid test, 6 cases (2.22%) were negative, after multiple inspections, 270 cases (100%) were positive. According to the number of lung segments involved in the lesion, the lesions range from <30% of the lung area (Common type), 30–50% (Severe type), and> 50% (Critical type). At the first CT exam, 136 cases (50.37%) of the common type, 89 cases (32.96%) of the severe type and 45 cases (16.67%) of the critical type. At the second CT exam, 84 cases (31.11%) of the common type, 103 cases (38.15%) of the severe type and 83 cases (30.74%) of the critical type. In the third CT exam, there were 151 cases (55.93%) of the common type, 86 cases (31.85%) of the severe type and 33 cases (12.22%) of the critical type. The differences in image typing were statistically significant (P < 0.05). During this study, a total of 173 patients (64.08%) were recovered after treatment. Conclusion: In some epidemiological backgrounds, CT imaging manifestations and evolutionary characteristics are of great significance for early warning of lung injury, assessment of disease severity, and assistance in clinical typing and post-treatment follow-up.


Debate: safeguarding democracy during pandemics. Social distancing, postal, or internet voting—the good, the bad or the ugly?


title: What is required to prevent a second major outbreak of the novel coronavirus SARS-CoV-2 upon lifting the metropolitan-wide quarantine of Wuhan city, China

text: Background: The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Method: We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results: We estimated that at the end of the epidemic, a total of 65,572 (46,156-95,264) individuals would be infected by the virus, among which 16,144 (14,422-23,447, 24.6%) would be infected through public contacts, 45,795 (32,390-66,395, 69.7%) through household contact, 3,633 (2,344-5,865, 5.5%) through hospital contacts (including 783 (553-1,134) non-COVID-19 patients and 2,850 (1,801-4,981) medical staff members). A total of 3,262 (1,592-6,470) would die of COVID-19 related pneumonia in Wuhan. For an early lifting date (21st March), facial mask needed to be sustained at a relatively high rate (≥85%) if public contacts were to recover to 100% of the pre-quarantine level. In contrast, lifting the quarantine on 18th April allowed public person-to-person contact adjusted back to the pre-quarantine level with a substantially lower level of facial mask usage (75%). However, a low facial mask usage (<50%) combined with an increased public contact (>100%) would always lead a significant second outbreak in most quarantine lifting scenarios. Lifting the quarantine on 25th April would ensure a smooth decline of the epidemics regardless of the combinations of public contact rates and facial mask usage. Conclusion: The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.


title: Analytical sensitivity and efficiency comparisons of SARS-COV-2 qRT-PCR primer-probe sets

text: The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for accurate and rapid diagnostic assays to prompt clinical and public health interventions. Currently, several quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays are being used by clinical, research, and public health laboratories. However, it is currently unclear if results from different tests are comparable. Our goal was to evaluate the primer-probe sets used in four common diagnostic assays available on the World Health Organization (WHO) website. To facilitate this effort, we generated RNA transcripts to be used as assay standards and distributed them to other laboratories for internal validation. We then used (1) RNA transcript standards, (2) full-length SARS-CoV-2 RNA, (3) pre-COVID-19 nasopharyngeal swabs, and (4) clinical samples from COVID-19 patients to determine analytical efficiency and sensitivity of the qRT-PCR primer-probe sets. We show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 virus copies per reaction, except for the RdRp-SARSr (Charite) confirmatory primer-probe set which has low sensitivity. Our findings characterize the limitations of currently used primer-probe sets and can assist other laboratories in selecting appropriate assays for the detection of SARS-CoV-2.


title: Adjusting confirmed COVID-19 case counts for testing volume

text: When assessing the relative prevalence of the novel coronavirus (COVID-19), observers often point to the number of COVID-19 cases that have been confirmed through viral testing. However, comparisons based on confirmed case counts alone can be misleading since a higher case count may reflect either a higher disease prevalence or a better rate of disease detection. Using weekly records of viral test results for each state in the US, I demonstrate how confirmed case counts can be adjusted based on the percentage of COVID-19 tests that come back positive. A regression analysis indicates that case counts track better with future hospitalizations and deaths when employing this simple adjustment for testing coverage. Viral testing results can be used as a leading indicator of COVID-19 prevalence, but data reporting standards should be improved, and care should be taken to account for testing coverage when comparing confirmed case counts.


