title: Effects of Anticoagulants and Corticosteroids therapy in patients affected by severe COVID-19 Pneumonia

text: Background In the absence of a standard of treatment for COVID-19, the combined use of anti-inflammatory (corticosteroids and Enoxaparin) and antiviral drugs may be more effective than using either modality alone in the treatment of COVID-19. Methods Patients hospitalized between April 10th, 2020, through May 10th, 2020, who had confirmed COVID-19 infection with clinical or radiographic evidence of pneumonia, in which 65 patients have moderate COVID-19 pneumonia, and 63 patients have severe COVID-19 pneumonia. All patients received early combination therapy of anti-inflammatory (corticosteroids and Enoxaparin) and antiviral drugs. They assessed for type and duration of treatment, and days need to wean from oxygen therapy, length of stay, virus clearance time, and complication or adverse events. All patients had more than 28 days follow up after discharge from the hospital. Results Moderate COVID-19 pneumonia group were 65 patients who received Enoxaparin, antiviral drugs, empirical antibiotics for pneumonia, and standard treatment for comorbidity. Male patients were 50 (76.9 %) and female patients were 15 (23.1 %). 34 (52.3 %) patients have comorbidity, 25 (38.5%) patients have Diabetes Mellitus and 2 (3.1 %) pregnant ladies. 19 (29.2 %) patients were on low flow oxygen therapy, 3L oxygen or less to maintain oxygen saturation more than 92%. All patients discharged home with no major or minor bleeding complications or significant complications. Severe COVID-19 pneumonia group were 63 patients who received methylprednisolone, enoxaparin, antiviral drugs, empirical antibiotics for pneumonia, and standard treatment for comorbidity. Male patients were 55 (87.3 %) and female patients were 8 (12.7 %). 37 (58.7 %) patients have comorbidity, and 24 (38.1%) patients have Diabetes Mellitus. 32 (50.8 %) patients were on low flow oxygen therapy, 4-9L oxygen, and 31 (49.2 %) patients were on low flow oxygen therapy, 10L oxygen or more, including 12 patients on a non-rebreathing mask. Patients received methylprednisolone were 37 (58.7 %) for 3 days, 16 (25.4 %) for 5 days and 10 (15.9 %) for more than 5 days. Sixty-two patients discharged home with one patient had a long stay, and the other two transferred to ICU. One long-stay patient transferred to ICU on low flow oxygen therapy. Conclusion Early use of a combined anti-inflammatory (corticosteroids and Enoxaparin) and antiviral drugs treatment in patients with moderate to severe COVID-19 pneumonia prevent complications of the disease and improve clinical outcomes.


title: High seroprevalence for SARS-CoV-2 among household members of essential workers detected using a dried blood spot assay

text: Objective: Serological testing is needed to investigate the extent of transmission of SARS-CoV-2 from front-line essential workers to their household members. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). Methods: An ELISA to the receptor binding domain of the SARS-CoV-2 spike protein was optimized to quantify IgG antibodies in DBS. Samples were self-collected from a community sample of 232 participants enriched with health care workers, including 30 known COVID-19 cases and their household members. Results: Among 30 individuals sharing a household with a virus-confirmed case of COVID-19, 80% were seropositive. Of 202 community individuals without prior confirmed acute COVID-19 diagnoses, 36% were seropositive. Of documented convalescent COVID-19 cases from the community, 29 of 30 (97%) were seropositive for IgG antibodies to the receptor binding domain. Conclusion: DBS ELISA provides a minimally-invasive alternative to venous blood collection. Early analysis suggests a high rate of transmission among household members. High rates of seroconversion were also noted following recovery from infection. Serological testing for SARS-CoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection.


title: A fractional differential equation model for the COVID-19 transmission by using the Caputo–Fabrizio derivative

text: We present a fractional-order model for the COVID-19 transmission with Caputo–Fabrizio derivative. Using the homotopy analysis transform method (HATM), which combines the method of homotopy analysis and Laplace transform, we solve the problem and give approximate solution in convergent series. We prove the existence of a unique solution and the stability of the iteration approach by using fixed point theory. We also present numerical results to simulate virus transmission and compare the results with those of the Caputo derivative.


title: The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights

text: From 29 to 31 January 2020, a total of 565 Japanese citizens were evacuated from Wuhan, China on three chartered flights. All passengers were screened upon arrival in Japan for symptoms consistent with novel coronavirus (2019-nCoV) infection and tested for presence of the virus. Assuming that the mean detection window of the virus can be informed by the mean serial interval (estimated at 7.5 days), the ascertainment rate of infection was estimated at 9.2% (95% confidence interval: 5.0, 20.0). This indicates that the incidence of infection in Wuhan can be estimated at 20,767 infected individuals, including those with asymptomatic and mildly symptomatic infections. The infection fatality risk (IFR)—the actual risk of death among all infected individuals—is therefore 0.3% to 0.6%, which may be comparable to Asian influenza pandemic of 1957–1958.


title: Risk and protective factors of SARS-CoV-2 infection - Meta-regression of data from worldwide nations

text: Although it has been reported that coexistent chronic diseases are strongly associated with COVID-19 severity, investigations of predictors for SARS-CoV-2 infection itself have been seldom performed. To screen potential risk and protective factors for SARS-CoV-2 infection, meta-regression of data from worldwide nations were herein conducted. We extracted total confirmed COVID-19 cases in worldwide 180 nations (May 31, 2020), nation total population, population ages 0-14/65 and above, GDP/GNI per capita, PPP, life expectancy at birth, medical-doctor and nursing/midwifery-personnel density, hypertension/obesity/diabetes prevalence, annual PM2.5 concentrations, daily ultraviolet radiation, population using safely-managed drinking-water/sanitation services and hand-washing facility with soap/water, inbound tourism, and bachelor's or equivalent (ISCED 6). Restricted maximum-likelihood meta-regression in the random-effects model was performed using Comprehensive Meta-Analysis version 3. To adjust for other covariates, we conducted the hierarchical multivariate models. A slope (coefficient) of the meta-regression line for the COVID-19 prevalence was significantly negative for population ages 0-14 (-0.0636; P = .0021) and positive for obesity prevalence (0.0411; P = .0099) and annual PM2.5 concentrations in urban areas (0.0158; P = .0454), which would indicate that the COVID-19 prevalence decreases significantly as children increase and that the COVID-19 prevalence increases significantly as the obese and PM2.5 increase. In conclusion, children (negatively) and obesity/PM2.5 (positively) may be independently associated with SARS-CoV-2 infection.


title: Evaluation of Viasure SARS-CoV-2 RT-qPCR kit (CerTest Biotec) using CDC FDA EUA RT-qPCR kit as a gold standard.

text: Abstract. Background. Several RT-qPCR kits are available for SARS-CoV-2 diagnosis, some of them with Emergency Use Authorization (EUA) by FDA, but most of them lacking of proper evaluation studies due to covid19 emergency. Objective. We evaluated Viasure RT-qPCR kit (CerTest Biotec, Spain) for SARS-CoV-2 diagnosis using CDC FDA EUA kit as gold standard. Results. Although we found the lack of RNA quality control probe as the main limitation for Viasure kit, the sensitivity was up to 97.5% and specificity was 100%. Conclusions. Viasure RT-qPCR kit is a reliable tool for SARS-CoV-2 diagnosis but improvement of an alternative RT-qPCR reaction for RNA extraction quality control as RNaseP is recommended.


