title: Obésité et COVID-19: le choc fatal entre deux pandémies

text: Résumé La pandémie actuelle de la maladie à coronavirus 2019 (COVID-19) se superpose à une autre pandémie bien connue dans notre société d’abondance, celle du surpoids et de l’obésité. L’obésité représente un risque accru d’infection COVID-19 sévère, amenant les patients en unité de soins intensifs (USI) pour une assistance respiratoire avec menace de décès. Les raisons en sont multiples: altération de la mécanique ventilatoire, présence de comorbidités comme le diabète, l’hypertension artérielle ou l’apnée obstructive du sommeil, enfin, des réactions immunologique et inflammatoire inappropriées et excessives, possiblement encore accentuées par des dépôts de graisse ectopique intrathoraciques. Ainsi, le COVID-19 pourrait remettre en cause le concept, appelé «obesity paradox», décrit dans les USI chez les patients avec détresse respiratoire aiguë. Par ailleurs, la présence d’une obésité fait en sorte que le COVID-19 sévère atteint des personnes plus jeunes que dans la population non-obèse. Ces données imposent de renforcer les mesures préventives et curatives chez les patients obèses pour limiter le risque d’évolution défavorable en cas de COVID-19. Summary The current pandemic caused by the coronavirus 2019 (COVID-19) is superimposed on another well-known pandemic in our society, that of overweight and obesity. Obesity represents a higher risk of severe COVID-19 infection, which may lead to the requirement of a mechanical ventilation in intensive care units (ICU) and premature death. The underlying mechanisms are multiple: alteration of the respiratory performance, presence of comorbidities such as diabetes, hypertension or obstructive sleep apnea, finally inadequate and excessive immunological responses, possibly aggravated by ectopic intrathoracic fat depots. Thus, COVID-19 may challenge the so-called «obesity paradox» commonly reported in ICU among patients with acute respiratory distress syndrome. Furthermore, the presence of obesity increases the risk of worse outcome at a younger age. These findings require reinforced preventive and curative measures among obese patients to limit the risk of progression towards an unfavorable outcome in case of COVID-19.


title: Evaluate the timing of resumption of business for the states of New York, New Jersey and California via a pre-symptomatic and asymptomatic transmission model of COVID-19

text: The United States has the highest numbers of confirmed cases and death of COVID-19, where confirmed cases took up nearly half in the hot spot states of New York, New Jersey and California. The workforce in these states was required to work from home except for essential services to minimize the risk of the spread of COVID-19. Premature reopening of economy will lead to broader spread of COVID-19, while the opposite situation would cause greater loss of economy. We proposed an epidemic compartmental model in considering the pre-symptomatic transmission and asymptomatic transmission of COVID-19, to estimate the numbers of unidentified infected cases and simulate the possible outcomes of resumption of economy at different forthcoming Mondays. The states of New York and New Jersey were not recommended to reopen the economy before May 18 since it may increase 22.44% and 60.18% for the numbers of cumulative confirmed cases if the second wave of the infection would happen, respectively. While that may be feasible for California to reopen business on May 11 if appropriate control measures for prevention of the second wave of the infection are implemented, because of the less benefit for delaying reopening the economy and the relatively smaller magnitude of Outbreak of COVID-19.


title: Decrease in ACE2 mRNA expression in aged mouse lung

text: Angiotensin-converting enzyme 2 (ACE2) has been identified as a critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This has led to extensive speculation on the role of ACE2 in disease severity, and in particular, whether variation in its expression can explain higher mortality in older individuals. We examine this question in mouse lung and show that 24-month old mice have significantly reduced ACE2 mRNA expression relative to 3-month old mice. The differences appear to be localized to ciliated cells.


title: Clinical features and high resolution CT imaging findings of preliminary COVID-19/ 新型冠状病毒肺炎初诊临床特征及高分辨率CT影像表现

text: Objective: To summarize the clinical and high resolution CT(HRCT) characteristics of 141 patients with COVID-19. Methods: From January 20 to 28, 2020, 141 COVID-19 patients, 77 males and 64 females, with a median age of 49 (9, 87), were enrolled in the study. The clinical features, laboratory test results and HRCT findings of all patients were analyzed retrospectively. Results: In all of the patients, the decreasing leukocyte countin 38 (26.95%) and lymphocyte ratio in 71 (50.35%), a fever over 37.5 ℃ in 139 (98.58%), coughing in 106 (75.18%), headache in 11 (7.80%), expectoration in 41 (29.08%), chest distress in 93 (65.96%), and diarrhea in 4 (2.84%) were found. The HRCT of all patients were abnormal, including ground glass opacity (GGO) with patchy opacity in 52 (36.88%) mainly distributed along subpleural area, GGO with focal consolidation in 23 (16.31%),small patchy opacity in 27 (19.15%),large patchy consolidation in 20 (14.18%),thickened bronchovascular bundleing and blood vessel crossing the lesion in 48 (34.04%), air bronchus sign in 5 (3.55%), small nodule in 7 (4.96%),fibrous stripes and reticular opacities in 5 (3.55%), bilateral pleural effusion in 7 (4.96%), and mediastinal or bilateral hilar lymphadenopathy in 4 (2.84%). Conclusions: The clinical and HRCT manifestations of COVID-19 are various. Under the specific epidemiological background of COVID-19, chest HRCT scan should be carried out as soon as possible for early warning of this disease.


title: Clinical characteristics of COVID-19 infection in pregnant women: a systematic review and meta-analysis

text: Background: On December 2019, Novel coronavirus disease (COVID-19) was detected in Wuhan, China, and then spread around the world. There is little information about effects of COVID-19 on Pregnant women and newborns as a sensitive population. The current study is a systemic review and Meta-analysis to measure the risks and determine the presentations of COVID-19 in pregnant women and newborn. Methods: online data bases were searched on march 20. Heterogeneity of the included studies was assessed using the Cochran Q test and Higgins I2 statistic and expressed as percentage. All data were analyzed with 95% confidence intervals. Results: A total of 7 studies involving 50 participants with Positive test of COVID-19 were enrolled. Mean age of pregnant women was 30.57 years old and the Mean Gestational age was 36.9 weeks. Other variables such as Apgar score, birth weight, Sign and symptoms, Complications and Laboratory data were Analyzed. Conclusion: Our findings showed same clinical characteristics in pregnant women as in non-pregnant adults, with the main symptoms being cough and fever. No vertical transmission was seen and all patients delivered healthy neonates. Our findings would be of great help to the decision making process, regarding the management of pregnant women diagnosed with COVID-19.


ddxof: Managing COVID-19 Hypoxic Respiratory Failure


title: Indonesia finally reports two coronavirus cases. Scientists worry it has many more

text: Indonesia finally reported its first two COVID-19 cases on Monday At a press conference in Jakarta, President Joko Widodo announced that two women aged 31 and 64 from Depok had contracted the virus But some scientists believe the country, which has close ties to China, almost certainly has a “silent epidemic” within its borders and should urgently boost its surveillance efforts Scientists at the Eijkman Institute for Molecular Biology tell Science they have offered to the Indonesian Ministry of Health to help test more people, but have been snubbed so far The detection of the first two cases, along with measures to prevent the spread of the disease, demonstrate Indonesia’s seriousness and capability to deal with the COVID-19 epidemic, Widodo said yesterday “Since the beginning, we have been serious in strictly following WHO [World Health Organization] guidelines regarding the coronavirus issue,” he said


title: SARS-CoV-2 Productively Infects Human Gut Enterocytes

text: COVID-19, caused by SARS-CoV-2, is an influenza-like disease with a respiratory route of transmission, yet clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids, enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were measured. mRNA expression analysis revealed strong induction of a generic viral response program. We conclude that intestinal epithelium supports SARS-CoV-2 replication. One Sentence Summary SARS-CoV-2 infection of enterocytes in human small intestinal organoids


title: Continuous Health Interface Event Retrieval

text: Knowing the state of our health at every moment in time is critical for advances in health science. Using data obtained outside an episodic clinical setting is the first step towards building a continuous health estimation system. In this paper, we explore a system that allows users to combine events and data streams from different sources to retrieve complex biological events, such as cardiovascular volume overload. These complex events, which have been explored in biomedical literature and which we call interface events, have a direct causal impact on relevant biological systems. They are the interface through which the lifestyle events influence our health. We retrieve the interface events from existing events and data streams by encoding domain knowledge using an event operator language.