title: Molecular analysis of binding region of an ACE2 as a receptor for SARS-CoV-2 between humans and mammals

text: In June 2020, a second wave of coronavirus disease-2019 (COVID-19) infections raised concern in Beijing, where salmon sold a fresh fish wholesale market was suspected of being the source of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. It has raised questions in the press and elsewhere about the scientific basis of salmon as a source of infection. With the number of cases growing, the surface of a salmon chopping board in the market was examined for the presence of SARS-CoV-2 and a positive reaction was observed. Following these test results, there has been debate over whether salmon can be infected with SARS-CoV-2. To find assess this, we investigated the structural homology of angiotensin-converting enzyme 2 (ACE2), a host-side receptor for SARS-CoV-2, between humans and other species including salmon and mink. As a result, a high structural homology between ACE2 and mink, which has reportedly transmitted SARS-CoV-2 to humans, was confirmed. However, a non-high structural homology of ACE2 between salmon and humans was observed. Further experiments are needed to find the source of SARS-CoV-2 transmission to the salmon.


title: What can the ideal gas say about global pandemics? Reinterpreting the basic reproduction number

text: Through analysis of the ideal gas, we construct a random walk that on average matches the standard susceptible-infective-removed (SIR) model. We show that the most widely referenced parameter, the 'basic reproduction number' (R0), is fundamentally connected to the relative odds of increasing or decreasing the infectives population. As a consequence, for R0 > 1 the probability that no outbreak occurs is 1/R0. In stark contrast to a deterministic SIR, when R0 = 1.5 the random walk has a 67% chance of avoiding outbreak. Thus, an alternative, probabilistic, interpretation of R0 arises, which provides a novel estimate of the critical population density {gamma}/r without fitting SIR models. We demonstrate that SARS-CoV2 in the United States is consistent with our model and attempt an estimate of {gamma}/r. In doing so, we uncover a significant source of bias in public data reporting. Data are aggregated on political boundaries, which bear no concern for dispersion of population density. We show that this introduces bias in fits and parameter estimates, a concern for understanding fundamental virus parameters and for policy making. Anonymized data at the resolution required for contact tracing would afford access to {gamma}/r without fitting. The random walk SIR developed here highlights the intuition that any epidemic is stochastic and recovers all the key parameter values noted by Kermack and McKendrick in 1927.


title: Should pets be tested for coronavirus?

text: Last Thursday, the first cat tested positive for the new coronavirus The feline had diarrhea, vomiting, and difficulty breathing, and it had come down with COVID-19 about 1 week after its owner did, Belgian health officials announced The same day, Hong Kong’s Agriculture, Fisheries and Conservation Department reported that a 17-year-old Pomeranian—which had initially tested “weak positive” for SARS-CoV-2—had indeed been infected by the virus, likely by its owner or another human


Coronavirus disease 2019 (COVID-19): What we need to know


title: COVID-19 Antibody in Thai Community Hospitals

text: Background COVID-19 seroprevalence data has been scarce, especially in less developed countries with a relatively low infection rate. Methods A locally developed rapid IgM/IgG test kit was used for screening hospital staff and patients who required procedural treatment or surgery in 33 hospitals in Thailand from April 8 to June 8, 2020. A total of 587 participants were tested--459 were hospital staff and 128 were pre-procedural patients. (Thai Clinical Trials Registry: TCTR20200426002) Results Overall, 3.4% of the participants (20 of 587) had positive immunoglobulin M (IgM) and none had positive immunoglobulin G. Hospitals located in the central part of Thailand had the highest IgM seroprevalence (7.4%). Preprocedural patients had a higher rate of positive IgM than the hospital staff (7.0% vs. 2.4%). Participants with present upper respiratory tract symptoms had a higher rate of positive IgM than those without (5.9% vs. 2.7%). Three quarter (77%, 452 of 587) of the participants were asymptomatic, of which, twelve had positive IgM (2.7%) which consisted of 7 of 369 healthcare workers (1.9%) and 5 of 83 preprocedural patients (6.0%). Conclusions COVID-19 antibody test could detect a substantial number of potential silent spreaders in Thai community hospitals. Antibody testing should be encouraged for mass screening, especially in asymptomatic individuals.