title: Nonparametric survival analysis of epidemic data

text: This paper develops nonparametric methods for the survival analysis of epidemic data based on contact intervals. The contact interval from person i to person j is the time between the onset of infectiousness in i and infectious contact from i to j, where we define infectious contact as a contact sufficient to infect a susceptible individual. We show that the Nelson-Aalen estimator produces an unbiased estimate of the contact interval cumulative hazard function when who-infects-whom is observed. When who-infects-whom is not observed, we average the Nelson-Aalen estimates from all transmission networks consistent with the observed data using an EM algorithm. This converges to a nonparametric MLE of the contact interval cumulative hazard function that we call the marginal Nelson-Aalen estimate. We study the behavior of these methods in simulations and use them to analyze household surveillance data from the 2009 influenza A(H1N1) pandemic. In an appendix, we show that these methods extend chain-binomial models to continuous time.


title: The arrival of COVID-19 in the Netherlands

text: The last three months have been the most memorable and the most tense period in the lives of the most of us. After Taking Wuhan (China) by storm, the coronavirus crossed all of the frontiers and reached to 202 countries, including the East Asian countries, Middle East, the Americas and then the European countries. The Netherlands was effected less, with about 1000 deaths and more than 12000 confirmed patients, than its neighbors – Italy and Spain, but had its share. This manuscript presents an outline of the public perceptions, and the guidelines to manage these patients at different stages of the disease, including ventilation and intubation protocols, based upon our experience of over two months. It does not claim to be complete and exhaustive, and the readers are directed to consult their National guidelines (if any).


title: Emergence of SARS-CoV-2 and its outlook

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported at the end of 2019 in China By the end of February 2020, the virus has spread worldwide through continuous human-to-human transmission via contact and droplet infection, demonstrating the ease with which emerging viruses disperse globally through the mass transport system Here, we summarize our knowledge of other coronaviruses that have infected humans in comparison with SARS-CoV-2


title: Risk factors associated with mortality of COVID-19 in 2692 counties of the United States

text: Background: The number of cumulative confirmed cases of COVID-19 in the United States has risen sharply since March. A county health ranking and roadmaps program has been established to identify factors associated with disparity in mobility and mortality of COVID-19 in all counties in the United States. Objective: To find out the risk factors associated with mortality of COVID-19 with various levels of prevalence. Design: A negative binomial design was applied to the county-level mortality counts of COVID-19 on April 15, 2020 in the United States. In this design, the infected counties were categorized into three levels of infections using clustering analysis based on time-variant cumulative confirmed cases from March 1 to April 15, 2020. Setting: United States Participants: COVID-19 patients in various counties of the United States from March 1 to April 15, 2020. Measurements: The county-level cumulative confirmed cases and mortality of COVID-19. Results. 2692 infected counties were assigned into three classes where the mild, moderate, and severe prevalence of infections were identified, respectively. Several risk factors are significantly associated with the mortality of COVID-19, where Hispanic (0.024, P=0.002), female (0.253, P=0.027), elder (0.218, P=0.017) and Native Hawaiian or other Pacific islander (2.032, P=0.027) individuals are more vulnerable to the mortality of COVID-19. More locations open to exercise (0.030, P=0.004), higher levels of air pollution (0.184, P=0.044), and segregation between non-White and White increased the mortality rate. Limitation: The study relied on mortality data on April 15, 2020. Conclusion. The mortality of COVID-19 depends on sex, ethnicity, and outdoor environment. The increasing awareness of these significant factors may lead to the reduction in the mortality rate of COVID-19.


title: Novel, Inexpensive Portable Respiratory Protection Unit (PRPU) for Healthcare Workers

text: INTRODUCTION: Given concern for increased aerosolization during intubation of patients with severe acute respiratory syndrome coronavirus, we sought to create a portable, inexpensive, and easily constructed device to help protect healthcare workers. METHODS: A respiratory protection unit can be constructed in approximately 30 minutes and for less than 50 United States dollars in materials, using polyvinylchloride pipe and automobile collision wrap. CONCLUSION: This device provides possible increased protection during video laryngoscopy and can easily be replicated.


title: Macrophage-mediated antibody dependent effector function in aggressive B-cell lymphoma treatment is enhanced by Ibrutinib via inhibition of JAK2

text: Targeted inhibition of Bruton’s Tyrosine Kinase (BTK) with ibrutinib and other agents has become important treatment options in chronic lymphocytic leukemia, Waldenström’s Macroglobulinemia, Mantle cell lymphoma and non-GCB DLBCL. Clinical trials combining small molecule inhibitors with monoclonal antibodies have been initiated at rapid pace, with the biological understanding between their synergistic interactions lagging behind. Here, we have evaluated the synergy between BTK inhibitors and monoclonal antibody therapy via macrophage mediated antibody dependent cellular phagocytosis (ADCP). Initially, we observed increased ADCP with ibrutinib, whilst second generation BTK inhibitors failed to synergistically interact with monoclonal antibody treatment. Kinase activity profiling under BTK inhibition identified significant loss of Janus Kinase 2 (JAK2) only under ibrutinib treatment. We validated this potential off-target effect via JAK inhibition in vitro as well as with CRISPR/Cas9 JAK2−/− experiments in vivo, showing increased ADCP and prolonged survival, respectively. This data supports inhibition of the JAK-STAT signaling pathway in B-cell malignancies in combination with monoclonal antibody therapy to increase macrophage mediated immune responses.


title: Who is dying from Covid-19 in the United Kingdom? A review of cremation authorisations from a single South Wales' crematorium.

text: Abstract Background: Covid 19 is pandemic in the UK. To date only studies in the UK on hospital deaths have been published in the peer reviewed literature. Legal requirements for cremation in England and Wales require the collection of information that can be used to improve understanding of Covid 19 deaths in both hospital and community settings. Aim: To document demographic and clinical characteristics, including likely place of infection, of individuals dying of Covid 19 to inform public health policy Design: A comprehensive case series of deaths from Covid 19 between 6 April and 30 May. Setting: A crematorium in South Wales Participants: Individuals for whom an application was made for cremation. Main outcome measures: Age, sex, date and place of death, occupation, comorbidities, where infection acquired. Results: Of 752 cremations, 215(28.6%) were Covid-19 of which 115 (53.5%) were male and 100 (46.5%) female. The median age was 82 years, with the youngest patient being 47 years and the oldest 103 years. Over half the deaths (121/215: 56.3%) were over 80 years. Males odds of dying in hospital, rather than the community were 1.96 times that of females (95% Confidence Intervals (CI) 1.03 -3.74, p=0.054) despite being of similar age and having a similar number of comorbidities. Only 21(9.8%) of 215 patients had no comorbidities recorded. Patients dying in nursing homes were significantly older than those dying in hospital(median 88y (IQ range 82-93y) v 80y (IQ range 71-87y): p<0.0001). Patients dying in hospital had significantly more comorbidities than those dying in nursing homes (median 2: IQ range 1-3 v. 1: IQ range 1-2: p <0.001). Conclusions: In a representative series, comprising both hospital and community deaths, persons over 80 with an average 2 comorbidities predominated. Although men and women were represented in similar proportions, men were more likely to die in hospital. Over half the infections were acquired in either hospitals or nursing and residential homes with implications for the management of the pandemic, historically and in the future.