title: High rate of increased level of plasma Angiotensin II and its gender difference in COVID-19: an analysis of 55 hospitalized patients with COVID-19 in a single hospital, WuHan, China

text: Background: 2019 Novel coronavirus disease (COVID-19) is turning into a pandemic globally lately. Angiotensin-converting enzyme 2 (ACE2) is identified as an important functional receptor for SARS-Cov-2. ACE2 and ACE are homologues with inverse functions in the renin-angiotensin system. ACE converts angiotensin I into a vital vasoactive peptide called angiotensin II(AngII), whereas ACE2 hydrolyzes AngII into a series of vasodilators. There were few reports illustrated the expression of AngII in COVID-19. This study aimed to demonstrate the expression of angiotensin II in COVID-19 and how it correlated to the disease. Methods: We enrolled 55 patients with COVID-19 admitted to renmin Hospital of Wuhan University from January 21st to February 21st, 2020. Demographic data were collected upon admission. COVID-19 nuclear acid, plasma AngII, Renin and aldosterone in the lying position without sodium restriction, and other laboratory indicators were together measured by the laboratory department of our hospital. Findings: Of the 55 patients with COVID-19, 34(61.8%) had an increased level of AngII. The severity of COVID-19 and male is positively related with the level of AngII. The level of blood lymphocyte, PCT, ALT, and AST were remarkably severe with those of normal level of AngII (P < 0.05). CD4/CD8 cells ratio was significantly higher whereas CD3+CD8+ cells amount, CD3+CD8+ cells proportion, CD56+CD16+CD3- cells amount and CD19+CD3- cells amount were considerably lower than those of normal level of AngII (P < 0.05). Abnormal rates of blood lymphocyte and PCT were significantly higher in Patients with elevated AngII level. The results of binary logistic regression analysis showed that the severity of COVID-19 (OR=4.123) and CD4/CD8 ratio(OR=4.050) were the co-directional impact factor while female(OR=0.146) was inverse impact factor of elevated AngII level. Interpretation: High rate of increased level of AngII was detected in COVID-19 patients. Patients with elevated AngII level were more likely to be critically ill with COVID-19. Considering the gender differences in ACE2 expression and no gender differences in angiotensin expression, the gender differences in AngII level might indicate less loss of ACE2 in female patients. Elevated AngII level was correlated with CD4/CD8 ratio, suggesting it might involve in immune disorder. Keywords: 2019 Novel coronavirus disease(COVID-19), Angiotensin-converting enzyme 2 (ACE2), Angiotensin II(AngII), gender differences


title: Japanese strategy to COVID-19: How does it work?

text: Despite substantial inflow of infected cases at the early stage of the pandemic, as of the end of April, Japan manages the outbreak of COVID-19 without systematic breakdown of health care This Japanese paradox – limited fatality despite loose restriction – may have multiple contributing factors, including general hygiene practice of the population, customs such as not shaking hands or hugging, lower prevalence of obesity and other risk factors Along with these societal and epidemiological conditions, health policy options, which are characteristic to Japan, would be considered as one of the contribution factors Some health policy factors relatively unique to Japan are described in this article


title: The smart city as time-space cartographer in COVID-19 control: the South Korean strategy and democratic control of surveillance technology

text: While the US, UK, France, Italy, and many other countries ended up implementing complete lockdown after tens of thousands of deaths from COVID-19, South Korea kept factories and offices running, flattened the curve, and maintained a low mortality rate. Extensive media coverage has focused on South Korea’s testing capacity as the primary reason, but there has been little discussion of the vital role of the smart city. In this paper, we describe how smart city technologies form a crucial part of disease control in South Korea, explain the social conditions for the extensive use of smart city technology, and offer critical insights into contemporary discussions on the issue of smart cities and surveillance.


title: A systematic review to assess seizure risk with chloroquine therapy in persons with epilepsy

text: Background: The goal of this systematic review is to assess the published literature for seizure risk with chloroquine therapy in persons with and without epilepsy. With the COVID-19 pandemic, there is a desperate need for therapy against the SARS CoV-2 virus. Chloroquine is one proposed medication that has received substantial public attention. However, drug labeling in the package insertion states that persons with epilepsy have the risk of chloroquine provoking seizures, and this has increased questions and anxiety in the epilepsy community. Methods: PubMed (1970 to March 27, 2020) and the Embase (1970 to March 27, 2020) were searched with the terms chloroquine and seizure or epilepsy. Selected studies were reviewed, and the adverse drug reaction was classified. Results: Only nine out of 27 studies were deemed eligible for systematic analysis. Out of the nine studies, only one was a prospective study (N=109), two were case series (N=6), and the remaining 6 were case reports. The dose of chloroquine ranged between 100-500 mg/day, except in one patient, the seizure was after taking 1000 mg. The strength of causality for the drug causing seizures in healthy and persons with epilepsy was mostly possible or unlikely, and none were certain. The only clinical trial that evaluated seizure risk with chloroquine failed to find any significant relation. Conclusion: Although the drug insertion label states an increased risk of seizure, the systematic review highlights that such a statement is not supported by any class I studies but by anecdotal case reports. The only randomized clinical study revealed that seizures were not associated with an increased blood level of chloroquine or its metabolite. The present systematic review should provide reassurance to busy clinicians and persons with epilepsy that chloroquine, if prescribed to treat COVID-19, lacks any substantial evidence to suggest that the medication increases the risk of seizure.


title: Metamorphosis of COVID-19 Pandemic

text: We show phase-wise growth of COVID 19 pandemic and explain it by comparing real time data with Discrete Generalized Growth model and Discrete Generalized Richard Model. The comparison of COVID 19 is made for China, Italy, Japan and the USA. The mathematical techniques makes it possible to calculate the rate of exponential growth of active cases, estimates the size of the outbreak, and measures the deviation from the exponential growth indicating slowing down effect. The phase-wise pandemic evolution following the real time data of active cases defines the impact-point when the preventive steps, taken to eradicate the pandemic, becomes effective. The study is important to devise the measures to handle emerging threat of similar COVID-19 outbreaks in other countries, especially in the absence of a medicine.


title: SARS-CoV-2 infection in health care workers: a retrospective analysis and a model study

text: Background There had been a preliminary occurrence of human-to-human transmissions between healthcare workers (HCWs), but risk factors in the susceptibility for COVID-19, and infection patterns among HCWs have largely remained unknown. Methods Retrospective data collection on demographics, lifestyles, contact status with infected subjects for 118 HCWs (include 12 COVID-19 HCWs) from a single-center. Sleep quality and working pressure were evaluated by Pittsburgh Sleep Quality Index (PSQI) and The Nurse Stress Index (NSI), respectively. Follow-up duration was from Dec 25, 2019, to Feb 15, 2020. Risk factors and transmission models of COVID-19 among HCWs were analyzed and constructed. Findings A high proportion of COVID-19 HCWs had engaged in night shift-work (75.0% vs. 40.6%) and felt they were working under pressure (66.7% vs. 32.1%) than uninfected HCWs. COVID-19 HCWs had higher total scores of PSQI and NSI than uninfected HCWs. Furthermore, these scores were both positively associated with COVID-19 risk. An individual-based model (IBM) estimated the outbreak duration among HCWs in a non-typical COVID-19 ward at 62-80 days and the basic reproduction number =1.27 [1.06, 1.61]. By reducing the average contact rate per HCW by a 1.35 factor and susceptibility by a 1.40 factor, we can avoid an outbreak of the basic case among HCWs. Interpretation Poor sleep quality and high working pressure were positively associated with high risks of COVID-19. A novel IBM of COVID-19 transmission is suitable for simulating different outbreak patterns in a hospital setting.


title: Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis

text: Emerging data indicate that complement and neutrophils are involved in the maladaptive host immune response that fuels hyper-inflammation and thrombotic microangiopathy increasing the mortality rate in coronavirus disease 2019 (COVID-19). Here, we investigated the interaction between complement and the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 clinical samples, cell-based inhibition studies and NETs/human aortic endothelial cell (HAEC) co-cultures. Increased plasma levels of NETs, TF activity and sC5b-9 were detected in patients. Neutrophils yielded high tissue factor (TF) expression and released NETs carrying functionally active TF. Confirming our ex vivo findings, treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAEC. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. Serum isolated from COVID-19 patients induces complement activation in vitro, which is consistent with high complement activity in clinical samples. Complement inhibition at the level of C3 with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis that reveals the pivotal role of complement and NETs in COVID-19 immmunothrombosis. This study supports emerging strategies against SARS-CoV-2 infection that exploit complement therapeutics or NETosis inhibition.


title: Global research trend in the treatment of the new Coronavirus diseases (COVID-19) : bibliometric analysis.

text: The Coronavirus 2019 (COVID-19) pandemic has caused worldwide concern and has become a major medical problem. Vaccines and therapeutics are important interventions for the management of this outbreak. This study aims to used bibliometric methods to identify research trends in the domain of therapeutics and vaccines to cure patients with COVID-19 since the beginning of the pandemic. The Web of Science Core Collection database was retrieved for articles on therapeutic approaches to coronavirus disease management published between January 1, 2020 and May 20, 2020. Identified and analyzed the data included title, corresponding author, language, publication time, publication type, research focus. A total of 1569 articles on coronavirus therapeutic means from 84 countries were published in 620 journals. We note the remarkable progressive increase in the number of publications related to research on therapies and vaccines for COVID-19. The United States provided the largest number of articles (405), followed by China (364). Journal of Medical Virology published most of them (n=40). 1005 (64.05%) were articles, 286 (18.23%) were letters, 230 (14.66%) were reviews. The terms "COVID- 19" or "SARS-CoV-2" or "Coronavirus" or "hydroxychloroquine" or "chloroquine" or "2019-nCOV" or "ACE2" or "treatment" or "remdesivir" or "pneumonia" were most frequently used, as shown in the density visualization map. A network analysis based on keyword co-occurrence revealed five distinct types of studies: clinical, biological, epidemiological, pandemic management, and therapeutics (vaccines and treatments). COVID-19 is a major disease that has had an impact on international public health at the global level. Several avenues for treatment and vaccines have been explored. Most of them focus on older drugs used to treat other diseases that have been effective for other types of coronaviruses. There is a discrepancy in the results obtained from the studies of the drugs included in this study. Randomized clinical trials are needed to evaluate older drugs and develop new treatment options.


title: The effect of COVID-19 lockdowns on political support: Some good news for democracy?

