title: Variation in Aerosol Production Across Oxygen Delivery Devices in Spontaneously Breathing Human Subjects

text: We sought to assess whether HHFNC results in greater production of aerosolized particles than 6 liters per minute nasal cannula, using state-of-the-art techniques of aerosol measurement, in spontaneously breathing human volunteers in a simulated hospital room. For each volunteer, we first measured background aerosol levels in the room immediately prior to testing. We then measured aerosol levels while the healthy volunteer laid in bed - - with the head of bed at 30 degrees - - wearing the following oxygen delivery devices: (a) 6L/min nasal canula (NC) with humidification; (b) non-re-breather mask (NRB) with 15L/min gas flow, non-humidified; (c) HHFNC with 30L/min gas flow; (d) HHFNC with 60L/min gas flow. Two scanning mobility particle sizing (SMPS) systems (TSI 3080/3030, TSI 3080/3750) were used to measure aerosols 10 to 500 nanometer (nm) in size for each of the oxygen delivery devices. There was no variation in aerosol level within patients between room air, 6 L/min NC, 15 L/min NRB, 30 L/min HHFNC, and 60 L/min HHFNC, regardless of coughing.


title: Development of Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assays Targeting SARS-CoV-2

text: Epidemics of Coronavirus Disease 2019 (COVID-19) now have more than 100,000 confirmed cases worldwide. Diagnosis of COVID-19 is currently performed by RT-qPCR methods, but the capacity of RT-qPCR methods is limited by its requirement of high-level facilities and instruments. Here, we developed and evaluated RT-LAMP assays to detect genomic RNA of SARS-CoV-2, the causative virus of COVID-19. RT-LAMP assays in this study can detect as low as 100 copies of SARS-CoV-2 RNA. Cross-reactivity of RT-LAMP assays to other human Coronaviruses was not observed. We also adapted a colorimetric detection method for our RT-LAMP assay so that the tests potentially performed in higher throughput.


title: Inferring the effective start dates of non-pharmaceutical interventions during COVID-19 outbreaks

text: During February and March 2020, several countries implemented non-pharmaceutical interventions, such as school closures and lockdowns, with variable schedules, to control the COVID-19 pandemic caused by the SARS-CoV-2 virus. Overall, these interventions seem to have successfully reduced the spread of the pandemic. We hypothesise that the official and effective start date of such interventions can significantly differ, for example due to slow adoption by the population, or due to unpreparedness of the authorities and the public. We fit an SEIR model to case data from 12 countries to infer the effective start dates of interventions and contrast them with the official dates. We find both late and early effects of interventions. For example, Italy implemented a nationwide lockdown on Mar 11, but we infer the effective date on Mar 16 ({+/-}0.47 days 95% CI). In contrast, Spain announced a lockdown on Mar 14, but we infer an effective start date on Mar 8 ({+/-}1.08 days 95% CI). We discuss potential causes and consequences of our results.


title: Guideline-based Chinese herbal medicine treatment plus standard care for severe coronavirus disease 2019 (G-CHAMPS): evidence from China

text: Abstract Objectives: To assess outcomes in patients who have severe coronavirus disease 2019 (COVID-19) and were treated with either China guideline based Chinese herbal medicines (CHMs) plus standard care or standard care alone. Design: A pilot randomized controlled trial. Setting Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, China Patients: A total of 42 adults with severe COVID-19. Interventions: Participants in the CHM plus standard care group received CHM and standard care, and the control group received standard care alone. Measurements and Main Results: The primary outcome was the change in the disease severity category of COVID-19 after treatment at 7 days. Among 42 participants who were randomized (mean [SD] age 60.43 years [12.69 years]; 21 [50%] were aged [≥] 65 years; and 35 [83%] women, 42 (100%) had data available for the primary outcome. For the primary outcome, one patient from each group died during treatment; the odds of a shift towards death was lower in the CHM plus group than the standard care alone group (common OR 0.59, 95% CI 0.148 to 2.352 P=.454). Three (2 from the CHM plus group and 1 from the standard care alone group) patients progressed from severe to critical illness. After treatment, mild, moderate, and severe COVID-19 disease accounted for 18% (5) vs 14% (2), 71% (20) vs 64% (9), and 0% (0) vs 7% (1) of the patients treated with CHM plus standard care vs. standard care alone. Conclusions: For the first time, the G-CHAMPS trial provided valuable information for the national guideline-based CHM treatment for hospitalized patients with severe COVID-19. CHM effects in COVID-19 may be clinically important and warrant further consideration and studies.


title: Crowdsourcing, Social Media, and Intercultural Communication About Zika: Use Contextualized Research to Bridge the Digital Divide in Global Health Intervention

text: This article presents a case study of the Smarter Crowdsourcing project the International Development Bank and Governance Lab cohosted to cope with the emerging Zika outbreaks in Latin America countries. Using the lenses of intercultural communication methodologies, user-centered design, and global cultural flow, I examine the exclusion of at-risk populations as marginalized end users of the project. I also examine the impacts of this oversight on the effectiveness of the technocratic solutions. I then conclude by discussing the implications this case has for international health intervention, global technical communication, and community-based research.


title: Safety, pharmacokinetics, and liver-stage Plasmodium cynomolgi effect of high-dose ivermectin and chloroquine in Rhesus Macaques

text: Previously, ivermectin (1–10 mg/kg) was shown to inhibit liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (IC50 = 10.42 μM) and hypnozoites (IC50 = 29.24 μM) in primary macaque hepatocytes when administered in high-dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for seven consecutive days was evaluated for prophylaxis or radical cure of Plasmodium cynomolgi liver-stages in Rhesus macaques. No inhibition or delay to blood-stage P. cynomolgi parasitemia was observed at any ivermectin dose (0.3, 0.6, and 1.2 mg/kg). Ivermectin (0.6 and 1.2 mg/kg) and chloroquine (10 mg/kg) in combination were well-tolerated with no adverse events and no significant pharmacokinetic drug-drug interactions observed. Repeated daily ivermectin administration for seven days did not inhibit ivermectin bioavailability. It was recently demonstrated that both ivermectin and chloroquine inhibit replication of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in vitro. Further ivermectin and chloroquine trials in humans are warranted to evaluate their role in Plasmodium vivax control and as adjunctive therapies against COVID-19 infections.


title: A control approach to the Covid-19 disease using a SEIHRD dynamical model

text: The recent worldwide epidemic of Covid-19 disease, for which there is no vaccine or medications to prevent or cure it, led to the adoption of public health measures by governments and populations in most of the affected countries to avoid the contagion and its spread. These measures are known as nonpharmaceutical interventions (NPIs) and their implementation clearly produces social unrest as well as greatly affects the economy. Frequently, NPIs are implemented with an intensity quantified in an ad hoc manner. Control theory offers a worthwhile tool for determining the optimal intensity of the NPIs in order to avoid the collapse of the healthcare system while keeping them as low as possible, yielding in a policymakers concrete guidance. We propose here the use of a simple proportional controller that is robust to large parametric uncertainties in the model used.


title: Non-selective inhibition of the motor system following unexpected and expected infrequent events

text: Motor inhibition is a key control mechanism that allows humans to rapidly adapt their actions in response to environmental events. One of the hallmark signatures of rapidly exerted, reactive motor inhibition is the non-selective suppression of cortico-spinal excitability (CSE): unexpected sensory stimuli lead to a suppression of CSE across the entire motor system, even in muscles that are inactive. Theories suggest that this reflects a fast, automatic, and broad engagement of inhibitory control, which facilitates behavioral adaptations to unexpected changes in the sensory environment. However, it is an open question whether such non-selective CSE suppression is truly due to the unexpected nature of the sensory event, or whether it is sufficient for an event to be merely infrequent (but not unexpected). Here, we report data from two experiments in which human subjects experienced both unexpected and expected infrequent events during a simple reaction time task while CSE was measured from a task-unrelated muscle. We found that expected infrequent events can indeed produce non-selective CSE suppression – but only when they occur during movement initiation. In contrast, unexpected infrequent events produce non-selective CSE suppression even in the absence of movement initiation. Moreover, CSE suppression due to unexpected events occurs at shorter latencies compared to expected infrequent events. These findings demonstrate that unexpectedness and stimulus infrequency have qualitatively different suppressive effects on the motor system. They also have key implications for studies that seek to disentangle neural and psychological processes related to motor inhibition and stimulus detection.


title: Sequential data assimilation of the stochastic SEIR epidemic model for regional COVID-19 dynamics

text: Newly emerging pandemics like COVID-19 call for better predictive models to implement early and precisely tuned responses to their deep impact on society. Standard epidemic models provide a theoretically well-founded description of dynamics of disease incidence. For COVID-19 with infectiousness peaking before and at symptom onset, the SEIR model explains the hidden build-up of exposed individuals which challenges containment strategies, in particular, due to delayed epidemic responses to non-pharmaceutical interventions. However, spatial heterogeneity questions the adequacy of modeling epidemic outbreaks on the level of a whole country. Here we show that sequential data assimilation of a stochastic version of the standard SEIR epidemic model captures dynamical behavior of outbreaks on the regional level. Such regional modeling of epidemics with relatively low numbers of infected and realistic demographic noise accounts for both spatial heterogeneity and stochasticity. Based on adapted regional models, population level short-term predictions can be achieved. More realistic epidemic models that include spatial heterogeneity are within reach via sequential data assimilation methods.