title: Evaluation of Turkish social distancing measures on the spread of COVID-19

text: The coronavirus disease (COVID-19) affecting across the globe. The government of different countries has adopted various policies to contain this epidemic and the most common were social distancing and lockdown. We use a simple log-linear model with intercept and trend break to evaluate whether the measures are effective preventing/slowing down the spread of the disease in Turkey. We estimate the model parameters from the Johns Hopkins University (2020) epidemic data between 15th March and 16th April 2020. Our analysis revealed that the measures can slow down the outbreak. We can reduce the epidemic size and prolong the time to arrive at the epidemic peak by seriously following the measures suggested by the authorities.


title: Early phases of COVID-19 are characterized by a reduction of lymphocyte populations and the presence of atypical monocytes

text: Background Severe acute respiratory syndrome coronavirus 2 is a recently discovered pathogen responsible of coronavirus disease 2019 (COVID-19). The immunological changes associated with this infection are largely unknown. Methods We evaluated the peripheral blood mononuclear cells profile of 63 patients with COVID-19 at diagnosis and the presence of association with inflammatory biomarkers and 28-days mortality. Results Lymphocytopenia was present in 51 of 63 (80.9%) patients. This reduction was mirrored also on CD8+ lymphocytes (128 cells/uL), natural killer cells (67 cells/uL) and natural killer T cells (31 cells/uL). Monocytes were preserved in total number but displayed a subpopulation composed mainly of cells with a reduced expression of both CD14 and HLA-DR. A direct correlation was found between serum values of IL-6 and the frequency of Th2 lymphocytes (R=0.17; p=0.04) but not with the monocytes count (R=0.01; p=0.60). Patients who died in the 28 days from admission (N=10, 15.9%), when compared to those who did not, displayed lower mean values of CD3+ (p=0.028) and CD4+ cells (p=0.042) and higher mean percentages of CD8+/CD38+/HLA-DR+ lymphocytes (p=0.026). Conclusions The early phases of COVID-19 are characterized by lymphocytopenia, predominance of Th2 lymphocytes and less immunocompetent monocytes, which include atypical mononuclear cells.


title: Cardiovascular Diseases and COVID-19 Mortality and Intensive Care Unit Admission: A Systematic Review and Meta-analysis

text: Importance: On 11th March, the World Health Organization declared a pandemic of COVID-19. There are over 1 million cases around the world with this disease and it continues to raise. Studies on COVID-19 patients have reported high rate of cardiovascular disease (CVD) among them and patients with CVD had higher mortality rate. Objectives: Since there were controversies between different studies about CVD burden in COVID-19 patients, we aimed to study cardiovascular disease burden among COVID-19 patients using a systematic review and meta-analysis. Data Sources: We have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar. Study Selection: Studies reported cardiovascular disease among hospitalized adult COVID-19 patients with mortality or ICU admission (primary outcomes) were included into meta-analysis. In addition, all of studies which reported any cardiovascular implication were included for descriptive meta-analysis. Cohort studies, case-control, cross-sectional, case-cohort and case series studies included into the study. Finally, 16 studies met the inclusion criteria for primary outcome and 59 studies for descriptive outcome. Data Extraction and Synthesis: Two investigators have independently evaluated quality of publications and extracted data from included papers. In case of disagreement a supervisor solved the issue and made the final decision. Quality assessment of studies was done using Newcastle-Ottawa Scale tool. Heterogeneity was assessed using I-squared test and in case of high heterogeneity (>%50) random effect model was used. Main Outcomes and Measures: Meta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs and Standardized Mean Difference (SMD) was calculated for Cardiac Troponin I. We have also performed a descriptive meta-analysis on different CVDs. Results: Sixteen papers including 3473 patients entered into meta-analysis for ICU admission and mortality outcome and fifty-nine papers including 9509 patients for descriptive outcomes. Results of meta-analysis indicated that acute cardiac injury, (OR: 15.94, 95% CI 2.31-110.14), hypertension (OR: 1.92, 95% CI 1.92-2.74), heart Failure (OR: 11.73, 95% CI 5.17-26.60), other cardiovascular disease (OR: 1.95, 95% CI 1.17-3.24) and overall CVDs (OR: 3.37, 95% CI 2.06-5.52) were significantly associated with mortality in COVID-19 patients. Arrhythmia (OR: 22.17, 95%CI 4.47-110.04), acute cardiac injury (OR: 19.83, 95%CI 7.85-50.13), coronary heart disease (OR: 4.19, 95%CI 1.27-13.80), cardiovascular disease (OR: 4.17, 95%CI 2.52-6.88) and hypertension (OR: 2.69, 95%CI 1.55-4.67) were also significantly associated with ICU admission in COVID-19 patients. Conclusion: Our findings showed a high burden of CVDs among COVID-19 patients which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations.


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title: Knowledge and Behaviors towards COVID-19 among University of Aleppo Students: An Online Cross-sectional Survey

text: Abstract Background: Coronavirus Disease 2019 (COVID-19) is an infection caused by a novel coronavirus that affects respiratory tract. People's awareness and knowledge of, and behavior and attitude toward COVID-19 are scarcely investigated , making medical literature related to this point poor. we aim to measure the knowledge of, and the reaction to COVID-19 among University of Aleppo students in Syria, and the determinants of their awareness and behavior regarding this disease. Materials and Methods: This was an online, questionnaire-based cross-sectional study, that was conducted from 21st March to 30 March 2020. We included undergraduate students of the University of Aleppo (Syria). The questionnaire consisted of three sections: Demographics ,knowledge and behaviours . Every participant's knowledge was scored from 0-13 depending on the number of correct answers in the knowledge section. The correctness was judged depending on WHO recommendations at the time of questionnaire administration. P-value of 0.05 was considered significant. Results: Among this well-educated and predominantly medical and health-related students, 682 (45.4%) students had a good knowledge level, which is somehow disappointing. The current study shows that 1st year students and non-medical specialties students and smokers had significantly lower knowledge levels than others. On contrary, residing with less people -which may indicate a higher socioeconomic status-, was associated with a higher knowledge level. We also found that commitment to preventive measures was in general satisfying and correlated significantly with knowledge level and gender in most cases. Conclusion: Junior students, non-medical specialties, smokers and those who live with high number of people are vulnerable to less knowledge level and awareness campaigns should concentrate on them. Increasing awareness is useful to increase commitment to preventive measures, and groups that have less adherence to preventive measures, as described in detail, should be taken into consideration while designing public health responses. Finally, we should be aware of the negative impact of quarantine on public health to take it into consideration for current campaigns and future policies.


title: Analysis of the scientific literature in the first 30 Days of the novel coronavirus outbreak.