text: Major crises can act as critical junctures or reinforce the political status quo, depending on how citizens view the performance of central institutions. We use an interrupted time series to study the political effect of the enforcement of a strict confinement policy in response to the COVID-19 pandemic. Specifically, we take advantage of a unique representative web-based survey that was fielded in March and April 2020 in Western Europe to compare the political support of those who took the survey right before and right after the start of the lockdown in their country. We find that lockdowns have increased vote intentions for the party of the Prime Minister/President, trust in government and satisfaction with democracy. Furthermore, we find that, while rallying individuals around current leaders and institutions, they have had no effect on traditional left–right attitudes.


title: Cyber Security Responsibilization: An Evaluation of the Intervention Approaches Adopted by the Five Eyes Countries and China

text: Governments can intervene to a greater or lesser extent in managing the risks that citizens face They can adopt a maximal intervention approach (e g , COVID‐19) or a hands‐off approach (e g , unemployment), effectively “responsibilizing” their citizens To manage the cyber risk, governments publish cyber‐related policies This article examines the intervention stances the governments adopt in supporting individual citizens managing their personal cyber risk The authors pinpoint the cyber‐related responsibilities that several governments espouse, applying a “responsibilization” analysis Those applying to citizens are identified, thereby revealing the governments' cyber‐related intervention stances The analysis reveals that most governments adopt a minimal cyber‐related intervention stance in supporting their citizens Given the increasing number of successful cyber attacks on individuals, it seems time for the consequences of this stance to be acknowledged and reconsidered The authors argue that governments should support individual citizens more effectively in dealing with cyber threats


title: SARS-CoV-2/COVID-19: Evidence-Based Recommendations on Diagnosis and Therapy

text: COVID-19, a new viral disease affecting primarily the respiratory system and the lung, has caused a pandemic posing serious challenges to healthcare systems around the world. In about 20% of patients, severe symptoms occur after a mean incubation period of 5 – 6 days; 5% of patients need intensive care therapy. Mortality is about 1 – 2%. Protecting healthcare workers is of paramount importance in order to prevent hospital-acquired infections. Therefore, during all procedures associated with aerosol production, personal protective equipment consisting of a FFP2/FFP3 (N95) respiratory mask, gloves, safety glasses and a waterproof overall should be used. Therapy is based on established recommendations issued for patients with acute lung injury (ARDS). Lung protective ventilation, prone position, restrictive fluid management and adequate management of organ failure are the mainstays of therapy. In case of fulminant lung failure, veno-venous extracorporeal membrane oxygenation may be used as a rescue in experienced centres. New, experimental therapies are evolving with ever increasing frequency; currently, however, no evidence-based recommendation is possible. If off-label and compassionate use of these drugs is considered, an individual benefit-risk assessment is necessary, since serious side effects have been reported.


title: The unseen and pervasive threat of COVID-19 throughout the US

text: For each US county, we calculated the probability of an ongoing COVID-19 epidemic that may not yet be apparent. Based on confirmed cases as of April 15, 2020, COVID-19 is likely spreading in 86% of counties containing 97% of US population. Proactive measures before two cases are confirmed are prudent.


title: Ongoing outbreak of COVID-19 in Iran: challenges and signs of concern

text: Since the first outbreak in China, the Coronavirus Disease 2019 (COVID-19) has rapidly spread around the world. Iran was one of the first countries outside of China to report infections with COVID-19. With nearly 100 exported cases to various other countries, it has since been the epicentre of the outbreak in the Middle east. By examining the age-stratified COVID-19 case fatality rates across the country and 14 university hospitals in Tehran, we find that, in younger age groups, the reported cases on 13/03/2020 only capture less than 10% of symptomatic cases in the population. This indicates significant levels of under-reporting in Iran. Using the 18 full-genome sequences from cases with a travel history or link to Iran, as well as the one full genome sequence obtained from within the country, we estimate the time to the most recent common ancestor of sequences which suggests the likely start of the outbreak on 21/01/2020 (95% HPD: 05/12/2019 - 14/02/2020) with an approximate doubling time of 3.07 (95% HPD: 1.68 - 16.27). Also, based on known exported cases to Oman, Kuwait, Lebanon, and China, we estimate the outbreak size on 25 February and 6 March to be around 13,700 (95% CI: 7,600 - 33,300) and 60,500 (43,200 - 209,200), respectively. Knowing the size of the outbreak at two time points and the typical doubling times associated with the COVID-19 epidemics in countries across Europe and North America, we can independently verify that the likely start of epidemic in Iran is around 15/01/2020 (27/12/2019 - 24/01/2020). Our assessment of the fate of the epidemic based on current levels of non-pharmaceutical interventions implemented by the government suggests upward of 10 million cases (IQR: 6.7M - 18M) and 100,000 ICU beds required (IQR: 77K - 140K) during the peak of the epidemic with more than 100,000 cumulative deaths (IQR: 180K - 240K). We also predict a peak in demand for ICU beds on 21/04/2020 (IQR: 06/04/2020 - 23/05/2020). The large span of the peak of the ICU demand is a result of two separate peaks, with the first occurring at around 15/4/2020 and the second in approximately a months time. The latter is also expected to last longer and is based on the relatively relaxed social distancing measures in place. The exact magnitude and timing of the peaks strictly depends on levels of interventions and can change significantly upon new information or change of policy. We caution that a lack of, or relaxed, stringent intervention measures, during a period of highly under-reported spread, would likely lead to the healthcare system becoming overwhelmed in the next few months.


title: DHP Framework: Digital Health Passports Using Blockchain -- Use case on international tourism during the COVID-19 pandemic

text: In order to contain the COVID-19 pandemic, several countries enforced extended social distancing measures for several weeks, effectively pausing the majority of economic activities. In an effort to resume economic activity safely, several Digital Contact Tracing applications and protocols have been introduced with success. However, DCT is a reactive method, as it aims to break existing chains of disease transmission in a population. Therefore DCT is not suitable for proactively preventing the spread of a disease; an approach that relevant to certain use cases, such as international tourism, where individuals travel across borders. In this work, we first identify the limitations characterising DCT related to privacy issues, unwillingness of the public to use DCT mobile apps due to privacy concerns, lack of interoperability among different DCT applications and protocols, and the assumption that there is limited, local mobility in the population. We then discuss the concept of a Health Passport as a means of verifying that individuals are disease risk-free and how it could be used to resume the international tourism sector. Following, we present the DHP Framework that uses a private blockchain and Proof of Authority for issuing Digital Health Passports. The framework provides a distributed infrastructure supporting the issuance of DHPs by foreign health systems and their verification by relevant stakeholders, such as airline companies and border control authorities. We discuss the attributes of the system in terms of its usability and performance, security and privacy. Finally, we conclude by identifying future extensions of our work on formal security and privacy properties that need to be rigorously guaranteed via appropriate security protocols.


title: Predictors of household food insecurity in the United States during the COVID-19 pandemic

text: Objective: To examine associations between sociodemographic and mental health characteristics with household food insecurity as a result of the COVID-19 outbreak. Design: Cross-sectional online survey analyzed using univariable tests and a multivariable logistic regression model. Setting: The United States during the week of March 30, 2020. Participants: Convenience sample of 1,965 American adults using Amazon's Mechanical Turk (MTurk) platform. Participants reporting household food insecurity prior to the pandemic were excluded from analyses. Results: 1,517 participants reported household food security before the COVID-19 outbreak. Among this subset, 30% reported food insecurity after the COVID-19 outbreak, 53% were women and 72% were white. On multivariable analysis, race, income, relationship status, anxiety, and depression were significantly associated with incident household food insecurity. Black respondents, Hispanic/Latino respondents, and respondents with annual income less than $100,000 were significantly more likely to experience incident household food insecurity. Individuals experiencing incident household food insecurity were 2.09 (95% CI 1.58-2.83) times more likely to screen positively for anxiety and 1.88 (95% CI 1.37-2.52) times more likely to screen positively for depression. Conclusions: Food insecurity due to the COVID-19 pandemic is common, and certain populations are particularly vulnerable. There are strong associations between food insecurity and anxiety/depression. Public health interventions to increase the accessibility of healthful foods, especially for Black and Hispanic/Latino communities, are crucial to relieving the economic stress of this pandemic.


title: Is COVID-19 a Message from Nature?

text: Claims have been made that the current COVID-19 pandemic is a message from nature to stop exploiting the earth to the extent that we have been. While there is no direct evidence that this pandemic is a result of human actions with respect to the earth, ample evidence exists that deforestation and other environmental changes, together with climate change, do make it more likely that viruses will cross from wildlife to humans. We humans are mammals and our welfare depends on the health of the earth. We are not so different from other living creatures in this regard. It is in our interests to look after the earth, something that Indigenous Australians knew well. Mother Earth must be cared for if she is to care for us. Nature perhaps is sending us a message in the same sense that my car does if I do not maintain it. It stops functioning properly. We have to modify nature to satisfy our needs but we must be careful how we modify it.