title: Prevalence of Mental Health Problems During Virus Epidemics in the General Public, Health Care Workers and Survivors: A Rapid Review of the Evidence

text: Background: The swift spread of SARS-CoV-2 provides a challenge worldwide. As a consequence of restrictive public health measures like isolation, quarantine, and community containment, the provision of mental health services is a major challenge. Evidence from past virus epidemics and the current SARS-CoV-2 outbreak indicate high prevalence rates of mental health problems (MHP) as short- and long-term consequences. However, a broader picture of MHP among different populations is still lacking. Methods: We conducted a rapid review on MHP prevalence rates published since 2000, during and after epidemics, including the general public, health care workers, and survivors. Any quantitative articles reporting on MHP rates were included. Out of 2855 articles screened, a total of 74 were included in this review. Results: Most original studies on MHP were conducted in China in the context of SARS-CoV-1, and reported on anxiety, depression, post-traumatic stress symptoms/disorder, general psychiatric morbidity, and psychological symptoms. The MHP rates across studies, populations, and epidemics vary substantially. While some studies show high and persistent rates of MHP in populations directly affected by isolation, quarantine, threat of infection, infection, or life-threatening symptoms (e.g. health care workers), other studies report minor effects. Furthermore, even less affected populations (e.g. distant to epidemic epicenter, no contact history with suspected or confirmed cases) can show high rates of MHP. Discussion: MHP vary largely across countries and risk-groups in reviewed studies. The results call attention to potentially high MHP during epidemics. Individuals affected directly by an epidemic might be at a higher risk of short or even long-term mental health impairments. This study delivers insights stemming from a wide range of psychiatric instruments and questionnaires. The results call for the use of validated and standardized instruments, reference norms, and pre-post measurements to better understand the magnitude of the MHP during and after the epidemics. Nevertheless, emerging MHP should be considered during epidemics including the provision of access to mental health care to mitigate potential mental impairments.


title: Indemnifying Precaution: Economic Insights for Regulation of a Highly-Infectious Disease

text: Economic insights are powerful for understanding the challenge of managing a highly infectious disease, such as COVID-19, through behavioral precautions including social distancing One problem is a form of moral hazard, which arises when some individuals face less personal risk of harm or bear greater personal costs of taking precautions Without legal intervention, some individuals will see socially-risky behaviors as personally less costly than socially-beneficial behaviors, a balance which makes those beneficial behaviors unsustainable For insights, we review health insurance moral hazard, agricultural infectious disease policy, and deterrence theory, but find that classic enforcement strategies of punishing non-compliant people are stymied One mechanism is for policymakers to indemnify individuals for losses associated with taking those social-desirable behaviors to reduce the spread We develop a coherent approach for doing so, based on conditional cash payments and precommitments by citizens, which may also be reinforced by social norms


title: Influenza-Negative Influenza-Like Illness (fnILI) Z-Score as a Proxy for Incidence and Mortality of COVID-19

text: Though ideal for determining the burden of disease, SARS-CoV2 test shortages preclude its implementation as a robust surveillance system in the US. We correlated the use of the derivative influenza-negative influenza-like illness (fnILI) z-score from the CDC as a proxy for incident cases and disease-specific deaths. For every unit increase of fnILI z-score, the number of cases increased by 70.2 (95%CI[5.1,135.3]) and number of deaths increased by 2.1 (95%CI[1.0,3.2]). FnILI data may serve as an accurate outcome measurement to track the spread of the and allow for informed and timely decision-making on public health interventions.


title: The Contribution of Age Structure to the Number of Deaths from Covid-19 in the UK by Geographical Units

text: This study investigates the contribution of population age structure to mortality from Covid-19 in the UK by geographical units. We project death rates at various spatial scales by applying data on age-specific fatality rates to the area's population by age and sex. Our analysis shows a significant variation in the projected death rates between the constituent countries of the UK, between its regions and within regions. First, Scotland and Wales have higher projected fatality levels from Covid-19 than England, whereas Northern Ireland has lower rate. Second, the infection fatality rates are projected to be substantially higher in small towns and rural areas than those in large urban areas. Third, our analysis shows that within urban regions there are also 'pockets' of high projected death rates. Overall, the areas with high and low fatality rates tend to cluster because of the high residential separation of different population age-groups in the UK. Our analysis also reveals that the Welsh-, Gaelic- and Cornish-speaking communities with relatively old populations are likely to experience heavy population losses if the virus spreads widely across the UK.


title: Work-related and Personal Factors Associated with Mental Well-being during COVID-19 Response: A Survey of Health Care and Other Workers

text: Objective: Measure the prevalence of stress, anxiety, depression, work-exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic, and describe work-related and personal factors associated with mental health and well-being. Design: Observational cohort study conducted between April 17 and May 1, 2020 using a web-based questionnaire. Setting: Medical and main campuses of a university. Participants: All faculty, staff, and post-doctoral fellows. Exposures: Work factors including supervisor support and exposure to high-risk clinical settings; personal factors including demographics and family/home stressors. Main Outcomes and Measures: Stress, anxiety, depression, work exhaustion, burnout, and decreased well-being. Results: There were 5550 respondents (overall response rate of 34.3%). 38% of faculty and 14% of staff (n=915) were providing clinical care, while 57% of faculty and 77% of staff were working from home. The prevalence of anxiety, depression, and work exhaustion were somewhat higher among clinicians than non-clinicians. Among all workers, anxiety, depression, and high work exhaustion were independently associated with community or clinical exposure to COVID-19 [Prevalence Ratios and 95% confidence intervals 1.37(1.09- 1.73), 1.28(1.03 - 1.59), and 1.24(1.13 - 1.36) respectively]. Poor family supportive behaviors by supervisors were also associated with these outcomes [1.40 (1.21 - 1.62), 1.69 (1.48 - 1.92), 1.54 (1.44 - 1.64)]. Age below 40 and a greater number of family/home stressors were also associated with poorer outcomes. Among the subset of clinicians, caring for patients with COVID-19 and work in high-risk clinical settings were additional risk factors. Conclusions and Implications: Our findings suggest that the pandemic has had negative effects on mental health and well-being among both clinical and non-clinical employees. Prevention of exposure to COVID-19 and increased supervisor support are modifiable risk factors that may protect mental health and well-being.


title: Temperature significant change COVID-19 Transmission in 429 cities

text: Background There is no evidence supporting that temperature changes COVID-19 transmission. Methods We collected the cumulative number of confirmed cases of all cities and regions affected by COVID-19 in the world from January 20 to February 4, 2020, and calculated the daily means of the average, minimum and maximum temperatures in January. Then, restricted cubic spline function and generalized linear mixture model were used to analyze the relationships. Results There were in total 24,232 confirmed cases in China and 26 overseas countries. In total, 16,480 cases (68.01%) were from Hubei Province. The lgN rose as the average temperature went up to a peak of 8.72℃ and then slowly declined. The apexes of the minimum temperature and the maximum temperature were 6.70℃ and 12.42℃ respectively. The curves shared similar shapes. Under the circumstance of lower temperature, every 1℃ increase in average, minimum and maximum temperatures led to an increase of the cumulative number of cases by 0.83, 0.82 and 0.83 respectively. In the single-factor model of the higher-temperature group, every 1℃ increase in the minimum temperature led to a decrease of the cumulative number of cases by 0.86. Conclusion The study found that, to certain extent, temperature could significant change COVID-19 transmission, and there might be a best temperature for the viral transmission, which may partly explain why it first broke out in Wuhan. It is suggested that countries and regions with a lower temperature in the world adopt the strictest control measures to prevent future reversal.