text: Introduction: Recent events highlight how emerging and re-emerging pathogens are becoming global challenges for public health. In December 2019, a novel coronavirus has emerged. This has suddenly turned out into global health concern. Objectives: Aim of this research is to focus on the bibliometric aspects in order to measure what is published in the first 30-days of a global epidemic outbreak Methods: We searched PubMed database in order to find all relevant studies in the first 30-days from the first publication. Results: From the initial 442 identified articles, 234 were read in-extenso. The majority of papers come from China, UK and USA. 63.7% of the papers were commentaries, editorials and reported data and only 17.5% of the sources used data directly collected on the field. Topics mainly addressed were epidemiology, preparedness and generic discussion. NNR showed a reduction for both the objectives assessed from January to February. Conclusions: Diagnosis and effective preventive and therapeutic measures were the fields in which more research is still needed. The vast majority of scientific literature in the first 30-days of an epidemic outbreak is based on reported data rather than primary data. Nevertheless, the scientific statements and public health decisions rely on these data.


title: Recomendaciones en reanimación cardiopulmonar en pacientes con COVID-19

text: RESUMEN La atención a la parada cardiorrespiratoria en una situación de elevada contagiosidad, como la pandemia por COVID-19, puede condicionar una serie de medidas con el fin de garantizar por un lado, una actuación precoz y eficaz y por otro, una adecuada protección y seguridad de reanimadores, paciente y entorno. Desde el Grupo de Trabajo de Reanimación Cardiopulmonar (RCP) de la Sociedad Española de Cardiología, y tras analizar la situación actual, hemos decidido elaborar este documento con el fin de resumir de forma práctica las principales recomendaciones en el contexto de la RCP durante la pandemia por COVID-19. Estas recomendaciones pueden estar sujetas a cambios posteriores, fruto de la progresiva evidencia y aprendizaje que hemos ido adquiriendo en esta etapa. ABSTRACT Attention to cardiac arrest in a highly contagious situation such as the COVID-19 pandemic may condition some focused measures, on the one hand, prior and effective cardiopulmonary resuscitation (CPR) action, in the other hand an adequate protection and safety of rescuers, patients and the environment. From the Cardiopulmonary Resuscitation Working Group of the Spanish Society of Cardiology, after analyzing the current situation, we have decided to prepare this document in order to summarize in a practical way the main recommendations in the context of CPR during the COVID-19 pandemic. These recommendations may be subject to subsequent changes, as a result of the progression of the evidence and the learning that we have acquired at this stage.


title: Analysis of early renal injury in COVID-19 and diagnostic value of multi-index combined detection

text: Objectives The aim of the study was to analyze the incidence of COVID-19 with early renal injury, and to explore the value of multi-index combined detection in diagnosis of early renal injury in COVID-19. Design The study was an observational, descriptive study. Setting This study was carried out in a tertiary hospital in Guangdong, China. Participants 12 patients diagnosed with COVID-19 from January 20, 2020 to February 20, 2020. Primary and secondary outcome measures The primary outcome was to evaluate the incidence of early renal injury in COVID-19. In this study, the estimated glomerular filtration rate (eGFR), endogenous creatinine clearance (Ccr) and urine microalbumin / urinary creatinine ratio (UACR) were calculated to assess the incidence of early renal injury. Secondary outcomes were the diagnostic value of urine microalbumin (UMA), 1-microglobulin (A1M), urine immunoglobulin-G (IGU), urine transferring (TRU) alone and in combination in diagnosis of COVID-19 with early renal injury. Results While all patients had no significant abnormalities in serum creatinine (Scr) and blood urea nitrogen (BUN), the abnormal rates of eGFR, Ccr, and UACR were 66.7%, 41.7%, and 41.7%, respectively. Urinary microprotein detection indicated that the area under curve (AUC) of multi-index combined to diagnose early renal injury in COVID-19 was 0.875, which was higher than UMA (0,813), A1M (0.813), IGU (0.750) and TRU (0.750) alone. Spearman analysis showed that the degree of early renal injury was significantly related to C-reactive protein (CRP) and neutrophil ratio (NER), suggesting that the more severe the infection, the more obvious the early renal injury. Hypokalemia and hyponatremia were common in patients with COVID-19, and there was a correlation with the degree of renal injury. Conclusions Early renal injury was common in patients with COVID-19. Combined detection of UMA, A1M, IGU, and TRU was helpful for the diagnosis of early renal injury in COVID-19.


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title: A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

text: Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design.


CoviD-19: General considerations and anesthetic management


title: A national cross-sectional survey of public perceptions, knowledge, and behaviors during the COVID-19 pandemic

text: Introduction: Efforts to mitigate the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have largely relied on broad compliance with public health recommendations, yet navigating the high volume of evolving information and misinformation related to SARS-CoV-2 can be challenging. We assessed national public perceptions (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) related to COVID-19 in Canada to understand public perspectives and inform future public health initiatives. Methods: We administered a national online survey with the goal of obtaining responses from 2000 adults residing in Canada. Respondent sampling was stratified by age, sex, and region. We used descriptive statistics to summarize respondent characteristics and tested for significant overall regional differences using chi-squared tests and t-tests, as appropriate. Results: We collected 1,996 eligible questionnaires between April 26th and May 1st, 2020. One-fifth (20%) of respondents knew someone diagnosed with COVID-19, but few had tested positive themselves (0.6%). Negative impacts of pandemic conditions were evidenced in several areas, including concerns about healthcare (e.g. sufficient equipment, 52%), pandemic stress (45%), and worsening social (49%) and mental/emotional (39%) health. Most respondents (88%) felt they had good to excellent knowledge of virus transmission, and predominantly accessed (74%) and trusted (60%) Canadian news television, newspapers/magazines, or non-government news websites for COVID-19 information. We found high compliance with distancing measures (80% either self-isolating or always physical distancing). We identified regional differences in perceptions, knowledge, and behaviors related to COVID-19. Discussion: We found that knowledge about COVID-19 is largely acquired through domestic news sources, which may explain high self-reported compliance with prevention measures. The results highlight the broader impact of a pandemic on the general public's overall health and wellbeing, outside of personal infection. The study findings should be used to inform public health communications during COVID-19 and future pandemics.


title: Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: a systematic review

text: Objective: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. Data sources: Google Scholar, PubMed, COVID-19 Open Research Dataset: a resource of over 128,000 scholarly articles, including over 59,000 articles with full text related to COVID-19, SARS-CoV-2, and coronaviruses. Methods: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. The search engine was built using a retrieval function that ranks a set of documents based on the query terms appearing in each document regardless of their proximity within the document. Filtering of the articles was then undertaken using keywords and questions, e.g. "Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?". The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. Findings: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Such reports could lead many oncologists and physicians to change their treatment strategies without solid evidence and recommendations. Further research regarding this relationship and its clinical management is warranted. Additionally, treatment options must be examined further to provide optimal treatment and ensure better outcomes for patients suffering from these comorbidities. It should be noted that, whether definitive measurements exist or not, the care of patients as well as the research involved should be largely prioritized to tackle this deadly pandemic.