O médico de família e o Covid-19


title: A retrospective study evaluating efficacy and safety of compassionate use of tocilizumab in 13 patients with severe-to-critically ill COVID-19: analysis of well-responding cases and rapidly-worsening cases after tocilizumab administration

text: We administered tocilizumab into 13 severe-to-critically ill patients with coronavirus disease 2019 (COVID-19) for compassionate use in combination with potential anti-viral agents in those who required an oxygen supply and showed increased laboratory inflammatory markers such as C-reactive protein (CRP) and ferritin. One injection of tocilizumab led to rapid improvements in clinical features, inflammatory findings, and oxygen supply in seven patients with severe COVID-19 and substantial amelioration in two patients who were critically ill, whereas four patients, who exhibited rapidly worsened respiratory function, required artificial ventilatory support even after tocilizumab treatment. Three of these four patients ultimately recovered from deterioration after methylprednisolone treatment. Administration of tocilizumab did not affect viral elimination nor IgG production specific for the virus. Compared with well-responding patients, rapidly-worsened patients showed a significantly higher ratio of ferritin vs. CRP. These findings suggest that tocilizumab has beneficial effects in severe-to-critically ill patients with COVID-19; however, in some cases, addition of methylprednisolone is required for disease rescue.


title: Air quality index, indicatory air pollutants and impact of covid-19 event on the air quality near central china

text: Both the air quality index (AQI) and indicatory air pollutants of Anqing, Hefei, and Suzhou near central China from 2017 to 2019, and the impact of COVID-19 epidemic prevention and control actions on air quality were investigated. The combined data for the three cities from 2017 to 2019 indicated that the lowest AQI (averaged 78.1) occurred in the summer season, for which the AQI proportions for classes I, II, III, IV, V, and VI were 25.6%, 49.9%, 21.9%, 2.7%, 0%, and 0%, respectively. The highest (AQI average of 112.6) was in winter, for which the proportions were 7.4%, 39.5%, 33.3%, 12.5%, 7.2%, and 0.1%, respectively. PM 2.5, PM 10, and NO 2in order were the most important indicatory air pollutants for AQI classes IV, V, and VI, which all prevailed in winter and spring, while O 3was the indicatory air pollutant that occurred most in summer. The COVID-19 event, which triggered global attention, broke out at the end of 2019. This study also investigated and compared the air quality levels in the three cities from January to March 2017–2019 with those in 2020. The results showed that during February 2020, in the three cities, the average ambient air concentrations of PM 2.5, PM 10, SO 2, CO, and NO 2were 41.9 µg m –3, 50.1 µg m –3, 2.18 ppb, 0.48 ppm, and 8.97 ppb, and were 46.5%, 48.9%, 52.5%, 36.2%, and 52.8%, respectively, lower than those in the same month in 2017–2019, respectively. However, the O 3average concentration (80.6 ppb) did not show significant fluctuations and even slightly increased by 3.6%. This is because a lower concentration of NO 2resulted in constraints on the reaction of NO + O 3, so the O 3level could not be effectively further reduced. In addition, this study also analyzed and compared the five highest daily AQIs from February 2017–2019 with those of 2020 for the three cities. The mean AQI for the 5 days with the highest daily AQI (averaged 122.6) in February 2020 was 45.1% lower than that for February 2017–2019 (averaging 223.2), and the indicatory air pollutant was always PM 2.5, which decreased by 46.7% (from 173.6 to 92.6 µg m –3). It is clear that during the COVID-19 epidemic prevention and control action periods, the air quality near central China improved significantly.


title: Unique transcriptional changes in coagulation cascade genes in SARS-CoV-2-infected lung epithelial cells: A potential factor in COVID-19 coagulopathies

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. While there are many theories for the cause of this pathology, including hyper inflammation and excess tissue damage, the cellular and molecular underpinnings are not yet clear. By analyzing transcriptomic data sets from experimental and clinical research teams, we determined that changes in the gene expression of genes important in the extrinsic coagulation cascade in the lung epithelium may be important triggers for COVID-19 coagulopathy. This regulation of the extrinsic blood coagulation cascade is not seen with influenza A virus (IAV)-infected NHBEs suggesting that the lung epithelial derived coagulopathies are specific to SARS-Cov-2 infection. This study is the first to identify potential lung epithelial cell derived factors contributing to COVID-19 associated coagulopathy. GRAPHICAL ABSTRACT AUTHOR SUMMARY Why was this study done? Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. Understanding the molecular basis of dysregulated blood coagulation during SARS-CoV-2 infection may help promote new therapeutic strategies to mitigate these complications in COVID-19 patients. What did the researchers do and find? We analyzed three publicly available RNA sequencing datasets to identify possible molecular etiologies of COVID-19 associated coagulopathies. These data sets include sequencing libraries from clinically isolated samples of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMCs) from SARS-CoV-2 positive patients and healthy controls. We also analyzed a publicly available RNA sequencing dataset derived from in vitro SARS-CoV-2 infected primary normal human bronchial epithelial (NHBE) cells and mock infected samples. Pathway analysis of both NHBE and BALF differential gene expression gene sets. We found that SARS-CoV-2 infection induces the activation of the extrinsic blood coagulation cascade and suppression of the plasminogen activation system in both NHBEs and cells isolated from the BALF. PBMCs did not differentially express genes regulating blood coagulation. Comparison with influenza A virus (IAV)-infected NHBEs revealed that the regulation of the extrinsic blood coagulation cascade is unique to SARS-CoV-2, and not seen with IAV infection. What do these findings mean? The hyper-activation of the extrinsic blood coagulation cascade and the suppression of the plasminogen activation system in SARS-CoV-2 infected epithelial cells may drive diverse coagulopathies in the lung and distal organ systems. The gene transcription pattern in SARS-CoV-2 infected epithelial cells is distinct from IAV infected epithelial cells with regards to the regulation of blood coagulation.


title: Public Exposure to Live Animals, Behavioural Change, and Support in Containment Measures in response to COVID-19 Outbreak: a population-based cross sectional survey in China

text: Background In response to the COVID-19 outbreak, we aimed to investigate behavioural change on exposure to live animals before and during the outbreak, and public support and confidence for governmental containment measures. Methods A population-based cross-sectional telephone survey via random dialing was conducted in Wuhan (the epicentre) and Shanghai (an affected city with imported cases) between 1 and 10 February, 2020. 510 residents in Wuhan and 501 residents in Shanghai were randomly sampled. Differences of outcome measures were compared before and during the outbreak, and between two cities. Findings Proportion of respondents visiting wet markets at usual was 23.3% (119/510) in Wuhan and 20.4% (102/501) in Shanghai. During the outbreak, it decreased to 3.1% (16) in Wuhan (p<0.001), and 4.4% (22) in Shanghai (p<0.001). Proportion of those consuming wild animal products declined from 10.2% (52) to 0.6% (3) in Wuhan (p<0.001), and from 5.2% (26) to 0.8% (4) in Shanghai (p<0.001). 79.0% (403) of respondents in Wuhan and 66.9% (335) of respondents in Shanghai supported permanent closure of wet markets (P<0.001). 95% and 92% of respondents supported banning wild animal trade and quarantining Wuhan, and 75% were confident towards containment measures. Females and the more educated were more supportive for the above containment measures. Interpretation The public responded quickly to the outbreak, and reduced exposure to live animals, especially in Wuhan. With high public support in containment measures, better regulation of wet markets and healthy diets should be promoted.


Erratum: Correction: Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19 (Annals of internal medicine (2020))


title: CLINICAL PROPERTIES AND DIAGNOSTIC METHODS OF COVID-19 INFECTION IN PREGNANCIES: META-ANALYSIS

text: We aimed to summarize reliable medical evidence by the meta-analysis of all published retrospective studies that examined data based on the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by clinical symptoms, molecular (RT-PCR) diagnosis and characteristic CT imaging features in pregnant women. MEDLINE PubMed, SCOPUS, ISI Web of Science, Clinical Key, and CINAHL databases were used to select the studies. Then, 384 articles were received, including the studies until 01/MAY/2020. As a result of the full-text evaluation, 12 retrospective articles covering all the data related were selected. A total of 181 pregnant cases with SARS-CoV-2 infections were included in the meta-analysis within the scope of these articles. According to the results, the incidence of fever was 38.1% (95% CI: 14.2-65%), and cough was 22% (95% CI: 10.8-35.2%) among all clinical features of pregnant cases with SARS-CoV-2 infection. So, fever and cough are the most common symptoms in pregnant cases with SARS-CoV-2 infection, and 91.8% (95% CI: 76.7-99.9%) of RT-PCR results are positive. Moreover, abnormal CT incidence is 97.9% (95% CI: 94.2-99.9%) positive. No case was death. However, as this virus spreads globally, it should not be overlooked that the incidence will increase in pregnant women and may be in the risky group. RT-PCR and CT can be used together in an accurate and safe diagnosis. In conclusion, these findings will provide important guidance for current studies regarding the clinical features and correct detection of SARS-CoV-2 infection in pregnant women, as well as whether it will create emergency tables that will require the use of a viral drug.


title: Gut microbiota may underlie the predisposition of healthy individuals to COVID-19

text: The COVID-19 pandemic is spreading globally with high disparity in the susceptibility of the disease severity. Identification of the key underlying factors for this disparity is highly warranted. Here we describe constructing a proteomic risk score based on 20 blood proteomic biomarkers which predict the progression to severe COVID-19. We demonstrate that in our own cohort of 990 individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discovered that a core set of gut microbiota could accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model, and that these gut microbiota features are highly correlated with proinflammatory cytokines in another set of 366 individuals. Fecal metabolomic analysis suggested potential amino acid-related pathways linking gut microbiota to inflammation. This study suggests that gut microbiota may underlie the predisposition of normal individuals to severe COVID-19.