title: Laboratory findings in coronavirus disease 2019 (COVID-19) patients: a comprehensive systematic review and meta-analysis

text: Background: In early December 2019, the first patient with COVID-19 pneumonia was found in Wuhan, Hubei Province, China. Recent studies have suggested the role of primary laboratory tests in addition to clinical symptoms for suspected patients, which play a significant role in the diagnosis of COVID-19. Therefore, the present study was conducted to evaluate laboratory findings in COVID-19 patients. Material and methods: The present meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. This protocol is registered with the code CRD42019145410 in PROSPERO International Database. Results: Finally, 52 studies involving 5490 patients with COVID-19 entered the meta-analysis process. The prevalence of leukopenia, lymphopenia, elevated c-reactive protein (CRP), elevated erythrocyte sedimentation rate (ESR), elevated serum amyloid A, elevated ferritin was estimated to be 20.9% (95%CI: 17.9-24.3), 51.6% (95%CI: 44.0-59.1), 63.6% (95%CI: 57.0-69.8), 62.5% (95%CI: 50.1-73.5), 63.6% (95%CI: 57.0-69.8), 62.5% (95%CI: 50.1-73.5), 74.7% (95%CI: 50.0-89.7), and 72.6% (95%CI: 58.1-83.5), respectively. The prevalence of elevated interleukin-6 was 59.9% (95%CI: 48.2-70.5), CD3 was 68.3% (95%CI: 50.1-82.2), reduced CD4 was 62.0% (95%CI: 51.1-71.6), reduced CD8 was 42.7% (95%CI: 32.2-53.9). The prevalence of elevated troponin-I was 20.6% (95%CI: 9.0-40.5), elevated creatine kinase-MB (CKMB) was 14.7% (95%CI: 7.1-28.0), elevated brain natriuretic peptide (BNP) was 48.9% (95%CI: 30.4-67.7), elevated blood urea nitrogen was 13.1% (95%CI: 6.6-24.4),, elevated creatinine was 7.2% (95%CI: 4.4-11.8), elevated lactate dehydrogenase (LDH) was 53.1% (95%CI: 43.6-62.4), hyperglycemia was 41.1% (95% CI: 28.2-55.5), elevated total bilirubin was 48.9% (95%CI: 30.4-67.7), reduced albumin was 54.7% (95%CI: 38.1-70.2), reduced pre-albumin was 49.0% (95%CI: 26.6-71.8), and reduced PT was 53.1% (95% CI: 43.6-62.4), and D-dimer was 44.9% (95%CI: 31.0-59.6). Conclusion This study provides a comprehensive description of laboratory characteristics in patients with COVID-19. The results show that lymphopenia, elevated CRP, elevated ESR, elevated ferritin, elevated serum amyloid A, elevated BNP, reduced albumin, reduced pre-albumin, reduced CD3, reduced CD4, reduced CD8, elevated D-dimer, reduced PT, elevated interleukin-2, elevated interleukin-6, elevated LDH and hyperglycemia are the common findings at the time of admission.


docid: nkphjlky

title: Reasonable Doubt: Hydroxychloroquine Studies for COVID-19 Are Methodological Garbage


title: Impact of blood analysis and immune function on the prognosis of patients with COVID-19

text: Introduction: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with 2019-coronavirus infected disease (COVID-19). Methods: Records were reviewed of 85 patients with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital mortality at 28 days. Results: Fourteen patients died. The baseline leukocyte count, neutrophil count and hemoglobin was significantly higher in non-survivors compared with survivors, while the reverse was true of lymphocyte count, platelet, PaO2/FiO2, CD3+ count and CD4+ count. The percentage of neutrophil count > 6.3*109/L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count was independently associated with mortality. However, there were not significant difference in IgG, IgM, IgA, C3, C4 and the percentage of IgE > 100 IU/ml between the death group and survival group. Areas under the receiver operating characteristic curves of the following at baseline could significantly predict mortality: leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts. Conclusions: For patients with COVID-19, lymphocyte, CD3+ and CD4+ counts that marked decrease suggest a poor outcome. A high neutrophil count is independently associated with mortality. At admission, leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts should receive added attention.


title: Core competencies for combatting crisis: fusing ethics, cultural competence, and cognitive flexibility in counseling

text: The fictional lives of Dr. Smith, Ruby, George, and his clients have all been overturned by the Covid-19 crisis. With each having to continue to fulfill their professional responsibility to an institution, to students, to supervisees, and to clients, they have little time to make the appropriate transitions into the world of telehealth, in conjunction with practicing self-care to maintain their own anxieties over the global pandemic. This necessitates a consideration of three core competencies–ethical practice, multicultural competence, and cognitive flexibility. Their unique individual commitment to these three competencies is discussed on a practical and applicable level. Additionally, these rapid changes have led to an assessment and report of where current research is deficient.


COVID-19: Reflections on trust, tradeoffs, and preparedness


title: Impact of Lockdown on the Epidemic Dynamics of COVID-19 in France

text: The COVID-19 epidemic was reported in the Hubei province in China in December 2019 and then spread around the world reaching the pandemic stage at the beginning of March 2020. Since then, several countries went into lockdown. Using a mechanistic-statistical formalism, we estimate the effect of the lockdown in France on the contact rate and the effective reproduction number R(e) of the COVID-19. We obtain a reduction by a factor 7 (R(e) = 0.47, 95%-CI: 0.45–0.50), compared to the estimates carried out in France at the early stage of the epidemic. We also estimate the fraction of the population that would be infected by the beginning of May, at the official date at which the lockdown should be relaxed. We find a fraction of 3.7% (95%-CI: 3.0–4.8%) of the total French population, without taking into account the number of recovered individuals before April 1st, which is not known. This proportion is seemingly too low to reach herd immunity. Thus, even if the lockdown strongly mitigated the first epidemic wave, keeping a low value of R(e) is crucial to avoid an uncontrolled second wave (initiated with much more infectious cases than the first wave) and to hence avoid the saturation of hospital facilities.


title: SARS-CoV-2 genomes recovered by long amplicon tiling multiplex approach using nanopore sequencing and applicable to other sequencing platforms

text: Genomic surveillance has become a useful tool for better understanding virus pathogenicity, origin and spread. Obtaining accurately assembled, complete viral genomes directly from clinical samples is still a challenging. Here, we describe three protocols using a unique primer set designed to recover long reads of SARS-CoV-2 directly from total RNA extracted from clinical samples. This protocol is useful, accessible and adaptable to laboratories with varying resources and access to distinct sequencing methods: Nanopore, Illumina and/or Sanger.


title: Development of an interactive, agent-based local stochastic model of COVID-19 transmission and evaluation of mitigation strategies illustrated for the state of Massachusetts, USA

text: Since its discovery in the Hubei province of China, the global spread of the novel coronavirus SARS-CoV-2 has resulted in millions of COVID-19 cases and hundreds of thousands of deaths. The spread throughout Asia, Europe, and the Americas has presented one of the greatest infectious disease threats in recent history and has tested the capacity of global health infrastructures. Since no effective vaccine is available, isolation techniques to prevent infection such as home quarantine and social distancing while in public have remained the cornerstone of public health interventions. While government and health officials were charged with implementing stay-at-home strategies, many of which had little guidance as to the consequences of how quickly to begin them. Moreover, as the local epidemic curves have been flattened, the same officials must wrestle with when to ease or cease such restrictions as to not impose economic turmoil. To evaluate the effects of quarantine strategies during the initial epidemic, an agent based modeling framework was created to take into account local spread based on geographic and population data with a corresponding interactive desktop and web-based application. Using the state of Massachusetts in the United States of America, we have illustrated the consequences of implementing quarantines at different time points after the initial seeding of the state with COVID-19 cases. Furthermore, we suggest that this application can be adapted to other states, small countries, or regions within a country to provide decision makers with critical information necessary to best protect human health.


title: SARS-CoV-2 codon usage bias downregulates host expressed genes with similar codon usage

text: Severe acute respiratory syndrome is quickly spreading throughout the world and was declared as a pandemic by the World Health Organisation (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral proteins synthesis and its relationship with the proteins synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could conduct to an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes, and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis contributes to understand some deleterious collateral effect as result of the viral replication. In this manner, our finding contribute to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.


title: High resolution CT features of COVID-19 in children/ 新型冠状病毒肺炎儿童高分辨率CT表现

text: Objective: To investigate the high resolution CT (HRCT) features of COVID-19 in children. Methods: A retrospective analysis was performed on the chest HRCT findings of 22 children who were diagnosed as COVID-19 by clinical and nucleic acid testing in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 25 to February 5, 2020. There were 12 boys and 10 girls, aged from 2 months to 14 years old, with a median age of 4 years, and 14 patients were under 5 years old. The characteristics of lung lesions on HRCT such as distribution, shape, density and so on and whether there were hilar and mediastinal lymph node enlargement and pleural changes were evaluated by 2 radiologists. Results: In all of the 22 patients, the chest CT manifestations were normal in 3 patients (3/22), meanwhile the lung involvement of the lesion was found in 19 patients (19/22). Among them, 7 patients had unilateral lung involvement, and 12 patients had bilateral involvement. The HRCT manifestations were as follows. The HRCT showed the ground glass opacity (GGO) in 6 patients, including 4 cases with light opacity and 2 with typical crazy paving sign. Four patients had lung consolidation, with local fibrous stripes and patchy hyperdensity. Six patients had mixed GGO, including 1 case with right white lung. The bronchopneumonia-like changes were seen in 3 cases with scattered spot-like or mixed patchy. The lesions in the lower lobe were more serious than those in the upper lobe, and the lesions in the lateroposterior zone of the lung were more common than those in the apical and central area of the lung. No enlarged lymph nodes and pleural effusion were seen in all patients, but 1 case had thickened interlobar pleura. Conclusions: The HRCT manifestations of COVID-19 in children are varied, and the comprehensive assessment need to be made in combination with epidemiological data, clinical manifestations and laboratory tests. However, the chest HRCT plays an important role in early diagnosis, prevention and management of COVID-19.


