title: Public attitudes towards COVID-19 contact tracing apps: A UK-based focus group study

text: OBJECTIVE: To explore public attitudes to the proposed COVID-19 contact tracing app in the United Kingdom. DESIGN: Qualitative study consisting of five focus groups carried out between 1st-4th May 2020 (39-42 days after the official start of the UK lockdown). SETTING: Online video-conferencing PARTICIPANTS: 22 participants, all UK residents aged 18 years and older, representing a range of different genders, ages, ethnicities and locations. RESULTS: Participants were split roughly equally in number across three groups: will use the app; will not be using the app; and undecided as to whether they will use the app. Analysis revealed five main themes: (1) Lack of information and misconceptions surrounding COVID-19 contact tracing apps; (2) concerns over privacy; (3) concerns over stigma; (4) concerns over uptake; and (5) contact tracing as the 'greater good'. These themes were found across the sample and the three groups. However, concerns over privacy, uptake and stigma were particularly significant amongst those state they will not be using the app and the view that the app is for the 'greater good' was particularly significant amongst those who stated they will be using the app. One of the most common misconceptions about the app was that it could allow users to specifically identify and map COVID-19 cases amongst their contacts and in their vicinity. CONCLUSIONS: We offer four recommendations: (1) To offset the fact that many people may not be accessing, or might be avoiding, news coverage on COVID-19, authorities must communicate to the public via a range of methods including but not limited to: social media ads, postal information, text messaging and other emergency alert systems. (2) Communications should emphasise that the app cannot enable the user to identify which of their contacts has reported COVID-19 symptoms or tested positive. (3) Communication should emphasise collective responsibility ('the greater good') to promote social norms around use of the app (4) Communication should provide a slogan that maximises clarity of message, for example: 'Download the app, protect the NHS, save lives'.


title: Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients

text: The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and world economy. Since approved drugs and vaccines are not available, new options for COVID-19 treatment and prevention are highly demanded. To identify SARS-CoV-2 neutralizing antibodies, we analysed the antibody response of 12 COVID-19 patients from 8 to 69 days post diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days post diagnosis. Among these, 28 potently neutralized authentic SARS-CoV-2 (IC100 as low as 0.04 μg/ml), showing a broad spectrum of V genes and low levels of somatic mutations. Interestingly, potential precursors were identified in naïve B cell repertoires from 48 healthy individuals that were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2 neutralizing antibodies are readily generated from a diverse pool of precursors, fostering the hope of rapid induction of a protective immune response upon vaccination.


title: Demographic and Clinical Characteristics of the Severe Covid-19 Infections: First Report from Mashhad University of Medical Sciences, Iran

text: Purpose. To report a comparison between fatalities and recovery of the severe Covid-19 infected patients based on demographic and clinical characteristics. Methods. Between 5 March and 12 May 2020, of 4,000 patients, 1,278 were laboratory confirmed to be Covid-19 infection in Mashhad, Iran. Finally, 334 deceased and 733 recovered cases were assessed in terms of demography, exposure history, health outcomes and clinical symptoms. Results. Mean (SD) age for confirmed patients, for deceased cases and for recovered cases. Mean (SD) age for all confirmed-patients was 56.9 (18.74), for the fatalities 67.26 (15.77) and for those recovered 52.82 (17.91) years. The rise of the mortality rate in relation to seniority was statistically significant. Despite a high frequency of Covid-19 infections accrued in the age groups of 30-39 and 40-49 years, most of these cases (88.2 and 85.8%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (9) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Fever (63.8%), cough (68.1%), and dyspnoea (72.7%) were the most frequent clinical symptoms. 5.2% of infected-cases were healthcare workers that two (3%) of them died. Most patients (48%) received both antiviral and antibiotic therapy. The mortality rate of Kaletra combination prescribed for severe cases was 46.7%. Conclusions. The characteristics of Covid-19 varied from died to survived infected patients. There were a higher number of fatalities in younger patients than in international studies. Diabetes and cardiovascular disorders were most prevalent co-morbidities. The study could not address the case-fatality rate of Covid-19 infection that remains for future studies.


title: COVID-19 incidence and R decreased on the Isle of Wight after the launch of the Test, Trace, Isolate programme

text: In May 2020 the UK introduced a Test, Trace, Isolate programme in response to the COVID-19 pandemic. The programme was first rolled out on the Isle of Wight and included Version 1 of the NHS contact tracing app. We used COVID-19 daily case data to infer incidence of new infections and estimate the reproduction number R for each of 150 Upper Tier Local Authorities in England, and at the National level, before and after the launch of the programme on the Isle of Wight. We used Bayesian and Maximum-Likelihood methods to estimate R, and compared the Isle of Wight to other areas using a synthetic control method. We observed significant decreases in incidence and R on the Isle of Wight immediately after the launch. These results are robust across each of our approaches. Our results show that the sub-epidemic on the Isle of Wight was controlled significantly more effectively than the sub-epidemics of most other Upper Tier Local Authorities, changing from having the third highest reproduction number R (of 150) before the intervention to the tenth lowest afterwards. The data is not yet available to establish a causal link. However, the findings highlight the need for further research to determine the causes of this reduction, as these might translate into local and national non-pharmaceutical intervention strategies in the period before a treatment or vaccination becomes available.


title: Aerosolized Hydrogen Peroxide Decontamination of N95 Respirators, with Fit-Testing and Virologic Confirmation of Suitability for Re-Use During the COVID-19 Pandemic

text: In response to the current urgent demand for N95 respirators by healthcare workers responding to the COVID-19 pandemic, with particular emphasis on needs within local medical systems, we initiated an N95 decontamination study using aerosolized hydrogen peroxide or aHP (7% H2O2 solution), via the Pathogo Curis® (Curis) decontamination system. The study has thus far included 10 cycles of respirator decontamination, with periodic qualitative and quantitative fit testing to verify ongoing respirator integrity through the decontamination process, and support a statistical evaluation of successful respirator fit. In addition, we have conducted virologic testing of respirator surfaces and materials to demonstrate a rigorous verification of decontamination. Given that the current pandemic entails a respiratory viral pathogen, it is critical to address these aspects of respirator safety for reuse. These measures are intended to provide a foundation for a suitable decontamination process, which maintains N95 function, and supports safe respirator reuse by healthcare providers. Current results from both respirator fit testing and virologic testing indicate that the process is effective on the basis of zero failure rate on fit-testing of selected respirators, and on complete decontamination of multiple virus species by aHP treatment, comparable to that observed with commercial spore-based biological indicators of sterilization.


title: Mathematical Modeling & the Transmission Dynamics of SARS-CoV-2 in Cali, Colombia: Implications to a 2020 Outbreak & public health preparedness

text: Introduction: As SARS-COV-2 and the disease COVID-19 is sweeping through countries after countries around the globe, it is critical to understand potential burden of a future outbreak in cities of Colombia. This pandemic has affected most of the countries in the world because the high global movement of individuals and excessive cost in interventions. Objective: Using demographic data from city of Cali, disease epidemiological information from affected countries and mathematical models, we estimated the rate of initial exponential growth of new cases and the basic reproductive rate for a potential outbreak in city of Cali in Colombia. Materials and methods: We used dynamical models with different modeling assumptions such as use of various types of interventions and/or epidemiological characteristics to compare and contrast the differences between Colombian cities and between Latin American countries. Results: Under the assumption of homogeneously mixing population and limited resources, we predicted expected number of infected, hospitalized, in Intensive Care Units (ICU) and deaths during this potential COVID-19 outbreak. Our results suggest that on a given day in Cali there may be up to around 73000 cases who might need hospitalization under no intervention. However, this number drastically reduces if we carry out only-isolation intervention (with 16 days of symptomatic infection; [~]13,000 cases) versus both quarantining for 6 days and isolation within 16 days ([~]3500 cases). The peak in Cali will reach in 2-3 months. Conclusions: The estimates from these studies provides different scenarios of outbreaks and can help Cali to be better prepared during the ongoing COVID-19 outbreak.


title: A systematic review and meta-analysis of published research data on COVID-19 infection-fatality rates

text: Introduction: An important unknown during the COVID-19 pandemic has been the infection-fatality rate (IFR). This differs from the case-fatality rate (CFR) as an estimate of the number of deaths as a proportion of the total number of cases, including those who are mild and asymptomatic. While the CFR is extremely valuable for experts, IFR is increasingly being called for by policy-makers and the lay public as an estimate of the overall mortality from COVID-19. Methods: Pubmed and Medrxiv were searched using a set of terms and Boolean operators on 25/04/2020. Articles were screened for inclusion by both authors. Meta-analysis was performed in Stata 15.1 using the metan command, based on IFR and confidence intervals extracted from each study. Google/Google Scholar was used to assess the grey literature relating to government reports. Results: After exclusions, there were 13 estimates of IFR included in the final meta-analysis, from a wide range of countries, published between February and April 2020. The meta-analysis demonstrated a point-estimate of IFR of 0.75% (0.49-1.01%) with significant heterogeneity (p<0.001). Conclusion: Based on a systematic review and meta-analysis of published evidence on COVID-19 until the end of April, 2020, the IFR of the disease across populations is 0.75% (0.49-1.01%). However, due to very high heterogeneity in the meta-analysis, it is difficult to know if this represents the "true" point estimate. It is likely that different places will experience different IFRs. More research looking at age-stratified IFR is urgently needed to inform policy-making on this front.