title: Nanotrap® particles improve detection of SARS-CoV-2 for pooled sample methods, extraction-free saliva methods, and extraction-free transport medium methods

text: Here we present a rapid and versatile method for capturing and concentrating SARS-CoV-2 from transport medium and saliva using affinity-capture magnetic hydrogel particles. We demonstrate that the method concentrates virus prior to RNA extraction, thus significantly improving detection of the virus using a real-time RT-PCR assay across a range of viral titers, from 100 to 1,000,000 viral copies/mL; in particular, detection of virus in low viral load samples is enhanced when using the method coupled with the IDT 2019-nCoV CDC EUA Kit. This method is compatible with commercially available nucleic acid extraction kits, as well with a simple heat and detergent method. Using transport medium diagnostic remnant samples that previously had been tested for SARS-CoV-2 using either the Abbott RealTime SARS-CoV-2 EUA Test (n=14) or the Cepheid Xpert Xpress SARS-CoV-2 EUA Test (n=35), we demonstrate that our method not only correctly identifies all positive samples (n = 17) but also significantly improves detection of the virus in low viral load samples. The average improvement in cycle threshold (Ct) value as measured with the IDT 2019-nCoV CDC EUA Kit was 3.1; n = 10. Finally, to demonstrate that the method could potentially be used to enable pooled testing, we spiked infectious virus or a confirmed positive diagnostic remnant sample into 5 mL and 10 mL of negative transport medium and observed significant improvement in the detection of the virus from those larger sample volumes.


title: The SARS-CoV-2 epidemic outbreak: a review of plausible scenarios of containment and mitigation for Mexico

text: We present here several variants of a mathematical model to explore three main issues related to SARS-CoV-2 spread in scenarios similar to those present in Mexico and elsewhere in Latin America. We explore the consequences for travel inside a given region, in this case Mexico, particularly focusing on airplane transportation but attempting to give a gross approximation to terrestrial movement since this is the main form of population movement across geographical areas in the country; then we proceed to study the effect of behavioral changes required to lower transmission by lowering the contact rate and infection probability and lastly, we explore the consequences of disease spread in a population subject to social isolation.These models are not suitable for predictive purposes although some rough predictions can be extracted from them. They are presented as a tool that can serve to explore plausible scenarios of spread and impact, effectiveness and consequences of contention and mitigation policies. Given the early stage at which the epidemic is at the date of writing in Mexico, we hope these ideas can be helpful for the understanding of the importance of isolation, social distancing and screening of the general population.


title: Detection and isolation of asymptomatic individuals can make the difference in COVID-19 epidemic management

text: Mathematical modeling of infectious diseases is a powerful tool for the design of management policies and a fundamental part of the arsenal currently deployed to deal with the COVID-19 pandemic. Here we present a compartmental model for the disease that can provide healthcare burden parameters allowing to infer possible containment and suppression strategies, explicitly including asymptomatic individuals. The main conclusion of our work is that efficient and timely detection and isolation of these asymptomatic individuals can have dramatic effects on the effective reproduction number and healthcare burden parameters. This intervention can provide a valuable tool complementary to other non-pharmaceutical interventions to contain the epidemic.


title: RAAS blockade, kidney disease, and expression of ACE2, the entry receptor for SARS-CoV-2, in kidney epithelial and endothelial cells

text: SARS-CoV-2, the coronavirus that causes COVID-19, binds to angiotensin-converting enzyme 2 (ACE2) on human cells. Beyond the lung, COVID-19 impacts diverse tissues including the kidney. ACE2 is a key member of the Renin-Angiotensin-Aldosterone System (RAAS) which regulates blood pressure, largely through its effects on the kidney. RAAS blockers such as ACE inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) are widely used therapies for hypertension, cardiovascular and chronic kidney diseases, and therefore, there is intense interest in their effect on ACE2 expression and its implications for SARS-CoV-2 pathogenicity. Here, we analyzed single-cell and single-nucleus RNA-seq of human kidney to interrogate the association of ACEi/ARB use with ACE2 expression in specific cell types. First, we performed an integrated analysis aggregating 176,421 cells across 49 donors, 8 studies and 8 centers, and adjusting for sex, age, donor and center effects, to assess the relationship of ACE2 with age and sex at baseline. We observed a statistically significant increase in ACE2 expression in tubular epithelial cells of the thin loop of Henle (tLoH) in males relative to females at younger ages, the trend reversing, and losing significance with older ages. ACE2 expression in tLoH increases with age in females, with an opposite, weak effect in males. In an independent cohort, we detected a statistically significant increase in ACE2 expression with ACEi/ARB use in epithelial cells of the proximal tubule and thick ascending limb, and endothelial cells, but the association was confounded in this small cohort by the underlying disease. Our study illuminates the dynamics of ACE2 expression in specific kidney cells, with implications for SARS-CoV-2 entry and pathogenicity.


title: Enforced inactivity in the elderly and diabetes risk: initial estimates of the burden of an unintended consequence of COVID-19 lockdown

text: Background: Older adults and those with underlying health conditions were advised to stay at home to help reduce the spread of COVID-19 however little advice on regular physical activity was given to those at risk. We modelled the effects of enforced inactivity on diabetes burden using published evidence. Methods: Using Health Survey for England data, we estimated the prevalence of pre-diabetes and physical activity in adults aged 70 and older. The number of new diabetes cases directly attributed to lockdown were calculated using population attributable risk. Unit cost estimates of the additional burden on primary care and the cost of complications to secondary care were taken from the literature. Results: From 9 million older (aged 70yrs and above) people living in England, 2.1 million could be defined as pre-diabetic (glycated haemoglobin > 42 < 48 mmol/mol). The estimated population attributable fraction (0.281) (assuming relative risk of diabetes from inactivity, 3.3; 40% physically active pre-lockdown) would give rise to 392,948 new cases of diabetes which we argue are directly attributed to a prolonged period of lockdown. We estimate that the cost of screening and testing these patients in primary care (GBP 35m), their subsequent treatment and management (GBP 229m), and complications (GBP 909m) would equate to an additional GBP 1.17bn to the health care system. Conclusions: Inactivity related to lockdown in previously active older adults may contribute up to GBP 1.17b in additional healthcare costs through a potential increase in diabetes. Clear advice about the importance of physical activity may reduce this potential economic burden during global pandemics.


title: The first month of the COVID-19 outbreak in 46 sub-Saharan African countries; a comparative analysis of growth rates

text: Background The COVID-19 outbreak in sub-Saharan African countries started after those in Asia, Europe and North America, on 28th February 2020. The susceptibility to infection of populations in that region has been debated. Outbreaks on the scale of those seen elsewhere would pose substantial challenges. There are reasons for concern that transmission may be high and difficult to control, rapidly exceeding capacity to meet the needs for hospitalization and critical care. Methods We obtained data on daily new confirmed cases for all 46 countries from the World Health Organization, and used these to model and visualize growth trajectories using an AutoRegressive Integrated Moving Average (ARIMA) model. We then estimated doubling times from growth rates estimated from Poisson regression models, and by back counting from the most recent observation. We also calculated the time from 1st to 50th case, and the time from 5th to 100th case. These indicators were compared with the same summary indicators of growth at the same stage of the outbreak in highly affected European countries. Results Kenya was the only country with clear evidence of exponential growth. Nineteen countries had either reported no cases, were in the first few days of the outbreak, or had reported fewer than 10 cases over a period of two or more weeks. For the remaining 27 countries we identified four growth patterns: slow linear growth, more rapid linear growth, variable growth patterns over the course of the outbreak, and early signs of possible exponential growth. For those in the last three groups, doubling times ranged from 3 to 4 days, times from 1st to 50th case from 12 to 29 days, and from 5th to 100th case from eight to 15 days. These early indicators are comparable to those in European countries that have gone on to have substantial outbreaks, and time to 50th case was shorter suggesting lesser effectiveness of contact-tracing and quarantine in the early phase. Conclusion The 46 sub-Saharan African countries, home to over one billion people, are at a tipping point with clear potential for the outbreak to follow a similar course as in HIC in the global north. Radical population-level physical distancing measures may be required, but their impact on poor, disadvantaged and vulnerable people and communities need mitigating. Health systems in the region need urgent technical and material support, with testing, personal protection, and hospital/ critical care.


title: Potential Factors for Prediction of Disease Severity of COVID-19 Patients

text: Abstract: Objective: Coronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed. Methods: In this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. Results: A total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9+/-9.4 vs 44.4+/-15.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients. Conclusion: Age and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients. Keyword: COVID-19, erythrocyte sedimentation rate, cytokines, lymphocytes


title: COVID-19 Spread in India: Dynamics, Modeling, and Future Projections

text: COVID-19 is an extremely infectious disease with a relatively large virus incubation period in the affected people who may be asymptomatic. Therefore, to reduce the transmission of this pathogen, several countries have taken many intervention measures. In this paper, we show that the impact of these measures in India is different from several other countries. It is shown that an early lockdown in late March 2020 changed the initial exponential growth curve of COVID-19 to a linear one, but a surge in the number of cases from late April 2020 brought India back to a quadratic trajectory. A regional analysis shows the disparate impact of the intervention in different states. It is further shown that the number of reported infections correlates with the number of tests, and therefore regions with limited diagnostics resources may not have a realistic estimate of the virus spread. This insufficiency of diagnostic test data is also reflected in an increasing positivity rate for India nearly 2.5 months after the lockdown, inconsistent with the trends observed for other geographical regions. Nonetheless, future projections are made using different epidemiological models based on the available data, and a comparative study is presented. In the absence of a reliable estimate of the true number of infections, these projections will have a limited accuracy: with that limitation, the most optimistic prediction suggests a continuing virus transmission through September 2020.