title: Advance of Novel Coronavirus Registration Clinical Trial

text: Background.This research aims to analyze the clinical characteristics of a novel Corona Virus Disease (COVID-19) registered in the Chinese Clinical Trial Registry (ChiCTR), and to provide an information-based data foundation and information reference for curbing the spread of the COVID-19 epidemic. Methods.The ChiCTR database was comprehensively searched, and the COVID-19 research registration information as of February 24, 2020 was counted. Descriptive analysis of registration time trends and geographical distribution. Chi-square test was used to compare the statistical differences between different study types, intervention methods, research phases and major sponsors. Frequency studies were used to analyze the characteristics of CMT and BI therapy. Results.232 COVID-19 studies registered at the ChiCTR Center were collected. The overall number of COVID-19 registrations was increased. Hubei Province, China has the largest number of registrations, followed by Guangdong, Zhejiang and Sichuan. There were significant differences between the number of participants (P=0.000), study duration (P=0.008), study assignment (P=0.000), and blind method (P=0.000) for different study types. Significant differences could be seen in the dimensions of multicenter study(P=0.022), of participants numbe(P=0.000), study duration(P=0.000) and study assignment(P=0.001) for the four intervention methods. There were significant differences in study assignment (P=0.043) between the early and late studies. CMT drugs with high research frequency are chloroquine, lopinavir / ritonavir, and I-IFN, which are all in phase 4; BI was Cell therapy, plasma therapy, Thymosin, and M/P-AB, which are all in early stages. Conclusion.There were problems of unclear classification of research types and irregular registration behavior. Also, within the studies researched, heterogeneity exists for various dimensions. Different research types, intervention methods, and research stages lead to significant differences in some dimensions of the COVID-19 study. Finally, statistical high-frequency research drugs can provide more treatment options and evidence-based evidence for the clinical practice.


title: A Simple Early Warning Signal for COVID-19

text: The paper provides some initial evidence that daily mortality rates (for any cause) by municipality or province can be used as a statistically reliable predictor of looming COVID-19 crises. Using recently published deaths figures for 1,689 Italian municipalities, we estimate the growth in daily mortality rates between the period 2015-2019 and 2020 by province. All provinces that experienced a major COVID-19 shock in mid-March 2020 had increases in mortality rates of 100% or above already in early February 2020. This increase was particularly strong for males and older people, two recognizable features of COVID-19. Using a panel fixed effect model, we show that the association between these early increases in mortality for any cause and the March 2020 COVID-19 shock is strong and significant. We conclude that the growth in mortality rates can be used as a statistically reliable predictor of COVID-19 crises.


Allocating medical resources during a mass casualty emergency: sometimes, ‘it’s OK to wait.’


title: Environmental and social analysis as risk factors for the spread of the novel coronavirus (SARS-CoV-2) using remote sensing, GIS and analytical hierarchy process (AHP): Case of Peru

text: The novel coronavirus disease (COVID-19) generated by the SARS-CoV-2 virus was originated in the city of Wuhan (China) in December 2019, the virus began to spread in other regions of China until it spread to the rest of the world. In this research, an analysis was made of environmental factors (tropospheric column of NO2, vertical airflow, percentage of solid waste disposed of in open dumps and percentage of the population without any mechanism of faeces disposal) and social factors (levels of monetary poverty, percentage of the number of hospitals per population and vulnerable population) that could directly and indirectly affect the spread of SARS-CoV-2 virus in the regions of Peru. Remote sensing techniques, geographic information systems and an analysis under the multi-parametric statistical approach proposed by Saaty were used to determine which regions present greater susceptibility, vulnerability and risk of spreading the SARS-CoV-2 virus. The results show that the prevalence of high values of tropospheric NO2 and values close to 0 Pa/s of the vertical airflow were directly related to the number of positive cases by COVID-19. In addition, it was found that 68% of the regions of Peru are at a "high" and "very high" risk of spreading SARS-CoV-2 virus, and most of them are in northern and central Peru (Callao, Tumbes, Piura, Loreto, Lambayeque, Huancavelica, Amazonas, Cajamarca, Ucayali, Huanuco and among others), therefore, special care should be taken with the measures adopted after social isolation in order to avoid the resurgence and collapse of the of health systems. It concludes that public policies on air quality management, integrated solid waste management and sanitation services should be improved in order to reduce the risk of spreading the SARS-CoV-2 virus. This research can be replicated on a longer scale, including more variables.


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title: Novel indicator of change in COVID-19 spread status

text: As the spread of COVID-19 worldwide progresses, it is important not only to protect human lives, but also to minimize social losses due to economic paralysis by detecting signs of spread at an early stage and predicting future trends accurately. This report introduces a new indicator (K) of the magnitude of the spread of COVID-19 based on daily number of infected people from publicly available data. Transitions of the K can predict effects of measures such as the blockage of cities and social distancing, signs of new spread, and possible regional dependence in the formation of population immunity.


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title: Immune alterations during SARS-CoV-2-related acute respiratory distress syndrome

text: We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2-3 fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in {gamma}{delta} T-cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a proinflammatory cytokine storm, Th1 and Th2 activation, and markers of T-cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response.


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title: The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis

text: Background The novel coronavirus COVID19 has been classified by the World Health Organisation as a pandemic due to its worldwide spread. The ability of countries to contain and control transmission is critical in the absence of a vaccine. We evaluated a range of social distancing measures to determine which strategies are most effective in reducing the peak daily infection rate, and consequential pressure on the health care system. Methods Using COVID19 transmission data from the outbreak source in Hubei Province, China, collected prior to activation of containment measures, we adapted an established individual based simulation model of the city of Newcastle, Australia, population 272,409. Simulation of virus transmission in this community model without interventions provided a baseline from which to compare alternative social distancing strategies. The infection history of each individual was determined, as was the time infected. From this model generated data, the rate of growth in cases, the magnitude of the epidemic peak, and the outbreak duration were obtained. Findings The application of all four social distancing interventions: school closure, workplace non-attendance, increased case isolation, and community contact reduction is highly effective in flattening the epidemic curve, reducing the maximum daily case numbers, and lengthening outbreak duration. These were also found to be effective even after 10 weeks delay from index case arrivals. The most effective single intervention was found to be increasing case isolation, to 100 percent of children and 90 percent of adults. Interpretation As strong social distancing intervention strategies had the most effect in reducing the epidemic peak, this strategy may be considered when weaker strategies are first tried and found to be less effective. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society. Tradeoffs may need to be made between the effectiveness of social distancing strategies and population willingness to adhere to them.


title: Machine Learning Analysis of Chest CT Scan Images as a Complementary Digital Test of Coronavirus (COVID-19) Patients

text: This paper reports on the development and performance of machine learning schemes for the analysis of Chest CT Scan images of Coronavirus COVID-19 patients and demonstrates significant success in efficiently and automatically testing for COVID-19 infection. In particular, an innovative frequency domain algorithm, to be called FFT-Gabor scheme, will be shown to predict in almost real-time the state of the patient with an average accuracy of 95.37%, sensitivity 95.99% and specificity 94.76%. The FFT-Gabor scheme is adequately informative in that clinicians can visually examine the FFT-Gabor feature to support their final diagnostic.