title: 10 Wochen alter Säugling mit Sepsisverdacht und SARS-CoV-2-Nachweis in Liquor und Rachen

text: A young male infant was referred to the emergency department with apparent acute sepsis. The laboratory results were compatible with a viral infection except for a slightly elevated procalcitonin level. Due to the clinical severity intravenous antibiotic treatment was started immediately. Cerebrospinal fluid and urine testing initially showed no infection focus but then SARS-CoV‑2 was detected in the lower pharynx and cerebrospinal fluid. The clinical condition of the infant rapidly improved but whether this was due to symptomatic or antibiotic treatment remained unknown. There is still a considerable lack of experience regarding diagnostics and treatment of pediatric SARS-CoV-2 infections.


title: A recommendation for the use of chloroquine, hydroxychloroquine, primaquine, or tafenoquine for prophylaxis against the 2019 novel coronavirus (COVID-19) with note to the ophthalmic considerations

text: With the ongoing pandemic of infectious disease termed coronavirus disease 2019 (COVID-19) caused by the novel coronavirus identified as severe acute respiratory syndrome coronavirus 2 (SARS-C0V-2), prevention of infection and spread is critical in preventing morbidity and mortality. Prophylaxis, specifically chemoprophylaxis, is particularly critical to breaking the spread and rapid rate of increase of SARS-CoV-2. Pre-exposure and post-exposure prophylaxis are both required components of this public health measure. As the use of anti-malarial agents, specifically the 4-aminoquinolones, chloroquine and hydroxychloroquine, for the treatment of SARS-CoV-2 is now being reported, attention must be turned to their role in the chemoprophylaxis of SARS-CoV-2. In a search of the peer-reviewed medical literature (using MEDLINE and cross-referenced literature), this report is first peer-reviewed publication to present the use of these anti-malarial agents as prophylaxis against SARS-CoV-2. The ophthalmic consideration of the use of these drugs is highlighted in this report.


title: Forecasting the impact of the first wave of the COVID-19 pandemic on hospital demand and deaths for the USA and European Economic Area countries

text: Summary Background: Hospitals need to plan for the surge in demand in each state or region in the United States and the European Economic Area (EEA) due to the COVID-19 pandemic. Planners need forecasts of the most likely trajectory in the coming weeks and will want to plan for the higher values in the range of those forecasts. To date, forecasts of what is most likely to occur in the weeks ahead are not available for states in the USA or for all countries in the EEA. Methods: This study used data on confirmed COVID-19 deaths by day from local and national government websites and WHO. Data on hospital capacity and utilisation and observed COVID-19 utilisation data from select locations were obtained from publicly available sources and direct contributions of data from select local governments. We develop a mixed effects non-linear regression framework to estimate the trajectory of the cumulative and daily death rate as a function of the implementation of social distancing measures, supported by additional evidence from mobile phone data. An extended mixture model was used in data rich settings to capture asymmetric daily death patterns. Health service needs were forecast using a micro-simulation model that estimates hospital admissions, ICU admissions, length of stay, and ventilator need using available data on clinical practices in COVID-19 patients. We assume that those jurisdictions that have not implemented school closures, non-essential business closures, and stay at home orders will do so within twenty-one days. Findings: Compared to licensed capacity and average annual occupancy rates, excess demand in the USA from COVID-19 at the estimated peak of the epidemic (the end of the second week of April) is predicted to be 9,079 (95% UI 253-61,937) total beds and 9,356 (3,526-29,714) ICU beds. At the peak of the epidemic, ventilator use is predicted to be 16,545 (8,083-41,991). The corresponding numbers for EEA countries are 120,080 (119,183-121,107), 32,291 (32,157-32,425) and 28,973 (28,868-29,085) at a peak of April 6. The date of peak daily deaths varies from March 30 through May 12 by state in the USA and March 27 through May 4 by country in the EEA. We estimate that through the end of July, there will be 60,308 (34,063-140,381) deaths from COVID-19 in the USA and 143,088 (101,131-253,163) deaths in the EEA. Deaths from COVID-19 are estimated to drop below 0.3 per million between May 4 and June 29 by state in the USA and between May 4 and July 13 by country in the EEA. Timing of the peak need for hospital resource requirements varies considerably across states in the USA and across regions of Europe. Interpretation: In addition to a large number of deaths from COVID-19, the epidemic will place a load on health system resources well beyond the current capacity of hospitals in the USA and EEA to manage, especially for ICU care and ventilator use. These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity. The estimated excess demand on hospital systems is predicated on the enactment of social distancing measures within three weeks in all locations that have not done so already and maintenance of these measures throughout the epidemic, emphasising the importance of implementing, enforcing, and maintaining these measures to mitigate hospital system overload and prevent deaths.