title: A Computational Approach to Design Potential siRNA Molecules as a Prospective Tool for Silencing Nucleocapsid Phosphoprotein and Surface Glycoprotein Gene of SARS-CoV-2

text: An outbreak, caused by a RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a magnitude which is daunting to all public health institutions in the absence of specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections by suppressing viral gene expression through hybridization and neutralization of target complementary mRNA. So, in this study, the power of RNA interference technology was harnessed to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of folding, free energy of binding, melting temperature and efficacy prediction process 8 siRNA molecules were selected which are proposed to exerts the best action. These predicted siRNAs should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in the response against SARS-CoV-2


title: SARS-CoV-2 neutralizing serum antibodies in cats: a serological investigation

text: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. Previous studies suggested cat could be a potential susceptible animal of SARS-CoV-2. Here, we investigated the infection of SARS-CoV-2 in cats by detecting specific serum antibodies. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. 15 of 102 (14.7%) cat sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among the positive samples, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between the SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). Our data demonstrates that SARS-CoV-2 has infected cat population in Wuhan during the outbreak.


title: Epidemiology and quarantine measures during COVID-19 outbreak on the cruise ship Diamond Princess docked at Yokohama, Japan in 2020: a descriptive analysis

text: The outbreak of coronavirus disease 2019 (COVID-19) on the cruise ship Diamond Princess docked at Yokohama, Japan was highlighted due to its number of cases in the early stage of the global epidemic when the picture of the virus itself, as well as epidemiological characteristics, were being established We conducted an observational epidemiological study of the outbreak, focusing on a total of 403 individuals who developed a fever of ≥ 37 5°C from 20 January to 22 February 2020 Quarantine measures are also discussed with a descriptive method Of a total of 3,711 individuals (2,031 males) from 57 countries, 2,666 (71 8%) and 1,045 (28 2%) were passengers and crew with mean age of 66 0 (range: 2-98) and 36 6 (range: 19-64), respectively Among 403 febrile individuals, 165 passengers and 58 crew members were diagnosed as laboratory-confirmed COVID-19 cases Until 6 February, the number of confirmed cases was three or less per day However, distribution of thermometers on 7 February revealed 43 confirmed cases, and it then started decreasing The outbreak was initiated from decks for passengers and expanded to areas for crew As of 17 March, when more than14 days had passed after disembarkation of all passengers and crew, there was no report of forming a cluster of infections in Japan from them At the time of the initiation of quarantine, the outbreak had already expanded to most of the decks from those for passengers, and the results might suggest the contribution of the set of quarantine measures in unprecedented challenges of the control operation


title: Age could be driving variable SARS-CoV-2 epidemic trajectories worldwide

text: Background Current geographic spread of documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections shows heterogeneity. This study explores the role of age in potentially driving differentials in infection spread, epidemic potential, and rates of disease severity and mortality across countries. Methods An age-stratified deterministic mathematical model that describes SARS-CoV-2 transmission dynamics was applied to 159 countries and territories with a population ≥1 million. Results Assuming worst-case scenario for the pandemic, the results indicate that there could be stark regional differences in epidemic trajectories driven by differences in the distribution of the population by age. In the African Region (median age: 18.9 years), the median R0 was 1.05 versus 2.05 in the European Region (median age: 41.7 years), and the median (per 100 persons) for the infections rate was 22.5 (versus 69.0), for severe and/or critical disease cases rate was 3.3 (versus 13.0), and for death rate was 0.5 (versus 3.9). Conclusions Age could be a driver of variable SARS-CoV-2 epidemic trajectories worldwide. Countries with sizable adult and/or elderly populations and smaller children populations may experience large and rapid epidemics in absence of interventions. Meanwhile, countries with predominantly younger age cohorts may experience smaller and slower epidemics. These predictions, however, should not lead to complacency, as the pandemic could still have a heavy toll nearly everywhere.


title: Stress Cardiomyopathy in COVID-19 Disease

text: Patients affected by COVID-19 pneumonia may develop stress cardiomyopathy, also known as Takotsubo syndrome (TTS), at different stages during the disease and with different degrees of left ventricular dysfunction. We describe three cases of TTS in COVID-19-positive patients with different clinical presentations and outcomes. One of them died, while in the other two coronary angiography confirmed the diagnosis but was postponed until after pneumonia resolution because of the risk of virus spread. LEARNING POINTS: An association between COVID-19 and cardiac involvement is highlighted. The incidence of Takotsubo syndrome has increased during this pandemic, possibly because it is caused by acute stress.


title: Deep phylogenetic analysis of Orthocoronavirinae genomes traces the origin, evolution and transmission route of 2019 novel coronavirus

text: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Today, it appears as a threat to human civilization. Scientists and medical practitioners across the world are involved to trace out the origin and evolution of SARS-CoV-2 (also called 2019 novel coronavirus and referred as 2019-nCoV), its transmission route, cause of pathogenicity, and possible remedial action. In this work, we aim to find out the origin, evolutionary patternthat led to its pathogenicity and possible transmission pathway of 2019-nCoV. To achieve the aims we conducted a large-scale deep phylogenetic analysis on the 162 complete Orthocoronavirinae genomes consisting of four genera namely Alphacoronavirus, Betacoronavirus, Deltacoronavirus and Gammacoronavirus, their gene trees analysis and subsequently genome and gene recombination analyses. Our analyses revealed that i) bat, pangolin and anteater are the natural hosts of 2019-nCoV, ii) outbreak of 2019-nCoV took place via inter-intra species transmission mode, iii) host-specific adaptive mutation made 2019-nCoV more virulent, and the presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity. Highlights Orthocoronavirinae genome phylogeny revealed that bat, pangolin and anteater are natural reservoir hosts of novel coronavirus (2019-nCoV/SARS-CoV-2). Host-specific adaptive mutation occurred among the coronaviruses. Transmission of 2019-nCoV to human took place by inter-intra species mode of transmission. Presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity.


title: SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

text: Understanding the determinants of adaptive immune response to SARS-CoV-2 is critical for fighting the ongoing COVID-19 pandemic. Here we assayed both antibody and T-cell reactivity to SARS-CoV-2 antigens in COVID-19 convalescent patients and healthy donors sampled before and during the pandemic. Our results show that while anti-SARS-CoV-2 antibodies can distinguish convalescent patients from healthy donors, the magnitude of T-cell response was more pronounced in healthy donors sampled during COVID-19 pandemic than in donors sampled before the outbreak. This hints at the possibility that some individuals have encountered the virus but were protected by T-cell cross-reactivity observed. A public and diverse T-cell response was observed for two A*02-restricted SARS-CoV-2 epitopes, revealing a set of T-cell receptor motifs displaying germline-encoded features. Bulk CD4+ and CD8+ T-cell response to SARS-CoV-2 glycoprotein S is characterized by multiple groups of homologous T-cell receptor sequences some of which are shared across multiple donors, indicating the existence of immunodominant epitopes. Overall, our findings indicate that T cells form an efficient response to SARS-CoV-2 and alongside the antibodies can serve as a useful biomarker for surveying SARS-CoV-2 exposure and immunity. We hope that data, including the set of specific T-cell receptors identified in this study can serve as a basis for future developments of SARS-CoV-2 vaccinations and monitoring.


title: The study of the effects of mobility trends on the statistical models of the covid-19 virus spreading

text: The history of the Pandemics makes a significant impact on the memory and behavior of the affected communities. It is important to study the connection between human mobility and the spread of viral infection. Specifically, we aimed to investigate whether there was a correlation between Mobility Trends and the spread of Covid-19 virus. Thus, in the conclusion it should be noted that the intensity of pedestrians, traffic and transit traffic during the study period, on average, after 15-20 days, affected the spread of the virus. If there was a positive slope and correlation coefficient between the variables presented in the period 22.01.2020-11.03.2020 (before the announcement of the pandemic), in the period 12.03.2020-14.04.2020 (after the announcement of the pandemic) the slope and correlation coefficients received negative values between the study variables, which indicates That on average, after 15-20 days, Due to the intensity of the movement, the center of the virus spread is identified, and the intensity of the movement itself is decreased.


title: The closer to the Europe Union headquarters, the higher risk of COVID-19? Cautions regarding ecological studies of COVID-19

text: Several ecological studies of the coronavirus disease 2019 (COVID-19) have reported correlations between group-level aggregated exposures and COVID-19 outcomes. While some studies might be helpful in generating new hypotheses related to COVID-19, results of such type of studies should be interpreted with cautions. To illustrate how ecological studies and results could be biased, we conducted an ecological study of COVID-19 outcomes and the distance to Brussels using European country-level data. We found that, the distance was negatively correlated with COVID-19 outcomes; every 100 km away from Brussels was associated with approximately 6% to 17% reductions (all P<0.01) in COVID-19 cases and deaths in Europe. Without cautions, such results could be interpreted as the closer to the Europe Union headquarters, the higher risk of COVID-19 in Europe. However, these results are more likely to reflect the differences in the timing of and the responding to the outbreak, etc. between European countries, rather than the 'effect' of the distance to Brussels itself. Associations observed at the group level have limitations to reflect individual-level associations - the so-called ecological fallacy. Given the public concern over COVID-19, ecological studies should be conducted and interpreted with great cautions, in case the results would be mistakenly understood.