Editor’s Note: Cognitive Computation and COVID-19


title: Hindsight is 2020 vision: Characterisation of the global response to the COVID-19 pandemic

text: Since the initial outbreak in Wuhan (Hubei, China) in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has rapidly spread to cause one of the most pressing challenges facing our world today: the COVID-19 pandemic. Within four months of the first reported cases, more than two and a half million cases were confirmed with over two hundred thousand deaths globally, and many countries had taken extreme measures to stop the spread. In this work, we analyse the response to the COVID-19 outbreak for 103 countries over the period 22 January to 13 April 2020. We utilise a novel stochastic epidemiological model that includes a regulatory mechanism that captures the level of tolerance to rising confirmed cases within the response behaviour. Using approximate Bayesian computation, we identify that the top ten outbreaks as of 31 March are characterised by a high tolerance to rising cases tallies, whereas countries that avoided severe outbreak have a low tolerance. Countries that recovered rapidly also have a higher identification rate. As of 13 April, almost all countries show declines in transmission rates and basic reproductive numbers. Furthermore, countries approaching recovery also increased their identification rate between 31 March and 13 April. We also demonstrate that uncertainty in undocumented infections dramatically impacts uncertainty in predictions. Overall, we recommend that broader testing is required to understand the magnitude of undocumented infections.


title: Suppressing the impact of the COVID-19 pandemic usingcontrolled testing and isolation

text: The Corona virus disease 2019 (COVID-19) has significantly affected lives of people around the world. Today, isolation policy is enforced by identifying infected individuals based on symptoms when these appear or by testing people and quarantining those who have been in close contact with infected people. In addition, many countries have imposed complete or partial lock-downs to control the spread of the disease. While this has resulted in some some success in slowing down the spread of the virus, lock-downs as well as widespread quarantine have devastating effects on the economy and social life. Thus, governments are urgently looking for efficient strategies to significantly relax lock-downs, while still controlling the spread of the virus. We argue that this can be done by using active feedback to control testing for infection by actively testing individuals with a high probability of being infected. We develop an active testing strategy to achieve this goal, and demonstrate that it would have tremendous success in controlling the spread of the virus on one million people, using 3; 000 tests per day. Our results show up to a 50% reduction in quarantine rate and morbidity rate in typical settings as compared to existing methods.


title: Evidence for and against vertical transmission for SARS-CoV-2 (COVID-19)

text: Abstract COVID-19 can severely affect pregnant women and the issue of vertical transmission of sars-cov-2 has also emerged. Sars-cov-2 could be recovered by real-time (RT) PCR from nasal and throat swabs, sputum and feces of symptomatic patients including neonates but not from vaginal swabs, amniotic fluid, placenta, cord blood, neonatal blood or breast milk. Viremia was present in 1% of symptomatic adults. We identified 12 articles published between February 10th and April 4th 2020 reporting on 68 deliveries and 71 neonates with maternal infection in the third trimester of pregnancy. Perinatal exposure, including mode of delivery and time interval from delivery to the diagnosis of neonatal infection are crucial in differentiating congenital from perinatal infection. Neonatal infection is usually asymptomatic. Neonatal infection was diagnosed within 48 hours of life in 4 cases. Detection rates of real-time PCR and the interpretation of IgM and IgG antibodies levels in cord and neonatal blood are discussed in relation with the immaturity of the fetal and neonatal immune system.


title: Mental Health Status among the South Indian Pharmacy Students during Covid-19 Pandemic Quarantine Period: A Cross-Sectional Study

text: Introduction: The COVID-19 outbreak created a major panic among all the citizens of the country owing to its severity, contagiousness within the community, lack of specific treatment and possibility of re-infection. All these factors along with the uncertain behaviour of the virus lead to state of fear and concern all throught out the nation. The current study represents the mental health survey conducted on the students of South India after the completion of one month quarantine period of the COVID-19 outbreak. Methodology: The present study is a cross-sectional, web-based online survey which consists of 21-item DASS questionnaire. This was used to assess the emotional states of depression, anxiety, and stress. Using Google Forms, the questionnaire was randomly distributed among the pharmacy students of selected colleges. Mean with standard deviation was calculated for continuous variables and the number with percentage was calculated for categorical variables. Results: A total of 500 participants responded to the questionnaire. More than half of the responses were received from females (65%). On assessment it was found that, 26 % of respondents reported severe to extremely severe depressive symptoms; 31.5 % of respondents reported severe to extremely severe anxiety symptoms, and 19 % reported severe to extremely severe stress levels. Conclusion: In India during the outbreak of COVID-19, an alarming number of students were found to have an impact on mental health due to the outbreak and were observed to have higher levels of stress, anxiety, and depression. The study findings shows the need of conducting more such studies and can be used to prepare appropriate psychological interventions to improve mental health among the young public during the pandemic.


title: Network pharmacological analysis and mechanism prediction of Xiaochaihu Decoction in treatment of COVID-19 with syndrome of pathogenic heat lingering in lung and obstructive cardinalate/ 小柴胡汤治疗早期新型冠状病毒肺炎（COVID-19）邪热郁肺、枢机不利证功效网络分析与机制预测

text: Objective: To study the efficacy network and potential mechanism of Xiaochaihu Decoction (XCHD) in the treatment of coronavirus disease 2019 (COVID-19) with syndrome of pathogenic heat lingering in the lung and obstructive cardinalat, and analyze the active ingredients of XCHD with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy. Methods: The correspondence between COVID-19 and XCHD was analyzed by literature consulting. Based on network pharmacology, Cytoscape 3.6.0 and other software were then used to construct XCHD efficacy network of “Chinese medicine prescription-active ingredient-key target” for pneumonia and immune regulation, in order to confirm anti-SARS-CoV-2 active ingredients in the prescription. Some softwares were used to analyze XCHD for COVID-19 treatment in multiple aspects. Results: A total of 48 active ingredients with potential anti-SARS-CoV-2 effect in herbs were collected; 140 active ingredients in XCHD for pneumonia treatment and immune regulation were analyzed, of which 12 ingredients had direct anti-SARS-CoV-2 activity including baicalein, formononetin, quercetin, etc. The active ingredients in XCHD exerted efficacy for pneumonia treatment and immunoregulation through 95 key targets such as IL-6, NOS2, and ESR1, involving multiple pathways such as the TNF signaling pathway, IL-17 signaling pathway, and influenza A. Analysis of gene co-expression and PPI interaction analysis found that ACE2 only co-expressed with NOS2 in the above targets, and also interacted with only five targets in the PPI interaction network. It is speculated that the ACE2 target only plays an important role when SARS-CoV-2 invaded the human body, and had little effect in the treatment of pneumonia after viral infection. Conclusion: The active ingredients in XCHD play a role in treating COVID-19 by inhibiting SARS-CoV-2 activity, blocking the SARS-CoV-2 invasion pathway, inhibiting cytokine storm, and regulating immunity. It is worth noting that drugs designed for the ACE2 target can block virus invasion, but may not be effective for diseases such as alveolar inflammation, Therefore, this study also provides a multi-target and multi-directional space for XCHD for early COVID-19 treatment. In addition, when XCHD is used in the early treatment of COVID-19, we should pay attention to the precise use of drugs based on syndrome accurate identification, one is to avoid adverse reactions, the other is to avoid cytokine damage caused by re-crown disease.


title: Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China

text: Background Although the outbreak of Coronavirus disease 2019 (COVID-19) has caused over 2200 deaths in China, there was no study about death yet. We aimed to describe the clinical characteristics of non-survivors with COVID-19. Methods For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed by real-time RT-PCR between Jan 21 and Feb 10, 2020 according to the recommended protocol. The epidemiological, demographic, clinical, laboratory, radiological and treatment data were collected and analyzed. Outcomes were followed up until Feb 14, 2020. This study was approved by the ethics commissions of the Fifth Hospital of Wuhan, with a waiver of informed consent due to a public health outbreak investigation. Results We included 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Lymphopenia occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83-225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had acute respiratory distress syndrome (ARDS). The median time from onset to ARDS was 11 days. One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. Interpretation Lots of patients died from COVID-19 till now. The median survival time of these non-survivors from onset to death was about 2 weeks. Most patients were older males with comorbidities. They finally progressed to ARDS. The median time from onset to ARDS was 11 days. Gradually decreased lymphocytes and increased inflammation biomarkers were common, and need to be monitored in the routine treatment.