title: Pushing beyond specifications: Evaluation of linearity and clinical performance of a fully automated SARS-CoV-2 RT-PCR assay for reliable quantification in blood and other materials outside recommendations

text: Background: The ongoing SARS-CoV-2 pandemic presents a unique challenge to diagnostic laboratories. There are preliminary studies correlating qRT-PCR results from different materials to clinical outcomes, yet, comparability is limited due to the plethora of different assays used for diagnostics. In this study we evaluate clinical performance and linear range for the SARS-CoV-2 IVD (cobas6800/8800 system, a fully automated sample-to-result platform) in different clinically relevant matrix materials outside official specifications. Methods: Assay performance was assessed in human plasma, BAL/BL and transport medium following chemical inactivation. For analytical evaluation, respective matrix materials were spiked with SARS-CoV-2 RNA in ten-fold dilution series. The efficacy of chemical inactivation by guanidine hydrochloride solution was confirmed in cell culture infectivity experiments. For correlation, a total of 235 predetermined clinical samples including respiratory swabs, plasma and BAL/BL were subjected to the SARS-CoV-2 IVD test and results were compared. Results: The SARS-CoV-2 IVD showed excellent linearity over five to seven log steps depending on matrix material. Chemical inactivation resulted in a reduction in plaque forming units of at least 3.5 log steps, while having no significant impact on assay performance. Inter-run consistency from three different testing sites demonstrated excellent comparability of RT-PCR results (maximum deviation was 1.53 CT). Clinical evaluation for respiratory swabs showed very good agreement with the comparator assay (Positive agreement 95.7%, negative agreement 98.9%). Conclusion: The SARS-CoV-2 IVD test for the cobas6800/8800 systems offers excellent linear range and inter-run consistency for quantification of SARS-CoV-2 RNA in different matrices outside official specifications.


title: CovidNLP: A Web Application for Distilling Systemic Implications of COVID-19 Pandemic with Natural Language Processing

text: The flood of conflicting COVID-19 research has revealed that COVID-19 continues to be an enigma. Although more than 14,000 research articles on COVID-19 have been published with the disease taking a pandemic proportion, clinicians and researchers are struggling to distill knowledge for furthering clinical management and research. In this study, we address this gap for a targeted user group, i.e. clinicians, researchers, and policymakers by applying natural language processing to develop a CovidNLP dashboard in order to speed up knowledge discovery. The WHO has created a repository of about more than 5000 peer-reviewed and curated research articles on varied aspects including epidemiology, clinical features, diagnosis, treatment, social factors, and economics. We summarised all the articles in the WHO Database through an extractive summarizer followed by an exploration of the feature space using word embeddings which were then used to visualize the summarized associations of COVID-19 as found in the text. Clinicians, researchers, and policymakers will not only discover the direct effects of COVID-19 but also the systematic implications such as the anticipated rise in TB and cancer mortality due to the non-availability of drugs during the export lockdown as highlighted by our models. These demonstrate the utility of mining massive literature with natural language processing for rapid distillation and knowledge updates. This can help the users understand, synthesize, and take pre-emptive action with the available peer-reviewed evidence on COVID-19. Our models will be continuously updated with new literature and we have made our resource CovidNLP publicly available in a user-friendly fashion at http://covidnlp.tavlab.iiitd.edu.in/.


title: Effect of Process Parameters on Weld Spatter in Robotic Welding

text: Abstract This research deals with the investigation of a real-life industrial problem of excessive weld spatter produced in an automated welding robot cell using gas metal arc welding process. Spatter generation was attributed to a number of sources including incorrect machine settings, surface contaminants, and erratic wire feeding. Random variation of different welding process parameters such as voltage, wire feed speed, and torch travel angle, affected spatter production, which served as a motivation to embark on a systematic study involving design of experiments. A total of ten most significant parameters were identified through a brainstorming process involving robotic cell operators, section managers, and subject matter experts. Using the selected ten parameters, preliminary experiments were conducted to determine the appropriate operating range for each process parameter that has the most significant impact on weld spatter. An Orthogonal L16 Array from Taguchi’s designs was chosen with four parameters at 4-levels, four parameters at 2-levels, and two parameters were held constant at 1-level. Following the establishment of a defined set of parameters and corresponding ranges of values, a series of designed experiments were conducted to measure the effect of process parameters on weld spatter production. During each designed experiment, six different responses were recorded that included, the weight of wire used, the weight of the weld bead deposited, the mass of spatter collected in a tray, audio signals generated, the spatter particle count using ImageJ, and the quality of the weld bead. The optimal process parameters identified in this study were of practical significance, and as such the recommended parameters were implemented in the industry.


title: Positive selection of ORF3a and ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic

text: In this study, we analyzed full-length SARS-CoV-2 genomes from multiple countries to determine early trends in the evolutionary dynamics of the novel COVID-19 pandemic. Results indicated SARS-CoV-2 evolved early into at least three phylogenetic groups, characterized by positive selection at specific residues of the accessory proteins OFR3a and ORF8a. We also report evidence of epistatic interactions among sites in the genome that may be important in the generation of variants adapted to humans. These observations might impact not only public health, but also suggest more studies are needed to understand the genetic mechanisms that may affect the development of therapeutic and preventive tools, like antivirals and vaccines.


Croatian society for schizophrenia and schizophrenia spectrum disorders croatian medical association guidelines for the treatment of patients with schizophrenia spectrum disorders during the COVID-19 pandemic


title: Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients

text: Summary Background The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. Methods In this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. Findings Among the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0.343, 95% CI 0.128-0.916, p=0.025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. Interpretation Elderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences


title: Investigating the Impact of Asymptomatic Carriers on COVID-19 Transmission

text: Coronavirus disease 2019 (COVID-19) is a novel human respiratory disease caused by the SARS-CoV-2 virus. Asymptomatic carriers of the virus display no clinical symptoms but are known to be contagious. Recent evidence reveals that this sub-population, as well as persons with mild, represent a major contributor in the propagation of COVID-19. The asymptomatic sub-population frequently escapes detection by public health surveillance systems. Because of this, the currently accepted estimates of the basic reproduction number (Ro) of the virus are inaccurate. It is unlikely that a pathogen can blanket the planet in three months with an Ro in the vicinity of 3, as reported in the literature. In this manuscript, we present a mathematical model taking into account asymptomatic carriers. Our results indicate that an initial value of the effective reproduction number could range from 5.5 to 25.4, with a point estimate of 15.4, assuming mean parameters. The first three weeks of the model exhibit exponential growth, which is in agreement with average case data collected from thirteen countries with universal health care and robust communicable disease surveillance systems; the average rate of growth in the number of reported cases is 23.3% per day during this period.


title: Multiple-Input Deep Convolutional Neural Network Model for COVID-19 Forecasting in China

text: COVID-19 is spreading all across the globe. Up until March 23, 2020, the confirmed cases in 173 countries and regions of the globe had surpassed 354,000, and more than 15,300 deaths had resulted. The confirmed cases outside of China had also reached over 81,000, with over 3,200 deaths. In this study, a Convolutional Neural Network (CNN) was proposed to analyze and predict the number of confirmed cases. Several cities with the most confirmed cases in China were the focus of this study, and a COVID-19 forecasting model, based on the CNN deep neural network method, was proposed. To compare the overall efficacies of different algorithms, the indicators of mean absolute error and root mean square error were applied in the experiment of this study. The experiment results indicated that compared with other deep learning methods, the CNN model proposed in this study has the greatest prediction efficacy. The feasibility and practicality of the model in predicting the cumulative number of COVID-19 confirmed cases were also verified in this study.


docid: elwmqqqq

title: Chest Computed Tomography for the Diagnosis of Patients with Coronavirus Disease 2019 (COVID-19): A Rapid Review and Meta-Analysis

text: Background: The outbreak of the coronavirus disease 2019 (COVID-19) has had a massive impact on the whole world. Computed tomography (CT) has been widely used in the diagnosis of this novel pneumonia. This study aims to understand the role of CT for the diagnosis and the main imaging manifestations of patients with COVID-19. Methods: We conducted a rapid review and meta-analysis on studies about the use of chest CT for the diagnosis of COVID-19. We comprehensively searched databases and preprint servers on chest CT for patients with COVID-19 between 1 January 2020 and 31 March 2020. The primary outcome was the sensitivity of chest CT imaging. We also conducted subgroup analyses and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: A total of 104 studies with 5694 patients were included. Using RT-PCR results as reference, a meta-analysis based on 64 studies estimated the sensitivity of chest CT imaging in COVID-19 was 99% (95% CI, 0.97-1.00). If case reports were excluded, the sensitivity in case series was 96% (95% CI, 0.93-0.99). The sensitivity of CT scan in confirmed patients under 18 years old was only 66% (95% CI, 0.11-1.00). The most common imaging manifestation was ground-glass opacities (GGO) which was found in 75% (95% CI, 0.68-0.82) of the patients. The pooled probability of bilateral involvement was 84% (95% CI, 0.81-0.88). The most commonly involved lobes were the right lower lobe (84%, 95% CI, 0.78-0.90) and left lower lobe (81%, 95% CI, 0.74-0.87). The quality of evidence was low across all outcomes. Conclusions: In conclusion, this meta-analysis indicated that chest CT scan had a high sensitivity in diagnosis of patients with COVID-19. Therefore, CT can potentially be used to assist in the diagnosis of COVID-19.