title: A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19

text: BACKGROUND: Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. The clinical symptoms of severe and non-severe patients vary, and the case-fatality rate (CFR) in severe COVID-19 patients is very high. However, the information on the risk factors associated with the severity of COVID-19 and of their prognostic potential is limited. METHODS: In this retrospective study, the clinical characteristics, laboratory findings, treatment and outcome data were collected and analyzed from 223 COVID-19 patients stratified into 125 non-severe patients and 98 severe patients. In addition, a pooled large-scale meta-analysis of 1646 cases was performed. RESULTS: We found that the age, gender and comorbidities are the common risk factors associated with the severity of COVID-19. For the diagnosis markers, we found that the levels of D-dimer, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in severe group compared with the non-severe group on admission (D-Dimer: 87.3% vs. 35.3%, P<0.001; CRP, 65.1% vs. 13.5%, P<0.001; LDH: 83.9% vs. 22.2%, P<0.001; PCT: 35.1% vs. 2.2%, P<0.001), while the levels of aspartate aminotransferase (ASP) and creatinine kinase (CK) were only mildly increased. We also made a large scale meta-analysis of 1646 cases combined with 4 related literatures, and further confirmed the relationship between the COVID-19 severity and these risk factors. Moreover, we tracked dynamic changes during the process of COVID-19, and found CRP, D-dimer, LDH, PCT kept in high levels in severe patient. Among all these markers, D-dimer increased remarkably in severe patients and mostly related with the case-fatality rate (CFR). We found adjuvant antithrombotic treatment in some severe patients achieved good therapeutic effect in the cohort. CONCLUSIONS: The diagnosis markers CRP, D-dimer, LDH and PCT are associated with severity of COVID-19. Among these markers, D-dimer is sensitive for both severity and CFR of COVID-19. Treatment with heparin or other anticoagulants may be beneficial for COVID-19 patients.


title: Modeling COVID-19 latent prevalence to assess a public health intervention at a state and regional scale

text: Background: Emergence of COVID-19 caught the world off-guard and unprepared, initiating a global pandemic. In the absence of evidence, individual communities had to take timely action to reduce the rate of disease spread and avoid overburdening their healthcare systems. Although a few predictive models have been published to guide these decisions, most have not taken into account spatial differences and have included assumptions that do not match the local realities. Access to reliable information that is adapted to local context is critical for policymakers to make informed decisions during a rapidly evolving pandemic. Objective: The goal of this study was to develop an adapted susceptible-infected-removed (SIR) model to predict the trajectory of the COVID-19 pandemic in North Carolina and the Charlotte metropolitan region and to incorporate the effect of a public health intervention to reduce disease spread, while accounting for unique regional features and imperfect detection. Methods: Three SIR models were fit to prevalence data from the state and the greater Charlotte region and then rigorously compared. One of these models (SIR-Int) accounted for a stay-at-home intervention and imperfect detection of COVID-19 cases. Results: Presently, the COVID-19 outbreak is rapidly decelerating in NC and the Charlotte region. Infection curves are flattening at both the state and regional level. Relatively speaking, the greater Charlotte region has responded more favorably to the stay-at-home intervention than NC as a whole. While an initial basic SIR model served the purpose of informing decision making in the early days of the pandemic, its forecast increasingly did not fit the data over time. However, as the pandemic and local conditions evolved, the SIR-Int model provided a good fit to the data. Conclusions: Using local data and continuous attention to model adaptation, our findings have enabled policymakers, public health officials and health systems to do capacity planning and evaluate the impact of a public health intervention. Our SIR-Int model for estimated latent prevalence was reasonably flexible, highly accurate, and demonstrated the efficacy of a stay-at-home order at both the state and regional level. Our results highlight the importance of incorporating local context into pandemic forecast modeling, as well as the need to remain vigilant and informed by the data as we enter into a critical period of the outbreak.


Long-Term Neurological Threats of COVID-19: A Call to Update the Thinking About the Outcomes of the Coronavirus Pandemic


title: MODELLING OF COVID-19 OUTBREAK INDICATORS IN CHINA BETWEEN JANUARY AND APRIL

text: Background: The aim of this study is to explain the changes of outbreak indicators for coronavirus in China with nonlinear models and time series analysis. There are lots of methods for modelling. But we want to determine the best mathematical model and the best time series method among other models. Methods: The data was obtained between January 22 and April 21, 2020 from China records. The number of total cases and the number of total deaths were used for the calculations. For modelling Weibull, Negative Exponential, Von Bertalanffy, Janoscheck, Lundqvist-Korf and Sloboda models were used and AR, MA, ARMA, Holt, Brown and Damped models were used for time series. The determination coefficient (R2), Pseudo R2 and mean square error were used for nonlinear modelling as criteria for determining the model that best describes the number of cases, the number of total deaths and BIC (Bayesian Information Criteria) was used for time series. Results: According to our results, the Sloboda model among the growth curves and ARIMA (0,2,1) model among the times series models were most suitable models for modelling of the number of total cases. In addition Lundqvist-Korf model among the growth curves and Holt linear trend exponential smoothing model among the times series models were most suitable model for modelling of the number of total deaths. Our time series models forecast that the number of total cases will 83311 on 5 May and the number of total deaths will be 5273. Conclusions: Because results of the modelling has providing information on measures to be taken and giving prior information for subsequent similar situations, it is of great importance modeling outbreak indicators for each country separately.


title: Modeling the Spring 2020 New York City COVID-19 Epidemic: New Criteria and Methods for Prediction

text: We report here on results obtained using the SIR model to study the spring 2020 COVID-19 epidemic in New York City. An approximate solution is derived for this non-linear system which is then used to derive an expression for the time to maximum infection. Additionally expressions are obtained for estimating the transmission and recovery parameters using data from the first ten days of the epidemic. Values for these parameters are then generated using data reported for the 2020 NYC COVID epidemic which are then used to estimate the time to maximum infection and the maximum number of infected. Complete details are given so that the method can be usef in the event of future epidemics. An additional result of this study us that we are able to suggest a unique mitigation strategy.


title: Public health interventions in India slowed the spread of COVID-19 epidemic dynamics

text: Background The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects on epidemic dynamics are yet to be understood. Methods Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt) were estimated for 4 periods (Pre-lockdown and Lockdown Phases 1 to 3) according to nationally implemented phased interventions. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Findings Daily case rates ranged from 0.03 to 30.05/10 million people across 4 discrete periods in India. From May 4-17, 2020, the National Capital Territory (NCT) of Delhi had the highest case rate (222/10 million people/day), whereas Kerala had the lowest (2.18/10 million/day). Average Rt was 1.99 (95% CI 1.93-2.06) for India; it ranged from 1.38 to 2.78, decreasing over time. Median mobility in India decreased in all contact domains, with the lowest being 21% in retail/recreation (95% CI 13-46%), except home which increased to 129% (95% CI 117-132%) compared to the 100% baseline value. Interpretation The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates and Rt will aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India. Funding Non-funded.


title: Bioinformatics prediction of molecular mechanism and intervention drugs of SARS-related immune injury and their significance for COVID-19 treatment/ SARS病毒感染相关免疫损伤分子机制和干预药物的生物信息学预测及其对COVID-19的意义

text: Objective: To investigate the omics mechanism of SARS-related immune injury and predict targeted therapeutic drugs through clinical bioinformatics analysis of the transcriptome data of SARS virus in order to provide reference for clinical treatment of COVID-19. Methods: The transcriptome data of SARA virus were collected from the Gene Expression Oibus (GEO) and used to screen differential genes. Enrichment analysis and protein interaction analysis were performed to investigate the mechanism of immune damage associated with SARS. A platform of epigenetics in precision medicine (EpiMed) was established to predict potential therapeutic drugs. Results: The mechanism of SARS-related immune injury was complex, involving affecting the function of immune cells through signaling pathways such as Toll-like receptors, increasing cytokines in plasma through Th17 signaling pathway and inducing autoimmune responses after autoantibodies were generated by molecules such as IL-6, NF-κB, and TNF. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage. Conclusions: SARS virus could cause abnormal expression of many immune-related molecules and signaling pathways. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage. This study might provide reference for clinical treatment of COVID-19.


title: Epidemic Models with Random Infectious Period

text: In this paper, we present an extension to the classical SIR epidemic transmission model that uses any general probability distribution for the length of the infectious period. The classical SIR model implicitly requires an exponential distribution for the length of this period of time. We will show how a general distribution can be easily taken into account using the Transient Little Law and present numerical methods to solve the model in an efficient way. Our numerical experiments show that in the presence of a more realistic distribution, with lower variability than the exponential distribution, the size of peak of infected individuals on the graph will be higher and occur earlier. Conversely, a higher-variability distribution will lead to a lower peak that takes longer to dissipate. We also discuss some extensions to the basic model, to include variants like SEIRD and SIS. These findings should have profound and important consequences in the design of public policy.