title: The emergence of COVID-19 in Indonesia: analysis of predictors of infection and mortality using independent and clustered data approaches

text: Background: Analyses of correlates of SARS-CoV-2 infection or mortality have usually assessed individual predictors. This study aimed to determine if patterns of combined predictors may better identify risk of infection and mortality. Methods: For the period of March 2nd to 10th 2020, the first 9 days of the COVID-19 pandemic in Indonesia, we selected all 18 confirmed cases, of which 6 died, and all 60 suspected cases, of which 1 died; and 28 putatively negative patients with pneumonia and no travel history. We recorded data for travel, contact history, symptoms, haematology, comorbidities, and chest x-ray. Hierarchical cluster analyses (HCA) and principal component analyses (PCA) identified cluster and covariance patterns for symptoms or haematology which were analysed with other predictors of infection or mortality using logistic regression. Results: For univariate analyses, no significant association with infection was seen for fever, cough, dyspnoea, headache, runny nose, sore throat, gastrointestinal complaints (GIC), or haematology. A PCA symptom component for fever, cough, and GIC tended to increase risk of infection (OR 3.41; 95% CI 1.06 - 14; p=0.06), and a haematology component with elevated monocytes decreased risk (OR 0.26; 0.07 - 0.79; 0.027). Multivariate analysis revealed that an HCA cluster of 3-5 symptoms, typically fever, cough, headache, runny nose, sore throat but little dyspnoea and no GIC tended to reduce risk (aOR 0.048; <0.001 - 0.52; 0.056). In univariate analyses for death, an HCA cluster of cough, fever and dyspnoea had increased risk (OR 5.75; 1.06 - 31.3, 0.043), but no other individual predictor, cluster or component was associated. Other significant predictors of infection were age >= 45, international travel, contact with COVID-19 patient, and pneumonia. Diabetes and history of contact were associated with higher mortality. Conclusions: Cluster groups and co-variance patterns may be stronger correlates of SARS-CoV-2 infection than individual predictors. Comorbidities may warrant careful attention as would COVID-19 exposure levels.


title: Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa

text: While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA). While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SA government announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes.


title: Congregate Shelter Characteristics and Prevalence of Asymptomatic SARS-CoV-2

text: Background: Individuals experiencing homelessness residing in congregate homeless have increased risk for SARS-CoV-2 infection. Prevalence of asymptomatic SARS-CoV-2 in congregate shelters is high, but shelter characteristics associated with SARS-CoV-2 transmission are currently unknown. Methods: We conducted a cross-sectional, multicenter cohort study across five congregate shelters in Rhode Island. We tested people 18 years of age and older staying in Rhode Island congregate shelters in April 2020 during the COVID-19 pandemic. A survey instrument was designed and implemented based on an a priori sample size. All consented participants reported basic demographics, recent travel, duration of time at the shelter, any symptomatology, and had their temperature and pulse oximetry measured. Each participant was tested for COVID-19 using nasopharyngeal swabbing. Shelter characteristics about location, occupancy, resident length of stay, and COVID-19 mitigation strategies were collected through structured phone questionnaire with shelter staff. Results: A total of 302 individuals were screened and 299 participated across five homeless shelters. The median age was 47.9 (range 18-85) and 20% were female. Of the 299 participants, 35 (11.7%) were positive for SARS-CoV-2; rates varied among shelters, ranging from 0% to 35%. Among the participants in the study, 5% had a new cough, 4% shortness of breath, and 3% reported loss of taste or smell. Symptom prevalence did not vary significantly between positive and negative SARS-CoV-2 groups. Regular symptom screening was not associated with lower infection rates. Shelters with higher rates of positivity were in more densely populated areas, cared for a more transient populations, and instituted fewer social distancing practices for sleeping arrangements or mealtimes. Conclusions and Relevance: Residents of congregate shelters are at increased risk for asymptomatic transmission of SARS-CoV-2. To reduce transmission and enable continuation of low-threshold shelter services, there is a need for universal testing, implementation of infection control and physical distancing measures within congregate shelters, and expansion of non-congregate supportive housing.


title: Closure of Universities Due to Coronavirus Disease 2019 (COVID-19): Impact on Education and Mental Health of Students and Academic Staff

text: The novel coronavirus disease 2019 (COVID-19), originated in Wuhan city of China, has spread rapidly around the world, sending billions of people into lockdown. The World Health Organization (WHO) declared the coronavirus epidemic a pandemic. In light of rising concern about the current COVID-19 pandemic, a growing number of universities across the world have either postponed or canceled all campus events such as workshops, conferences, sports, and other activities. Universities are taking intensive measures to prevent and protect all students and staff members from the highly infectious disease. Faculty members are already in the process of transitioning to online teaching platforms. In this review, the author will highlight the potential impact of the terrible COVID-19 outbreak on the education and mental health of students and academic staff.


title: Climatic influences on the worldwide spread of SARS-CoV-2

text: The rapid global spread of the novel, pathogenic, SARS-CoV-2 causing the severe acute respiratory disease COVID-19, becomes a major health problem worldwide and pose the need for international predictive programs. Given the lack of both specific drugs and an efficient preventive vaccine, the expectation that SARS-CoV-2 transmission rate might decrease in temperate regions during summer, dominated the social scene. Here, we attempted a prediction of the worldwide spread of the infections based on climatic data, expressed by 19 bioclimatic variables. The calculated probability maps shown that potential areas of infection follow a shift from the Tropical to Temperate and Mediterranean Bioclimatic regions, and back to the Tropics again. Maps show an increased probability of infections in Europe, followed by an expansion covering areas of the Middle East and Northern Africa, as well as Eastern coastal areas of North America, South-Eastern coastal areas of Latin America and two areas of Southern Australia, and later return to areas of Southeastern Asia, in a manner similar to that of influenza strains (H3N2). Our approach may therefore be of value for the worldwide spread of SARS-CoV-2, suggesting an optimistic scenario of asynchronous seasonal global outbreaks, like other viral respiratory diseases. Consequently, we suggest the incorporation of a climatic impact in the design and implementation of public health policies. Maps of our model are available (constantly updated up to the saturation of the model) at: https://navaak.shinyapps.io/CVRisk/.


Efficient adaptive designs for clinical trials of interventions for COVID-19


title: Thermal Disinfection Inactivates SARS-CoV-2 in N95 Respirators while Maintaining Their Protective Function

text: Background: The unprecedented demand and consequent global shortage of N95 respirators during the COVID-19 pandemic have left frontline workers vulnerable to infection. To expand the supply, we validated a rapidly applicable low-cost decontamination protocol in compliance with US-regulatory guidelines to enable the safe reuse of personalized, disposable N95-respirators. Methods: Four common models of N95-respirators were disinfected for 60 minutes at {degrees}C either at 0% or 50% relative humidity (RH). Effective inactivation of SARS-CoV-2 and E. coli was evaluated in inoculated masks. The N95 filter integrity was examined with scanning electron microscopy. The protective function of disinfected N95 respirators was tested against US NIOSH standards for particle filtration efficiency, breathing resistance and respirator fit. Results: A single heat treatment inactivated SARS-CoV-2 (undetectable, detection limit: 100 TCID50/ml) and E. coli (0 colonies at 50%RH) in all four respirator models. Even N95-respirators that underwent ten dry heat, or up to five 50%RH-controlled decontamination cycles maintained their integrity and met US-governmental criteria for approval regarding fit (10x dry heat: 194.48 {+/-} 15.5; 99%CI: 185.5 to 203.5; 5x at 50%RH: 198.2 {+/-} 6.3; 99%CI: 189.4 to 207; n=23 each, pass value [≥] 100,), breathing resistance (10x dry heat: 68.0 {+/-} 8.4 Pa, 99%CI: 61.8 to 74.1, n=16; 5x at 50%RH: 78.5 {+/-} 19.7 Pa, 99%CI: 21 to 135.9, n=4, pass value [≤] 343.23Pa), and filtration levels (10x dry heat: 97.6 {+/-} 1.1%, 99%CI: 96.8 to 98.4; n=16; 5x at 50%RH: 97.18 {+/-} 0.49, 99%CI: 95.7 to 98.6, n=4, pass value [≥] 95 %). Interpretation: This rapid process enables large-scale decontamination of existing N95-respirators using commonly sourced equipment during the COVID-19 pandemic.


title: Modelling the Potential Health Impact of the COVID-19 Pandemic on a Hypothetical European Country

text: A SEIR simulation model for the COVID-19 pandemic was developed (http://covidsim.eu) and applied to a hypothetical European country of 10 million population. Our results show which interventions potentially push the epidemic peak into the subsequent year (when vaccinations may be available) or which fail. Different levels of control (via contact reduction) resulted in 22% to 63% of the population sick, 0.2% to 0.6% hospitalised, and 0.07% to 0.28% dead (n=6,450 to 28,228).