Alcohol-related self-harm due to COVID-19 pandemic: Might be an emerging crisis in the near future: A case report


Anti-inflammatory properties of stingless bee honey may reduce the severity of pulmonary manifestations in COVID-19 infections


title: EXPOSED: An occupant exposure model for confined spaces to retrofit crowd models during a pandemic

text: Crowd models can be used for the simulation of people movement in the built environment. Crowd model outputs have been used for evaluating safety and comfort of pedestrians, inform crowd management and perform forensic investigations. Microscopic crowd models allow the representation of each person and the obtainment of information concerning their location over time and interactions with the physical space/other people. Pandemics such as COVID-19 have posed several questions on safe building usage, given the risk of disease transmission among building occupants. Here we show how crowd modelling can be used to assess occupant exposure in confined spaces. The policies adopted concerning building usage and social distancing during a pandemic can vary greatly, and they are mostly based on the macroscopic analysis of the spread of disease rather than a safety assessment performed at a building level. The proposed model allows the investigation of occupant exposure in buildings based on the analysis of microscopic people movement. Risk assessment is performed by retrofitting crowd models with a universal model for exposure assessment which can account for different types of disease transmissions. This work allows policy makers to perform informed decisions concerning building usage during a pandemic.


title: A model-based evaluation of the efficacy of COVID-19 social distancing, testing and hospital triage policies

text: We present a stochastic compartmental network model of SARS-CoV-2 and COVID-19 exploring the effects of policy choices in three domains: social distancing, hospital triaging, and testing. We distinguished between high-risk and low-risk members of the population, and modeled differences in social interactions due to context, risk level, infection status, and testing status. The model incorporates many of the currently important characteristics of the disease, including overcapacity in the healthcare system and uncertainties surrounding the proportion and transmission potential of asymptomatic cases. We compared current policy guidelines from public health agencies with alternative options, and investigated the effects of policy decisions on the overall proportion of COVID-19-related deaths. Our results support current policies to contain the outbreak but also suggest possible refinements, including emphasizing the need to reduce public, random contacts more than private contacts, and testing low-risk symptomatic individuals before high-risk symptomatic individuals. Our model furthermore points to interactions among the three policy domains; the efficacy of a particular policy choice depends on other implemented policies. Finally, our results provide an explanation for why societies like Germany, with lower average rates of social contact, are more successful at containing the outbreak than highly social societies such as Italy, despite the implementation of similar policy measures.


title: A Simple Method for Estimating the Number of Unconfirmed COVID-19 Cases in a Local Area that Includes a Confidence Interval: A Case Study of Whatcom County, Washington

text: Along with many other data problems affecting the unfolding of the COVID-10 pandemic in the United States, virtually nothing is known about the number of positive, unconfirmed cases, especially in local areas. We show that it is possible to estimate the number of positive, unconfirmed COVID-19 cases using a simple, long-established method employed by demographers to estimate a population in the absence of a census count. We go on to show how a confidence interval can be constructed around an estimate of positive, unconfirmed COVID-19 cases constructed from this method, using Whatcom County, Washington as a case study.


title: Trends of tweets on the coronavirus disease-2019 (COVID-19) pandemic

text: The Severe Acute Respiratory Syndrome Corona-virus 2 is a virus causing the COVID-19 pandemic around the world. The World Health Organization (WHO) raised it to the highest level of global alert. The English, Chinese, and Japanese language Twitter data related to this disease during the first period after the WHO started releasing the situation reports were collected and compared with the tweet trends. This study also used quantitative text analysis to extract and analyze the co-occurrence network of English tweets. The findings show that trends and public concerns in social media are related to the breaking news and global trends such as the confirmed cases, the reported death tolls, the quarantined cruise news, the informer, etc.


title: A SYSTEMATIC ANALYSIS OF THE TIME COURSE TO DEVELOP TREATMENTS FOR COVID-19

text: ABSTRACT Background. The spread of COVID-19 from Wuhan in China throughout the world has been alamingly rapid. Epidemiologic techniques succeeded in containing the disease in China, but efforts were not as successful in the rest of the world, particularly the United States where there have been 1,592, 599 cases with 95,863 deaths as of May 25, 2020. Projections are for continued new infections and deaths if no effective treatments can be activated over the next six months.. We performed a systematic review to determine the potential time course of development of treatments and vaccines focusing on availability in the last half of 2020. Methods. Our search was performed during the week of May 17, 2020. Publications: We reviewed up to date information from several sources to identify potential treatments for COVID-19: We used the Reagan-Udall Expanded Access Navigator COVID-19 Treatment Hub to track the efforts of companies to develop treatments. We then used the results to search for publications on pubmed.gov and on MedRxiv, the preprint server. We further used a targeted Google search to find announcements of trial results. Clinical Trials: We searched for all investigational trials involving potential treatments using several different sources: (A) covid-trials.org, then validated results on (B) clinicaltrials.gov and the (C) World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP). We focused on trials which were completed or currently recruiting for patients, reasoning that the timeline to arrive at treatments by the end of the year would require completion within the next 6 months. We excluded studies which were clearly observational, with no randomization, control or comparison group. We furtherset a cutoff of 100 for numbers of subjects since smaller trial size could lack statistical power to establish superiority of the intervention over the control condition. Results. Published Data: We found 19 publications reporting findings on 6 classes of agents. There were 9 publications related to hydroxychloroquine (HCQ), three on lopanovir/ritonavir (LPV/R) (one of which was combined with interferon beta-1),three on remdesivir, two on favipiravir, one on mepaluzamab, and one on tocilizumab. Ten publications reported randomized controlled trials, the rest were retrospective observational. Only one publication touched on outpatient management, the rest on hospitalized patients. Clinical Trials: We found 409 trials meeting our minimum requirement of 100 subjects which were recruiting or completed. The WHO has launched the Solidarity megatrial performed in over 100 countries actively comparing HCQ, lopanovir/ritonavir (LPV/R) alone and in combination with interferon beta-1, and remdesivir. That trial is scheduled to complete enrollment in the first quarter of 2021. In addition, we found 46 trials of HCQ, 11 trials of LPV/R and 8 trials of interferons. There were 18 ongoing trials of antiviral agents, 24 immune modulator trials, 9 vaccine trials, and 62 trials of other agents.We excluded a large number of trials of Chinese traditional medications, reasoning that there was insufficient clinical experience with these agents outside China to offer these treatments to the rest of the world. Forty four trials were hoping to complete enrollment by the end of the second quarter of 2020. Of these, only 9 were conducted on outpatients. A few vaccine trials are hoping to complete Phase 3 enrollment by the end of the third quarter, but a prolonged follow-up of patients will likely be required. Conclusion. Several treatments for severe disease in hospitalized patients have now been granted emergency authorization. However, the disease is propagated primarily by infected ambulatory individuals. There are only a few randomized controlled studies in outpatients which can be expected to yield results in time to impact on the continuing spread of the epidemic in 2020. It will be necessary for public health authorities to make hard decisions with limited data. The choices will be hardest in dealing with potential early release of vaccines. Keywords: Coronavirus, COVID-19, SARS-Cov-2, remdesivir, hydroxychloroquine


title: Mobility traces and spreading of COVID-19

text: We use human mobility models, for which we are experts, and attach a virus infection dynamics to it, for which we are not experts but have taken it from the literature, including recent publications. This results in a virus spreading dynamics model. The results should be verified, but because of the current time pressure, we publish them in their current state. Recommendations for improvement are welcome. We come to the following conclusions: 1. Complete lockdown works. About 10 days after lockdown, the infection dynamics dies down. This assumes that lockdown is complete, which can be guaranteed in the simulation, but not in reality. Still, it gives strong support to the argument that it is never too late for complete lockdown. 2. As a rule of thumb, we would suggest complete lockdown no later than once 10% of hospital capacities available for COVID-19 are in use, and possibly much earlier. This is based on the following insights: a. Even after lockdown, the infection dynamics continues at home, leading to another tripling of the cases before the dynamics is slowed. b. There will be many critical cases coming from people who were infected before lockdown. Because of the exponential growth dynamics, their number will be large. c. Researchers with more detailed disease progression models should improve upon these statements. 3. Our simulations say that complete removal of infections at child care, primary schools, workplaces and during leisure activities will not be enough to sufficiently slow down the infection dynamics. It would have been better, but still not sufficient, if initiated earlier. 4. Infections in public transport play an important role. In the simulations shown later, removing infections in the public transport system reduces the infection speed and the height of the peak by approximately 20%. Evidently, this depends on the infection parameters, which are not well known. -- This does not point to reducing public transport capacities as a reaction to the reduced demand, but rather use it for lower densities of passengers and thus reduced infection rates. 5. In our simulations, removal of infections at child care, primary schools, workplaces, leisure activities, and in public transport may barely have been sufficient to control the infection dynamics if implemented early on. Now according to our simulations it is too late for this, and (even) harsher measures will have to be initiated until possibly a return to such a restrictive, but still somewhat functional regime will again be possible. Evidently, all of these results have to be taken with care. They are based on preliminary infection parameters taken from the literature, used inside a model that has more transport/movement details than all others that we are aware of but still not enough to describe all aspects of reality, and suffer from having to write computer code under time pressure. Optimally, they should be confirmed independently. Short of that, given current knowledge we believe that they provide justification for "complete lockdown" at the latest when about 10% of available hospital capacities for COVID-19 are in use (and possibly earlier; we are no experts of hospital capabilities). What was not investigated in detail in our simulations was contact tracing, i.e. tracking down the infection chains and moving all people along infection chains into quarantine. The case of Singapore has so far shown that this may be successful. Preliminary simulation of that tactic shows that it is difficult to implement for COVID-19, since the incubation time is rather long, people are contagious before they feel sick, or maybe never feel sufficiently sick at all. We will investigate in future work if and how contact tracing can be used together with a restrictive, but not totally locked down regime. When opening up after lockdown, it would be important to know the true fraction of people who are already immune, since that would slow down the infection dynamics by itself. For Wuhan, the currently available numbers report that only about 0.1% of the population was infected, which would be very far away from "herd immunity". However, there have been and still may be many unknown infections.