title: Effectiveness of control strategies for Coronavirus Disease 2019: a SEIR dynamic modeling study

text: Background: Since its first cases occurrence in Wuhan, China, the Coronavirus Disease 2019 (COVID-19) has been spreading rapidly to other provinces and neighboring countries. A series of intervention strategies have been implemented, but didn't stop its spread. Methods: Two mathematical models have been developed to simulate the current epidemic situation in the city of Wuhan and in other parts of China. Special considerations were given to the mobility of people for the estimation and forecast the number of asymptomatic infections, symptomatic infections, and the infections of super-spreading events (Isse). Findings: The basic reproductive number (R0) was calculated for the period between 18 January 2020 and 16 February 2020: R0 declined from 5.75 to 1.69 in Wuhan and from 6.22 to 1.67 in the entire country (not including the Wuhan area). At the same time, Wuhan is estimated to observe a peak in the number of confirmed cases around 6 February 2020. The number of infected individuals in the entire country (not including the Wuhan area) peaked around February 3. The results also show that the peak of new asymptomatic cases per day in Wuhan occurred on February 6, and the peak of new symptomatic infections have occurred on February 3. Concurrently, while the number of confirmed cases nationwide would continue to decline, the number of real-time COVID-19 inpatients in Wuhan has reached a peak of 13,030 on February 14 before it decreases. The model further shows that the COVID-19 cases will gradually wane by the end of April 2020, both in Wuhan and the other parts of China. The number of confirmed cases would reach the single digit on March 27 in Wuhan and March 19 in the entire country. The five cities with top risk index in China with the exclusion of Wuhan are: Huanggang, Xiaogan, Jingzhou, Chongqing, and Xiangyang city. Interpretations: Although the national peak time has been reached, a significant proportion of asymptomatic patients and the infections of super-spreading events (Isse) still exist in the population, indicating the potential difficulty for the prevention and control of the disease. As the Return-to-Work tide is approaching and upgrading, further measures (e.g., escalatory quarantine, mask wearing when going out, and sit apart when taking vehicles) will be particularly crucial to stop the COVID-19 in other cities outside of Wuhan.


title: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism

text: As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh.


COVID 19: What Other Respiratory Viruses Can Reveal About Neurologic Symptoms


title: How did governmental interventions affect the spread of COVID-19 in European countries?

text: Background To reduce transmission of Coronavirus Disease 2019, European governments have implemented successive measures to encourage social distancing. However, it remained unclear how effectively measures reduced the spread of the virus, due to data complications. We examined how the effective-contact rate (ECR) among European citizens evolved over the period with implemented measures using a new data-oriented approach that is based on an extended Susceptible-Exposed-Infectious-Removed (SEIR) model. Methods Using the available data on the confirmed numbers of infections and hospitalizations, we first estimated the daily number of infectious-, exposed- and susceptible individuals and subsequently estimated the ECR with an iterative Poisson regression model, disregarding information on governmental measures. We then studied change points in the daily ECRs to the moments of the governmental measures. Results The change points in the daily ECRs were found to align with the implementation of governmental interventions. At the end of the considered time-window, we found similar ECRs for Italy (0{middle dot}29), Spain (0{middle dot}24), and Germany (0{middle dot}27), while the ECR in the Netherlands (0{middle dot}34), Belgium (0{middle dot}35) and the UK (0{middle dot}37) were somewhat higher. The highest ECR was found for Sweden (0{middle dot}45). Interpretation There seemed to be an immediate effect of banning events and closing schools, typically among the first measures taken by the governments. The effect of additionally closing bars and restaurants seemed limited. For most countries a somewhat delayed effect of the full lockdown was observed, and the ECR after a full lockdown was not necessarily lower than an ECR after (only) a gathering ban.


title: COVID-19 AND PATIENTS UNDERGOING PHARMACOLOGICAL TREATMENTS FOR IMMUNE-MEDIATED INFLAMMATORY DISEASES: PROTOCOL FOR A RAPID LIVING SYSTEMATIC REVIEW

text: CONTEXT AND OBJECTIVE: We propose to systematically review the available evidence to evaluate if patients with immune mediated inflammatory diseases under pharmacological treatment with immunosuppressants, immunobiologics, Disease-Modifying Anti-Rheumatic Drugs (DMARD) or targeted synthetic DMARDs have better or worse outcomes when infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study is a protocol for our rapid living systematic review. METHODS: Protocol for a rapid living systematic review methodology following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidance. To conduct the rapid systematic review, we will employ abbreviated systematic review methods, including: not performing independent screens of abstracts and not searching grey literature. As this will be a living review, it will be continuously updated.


Family cluster of asymptomatic infections with COVID-19: a case series of 4 patients.


title: Any contribution of the season change to the spread of covid-19 caused by sars-cov-2?

text: Background: Most people raise a similar concern during this tough time of the COVID-19 pandemic caused by SARS-CoV-2 infection regarding when this outbreak will come to end. A recent thorough-general study on the success of China dealing with COVID-19 outbreak has concluded to recommend the need for a multi-sectoral approach to prevent future outbreaks of emerging infectious diseases including for the still-occurring COVID-19 outbreak with the initiative for the highest interest of the health of mankind Discussion: The prevalence of SARS-CoV as the predecessor of SARS-CoV-2 has been concluded to be more suitable in spring than autumn and winter, with nothing prevalence in summer. No coincidence that SARS-CoV-2 infection has outbreak around the world from January 2020 to the present, April 2020, as ever predicted to reoccur based on its predecessor, SARS-CoV, that have prevalence been high since January, February, March, April, until early May 2003. As opposed to other seasons, summer has low atmospheric pressure as its exemption that provenly causes virus inactivation. Conclusions: The denotative nature of SARS-CoV-2 seems to reflect its predecessor, SARS-CoV, which begins nearing the end of the year and reaches its optimum hence in spring, thereafter, finally ends in summer. Low atmospheric pressure in the summer impresses that it is the potential cause of ending the outbreak by deactivating SARS-CoV-2, apart from the hot temperature of weather. The knowledge to be gained here is further closely correlated to the fact that coronavirus is able to have genetic recombination that may bring about new genotypes and, consequently, outbreaks later occurring.


title: Pharmacokinetic bases of the hydroxychloroquine response in COVID-19: implications for therapy and prevention

text: Chloroquine/hydroxychloroquine has recently been the subject of intense debate in regard to its potential antiviral activity against SARS-Cov-2, the etiological agent of COVID-19. Some report possible curative effects, others do not. In order to shed some light on this rather controversial topic, we used mathematical modelling to simulate possible scenarios of response to hydroxychloroquine in COVID-19 patients. Our computer-aided simulations show that hydroxychloroquine may have an impact on the amplitude of the viral load peak but that viral clearance is not significantly accelerated if the drug is not administered early enough (i.e. when viral loads range from 1 to 1,000 copies/mL). Although some authors had used the trough plasma concentrations or the theoretical drug distribution in the lung to model the effect of chloroquine/hydroxychloroquine on COVID-19, the theoretical drug response based on the trough whole blood concentrations of the drug agreed well with the results of the clinical trials so far reported. Moreover, the effects of chloroquine/hydroxychloroquine could be fully explained when taking into account also the capacity of this drug to raise cell-mediated responses against the productively SARS-Cov-2-infected cells. On the whole, the present study suggests that chloroquine/hydroxychloroquine has a narrow therapeutic window, which overlaps with the highest tolerated doses. These considerations may have implications for development of anti-COVID-19 combination therapies and prevention strategies.


title: Research on Artificial Intelligence and Primary Care: A Scoping Review

text: Objective: The purpose of this study was to assess the nature and extent of the body of research on artificial intelligence (AI) and primary care. Methods: We performed a scoping review, searching 11 published and grey literature databases with subject headings and key words pertaining to the concepts of 1) AI and 2) primary care: MEDLINE, EMBASE, Cinahl, Cochrane Library, Web of Science, Scopus, IEEE Xplore, ACM Digital Library, MathSciNet, AAAI, arXiv. Screening included title and abstract and then full text stages. Final inclusion criteria: 1) research study of any design, 2) developed or used AI, 3) used primary care data and/or study conducted in a primary care setting and/or explicit mention of study applicability to primary care; exclusion criteria: 1) narrative, editorial, or textbook chapter, 2) not applicable to primary care population or settings, 3) full text inaccessible in the English Language. We extracted and summarized seven key characteristics of included studies: overall study purpose(s), author appointments, primary care functions, author intended target end user(s), target health condition(s), location of data source(s) (if any), subfield(s) of AI. Results: Of 5,515 non-duplicate documents, 405 met our eligibility criteria. The body of literature is primarily focused on creating novel AI methods or modifying existing AI methods to support physician diagnostic or treatment recommendations, for chronic conditions, using data from higher income countries. Meaningfully more studies had at least one author with a technology, engineering, or math appointment than with a primary care appointment (57 (14%) compared to 217 (54%)). Predominant AI subfields were supervised machine learning and expert systems. Discussion: Overall, AI research associated with primary care is at an early stage of maturity with respect to widespread implementation in practice settings. For the field to progress, more interdisciplinary research teams with end-user engagement and evaluation studies are needed.


title: COVID-19 risk governance_ drivers, responses and lessons to be learned

text: The COVID-19 outbreak was neither unpredictable nor unforeseen, yet it blind-sided policymakers when it emerged, leading to unprecedented global restrictions on human activity and almost certainly triggering the first global economic contraction since WWII. This paper considers the key factors in the eruption of the crisis, as well as the lessons that should be learned from it. The paper begins with an outline of COVID-19’s spread, highlighting six key drivers that have determined its severity: the exponential pace of transmission, global interconnectedness, health-sector capacity, wider state capacity, the economic impact of suppression measures, and fragilities caused by the 2008 financial crisis. The paper then proceeds by considering the steps that have been taken in response to five key challenges, corresponding to elements of the IRGC risk governance framework: technical assessment, risk perception, evaluation, management and communication. While acknowledging that only tentative conclusions can be drawn at this early stage, the paper ends with a series of ten recommendations designed to increase preparedness for future crises.