Letter to the Editor: Holding the (Front) Line Against COVID-19 Breaking News: What Should EPs Say about COVID-19 to Discharged ED Patients?


title: Bats Possess Unique Variants of the Antiviral Restriction Factor Tetherin

text: Bats are recognized as important reservoirs of viruses deadly to other mammals, including humans. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and other mammals. Tetherin is an important restriction factor which inhibits the release of a diverse range of viruses from host cells, including retroviruses, coronaviruses, filoviruses, and paramyxoviruses, some of which are deadly to humans and transmitted by bats. Here we characterise the tetherin genes from 27 species of bats, revealing that they are under strong selective pressure, and that fruit bats and vesper bats express unique structural variants of the tetherin protein. The expression of two computationally predicted splice isoforms of fruit bat tetherin is verified here, and we identify an additional third unique splice isoform which includes a C-terminal region that is not homologous to known mammalian tetherin variants. We also report that vesper bats possess and express at least five tetherin genes, including structural variants, a greater number than any other mammal reported to date. These findings support the hypothesis of differential antiviral gene evolution in bats relative to other mammals.


title: Feasibility and sociopsychological impact of video consultations in medical oncology - a randomized controlled open label trial

text: Background: Mobile phone video call applications generally did not undergo testing in randomized controlled clinical trials prior to their implementation in patient care regarding the rate of successful patient visits and impact on the physician-patient relationship. Methods: The NCT MOBILE trial was a monocentric open-label randomized controlled clinical trial of patients with solid tumors undergoing systemic cancer therapy with need of a follow-up visit with their consulting physician at outpatient clinics. 66 patients were 1:1 randomized to receive either a standard in-person follow-up visit at outpatient clinics or a video call via a mobile phone application. The primary outcome was feasibility defined as the number of successful appointments at the first follow up visit. Secondary outcomes included success rate of further video calls, time spent by patient and physician, patient satisfaction, and quality of physician-patient relationship. Findings: Success rate of the first follow up visit in the intention-to-treat cohort was 87.8% for in-person visits and 78.7% for video calls (p=0.51, RR=0.88-1.43 95%CI). The most common reasons for failure were software incompatibility (12%) in the video call and no-show (6%) in the in-person visit arm. The success rate for further video visits was 91.6% (11 of 12 calls). Standardized patient questionnaires showed significantly decreased total time spent and less direct costs for patients (95 to 246min 95%CI, & 4.8 to 23.9 Euro 95%CI) and comparable time spent for physicians in the video call arm (-6.4 to 5.4min 95%CI). Doctor-patient relationship quality mean scores assessed by the validated standardized 'questionnaire on quality of physician-patient interaction' (QQPPI) were higher in the video call arm (video call/in-person = 1.12 fold, p=0.02). Interpretation: Follow-up visits with the tested mobile phone video call application were feasible but software compatibility should be critically evaluated. Trial registration: Retrospectively registered in the German Clinical Trials Register DRKS00015788, 26th October 2018


title: Two-Dimensional Matter: Order, Curvature and Defects

text: Many systems in nature and the synthetic world involve ordered arrangements of units on two-dimensional surfaces. We review here the fundamental role payed by both the topology of the underlying surface and its detailed curvature. Topology dictates certain broad features of the defect structure of the ground state but curvature-driven energetics controls the detailed structured of ordered phases. Among the surprises are the appearance in the ground state of structures that would normally be thermal excitations and thus prohibited at zero temperature. Examples include excess dislocations in the form of grain boundary scars for spherical crystals above a minimal system size, dislocation unbinding for toroidal hexatics, interstitial fractionalization in spherical crystals and the appearance of well-separated disclinations for toroidal crystals. Much of the analysis leads to universal predictions that do not depend on the details of the microscopic interactions that lead to order in the first place. These predictions are subject to test by the many experimental soft and hard matter systems that lead to curved ordered structures such as colloidal particles self-assembling on droplets of one liquid in a second liquid. The defects themselves may be functionalized to create ligands with directional bonding. Thus nano to meso scale superatoms may be designed with specific valency for use in building supermolecules and novel bulk materials. Parameters such as particle number, geometrical aspect ratios and anisotropy of elastic moduli permit the tuning of the precise architecture of the superatoms and associated supermolecules. Thus the field has tremendous potential from both a fundamental and materials science/supramolecular chemistry viewpoint.


title: Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes

text: Our researchers took a look at a sequence of DNA known as the ACE2 gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it’s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at the ACE2 gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case the ACE2 gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven’t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic). We found that there are a number of variations observed among people in a specific part of the ACE2 gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don’t yet know what the real-life significance of this variation is, but it’s possible that these variants decrease the protein’s ability to interact with the SARS-CoV-2 virus, thus decreasing the person’s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of the ACE2 gene may be one of the reasons. The research we presented here shines a light on this part of the ACE2 gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.


title: SARS-CoV-2 in first trimester pregnancy - does it affect the fetus?

text: Background Several viral infections are known to be harmful to the fetus in the first trimester of pregnancy and can cause increased nuchal translucency thickness and pregnancy loss. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. Methods Cohort 1 included pregnant women with a double test taken between Feb. 17 and Apr. 23, 2020, during the SARS-CoV-2 epidemic peak in Denmark. The double test was taken as part of the first trimester risk assessment. Cohort 2 included women with a first trimester pregnancy loss before double test. Serum from the double test or from a blood sample, in case of pregnancy loss, was analyzed for SARS-CoV-2 antibodies. The results were correlated to the nuchal translucency thickness and the number of pregnancy losses. Results In total, 1,019 pregnant women with double test and 36 women with pregnancy loss participated in the study. Thirty (2.9%) women had SARS-CoV-2 antibodies in the serum from the double test. All women with pregnancy loss prior to the double test were negative for SARS-CoV-2 antibodies. There were no significant differences in nuchal translucency thickness for women testing positive (n=14) versus negative (p=0.20) or grey zone (n=16) versus negative (p=0.28). In total, 54 women experienced a pregnancy loss of whom two had grey zone or positive SARS-CoV-2 antibodies. Conclusion Maternal SARS-CoV-2 infection did not seem harmful in first trimester pregnancies. Infection had no effect on the nuchal translucency thickness and women with SARS-CoV-2 antibodies were not overrepresented among women with pregnancy loss.


title: Knowledge, Attitude and Practice among Healthcare Professionals regarding COVID-19: A cross-sectional survey from Pakistan

text: Introduction Coronavirus disease (COVID-19) is a highly transmittable infection and Pakistan due to its geographical location is vulnerable to a worst outbreak. Pakistan faces sudden hike in number of positive cases including number of healthcare professionals (HCPs) also acquired infection. Therefore, the aim of study is to assess knowledge, attitude and practice among HCPs in Pakistan regarding COVID-19. Methods An online survey-based study was conducted during the month of March among healthcare professionals including physicians, pharmacists and nurses. A self-administered validated (Cronbach alpha= 0.077) questionnaire comprised of five sections (Demographics, Knowledge, attitude, practice and perceived barriers) were used for data collection. Descriptive and inferential statistics were applied by using SPSS version 21. Results Of 414 participants, 29.98% (n=120) physicians, 46.65% (n= 189) pharmacists and 25.36% (n= 105) nurses. Most commonly utilized information source was social media. Findings showed HCPs have good knowledge (93.2%, n=386), positive attitude and good practice regarding COVID-19. HCPs perceived that limited infection control material and poor knowledge regarding transmission of COVID-19 are the major barriers in infection control practice. Factors such as age, experience and job were significantly associated with good knowledge and practice. Conclusion HCPs in Pakistan have good knowledge, reflected by positive attitude and good practice. Yet, there are areas where gaps in knowledge and practice was observed. To effectively control infection spread, well-structured training programs must be launched by government targeting all kinds of HCPs to raise their existed knowledge.


title: Sensitivity and specificity of a rapid test for assessment of exposure to SARS-CoV-2 in a community-based setting in Brazil

text: Background: While the recommended laboratory diagnosis of COVID-19 is a molecular based assay, population-based studies to determine the prevalence of COVID-19 usually use serological assays. Objective: To evaluate the sensitivity and specificity of a rapid diagnostic test for COVID-19 compared to quantitative reverse transcription polymerase chain reaction (qRT-PCR). Methods: We evaluated the sensitivity using a panel of finger prick blood samples from participants >18 years of age that had been tested for COVID-19 by qRT-PCR. For assessing specificity, we used serum samples from the 1982 Pelotas (Brazil) Birth Cohort participants collected in 2012 with no exposure to SARS-CoV-2. Results: The sensitivity of the test was 77.1% (95% CI 66.6 - 85.6), based upon 83 subjects who had tested positive for qRT-PCR at least 10 days before the rapid diagnostic test (RDT). Based upon 100 sera samples, specificity was 98.0% (95% CI 92.9 - 99.8). There was substantial agreement (Kappa score 0.76) between the qRT-PCR results and the RDT. Interpretation. The validation results are well in line with previous assessments of the test, and confirm that it is sufficiently precise for epidemiological studies aimed at monitoring levels and trends of the COVID-19 pandemic.