title: The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen,Hubei,China

text: Summary Background: Some articles have reported the epidemiological and clinical characteristics of coronavirus disease (COVID-19) in Wuhan, but other cities have rarely been reported. This study explored the epidemiology of COVID-19 in Jingmen. Methods: All confirmed cases of COVID-19 in the First People′s Hospital of Jingmen are included from January 12 to February 14,2020. Cases were analyzed for epidemiological data and were confirmed by real-time PCR. Findings: Of the 213 cases (108 men and 105 women) , 88 (41%) had exposure to Wuhan. The median age was 48 years ( range,2-88 years;IQR,35-58.5). Thirty-three severe patients with a median age of 66 years(range,33-82 years,IQR, 57-76) were treated in intensive care units; out of these patients, 66.7 %(22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the controlled measures, the number of new patients gradually decreased and nearly disappeared after 20 days. Interpretation: All people are susceptible to the COVID-19, but older males and those with comorbid conditions are more likely to have severe symptoms. Even though COVID-19 is highly contagious, control measures have proven to be very effective.


title: A study of SARS-CoV-2 evolution in Italy: from early days to secondary effects after social distancing

text: Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 101739 confirmed cases, in Italy, as of March 30th, 2020. While the analogous event in China appears to be rather under control at the moment, the outbreaks in western countries are still at an early stage of the evolution. Italy at present is playing a major role in understanding transmission dynamics of these new infections and evaluating the effectiveness of control measures in a western social context. Methods: We combined a quarantined models with early stage evolution data in Italy (during February 20th - March 30th) to predict longer term evolution (March 30th, on ...) within different control measures. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies leading to faster confirmation of the SARS-CoV-2 infections, we made use of time-dependent contact and diagnose rates to estimate when the effective daily reproduction ratio can fall below 1. Within the same framework we analyze the possible event of a secondary infection after relaxing the isolation measures. Outcomes and interpretation: We study two simplified scenarios compatible with the observation data and the effects of two stringent measures on the evolution of the epidemic. On one side the contact rate must obviously kept as low as possible, but it is also clear that, in a modern developed country, it cannot fall under certain minimum levels and for long time. The complementary parameter tuned is the transition rate of the symptomatic infected individuals to the quarantined class, a parameter δ_I connected with the time t_I=1/δ_I needed to perform diagnostic tests. Within the conditions of the outbreak in Italy this time must fall under 12-8 hours in order to make the reproduction number less than 1 to minimize the case numbers. Moreover we show how the same parameter plays an even more relevant role in mitigating the effects of a possible secondary infection event.


title: COVID‐19: Infection prevention and control guidance for all ultrasound practitioners

text: The severe acute respiratory syndrome coronavirus (SARS‐CoV‐2), an enveloped virus, is the causative agent of the disease known as COVID‐19 (coronavirus disease‐2019). Proper infection prevention and control measures and good hygiene practices are essential to prevent spread of COVID‐19 and protect both patients and the healthcare worker. These guidelines are relevant to all ultrasound practitioners and provides guidance on cleaning and disinfection of ultrasound equipment, the environment and PPE (protective personal equipment) during the COVID‐19 outbreak in the Australasian region.


title: Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020

text: Policies widely adopted in response to the ongoing pandemic of Covid-19, particularly lockdowns and reassignments of health personnel and equipment, are impacting the performance of TB prevention and care programmes at a level varying significantly between countries. Estimates of the impact of reductions in the performance of global TB detection and care on TB mortality over 2020 are presented.


title: Clinical characteristics of Coronavirus Disease 2019 and development of a prediction model for prolonged hospital length of stay.

text: Background The epidemic of Coronavirus Disease 2019 (COVID-19) has become a global health emergency, but the clinical characteristics of COVID-19 are not fully described. We aimed to describe the clinical characteristics of COVID-19 outside of Wuhan city; and to develop a multivariate model to predict the risk of prolonged length of stay in hospital (ProLOS). Methods The study was conducted in a tertiary care hospital in Zhejiang province from January to February 20, 2020. Medical records of all confirmed cases of COVID-19 were retrospectively reviewed. Patients were categorized into the ProLOS and non-ProLOS groups by hospital length of stay greater and less than 14 days, respectively. Conventional descriptive statistics were applied. Multivariate regression model was built to predict the risk of ProLOS, with variables selected using stepwise approach. Results A total of 75 patients with confirmed COVID-19 were included for quantitative analysis, including 25 (33%) patients in the ProLOS group. ProLOS patients were more likely to have history of traveling to Wuhan (68% vs. 28%; P=0.002). Patients in the ProLOS group showed lower neutrophil counts [median (IQR): 2.50 (1.77-3.23) ×109/L vs. 2.90 (2.21-4.19) ×109/L; P=0.048], higher partial thrombin time (PT) (13.42±0.63 vs. 13.10±0.48 s; P=0.029), lower D-Dimer [0.26 (0.22-0.46) vs. 0.44 (0.32-0.84) mg/L; P=0.012]. There was no patient died and no severe case in our cohort. The overall LOS was 11 days (IQR, 5-15 days). The median cost for a hospital stay was 7,388.19 RMB (IQR, 5,085.39-11,145.44). The prediction model included five variables of procalcitonin, heart rate, epidemiological history, lymphocyte count and cough. The discrimination of the model was 84.8% (95% CI: 75.3% to 94.4%). Conclusions Our study described clinical characteristics of COVID-19 outside of Wuhan city and found that the illness was less severe than that in the core epidemic region. A multivariate model was developed to predict ProLOS, which showed good discrimination.


title: Using ICU data to improve the real-time estimation of the effective reproductive number of the COVID-19 epidemic in 9 European countries

text: We replicate a recent study by the Imperial College COVID-19 Response Team (Flaxman et al, 2020) that estimates both the effective reproductive number, Rt, of the current COVID-19 epidemic in 11 European countries, and the impact of different nonpharmaceutical interventions that have been implemented to try to contain the epidemic. We improve on their estimation by using data from the number of patients in intensive care, which provides two advantages over the number of deaths: first, it can be used to construct a signal with less bias: as the healthcare system of a country reaches saturation, the mortality rate would be expected to increase, which would bias the estimates of Rt and of the impact of measures implemented to contain the epidemic; and second, it is a signal with less lag, as the time from onset of symptoms to ICU admission is shorter than the time from onset to death. The intensive care signal we use is not just the number of people in ICU, as this would also be biased if the healthcare system has reached saturation. Instead, we estimate the daily demand of intensive care, as the sum of two components: the part that is satisfied (new ICU admissions) and the part that is not (which results in excess mortality). Thanks to the advantages of this ICU signal in terms of timeliness and bias, we find that most of the countries in the study have already reached Rt<1 with 95% confidence (Italy, Spain, Austria, Denmark, France, Norway and Switzerland, but not Belgium or Sweden), whereas the original methodology of Flaxman et al (2020), even with updated data, would only find Rt<1 with 95% confidence for Italy and Switzerland.


title: Structural landscape of the complete genomes of Dengue serotypes and other viral hemorrhagic fevers

text: Background With more than 300 million potentially infected people every year, and with the expanded habitat of mosquitoes due to climate change, dengue cannot be considered anymore only a tropical disease. The RNA secondary structure is a functional characteristic of RNA viruses, and together with the accumulated high-throughput sequencing data could provide general insights towards understanding virus biology. Here, we profiled the RNA secondary structure of >7500 complete viral genomes from 11 different species of viral hemorrhagic fevers, including dengue serotypes, ebola, and yellow fever. Results We achieved hig prediction scores (AUC up to 0.85 with experimental data), and computed consensus secondary structure profiles using hundreds of structural in silico models. We observed that virulent viruses such as DENV-2 and ebola tend to be less structured than the other viruses. Furthermore, we observed virus-specific correlations between secondary structure and the number of interaction sites with human proteins, reaching a correlation of 0.89 in the case of zika. We demonstrate that the secondary structure and presence of protein-binding domains in the genomes can be used as intrinsic signature to further classify the viruses. We also used structural data to study the geographical distribution of dengue, finding a significant difference between DENV-3 from Asia and South-America, which could imply different evolutionary routes of this subtype. Conclusions Our massive computational analysis provided novel results regarding the secondary structure and the interaction with human proteins, not only for Dengue serotypes, but also for other viral hemorrhagic fevers. We also provided a new approach to classify viruses according ot their structure, which could be useful for future cassifications. We envision that these approaches can be used by the scientific community to further classify and characterise these complex viruses.