title: Knowledge, Attitude and Practice Towards Novel Corona Virus among Bangladeshi People: Implications for mitigation measures

text: The current novel coronavirus (nCoV) outbreak, COVID-19, was first reported in December 2019 in Wuhan, China has spread all over the world causing startling loss of lives, stalling the global economy and disrupting the social life. One of the challenges to contain the COVID-19 is making people adopt personal hygiene, social distancing and self-quarantine practices which are all related to knowledge, attitude and practice (KAP) of the people in respective countries. Bangladesh, the most densely populated countries with a fast-growing economy and moderate literacy rate, has shown many hiccups in its efforts to implement COVID-19 policies. Understanding KAP may give the policy makers to make informed decisions. Hence, this study aimed to make a quick assessment of KAP of people in relation to COVID-19 in Bangladesh. An online survey using a pre-tested questionnaire conducted in late March 2020 attained 1837 responses across Bangladesh. However, 1589 completed responses were included in statistical analysis to calculate KAP scores, their interrelations with socio-demographic variables. The overall KAP is poor with only 10% of the respondents showed good knowledge with parallel attitudes and practices. Socio-demographic factors have strong bearings on the KAP scores. Significantly higher KAP score is evident in female over male respondents, among aged (45 years and above) over younger respondents and among retired and homemakers above students and public service holders. The study indicated a panic fuelled by poor understanding of COVID-19 associated facts and the need for the government to ensure more granular and targeted awareness campaigns in a transparent and factual manner to gain public confidence and arrest more meaningful public participation in mitigation measures. The study provides a baseline of KAP among people in Bangladesh on COVID-19.


title: The relevance of the risk of prevalence of infections associated with the provision of medical care among medical professionals at the present stage

text: An overview of the incidence of health care-associated infection (HAIs) is presented. It is shown that most often medical workers are infected with infections transmitted through the blood and other biomaterials of patients, such as viral hepatitis B (HBV) and C (HCV), HIV infection. The significant frequency of occupational injuries among medical workers is emphasized. It is established that at the present stage, relatively new infections require some attention, which can lead to infection of medical workers in the course of their professional activities. These infections include atypical pneumonia (TOPC or SARS-severe acute respiratory syndrome), middle Eastern respiratory syndrome coronavirus (BRVS-Cov), African hemorrhagic fevers (Marburg, Ebola, Lassa), Crimea-Congo hemorrhagic fever (CCGL), and others. All these infections are quite severe, with a large number of deaths. Special attention is paid to the polyethyleneological nature of HAIs, which determines the need for a multi-modal approach to organizing preventive measures to protect medical workers from infection.


title: Quarantine the cat? Disinfect the dog? The latest advice about the coronavirus and your pets

text: When a Pomeranian in Hong Kong tested positive for SARS-CoV-2 last week, pets quickly became part of the coronavirus conversation The case raised the alarming possibility that pets could become part of the transmission chain for the severe acute respiratory syndrome coronavirus 2, which could potentially harm both them and us But many questions remain about this possibility and how best to respond


Best Practices for Implementing Remote Learning during a Pandemic


COVID-19: emerging challenges for oncological surgery


Coronavirus: Economic prospects, healthcare policies and a statistical model for Italy


title: The effect of COVID-19 pandemic on the Turkish society

text: Pandemics leave significant marks on the memories of societies with their permanent impacts. Going beyond a cause of disease or death, they can have consequences in many aspects, psychological, social and economic ones being in the first place. The Covid-19 outbreak, which first emerged in China and has spread to the whole world as of the first months of 2020, has the potential to constitute a breaking the course of history, as well. Turkey is located on the transit point between Asia and Europe with its geographical position, and thus, received its share from the outbreak of Covid-19, which spreads through social contact. The first official case was recorded on 11 March 2020, and then the virus spread rapidly. This study aims to assess the attitude of the public towards Covid-19 at times when the impact of the disease reached maximum. To this end, data were collected from 1586 people with different socio-demographic features through Covid-19 Pandemic Community Scale. The impact of the pandemic on the society was measured in three dimensions as Sensitivity to Pandemic, Protection against Pandemic and Social Trust. The research results showed that the people had high levels of sensitivity to the pandemic, exerted the maximum effort for protection and social trust was above the average although it fell behind the other dimensions. As a consequence, it can be concluded that Covid-19 has had a significant impact on the Turkish people.


title: Evaluation of commercial qPCR kits for detection of SARS-CoV-2 in pooled samples

text: Due to the current pandemic, global shortage of reagents has drawn interest in developing alternatives to increase the number coronavirus tests. One such alternative is sample pooling. Here we compared commercial kits that are used in COVID-19 diagnostics, in terms of sensitivity and feasibility for use in pooling. We showed that pooling of up to 60 samples did not affect the efficiency of the kits. Also, the RNA dependent RNA polymerase (RdRp) is a more suitable target in pooled samples than the Envelope (E) protein. This approach could provide an easy method of screening large number of samples and help adjust different government regulations.


title: Efficient codes for memory determine pitch representations

text: Perceptual systems have finite memory resources and must store incoming signals in compressed formats. To test whether representations of a sound’s pitch might derive from this need for compression, we compared discrimination of harmonic and inharmonic sounds across delays. In contrast to inharmonic spectra, harmonic spectra can be summarized, and thus compressed, using their fundamental frequency (f0). Despite being comparable for sounds presented back-to-back, discrimination was better for harmonic than inharmonic stimuli when sounds were separated in time, implicating memory representations unique to harmonic sounds. Patterns of individual differences indicated that listeners use different representations depending on the time delay between sounds, directly comparing the spectra of temporally adjacent sounds, but transitioning to comparing f0s across delays. The need to compress sound into memory appears to determine reliance on f0-based pitch, and may explain its importance in music, in which listeners must extract relationships between notes separated in time.


title: Risk of SARS-CoV-2 infection from contaminated water systems

text: Following the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in China, airborne water droplets (aerosols) have been identified as the main transmission route, although other transmission routes are likely to exist. We quantify SARS-CoV-2 virus survivability within water and the risk of infection posed by faecal contaminated water within 39 countries. We identify that the virus can remain stable within water for up to 25 days, and country specific relative risk of infection posed by faecal contaminated water is related to the environment. Faecal contaminated rivers, waterways and water systems within countries with high infection rates can provide infectious doses >100 copies within 100 ml of water. The implications for freshwater systems, the coastal marine environment and virus resurgence are discussed.


title: Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis

text: The outbreak of COVID-19 has caused serious epidemic events in China and other countries. With the rapid spread of COVID-19, it is urgent to explore the pathogenesis of this novel coronavirus. However, the foundational research of COVID-19 is very weak. Although angiotensin converting enzyme 2 (ACE2) is the reported receptor of SARS-CoV-2, information about SARS-CoV-2 invading airway epithelial cells is very limited. Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. In addition, we found that these proteins were associated with virus reactive proteins in host airway epithelial cells, which may promote the activation of the immune system and the release of inflammatory factors. Our findings provide a new research direction for understanding the potential microenvironment required by SARS-CoV-2 infection in airway epithelial, which may assist in the discovery of potential drug targets against SARS-CoV-2 infection.


title: Predicting social distancing index during COVID-19 outbreak through online search engines trends

text: Online-available information has been considered an accessory tool to estimate epidemiology and collect data on diseases and population behavior patterns. This study aimed to explore the potential use of Google and YouTube relative search volume to predict social distancing index in Brazil during COVID-19 outbreak and verify the correlation between social distancing measures with the course of the epidemic. Data concerning the social distancing index, epidemiological data on COVID-19 in Brazil and the search engines trends for Coronavirus were retrieved from online databases. Multiple linear regression was performed and resulted in a statistically significant model evidencing that Google and YouTube relative search volumes are predictors of the social distancing index. The Spearman correlation test revealed a weak correlation between social distancing measures and the course of the COVID-19 epidemic. Health authorities can apply these data to define the proper timing and location for practicing appropriate risk communication strategies.