title: In silico Proteome analysis of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (2019-nCoV), is a positive-sense, single-stranded RNA coronavirus. The virus is the causative agent of coronavirus disease 2019 (COVID-19) and is contagious through human-to-human transmission. The present study reports sequence analysis, complete coordinate tertiary structure prediction and in silico sequence-based and structure-based functional characterization of full SARS-CoV-2 proteome based on the NCBI reference sequence NC_045512 (29903 bp ss-RNA) which is identical to GenBank entry MN908947 and MT415321. The proteome includes 12 major proteins namely orf1ab polyprotein (includes 15 proteins), surface glycoprotein, ORF3a protein, envelope protein, membrane glycoprotein, ORF6 protein, ORF7a protein, orf7b, ORF8, Nucleocapsid phosphoprotein and ORF10 protein. Each protein of orf1ab polyprotein group has been studied separately. A total of 25 polypeptides have been analyzed out of which 15 proteins are not yet having experimental structures and only 10 are having experimental structures with known PDB IDs. Out of 15 newly predicted structures six (6) were predicted using comparative modeling and nine (09) proteins having no significant similarity with so far available PDB structures were modeled using ab-initio modeling. Structure verification using recent tools QMEANDisCo 4.0.0 and ProQ3 for global and local (per-residue) quality estimates indicate that the all-atom model of tertiary structure of high quality and may be useful for structure-based drug designing targets. The study has identified nine major targets (spike protein, envelop protein, membrane protein, nucleocapsid protein, 2’-O-ribose methyltransferase, endoRNAse, 3’-to-5’ exonuclease, RNA-dependent RNA polymerase and helicase) for which drug design targets could be considered. There are other 16 nonstructural proteins (NSPs), which may also be percieved from the drug design angle. The protein structures have been deposited to ModelArchive. Tunnel analysis revealed the presence of large number of tunnels in NSP3, ORF 6 protein and membrane glycoprotein indicating a large number of transport pathways for small ligands influencing their reactivity.


title: Various RNA-binding proteins and their conditional networks explain miRNA biogenesis and help to reveal the potential SARS-CoV-2 host miRNAome system

text: Background In-spite of ubiquitous expression of DROSA/DICER, miRNA formation and maturation are highly spatiotemporal implying involvement of other factors in their biogenesis. Several key studies have elucidated functions of few other RNA-binding proteins (RBPs) in miRNAs biogenesis, making it necessary to look miRNA biogenesis models with fresh approach. Results A comprehensive study of >25TB of high-throughput data revealed that various combinations of RBPs and their networks determine the miRNA pool, regardless of DROSHA/DICER. The discovered RBP and miRNA associations displayed strong functional alliances. An RBP, AAR2, was found highly associated with miRNAs biogenesis, which was experimentally validated. The RBPs combinations and networks were tested successfully across a large number of experimentally validated data and cell lines for the observed associations. The RBP networks were finally modeled into a XGBoosting-regression based tool to identify miRNA profiles without any need of doing miRNA-seq, which scored a reliable average accuracy of 91% on test sets. It was further tested across >400 independent experimental samples and scored consistently high accuracy. This tool was applied to reveal the miRNAome of Covid19 patients about which almost negligible information exists. A significant number of Covid19 specific miRNA targets were involved in IFN-gamma, Insulin/IGF/P3K/AKT, and Ub-proteasome systems, found in cross-talk with each other and down-regulated heavily, holding promise as strong candidates for therapeutic solution. A large number of them belonged to zinc-finger family. Conclusion There are several RBPs and their networks responsible for miRNA biogenesis, regardless of DROSHA/DICER. Modeling them successfully can reveal miRNAomes with deep reaching impact.


title: Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic

text: Given the higher mortality rate and widespread phenomenon of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) within the United States (US) population, understanding the mutational pattern of SARS CoV-2 has global implications for detection and therapy to prevent further escalation. Los Angeles has become an epicenter of the SARS-CoV-2 pandemic in the US. Efforts to contain the spread of SARS-CoV-2 require identifying its genetic and geographic variation and understanding the drivers of these differences. For the first time, we report genetic characterization of SARS-CoV-2 genome isolates in the Los Angeles population using targeted next generation sequencing (NGS). Samples collected at Cedars Sinai Medical Center were collected from patients with confirmed SARS-CoV-2 infection. We identified and diagnosed 192 patients by our in-house qPCR assay. In this population, the highest frequency variants were in known mutations in the 5'UTR, AA193 protein, RdRp and the spike glycoprotein. SARS-CoV-2 transmission within the local community was tracked by integrating mutation data with patient postal codes with two predominant community spread clusters being identified. Notably, significant viral genomic diversity was identified. Less than 10 percent of the Los Angeles community samples resembled published mutational profiles of SARS-CoV-2 genomes from China, while >50 percent of the isolates shared closely similarities to those from New York State. Based on these findings we conclude SARS-CoV-2 was likely introduced into the Los Angeles community predominantly from New York State but also via multiple other independent transmission routes including but not limited to Washington State and China.


title: Analysis of pathogenesis clauses and prescriptions of “Treatise on differentiation and treatment of epidemic febrile disease” related to clinical symptoms of COVID-19/ 《温病条辨》中与新型冠状病毒肺炎临床表现相关条文病机和方药分析

text: Objective: To collect the clinical symptoms of novel coronavirus pneumonia, explore and analyze the clauses and prescriptions related to the clinical symptoms of 2019 novel coronavirus pneumonia in “Treatise on differentiation and treatment of epidemic febrile disease”, in order to provide a reference for clinical treatments of the disease. Methods: Searching literature from the databases CNKI and PubMed by entering “novel coronavirus” (in Chinese) and “2019 Novel Coronavirus” as key words, classifying typical symptoms depending on their reported frequencies of occurrence, comparing with related pathogenesis in “Treatise on differentiation and treatment of epidemic febrile disease”, and analyzing clauses and prescriptions combined with the sixth version of “New coronavirus pneumonia diagnosis and treatment scheme”. Results: We optimized 20 literatures published in Chinese or English for the review, in which, a total of 647 clinical cases were reported. Based on that, 28 typical symptoms were summarized, including respiratory symptoms, such as fever and cough; Gastrointestinal symptoms, such as poor appetite, nausea, vomiting, diarrhea; Other symptoms, such as myalgia, fatigue, and so forth. Among them, fever (558 cases), cough (395 cases), and fatigue (257 cases) were the top three clinical symptoms. By analysis, we optimized 15 clauses, 18 prescriptions, and 46 traditional Chinese medicines from “Treatise on differentiation and treatment of epidemic febrile disease”, including two clauses in the upper energizer, nine in the middle energizer, and four in the lower energizer; A total of seven prescriptions for treating dampness-heat, five for cold-dampness, and six for warm-heat diseases; as well as Chinese medicines Pinellia ternata (mentioned for six times), Cinnamomi Ramulus (five times), Tetrapanacis Medulla (five times), Poria cocos (four times), Talcum (four times), Coptis chinensis (four times) and Coicis Semen (four times), etc. P. ternata, Cinnamomi Ramulus, C. chinensis, Scutellaria baicalensis, and Zingiberis Rhizoma were selected to treat dampness-heat diseases, in order to “pungency opening and bitter discharging”; P. cocos, Tetrapanacis Medulla, Talcum, and Coicis Semen were selected for “eliminating dampness with bland medicinal”; Almond, Amomum kravanh, and Magnolia officinalis were used to “regulating qi movement”; Anemarrhenae Rhizoma, Gypsum Fibrosum, and Forsythiae Fructus were used to treat warm-hot diseases for “purging fire and removing toxin”. The formula of Sanren Decoction, Yiyizhuye Powder can be used for people in the stage of medical observation period; Sanren Decoction, Yiyizhuye Powder, Xingrenyiyi Decoction, Wuling Powder, Baihujiaguizhi Decoction, and Lingjiangzhugui Decoction for treating mild cases; Huangqin Huashi Tang, Xingren Huashi Decoction, and Fulingpi Decoction for severe cases; Jiaomei Decoction, Jianweiwumei Pill, Sini Decoction, and Taohua Porridge for critical patients, and Maidong Maren Decoction, Wuzhi Yin, and Niuru Yin for convalescents. Conclusion: The prescriptions of “Treatise on differentiation and treatment of epidemic febrile disease” can provide reference for the clinical treatments of 2019 novel coronavirus pneumonia.