title: With crisis comes opportunity: Building ethical competencies in light of COVID-19

text: The emergence of the coronavirus disease 2019 (COVID-19) pandemic has wide-ranging implications for the field of professional psychology. As clinical practice has rapidly adapted to ensure continuity of care, doctoral students have encountered unique opportunities for ethics-related competency development across practicum training settings. This article discusses the relevant American Psychological Association (APA) Ethics Code standards and additional ethical considerations facing trainees as they navigate their foundational clinical experiences and develop as professional psychologists in light of a pandemic.


title: Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase)

text: Inositol monophosphatase (IMPase) is inhibited by lithium, the most efficacious treatment for bipolar disorder. Several therapies have been approved, or are going through clinical trials, aimed at the replacement of lithium in the treatment of bipolar disorder. One candidate small molecule is ebselen, a selenium-containing antioxidant, which has been demonstrated to produce lithium-like effects, both in a murine model and in clinical trials. Here we present the crystallization and first structure of human IMPase covalently complexed with ebselen, a 1.47Å crystal structure (PDB entry 6ZK0). In the human-IMPase-complex ebselen, in a ring opened conformation, is covalently attached to Cys141, a residue located away from the active site. IMPase is a dimeric enzyme and, in the crystal structure, two adjacent dimers share four ebselen molecules, creating a tetramer with ~222 symmetry. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor, or may block the binding of partner proteins. Synopsis Here we present a 1.47Å crystal structure of human inositol monophosphatase (IMPase) bound to the inhibitor ebselen. In the structure, ebselen forms a seleno-sulfide bond with cysteine 141 and ebselen-mediated contacts between two dimers give a ~222 tetramer.


title: Forecasting ultra-early intensive care strain from COVID-19 in England

text: The COVID-19 pandemic has led to unprecedented strain on intensive care unit (ICU) admission in parts of the world. Strategies to create surge ICU capacity requires complex local and national service reconfiguration and reduction or cancellation of elective activity. Theses measures require time to implement and have an inevitable lag before additional capacity comes on-line. An accurate short-range forecast would be helpful in guiding such difficult, costly and ethically challenging decisions. At the time this work began, cases in England were starting to increase. Here we present an attempt at an agile short-range forecast based on published real-time COVID-19 case data from the seven National Health Service commissioning regions in England (East of England, London, Midlands, North East and Yorkshire, North West, South East and South West). We use a Monte Carlo approach to model the likely impact of current diagnoses on regional ICU capacity over a 14 day horizon. Our model is designed to be parsimonious and based on plausible epidemiological data from the literature available. On the basis of the modelling assumptions made, ICU occupancy is likely to increase dramatically in the the days following the time of modelling. If the current exponential growth continues, 5 out of 7 commissioning regions will have more critically ill COVID-19 patients than there are ICU beds within two weeks\todo{last thing to do}. Despite variable growth in absolute patients, all commissioning regions are forecast to be heavily burdened under the assumptions used. Whilst, like any forecast model, there remain uncertainties both in terms of model specification and robust epidemiological data in this early prospective phase, it would seem that surge capacity will be required in the very near future. We hope that our model will help policy decision makers with their preparations. The uncertainties in the data highlight the urgent need for ongoing real-time surveillance to allow forecasts to be constantly updated using high quality local patient-facing data as it emerges.