Science in the shadow of a pandemic


title: Sequence-based prediction of vaccine targets for inducing T cell responses to SARS-CoV-2 utilizing the bioinformatics predictor RECON

text: Background The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Consistent with observations for SARS-CoV, a closely related coronavirus responsible for the 2003 SARS outbreak, early reports identify a protective role for both humoral and cell-mediated immunity for SARS CoV-2. Methods In this study, we leveraged HLA-I and HLA-II T cell epitope prediction tools from RECON® (Real-time Epitope Computation for ONcology), our bioinformatic pipeline that was developed using proteomic profiling of individual HLA-I and HLA-II alleles to predict rules for peptide binding to a diverse set of such alleles. We applied these binding predictors to viral genomes from the Coronaviridae family, and specifically to identify SARS-CoV-2 T cell epitopes. Results To test the suitability of these tools to identify viral T cell epitopes, we first validated HLA-I and HLA-II predictions on Coronaviridae family epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then use our HLA-I and HLA-II predictors to identify 11,776 HLA-I and 7,991 HLA-II candidate binding peptides across all 12 open reading frames (ORFs) of SARS-CoV-2. This extensive list of identified candidate peptides is driven by the length of the ORFs and the significant number of HLA-I and HLA-II alleles that we are able to predict (74 and 83, respectively), providing over 99% coverage for the US, European and Asian populations, for both HLA-I and HLA-II. From our SARS-CoV-2 predicted peptide-HLA-I allele pairs, 368 pairs identically matched previously reported pairs in the ViPR database, originating from other forms of coronaviruses. 320 of these pairs (89.1%) had a positive MHC-binding assay result. This analysis reinforces the validity our predictions. Conclusions Using this bioinformatic platform, we identify multiple putative epitopes for CD4+ and CD8+ T cells whose HLA binding properties cover nearly the entire population and thus may be effective when included in prophylactic vaccines against SARS-CoV-2 to induce broad cellular immunity.


title: Epidemiological Trends of Coronavirus Disease 2019 in China

text: Background: The Coronavirus Disease 2019 (COVID-19) epidemic broke out in Wuhan, China, and it spread rapidly. Since January 23, 2020, China has launched a series of unusual and strict measures, including the lockdown of Wuhan city to contain this highly contagious disease. We collected the epidemiological data to analyze the trend of this epidemic in China. Methods: We closely tracked the Chinese and global official websites to collect the epidemiological information about COVID-19. The number of total and daily new confirmed cases of COVID-19 in China was presented to illustrate the trend of this epidemic. Results: On January 23, 2020, 835 confirmed COVID-19 cases were reported in China. On February 6, 2020, there were 31211 cases. By February 20, 2020, the number reached as high as 75,993. Most cases were distributed in and around Wuhan, Hubei province. Since January 23, 2020, the number of daily new cases in China except Hubei province reached a peak of 890 on the eleventh day and then it declined to a low level of 34 within two full-length incubation periods (28 days), and the number of daily new cases in Hubei also started to decrease on the twelfth day, from 3156 on February 4, 2020 to 955 on February 15, 2020. Conclusion: The COVID-19 epidemic has been primarily contained in China. The battle against this epidemic in China has provided valuable experiences for the rest of the world. Strict measures need to be taken as earlier as possible to prevent its spread.


title: Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

text: Abstract Objectives To assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. Design Multicenter, open-label, randomized controlled trial. Setting 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants 150 patients hospitalized with COVID-19. 75 patients were assigned to HCQ plus SOC and 75 were assigned to SOC alone (control group). Interventions HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measures The primary endpoint was the 28-day negative conversion rate of SARS-CoV-2. The assessed secondary endpoints were negative conversion rate at day 4, 7, 10, 14 or 21, the improvement rate of clinical symptoms within 28-day, normalization of C-reactive protein and blood lymphocyte count within 28-day. Primary and secondary analysis was by intention to treat. Adverse events were assessed in the safety population. Results The overall 28-day negative conversion rate was not different between SOC plus HCQ and SOC group (Kaplan-Meier estimates 85.4% versus 81.3%, P=0.341). Negative conversion rate at day 4, 7, 10, 14 or 21 was also similar between the two groups. No different 28-day symptoms alleviation rate was observed between the two groups. A significant efficacy of HCQ on alleviating symptoms was observed when the confounding effects of anti-viral agents were removed in the post-hoc analysis (Hazard ratio, 8.83, 95%CI, 1.09 to 71.3). This was further supported by a significantly greater reduction of CRP (6.986 in SOC plus HCQ versus 2.723 in SOC, milligram/liter, P=0.045) conferred by the addition of HCQ, which also led to more rapid recovery of lymphopenia, albeit no statistical significance. Adverse events were found in 8.8% of SOC and 30% of HCQ recipients with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea (10%). Conclusions The administration of HCQ did not result in a higher negative conversion rate but more alleviation of clinical symptoms than SOC alone in patients hospitalized with COVID-19 without receiving antiviral treatment, possibly through anti-inflammatory effects. Adverse events were significantly increased in HCQ recipients but no apparently increase of serious adverse events. Trial registration ChiCTR2000029868.


title: Photo-Fenton disinfection at near neutral pH: Process, parameter optimization and recent advances

text: The photo-Fenton process is an advanced oxidation process that uses the hydroxyl radical to disinfect and decontaminate water Its non-selectivity makes it ideal for the removal of a range of microorganisms including those with antimicrobial resistance Optimum parameters such as pH, temperature, hydrogen peroxide and iron concentrations and the intensity and wavelength of light irradiation are important to carry out an efficient photo-Fenton process Traditionally photo-Fenton has been carried out at low acidic pH to obtain greater efficiency, but recent studies have been performed at near neutral The current review examines the effectiveness of the photo-Fenton process at a near neutral pH for the disinfection of water The optimal pH was seen to be at 2 8, with the efficiency of the photo-Fenton process decreasing as the pH rises The optimal reagent concentrations showed considerable variation depending on the iron catalyst used and the iron to hydrogen peroxide concentration used The effect of irradiance and temperature showed improved efficiency with higher levels Different types of microorganisms such as E coli, Pseudomonas sp , Enterococcus faecalis, Klebsiella pneumonia, Salmonella spp , total Coliforms, MRSA, MSSA, B subtilis, Clostridium sp , Faecal Coliform, MS2 coliphage and Curvularia sp are also examined and the effect the process will have on them The design of reactors, such as compound parabolic reactors are also examined The impact of light sources, including the recent reports on LEDs, on the production of hydrogen peroxide and thereby the improvement in the overall photo-Fenton disinfection is also discussed in detail Finally, a techno-economic analysis to explain various costs associated with photo-Fenton process has also been carried out It is concluded that the development of new heterogeneous supported immobilised catalysts that could work at the near neutral pH is an area, which require considerable future research