title: Regression models predicting the number of deaths from the new coronavirus infection

text: Predicting the development of epidemic infection caused by the COVID-19 coronavirus is a matter of the utmost urgency for health care and effective anti-epidemic measures. Given the rapidly changing initial information and the ambiguous quality of data coming from various sources, it is important to quickly optimize the existing prognostic models by using more sophisticated algorithms. The aim of the study is to test the originally developed mathematical algorithms for predicting the development of the COVID-19 epidemic process. Materials and Methods. To assess the situation in China, Italy, and the USA, we used the information from Russian- and Englishlanguage sources available in official websites. The generally accepted descriptive statistics were used; mathematical modeling was based on linear regression. Statistical data processing was performed using the IBM SPSS Statistics 24.0 and R (RStudio) 3.6.0. Results. We found significant differences not only in the incidence rate of COVID-19 in the countries in question, but also in the death rate. The risk of death associated with COVID-19 is high due to the high number of severe clinical cases of the disease reported from these countries. Two preliminary regression models were created. The first, initial model was based on the increase in new cases of infection — this factor was significantly associated with the outcome; the regression coefficient was 0.02 (95% CI 0.01–0.03). In the second, expanded model, in addition to the increase in new cases, the increase in the number of severe forms of infection was also considered; the regression coefficients were 0.017 (95% CI 0.012–0.022) and 0.01 (95% CI 0.008–0.011), respectively. Adding the second variable contributed to a more accurate description of the available data by the model. Conclusion. The developed regression models for infection control and predicting the number of lethal outcomes can be successfully used under conditions of spreading diseases from the group of “new infections” when primary data received from various sourced are changing rapidly and updates of the information are continually required. In addition, our initial model can produce a preliminary assessment of the situation, and the expanded model can increase the accuracy and improve the analytic algorithm.


Maintaining emotional well-being during the COVID-19 pandemic: A resource for your patients


title: First Case of an Infant with COVID-19 in the Middle East

text: The novel coronavirus (COVID-19) has been declared a worldwide pandemic. It was initially thought to spare children and adolescents as significantly smaller number of cases have been reported in the pediatric population in comparison to adults. Here, we report the case of a 16-month-old female infant from Lebanon who presented with fever and severe diarrhea and tested positive for COVID-19. Her symptoms started six days prior to presentation with no cough, rhinorrhea, or other respiratory manifestations reported. Chest radiography showed lobar consolidation and bronchial infiltrates. Blood culture was positive for Streptococcus pneumoniae. Stool and urine cultures were negative. She was treated with ceftriaxone and metronidazole. Her RT-PCR test was negative after five days of treatment, suggesting that children can clear the virus faster than adults. The patient likely contracted the virus from her parents, who because of the fear of social stigma hide recent history of respiratory illness. These findings serve as a practical reference for the clinical diagnosis and medical treatment of children with COVID-19.


title: Fast initial Covid-19 response means greater caution may be needed later

text: As the Covid-19 pandemic unfolds it is becoming increasingly clear that the strength of the first wave of the epidemic varies significantly between countries. In this study a simple numerical model is used to illustrate the impact the timing of initial measures against Covid-19 has on the first wave of infection and possible implications this may have for the measures taken as the first wave is ebbing. The results highlight that delaying measures by 10 days is sufficient to largely account for the differences seen between countries such as the UK and Germany for the first wave of infections. A pronounced first wave means that a larger fraction of the total population will have been infected and is therefore likely to display immunity. Even if this fraction is far below the level needed for "herd immunity" the effective reproduction factor Re is decreased compared to a population that had no prior exposure to the virus. Even a small reduction in Re can have major influence on the evolution of the epidemic after the first wave of infections. A large first wave means the resulting value for Re will be lower than if the first wave was mild. Without either vaccine or effective treatment countries who experienced a small first wave should therefore relax measures at a slightly lower pace than countries where the first wave was strong.


title: Structural interactions between pandemic SARS-CoV-2 spike glycoprotein and human Furin protease

text: The SARS-CoV-2 pandemic is an urgent global public health emergency and warrants investigating molecular and structural studies addressing the dynamics of viral proteins involved in host cell adhesion. The recent comparative genomic studies highlight the insertion of Furin protease site in the SARS-CoV-2 spike glycoprotein alerting possible modification in the viral spike protein and its eventual entry to host cell and presence of Furin site implicated to virulence. Here we structurally show how Furin interacts with the SARS-CoV-2 spike glycoprotein homotrimer at S1/S2 region, which underlined the mechanism and mode of action, which is a key for host cell entry. Unravelling the structural features of biding site opens the arena in rising bonafide antibodies targeting to block the Furin cleavage and have great implications in the development of Furin inhibitors or therapeutics.


docid: yasxgzgp

title: Recomendaciones para el manejo de pacientes que requieren atención oftalmológica durante la pandemia de SARS-CoV-2/ Recommendations for the management of patients that require eye care during the SARS-CoV-2 pandemic


title: Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials

text: Purpose: This study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. Method: A rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. Results: A total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. Conclusion: Based on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties. Keywords: COVID-19, Systematic review, Clinical trial, Chloroquine, Hydroxychloroquine


High Anxiety: Helping Your Patients (and Yourself) Cope With the Impact of COVID-19


title: Using newspapers obituaries to nowcast daily mortality: evidence from the Italian COVID-19 hot-spots

text: Real-time tracking of infectious disease outbreaks helps policymakers to make timely data-driven decisions. Official mortality data, whenever available, may be incomplete and published with a substantial delay. We report the results of using newspapers obituaries to nowcast the mortality levels observed in Italy during the COVID-19 outbreak between February 24, 2020 and April 15, 2020. We find that the mortality levels predicted using newspapers obituaries outperforms forecasts based on past mortality according to several performance metrics, making obituaries a potentially powerful alternative source of information to deal with real-time tracking of infectious disease outbreaks.


title: Compassionate drug (mis)use during pandemics: lessons for COVID-19 from 2009.

text: Background: New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions, and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed, and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics. Methods: We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease. Results: 33869 treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. 592 patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results were available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended. Conclusion: Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.


docid: ebsqjwmd

title: Incidence, risk factors and mortality outcome in patients with acute kidney injury in COVID-19: a single-center observational study


title: Association of County-Level Socioeconomic and Political Characteristics with Engagement in Social Distancing for COVID-19

text: The U.S. is the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. In response, governments have implemented measures to slow transmission through "social distancing." However, the practice of social distancing may depend on prevailing socioeconomic conditions and beliefs. Using 15-17 million anonymized cell phone records, we find that lower per capita income and greater Republican orientation were associated with significantly reduced social distancing among U.S. counties. These associations persisted after adjusting for county-level sociodemographic and labor market characteristics as well as state fixed effects. These results may help policymakers and health professionals identify communities that are most vulnerable to transmission and direct resources and communications accordingly.


title: The relative power of individual distancing efforts and public policies to curb the COVID-19 epidemics

text: Lockdown curbs the COVID-19 epidemics but at huge costs. Public debates question its impact ompared with reliance on individual responsibility. We aim at understanding how rationally chosen self-protective behavior impacts the spread of the epidemics. We want to, first, assess the value of lockdown compared to a counterfactual that incorporates self-protection efforts under unknown disease prevalence; and second, assess how individual behavior modify the epidemic dynamics when mandatory policies are relaxed. We couple an SLIAR model, that includes asymptomatic transmission, with utility maximization: Individuals trade off economic and wellbeing costs from physical distancing with a lower infection risk. Effort depends on risk aversion, perceptions, and the value of contacts. In a Nash equilibrium, individual uncoordinated efforts yield average contact intensity, which drives epidemic transmission. Equilibrium effort differs markedly from constant, stochastic or proportional contacts reduction. It adjusts to reported cases in a way that creates a slightly decreasing plateau in epidemic prevalence. Calibration on French data shows that the number of deaths with no lockdown but equilibrium efforts is only 1/6 to 1/10 of the number predicted with business-as-usual. However, lockdown saves at least 50% more lives than individual efforts alone. Prolonged weaker restrictions prevent an exponential rebound. Public policies post-lockdown have a limited impact as they partly crowd out individual efforts. Compulsory mask wearing helps resume activity but has no impact on the epidemic. Communication that increases risk salience is more effective.