title: Public governance mechanism in the prevention and control of the COVID-19: information, decision-making and execution

text: In China, sub-provincial governments are responsible for managing public health emergencies. In the context of coordinating multiple stakeholders, the role of the local government can be defined as ‘meta-governance’. It shall provide rules to facilitate collective action and co-produce quality public services. However, the case of Wuhan suggests that some local governments still rely on the traditional administrative system, which hampers them in terms of issuing a sufficient response to the COVID-19 outbreak. Three measures can be taken to facilitate a public governance mechanism in public health emergency management. First, local governments can use the ICTs to create a more transparent information mechanism. The free flow of information could alert all stakeholders to potential emergencies, while the open government data form the base for cross-border collaboration. Second, a more comprehensive Public Health Emergency Preparedness is constructive for local governments in making quality and immediate decisions. This preparedness shall clearly define the responsibility of the involved agencies based on a careful evaluation of their qualification and capability. Third, the local government shall note that good governance requires more than an executive capacity based on command-and-control. It is necessary to develop the ability to work with stakeholders outside the bureaucratic system.


title: Genomic analysis of early SARS-CoV-2 strains introduced in Mexico

text: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described in the country. Within this Mexican cluster, we also identified an H49Y amino acid change in the spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. This work is the result of the collaboration of five institutions into one research consortium: three public health institutes and two universities. From the beginning of this work, it was agreed that the experimental leader of each institution would share the first authorship. Those were the criteria followed to assign first co-first authorship in this manuscript. The order of the other authors was randomly assigned. IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.


docid: gvjiexfm

title: Age-dependent risks of Incidence and Mortality of COVID-19 in Hubei Province and Other Parts of China

text: New coronavirus SARS-CoV-2 poses a big challenge for global public health in early 2020. Coronavirus Disease 2019 (COVID-19) caused by the virus rapidly spreads all over the world and takes thousands of lives in just two months. It is critical to refine the incidence and mortality risks of COVID-19 for the effective management of the general public and patients in the outbreak. In this report, we investigate the incidence and mortality risks of the infection by analyzing the age composition of 5319 infected patients, 76 fatal cases, and 1,144,648 individuals of the general public in China. Our result shows a relatively low incidence risk for young people but a very high mortality risk for seniors. Notably, mortality risk could be as high as 0.48 for people older than 80 years. Furthermore, our study suggests that a good medical service can effectively reduce the mortality rate of the viral infection to 1% or less.


title: Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

text: The current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor-binding domain (RBD) of SARS-CoV, cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2, and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs. Summary Serum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.


title: Textile Masks and Surface Covers - A 'Universal Droplet Reduction Model' Against Respiratory Pandemics

text: The main form of COVID-19 transmission is via oral-respiratory droplet contamination (droplet; very small drop of liquid) produced when individuals talk, sneeze or cough. In hospitals, health-care workers wear facemasks as a minimum medical droplet precaution to protect themselves. Due to the shortage of masks during the pandemic, priority is given to hospitals for their distribution. As a result, the availability/use of medical masks is discouraged for the public. However, given that asymptomatic individuals, not wearing masks within the public, can be highly contagious for COVID-19, prevention of environmental droplet contamination (EnDC) from coughing/sneezing/speech is fundamental to reducing transmission. As an immediate solution to promote public droplet safety, we assessed household textiles to quantify their potential as effective environmental droplet barriers (EDBs). The synchronized implementation of a universal community droplet reduction solution is discussed as a model against COVID-19. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which widely available clothing fabrics reduce the dispersion of droplets onto surfaces within 1.8m, the minimum distance recommended for COVID-19 social distancing. All textiles reduced the number of droplets reaching surfaces, restricting their dispersion to <30cm, when used as single layers. When used as double-layers, textiles were as effective as medical mask/surgical-cloth materials, reducing droplet dispersion to <10cm, and the area of circumferential contamination to ~0.3%. The synchronized implementation of EDBs as a community droplet reduction solution (i.e., face covers/scarfs/masks & surface covers) could reduce EnDC and the risk of transmitting or acquiring infectious respiratory pathogens, including COVID-19.


COVID-19 Study Predicts Lockdown Difficult to Remove Safely


title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis

text: COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.


title: An imperfect tool: COVID-19 'test & trace' success relies on minimising the impact of false negatives and continuation of physical distancing.

text: Background: Following a consistent decline in COVID-19-related deaths in the UK throughout May 2020, it is recognised that contact tracing will be vital to relaxing physical distancing measures. The increasingly evident role of asymptomatic and pre-symptomatic transmission means testing is central to control, but test sensitivity estimates are as low as 65%. Methods: We extend an existing UK-focused branching process model for contact tracing, adding diagnostic testing and refining parameter estimates to demonstrate the impact of poor test sensitivity and suggest mitigation methods. We also investigate the role of super-spreading events, providing estimates of the relationship between infections, cases detected and hospitalisations, and consider how tracing coverage and speed affects outbreak risk. Findings: Incorporating poor sensitivity testing into tracing protocols could reduce efficacy, due to false negative results impacting isolation duration. However, a 7-day isolation period for all negative-testing individuals could mitigate this effect. Similarly, reducing delays to testing following exposure has a negligible impact on the risk of future outbreaks, but could undermine control if negative-testing individuals immediately cease isolating. Even 100% tracing of contacts will miss cases, which could prompt large localised outbreaks if physical distancing measures are relaxed prematurely. Interpretation: It is imperative that test results are interpreted with caution due to high false-negative rates and that contact tracing is used in combination with physical distancing measures. If the risks associated with imperfect test sensitivity are mitigated, we find that contact tracing can facilitate control when the reproduction number with physical distancing, Rs, is less than 15.


title: Integrated analysis of bulk multi omic and single-cell sequencing data confirms the molecular origin of hemodynamic changes in Covid-19 infection explaining coagulopathy and higher geriatric mortality

text: Besides severe respiratory distress, recent reports in Covid-19 patients have found a strong association between platelet counts and patient survival. Along with hemodynamic changes such as prolonged clotting time, high fibrin degradation products and D-dimers, increased levels of monocytes with disturbed morphology have also been identified. In this study, through an integrated analysis of bulk RNA-sequencing data from Covid-19 patients with data from single-cell sequencing studies on lung tissues, we found that most of the cell-types that contributed to the altered gene expression were of hematopoietic origin. We also found that differentially expressed genes in Covid-19 patients formed a significant pool of the expressing genes in phagocytic cells such as Monocytes and Platelets. Interestingly, while we observed a general enrichment for Monocytes in Covid-19 patients, we found that the signal for FCGRA3+ Monocytes was depleted. Further, we found evidence that age-associated gene expression changes in Monocytes and Platelets, associated with inflammation, mirror gene expression changes in Covid-19 patients suggesting that pro-inflammatory signalling during aging may worsen the infection in older patients. We identified more than 20 genes that change in the same direction between Covid-19 infection and aging cells that may act as potential therapeutic targets. Of particular interest were IL2RG, GNLY and GMZA expressed in Platelets, which facilitates cytokine signalling in Monocytes through an interaction with Platelets. To understand whether infection can directly manipulate the biology of Monocytes and Platelets, we hypothesize that these non-ACE2 expressing cells may be infected by the virus through the phagocytic route. We observed that phagocytic cells such as Monocytes, T-cells, and Platelets have a significantly higher expression of genes that are a part of the Covid-19 viral interactome. Hence these cell-types may have an active rather than a reactive role in viral pathogenesis to manifest clinical symptoms such as coagulopathy. Therefore, our results present molecular evidence for pursuing both anti-inflammatory and anticoagulation therapy for better patient management especially in older patients.


title: Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies

text: Rapid and accurate diagnosis is crucial for successful outbreak containment. During the current coronavirus disease 2019 (COVID-19) public health emergency, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is the detection of viral RNA by reverse transcription (RT)-PCR. Additional diagnostic methods enabling the detection of current or past SARS-CoV-2 infection would be highly beneficial to ensure the timely diagnosis of all infected and recovered patients. Here, we investigated several serological tools, i.e., two immunochromatographic lateral flow assays (LFA-1 (Biosynex COVID-19 BSS) and LFA-2 (COVID-19 Sign IgM/IgG)) and two enzyme-linked immunosorbent assays (ELISAs) detecting IgA (ELISA-1 Euroimmun), IgM (ELISA-2 EDI) and/or IgG (ELISA-1 and ELISA-2) based on well-characterized panels of serum samples from patients and healthcare workers with PCR-confirmed COVID-19 and from SARS-CoV-2-negative patients. A total of 272 serum samples were used, including 62 serum samples from hospitalized patients (panel 1 and panel 3), 143 serum samples from healthcare workers (panel 2) diagnosed with COVID-19 and 67 serum samples from negative controls. Diagnostic performances of each assay were assessed according to days after symptom onset (dso) and the antigenic format used by manufacturers. We found overall sensitivities ranging from 69% to 93% on panels 1 and 2 and specificities ranging from 83% to 98%. The clinical sensitivity varied greatly according to the panel tested and the dso. The assays we tested showed poor mutual agreement. A thorough selection of serological assays for the detection of ongoing or past infections is advisable.


title: The effectiveness of non-pharmaceutical interventions in containing epidemics: a rapid review of the literature and quantitative assessment

text: The number of confirmed COVID-19 cases has rapidly increased since discovery of the disease in December 2019. In the absence of medical countermeasures to stop the spread of the disease (i.e. vaccines), countries have responded by implementing a suite of non-pharmaceutical interventions (NPIS) to contain and mitigate COVID-19. Individual NPIs range in intensity (e.g. from lockdown to public health campaigns on personal hygiene), as does their impact on reducing disease transmission. This study uses a rapid review approach and investigates evidence from previous epidemic outbreaks to provide a quantitative assessment of the effectiveness of key NPIs used by countries to combat the COVID-19 pandemic. Results from the study are designed to help countries enhance their policy response as well as inform transition strategies by identifying which policies should be relaxed and which should not.