title: The differential impact of physical distancing strategies on social contacts relevant for the spread of COVID-19

text: Physical distancing measures are intended to mitigate the spread of COVID-19. However, the impact these measures have on social contact and disease transmission patterns remains unclear. We ran the first comparative contact survey (N=53,708) across eight countries (Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States) for the period March 13 - April 13, 2020. Our results show that social contact numbers mainly decreased after governments issued physical distancing guidelines rather than after announcing national lockdown measures. Compared to pre-COVID levels, social contact numbers decreased by 48% - 85% across countries. Except in Italy, these reductions were smaller than those observed in Wuhan (China). However, they sufficed to bring the R0 below one in almost every context considered. Finally, in all countries studied, the numbers of contacts decreased more rapidly among older people than among younger people, indicating higher levels of protection for groups at greater risk.


title: Does susceptibility to novel coronavirus (COVID-19) infection differ by age?: Insights from mathematical modelling

text: Among Italy, Spain, and Japan, the age distributions of novel coronavirus (COVID-19) mortality show only small variation even though the number of deaths per country shows large variation. To understand the determinant for this situation, we constructed a mathematical model describing the transmission dynamics and natural history of COVID-19 and analyzed the dataset of fatal cases of COVID-19 in Italy, Spain, and Japan. We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, taking into account the effect of change in contact patterns during the outbreak of COVID-19, and the fraction of symptomatic COVID-19 infections. Our modelling study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R0). Variation of susceptibility by age itself cannot explain the robust age distribution in mortality by COVID-19 in those three countries, however it does suggest that the age-dependencies of i) the mortality rate and ii) the fraction of symptomatic infections among all COVID-19 cases determine the age distribution of mortality by COVID-19.


title: Luteolin transforms the BMDM polarity to regulate the expression of inflammatory factors

text: Macrophage are indispensable regulator cells in inflammatory response. Macrophage polarization and its secreted inflammatory factors have affinity with the outcomes of inflammation. Luteolin, a flavonoid abundant in plants has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarization of BMDM to suppress inflammation is still veiled. The purpose of this study was to observe the effects of luterolin on the polarity of BMDM derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism of luteolin regulating the BMDM polarity. M1-polarized BMDM were induced by LPS+IFN-γ, M2-polarization were stimulated with IL-4. BMDM morphology was observed by laser confocal microscopy; levels of BMDM differentiation and CD11c or CD206 on membrane surface were assessed by FCM; mRNA and protein of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. The isolated mouse bone marrow cells were successfully differentiated into BMDM, LPS+IFN-γ induced BMDM M1-phenotype polarization, and IL-4 induced its M2-phenotype polarization. After M1-polarized BMDM treated with luteolin, M1-type pro-inflammatory factors including IL-6, TNF-α□iNOS, CD86 were down-regulated while M2-type anti-inflammatory factors including IL-10, Arg1, CD206 were up-regulated; the expression of M1-type surface marker CD11c decreased, nevertheless, M2-type marker CD206 increased; levels of inflammatory signaling protein p-STAT1 and p-STAT6 were attenuated and enhanced respectively. Our study suggests luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin hold promise as an anti-inflammatory and immunomodulatory agent.


title: Smoking Prevalence is Low in Symptomatic Patients Admitted for COVID-19.

text: There is currently little information regarding the role of active smoking in predisposing to SARS-CoV-2 infection. This retrospective case series includes 441 patients with confirmed Covid-19, who were consecutively admitted between March 5 and March 31, 2020, at a tertiary referral center in Parma, Northern Italy, with laboratory-confirmed COVID-19. 273 (62%) patients were males. Median age was 71 y/o, 156 patients (35%) died during hospitalization and 285 (65%) were discharged because clinically healed. 21 patients (5%) were active smokers and 44 (10%) were ex-smokers, while 376 (85%) were non-smokers. Male sex, history of prior cardiovascular disease, D-dimer and C-reactive protein were significantly more prevalent or higher in the subgroup of 156 patients who died during hospital stay, compared with 285 patients discharged alive. Active smokers were only 21, this number corresponding to less than 5% prevalence of active smokers, which is disproportionately low compared with the 24% prevalence of smokers in the general Italian population (p<0.001). The very low prevalence of smokers in our COVID-19 cohort seemingly replicates the findings that can be extracted from descriptive tables in Chinese reports and also in the recent US reports from New York City. The current study is useful since it suggests that smokers may carry some type of protective mechanism from symptomatic SARS-CoV-2 infection, although this should definitely be confirmed in specifically-designed, controlled studies.


title: Heterogeneity in SIR epidemics modeling: superspreaders

text: Deterministic epidemic models, such as the Susceptible-Infected-Recovered (SIR) model, are immensely useful even if they lack the nuance and complexity of social contacts at the heart of network science modeling. Here we present a simple modification of the SIR equations to include the heterogeneity of social connection networks. A typical power-law model of social interactions from network science reproduces the observation that individuals with a high number of contacts, ``hubs'' or ``superspreaders'', can become the primary conduits for transmission. Conversely, once the tail of the distribution is saturated, herd immunity sets in at a smaller overall recovered fraction than in the analogous SIR model. The new dynamical equations suggest that cutting off the tail of the social connection distribution, i.e., stopping superspreaders, is an efficient non-pharmaceutical intervention to slow the spread of a pandemic, such as COVID-19.


title: Assessment of N95 and K95 respirator decontamination: fiber integrity, filtration efficiency, and dipole charge density.

text: Personal protective equipment (PPE) including N95 respirators are critical for persons exposed to SARS-CoV-2. KN95 respirators and N95 decontamination protocols have been described as solutions to a lack of such PPE. However, there are a few materials science studies that characterize the charge distribution and physical changes accompanying disinfection treatments particularly heating. Here, we report the filtration efficiency, dipole charge density, and fiber integrity of pristine N95 and KN95 respirators before and after various decontamination methods. We found that the filter layer of N95 is 8-fold thicker than that of KN95, which explains its 10% higher filtration efficiency (97.03 %) versus KN95 (87.76 %) under pristines condition. After 60 minutes of 70 {degrees}C treatment, the filtration efficiency and dipole charge density of N95 became 97.16% and 12.48 {micro}C/m2, while those of KN95 were 83.64% and 1.48 {micro}C/m2 ; moreover, fit factor of N95 was 55 and that of KN95 was 2.7. In conclusion, the KN95 respirator is an inferior alternative of N95 respirator. In both systems, a loss of electrostatic charge does not directly correlate to a decrease in performance.


title: Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model

text: Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Reports indicate that 30-60% of patients with COVID-19 suffer from CNS symptoms. Yet, there is no consensus whether the virus can infect the brain, or what the consequences of infection are. Following SARS-CoV-2 infection of human brain organoids, clear evidence of infection was observed, with accompanying metabolic changes in the infected and neighboring neurons. Further, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Finally, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV2.


title: Implementing a Negative Pressure Isolation Space within a Skilled Nursing Facility to Control SARS-CoV-2 Transmission

text: Background: Isolation space must be expanded during pandemics involving airborne transmission. Little to no work has been done to establish optimal design strategies and implementation plans to ease surge capacity and expand isolation capacity over long periods in congregate living facilities. The COVID-19 pandemic has an airborne transmission component and requires isolation, which is difficult to accomplish in skilled nursing facilities. Purpose: In this study we designed, implemented, and validated an isolation space at a skilled nursing facility in Lancaster, PA. The overall goal was to minimize disease transmission between residents and staff within the facility. Basic Procedures: We created an isolation space by modifying an existing HVAC system of the SNF. We measured pressure on-site and performed computational fluid dynamics and Lagrangian particle-based modeling to test containment and possible transmission extent given the isolation space is considered negative rather than individual rooms. Main Findings: Pressure data shows the isolation space maintained an average hourly value of (standard deviation) -2.3 Pa (0.12 Pa) pressure differential between it and the external hallway connected to the rest of the facility. No transmission of SARS-CoV-2 between residents isolated to the space occurred, nor did any transmission to the staff or other residents occur. The isolation space was successfully implemented and, as of writing, continues to be operational through the pandemic. Key Words: aerosol transmission, airborne transmission, surge capacity, engineering controls, congregate living facilities


title: Immunization and participation in amateur youth sports

text: Although inadequate immunization is a significant public health problem, as covid-19 is an urgent reminder, it has been largely ignored in amateur youth sports. By comparison, safety issues such as concussions have drawn extensive concern. This article examines the case for immunizing athletes who participate in amateur sports for youth. It begins with risks of transmission and current gaps in addressing immunization of amateur athletes. It then considers arguments for immunization, along with objections to immunization requirements for participation. The article concludes that amateur youth sports organizations must pay far more attention to immunization than they currently do, have published policies about immunization, inform participants of these policies, and educate athletes, coaches, and officials about contagion risks.


title: Neutralization of SARS-CoV-2 by destruction of the prefusion Spike

text: There are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding would facilitate conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment. Highlights CR3022 neutralises SARS-CoV-2 Neutralisation is by destroying the prefusion SPIKE conformation This antibody may have therapeutic potential alone or with one blocking receptor attachment


title: The COVID-19 Crisis: A Mental Health Perspective and Response Using Telemedicine

text: With the outbreak of COVID-19, patients and providers were forced to isolate and become innovative in ways to continue exceptional patient care. The Cleveland Clinic went from mostly in-person medical appointments to all virtual/telemedicine care in about 2 weeks’ time. In this piece, we show specifically the thought process and our conversion of the Mellen Center for Multiple Sclerosis Behavioral Medicine to ensure that our patients still receive exceptional care and patient experience. Additionally, we discuss the importance of innovating the training and supervision of postdoctoral trainees using telepsychology and virtual options.


SARS-CoV-2: Deutsche Rückkehrer aus Wuhan betroffen?


title: The Rapid Deployment of a 3D Printed Latticed Nasopharyngeal Swab for COVID-19 Testing Made Using Digital Light Synthesis

text: The novel coronavirus disease (COVID-19) has caused a pandemic that has disrupted supply chains globally. This black swan event is challenging industries from all sectors of the economy including those industries directly needed to produce items that safeguard us from the disease itself, especially personal protection equipment (N95 masks, face shields) and much needed consumables associated with testing and vaccine delivery (swabs, vials and viral transfer medium). Digital manufacturing, especially 3D printing, has been promulgated as an important approach for the rapid development of new products as well as a replacement manufacturing technique for many traditional manufacturing methods, including injection molding, when supply chains are disrupted. Herein we report the use of Digital Light Synthesis (DLS) for the design and large-scale deployment of nasopharyngeal (NP) swabs for testing of coronavirus SARS-CoV-2 infections in humans. NP swabs have been one of society's essential products hardest hit by the supply chain disruptions caused by COVID-19. A latticed tip NP swab was designed and fabricated by DLS from a liquid resin previously developed and approved for use to make dental night guard devices. These latticed NP swabs demonstrated non-inferiority in a human clinical study of patients suspected of being infected with SARS-CoV-2.


title: No SARS-CoV-2 in expressed prostatic secretion of patients with coronavirus disease 2019: a descriptive multicentre study in China

text: Abstract Purpose: The aim of the present study was to assess whether SARS-CoV-2 can be detected in the expressed prostatic secretion (EPS) of patients with corona virus disease 2019 (COVID-19). Methods: 18 cases of COVID-19, and 5 suspected cases, were selected from three medical centers to detect the RNA expression of SARS-CoV-2 in their EPS with RT-PCR. Results: Results were negative in all EPS samples for SARS-CoV-2 of suspected and confirmed patients. Conclusions: No SARS-CoV-2 was expressed in EPS of patients with COVID-19.


title: The Potential Use of Unprocessed Sample for RT-qPCR Detection of COVID-19 without an RNA Extraction Step

text: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection.1–4 It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. With many PCR-based molecular assays, an extraction step is routinely used as part of the protocol. This step can take up a significant amount of time and labor, especially if the extraction is performed manually. Long assay time, partly caused by slow sample preparation steps, has created a large backlog when testing patient samples suspected of COVID-19. Using flu and RSV clinical specimens, we have collected evidence that the RT-qPCR assay can be performed directly on patient sample material from a nasal swab immersed in virus transport medium (VTM) without an RNA extraction step. We have also used this approach to test for the direct detection of SARS-CoV-2 reference materials spiked in VTM. Our data, while preliminary, suggest that using a few microliters of these untreated samples still can lead to sensitive test results. If RNA extraction steps can be omitted without significantly affecting clinical sensitivity, the turn-around time of COVID-19 tests and the backlog we currently experience can be reduced drastically. Next, we will confirm our findings using patient samples.


title: A novel cohort analysis approach to determining the case fatality rate of COVID-19 and other infectious diseases

text: As the Coronavirus contagion develops, it is increasingly important to understand the dynamics of the disease. Its severity is best described by two parameters: its ability to spread and its lethality. Here, we combine a mathematical model with a cohort analysis approach to determine the range of case fatality rates (CFR). We use a logistical function to describe the exponential growth and subsequent flattening of COVID-19 CFR that depends on three parameters: the final CFR (L), the CFR growth rate (k), and the onset-to-death interval (t0). Using the logistic model with specific parameters (L, k, and t0), we calculate the number of deaths each day for each cohort. We build an objective function that minimizes the root mean square error between the actual and predicted values of cumulative deaths and run multiple simulations by altering the three parameters. Using all of these values, we find out which set of parameters returns the lowest error when compared to the number of actual deaths. We were able to predict the CFR much closer to reality at all stages of the viral outbreak compared to traditional methods. This model can be used far more effectively than current models to estimate the CFR during an outbreak, allowing for better planning. The model can also help us better understand the impact of individual interventions on the CFR. With much better data collection and labeling, we should be able to improve our predictive power even further.


title: Temperature and relative humidity are not major contributing factor on the occurrence of COVID-19 pandemic: An observational study in 57 countries

text: The world searching for hope has already experienced a huge loss of lives due to COVID-19 caused by SARS-CoV-2 started in Wuhan, China. There are speculations that climatic conditions can slowdown the transmission of COVID-19.Findings from the early outbreak indicated the possible association of air temperature and relative humidity in COVID-19 occurrence in China. Current study focused on whether climatic conditions(temperature and relative humidity)are having any influence in the occurrence of COVID-19 when the outbreak has been classified as pandemic. To determine the effect of daily average temperature and average relative humidity on log-transformed total daily cases of COVID-19, polynomial regression as a quadratic term and linear regression were done. Linear regression analysis was also carried out to explore the same effect on selected countries. Present study observed no correlation between the climatic conditions (the daily average temperature and relative humidity) and the number of cases of COVID-19. Similar result was found in relation between daily average temperature and average number of cases per day in country-wise analysis. However, about 93.5% cases of COVID-19 occurred between 10C to 160C and the average number of cases per day was lower in high temperature country than low temperature country with exceptions. The minimum effect of summer temperature may not be effective to control the pandemic rather need to apply the control measures of COVID-19.


title: Impacts of regional climate on the COVID-19 pandemic

text: The COVID-19 pandemic has led to six million confirmed cases by May 31, 2020. Impacts of regional weather and climate on epidemics have been investigated but need further study with new methods. We combined the number of monthly confirmed new cases and death with month, latitude, temperature, humidity, rainfall, and sunshine ultraviolet (UV) to explore the climate impact on epidemics in 116 countries and territories with at least 1000 confirmed cases. Correlation and regression analyses were performed with Stata. Humid subtropical climate regions had the most confirmed COVID-19 cases (24.4%). The case mortality in temperate marine regions was the highest (11.6%). Case-weighted means of the latitude, monthly maximum temperature, relative humidity, rainfall, and sunshine UV were 36.7 degrees, 20.5, 63%, 63mm, and 53.5, respectively. The case mortality was 7.44% in cold regions but only 4.68% in hot regions, 7.14% in rainy regions but only 3.86% in rainless regions, and 7.40% in cloudy regions but only 4.64% in sunny regions. Monthly confirmed cases increase as the temperature, rainfall, and sunshine UV rise in cold regions (r=0.34, 0.26, 0.26, respectively), but no correlation in hot regions. Every 1 increase in monthly maximum temperature leads to an increase in the natural logarithm of monthly confirmed new cases by 2.4% in cold regions. Monthly confirmed cases increase as the temperature, rainfall, and sunshine UV rise in arid regions (r=0.29, 0.28, 0.26, respectively), but no correlation in humid regions. Monthly confirmed new cases increase as the temperature and sunshine UV rise in rainy regions (r=0.30, 0.29), but no correlation in rainless regions. Monthly confirmed new deaths increase as the temperature and sunshine UV rise in cloudy regions (r=0.30, 0.30), but no correlation in sunny regions. It is wise to escape from an epicenter full of miasma to a hot sunny place in dry season without pollution. As peaking in the spring depends on the climate, the peak will go in the summer.


title: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2

text: We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified thirteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.


title: Chaos theory applied to the outbreak of Covid-19: an ancillary approach to decision-making in pandemic context

text: Predicting the course of an epidemic is difficult, predicting the course of a pandemic from an emerging virus even more so. The validity of most predictive models relies on numerous parameters, involving biological and social characteristics often unknown or highly uncertain. COVID-19 pandemic brings additional factors such as population density and movements, behaviours, quality of the health system. Data from the COVID-19 epidemics in China, Japan and South Korea were used to build up data-driven deterministic models. Epidemics occurring in selected European countries rapidly evolved to overtake most Chinese provinces, to overtake South Korean model for France and even Hubei in the case of Italy and Spain. This approach was applied to other European countries and provides relevant information to inform disease control decision-making.


title: Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus.

text: After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.


Effects of infection control policies on the final size