Imported cases of 2019-novel coronavirus (2019-nCoV) infections in Thailand: Mathematical modelling of the outbreak


title: Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: an in silico approach

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19), a public health emergency of international concern declared by the World Health Organization (WHO). An immuno-informatics approach along with comparative genomic was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M and E proteins. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of ≥ 90.0% world population coverage for different ethnic groups. Molecular docking of the chimeric vaccine peptide with the immune receptors (TLR3 and TLR4) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased INF-γ and IL-2 cytokines. The codon optimization and mRNA secondary structure prediction revealed the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19.


title: Expected impact of lockdown in Île-de-France and possible exit strategies

text: More than half of the global population is currently under strict forms of social distancing, with more than 90 countries in lockdown, including France. Estimating the expected impact of the lockdown, and the potential effectiveness of different exit strategies is critical to inform decision makers on the management of the COVID-19 health crisis. We use a stochastic age-structured transmission model integrating data on age profile and social contacts in the Île-de-France region to (i) assess the current epidemic situation, (ii) evaluate the expected impact of the lockdown implemented in France on March 17, 2020, and (iii) estimate the effectiveness of possible exit strategies. The model is calibrated on hospital admission data of the region before lockdown and validated on syndromic and virological surveillance data. Different types and durations of social distancing interventions are simulated, including a progressive lifting of the lockdown targeted on specific classes of individuals (e.g. allowing a larger proportion of the population to go to work, while protecting the elderly), and large-scale testing. We estimate the basic reproductive number at 3.0 [2.8, 3.2] (95% confidence interval) prior to lockdown and the population infected by COVID-19 as of April 5 to be in the range 1% to 6%. The average number of contacts is predicted to be reduced by 80% during lockdown, leading to a substantial reduction of the reproductive number (RLD = 0.68 [0.62-0.73]). Under these conditions, the epidemic curve reaches ICU system capacity and slowly decreases during lockdown. Lifting the lockdown with no exit strategy would lead to a second wave largely overwhelming the healthcare system. Extensive case-finding, testing and isolation are required to envision social distancing strategies that gradually relax current constraints (larger fraction of individuals going back to work, progressive reopening of activities), while keeping schools closed and seniors isolated. As France faces the first wave of COVID-19 pandemic in lockdown, intensive forms of social distancing are required in the upcoming months due to the currently low population immunity. Extensive case-finding and isolation would allow the partial release of the socio-economic pressure caused by extreme measures, while avoiding healthcare demand exceeding capacity. Response planning needs to urgently prioritize the logistics and capacity for these interventions.


title: Disparities in Age-Specific Morbidity and Mortality from SARS-CoV-2 in China and the Republic of Korea

text: We analyzed age- and sex-specific morbidity and mortality data from SARS-COV-2 pandemic in China and Republic of Korea (ROK). Data from China exhibit a standard Gaussian distribution with peak morbidity in the 50-59 years cohort, while the ROK data have a bimodal distribution with highest morbidity in the 20-29 years cohort.


title: Sub-Surface Microstructural Evolution and Chip Formation During Turning of AF 9628 Steel

text: Abstract High-strength low-alloy (HSLA) steels are desired for their high strength-to-weight ratio, relatively low cost, good overall mechanical properties, and relative ease of processing. The development of Eglin steel and AF 9628 has facilitated the current wave of research into next-generation HSLA steels. These alloys are characterized by both high levels of strength and increased levels of ductility and impact toughness over traditional HSLA alloys such as AISI 4340/4330. AF 9628 has proven difficult to machine due to strain hardening while turning. Manual and CNC turning experiments were carried out on AF 9628 cylindrical bars based on current machining practices. In an effort to optimize material removal rate and tool life, quantitative measurements of tool flank wear, surface roughness, hardness, microhardness, and chip thickness were taken. Qualitative observations made on microstructural evolution and chip color and morphology are also discussed.


title: Molecular conservation and Differential mutation on ORF3a gene in Indian SARS-CoV2 genomes

text: A global emergency due to the COVID-19 pandemic demands various studies related to genes and genomes of the SARS-CoV2. Among other important proteins, the role of accessory proteins are of immense importance in replication, regulation of infections of the coronavirus in the hosts. The largest accessory proteins in the SARS-CoV2 genome is ORF3a which modulates the host response to the virus infection and consequently it plays an important role in pathogenesis. In this study, an attempt is made to decipher the conservation of nucleotides, dimers, codons and amino acids in the ORF3a genes across thirty two genomes of Indian patients. ORF3a gene possesses single and double point mutations in Indian SARS-CoV2 genomes suggesting the change of SARS-CoV2’s virulence property in Indian patients. We find that the parental origin of the ORF3a gene over the genomes of SARS-CoV2 and Pangolin-CoV is same from the phylogenetic analysis based on conservations of nucleotides and so on. This study highlights the accumulation of mutation on ORF3a in Indian SARS-CoV2 genomes which may provide the designing therapeutic approach against SARS-CoV2.


The Speed of Sound: Ultrasound a Potential Tool for Detecting COVID-19


title: LxxIxE-like Motif in Spike Protein of SARS-CoV-2 that is Known to Recruit the Host PP2A-B56 Phosphatase Mimics Artepillin C, an Immunomodulator, of Brazilian Green Propolis

text: SARS-CoV-2 is highly contagious and can cause acute respiratory distress syndrome (ARDS) and multiple organ failure that are largely attributed to the cytokine storm. The surface coronavirus spike (S) glycoprotein is considered as a key factor in host specificity because it mediates infection by receptor-recognition and membrane fusion. Here, the analysis of SARS-CoV-2 S protein revealed two B56-binding LxxIxE-like motifs in S1 and S2 subunits that could recruit the host protein phosphatase 2A (PP2A). The motif in S1 subunit is absent in SARS-CoV and MERS-CoV. Phosphatases and kinases are major players in the regulation of pro-inflammatory responses during pathogenic infections. Moreover, studies have shown that viruses target PP2A in order to manipulate host’s antiviral responses. Recent researches have indicated that SARS-CoV-2 is involved in sustained host inflammation. Therefore, by controlling acute inflammation, it is possible to eliminate its dangerous effects on the host. Among efforts to fight COVID-19, the interaction between LxxIxE-like motif and the PP2A-B56-binding pocket could be a target for the discovery and/or development of a bioactive ligand inhibitor for therapeutic purposes. Indeed, a small molecule called Artepillin C (ArtC), a main compound in Brazilian honeybee green propolis, mimics the side chains of LxxLxE motif. Importantly, ArtC is known, among other effects, to have anti-inflammatory activity that makes it an excellent candidate for future clinical trials in COVID-19 patients.


title: Former FDA leaders decry emergency authorization of malaria drugs for coronavirus

text: The recent Food and Drug Administration (FDA) emergency use authorization (EUA) for two malaria drugs to treat COVID-19, based on thin evidence of efficacy, has jeopardized research to learn the drugs’ real value against the pandemic coronavirus, say former agency executives under President Donald Trump and former President Barack Obama They also charge that the 28 March EUA for chloroquine phosphate and hydroxychloroquine sulfate undermines FDA’s scientific authority because it appeared to be a response not to scientific evidence, but to fervent advocacy of the drugs by Trump and other political figures FDA has multiple mechanisms to allow the use of unapproved, experimental drugs for small numbers of desperately ill patients outside of clinical trials Because chloroquine and hydroxychloroquine are approved for malaria, doctors could prescribe them “off label” for COVID-19 patients even without the EUA Since Trump first endorsed the drugs on 19 March, however, shortages have been reported, depriving some people with autoimmune disorders such as lupus who also depend on hydroxychloroquine The EUA will immediately add tens of millions of doses of the drugs for distribution to hospitalized COVID-19 patients through health care centers


title: Mothers, childcare duties, and remote working under COVID-19 lockdown in Italy: Cultivating communities of care

text: Drawing on a virtual ethnography, we explore how the increase in remote working has created unequal domestic rearrangements of parenting duties with respect to gender relations during the COVID-19 lockdown in Italy. We also discuss the resources that mothers have mobilized to create a network of social support in the organization of care.