title: Recurrent respiratory viral diseases and chronic sequelae due to dominant negative IFIH1

text: Viral respiratory infections are the most common childhood infection worldwide. However, even common pathogens can have significant consequences in the context of patients with primary immunodeficiency diseases. More than half or viral infections annually are due to rhinovirus/enterovirus strains. Most clinical manifestations of viral infection are mild. However 3% of cases result in hospitalization in patients who have no other known risk factors. These patients may have an inborn error of immunity, a genetic susceptibility to viral infections. Here we present the case of an adult male who suffered respiratory viral infections his whole life and developed chronic, inflammatory damage to sinuses and lungs as a consequence. Genomic sequencing identified compound heterozygous variants in the IFIH1 gene, encoding the protein Melanoma Differentiation Association Protein 5 (MDA5), a RIG-I-like cytoplasmic sensor of RNA intracellular infections. We show a dominant negative effect on these variants on the level of interferon-induced expression of MDA5 protein. This work supports that loss-of-function variants in IFIH1 affect the sensing of viral infections. Underlying genomic variants may dictate the point at which recurrent, respiratory viral infections leave commonplace experience and incur lasting damage.


title: Comparative Efficacy and Safety of Pharmacological Managements for Hospitalized COVID-19 Patients: Protocol for Systematic Review and Trade-Off Network Meta-Analysis.

text: Coronavirus-Disease 2019 (COVID-19) is the clinical disease caused by the SARS-CoV-2 virus, the infectious agent causing the ongoing pandemic that has impacted the lives of hundreds of millions of people in almost every nation worldwide. It is a potentially fatal disease to many vulnerable patients including the elderly and those with chronic illnesses; but because this virus is a novel one, there are no firmly established treatment protocols. Many treatment methods are being investigated worldwide, and scientific conclusions drawn from these endeavors are crucial for healthcare professionals in combating this disease. In this network meta-analysis, we focus specifically on the pharmacologic agents that have been investigated for the treatment of COVID-19 and aim to produce a comprehensive picture of the evidence from current data in order to produce relevant insights on the comparative efficacy and safety profiles of various pharmacologic agents against COVID-19.


title: Resistive Joining – A Novel Dissimilar Welding Method for Thin Sheet Metals

text: Abstract Next-Generation batteries requires more energy and output power due to the high demands of applications to large-size vehicles, e.g. SUVs and trucks. As a result, multiple dissimilar battery cell tabs are joined together in parallel and carry larger currents in the electrical circuit. Ultrasonic and laser welding have been the two dominant battery cell joining processes in the automotive industry. However, both of them have limitations for joining a large number of stacked battery tabs at one time. Since failure of a single joint can impact the battery and eventually the vehicle, it is important to ensure process robustness and soundness of the resulting battery tab joints. In this study a new joining method, resistive joining (RJ), has been developed for welding multiple dissimilar (copper and aluminum) battery tabs. First, nickel-phosphorus (Ni-P, with ~7 wt% phosphorus) is electroless plated on both sides of selected tabs. In the subsequent resistive joining process, heat is concentrated at the high-electrical-resistivity Ni-P coatings as an electric current is passed through the joint. Aluminum is melted adjacent to the Ni-P coating due to its low melting temperature, and a portion of the Ni-P coating is dissolved into the liquid aluminum and a metallurgical bond is formed as the aluminum re-solidifies. In the meantime, solid-state bonds are formed between the Ni-P coating and copper due to material interdiffusion. Consequently, no Al-Cu intermetallic compound (IMC) is generated at the joint, and the strengths of RJ joints are higher than the base metal when tested in a lap-shear configuration.


COVID-19’s CO2 impact


title: Characteristics of lymphocyte subsets and their predicting values for the severity of COVID-19 patients

text: Severe COVID-19 patients showed worse clinical outcomes compared to mild and moderate patients. However, effective indicators are still lacking to predict the severity of the disease. In the present study, we retrospectively analyzed the clinical and laboratory data of 16 COVID-19 patients and found that the absolute counts of three T-cells (CD3+, CD4+, and CD8+) were significantly lower in the moderate and severe patients than those in mild patients and were significantly lower in severe patients than in moderate patients on admission. With the recovery of the COVID-19, serum levels of inflammatory biomarkers (CRP, PCT, and IL6) of moderate and severe patients gradually decreased. In contrast, the counts of lymphocytes and their subsets including CD3+, CD4+, and CD8+ T cells gradually increased in severe patients, and eventually showed comparable levels with moderate patients. ROC analysis showed that the counts of CD3+, CD4+, and CD8+ T-cells with AUC > 0.9 have potential values for predicting the severity of COVID-19 patients. In conclusion, the reduction of CD3+, CD4+, and CD8+ T-cells is related to the severity of COVID-19 and dynamic detection of these T-lymphocyte subsets may help predict the outcome of the patients.


Neurology APPs on the Front Lines of COVID-19: New Demands, New Skills


title: Amged El-Hawrani

text: The death of Amged El-Hawrani from covid-19 family, colleagues and the wider ENT community It became evident during the pandemic that ENT doctors were at particular risk of covid-19 infection Amged died after three traumatic weeks in critical care He was considered by the NHS to be one of the first UK frontline doctors to die during the pandemic He was born in Sudan in 1964, the son of a doctor and the second of six boys …


title: Estimating the generation interval for COVID-19 based on symptom onset data

text: Background: Estimating key infectious disease parameters from the COVID-19 outbreak is quintessential for modelling studies and guiding intervention strategies. Whereas different estimates for the incubation period distribution and the serial interval distribution have been reported, estimates of the generation interval for COVID-19 have not been provided. Methods: We used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates we obtained the proportions pre-symptomatic transmission and reproduction numbers. Results: The mean generation interval was 5.20 (95%CI 3.78-6.78) days for Singapore and 3.95 (95%CI 3.01-4.91) days for Tianjin, China when relying on a previously reported incubation period with mean 5.2 and SD 2.8 days. The proportion of pre-symptomatic transmission was 48% (95%CI 32-67%) for Singapore and 62% (95%CI 50-76%) for Tianjin, China. Estimates of the reproduction number based on the generation interval distribution were slightly higher than those based on the serial interval distribution. Conclusions: Estimating generation and serial interval distributions from outbreak data requires careful investigation of the underlying transmission network. Detailed contact tracing information is essential for correctly estimating these quantities.


title: Two New Models for Epidemics with Application to the COVID-19 Pandemic in the United States, Italy, and the United Kingdom

text: The Distributed Logistic Model and the Adaptive Logistic Model of epidemics are formulated and used to study the course of cases and deaths during the COVID-19 pandemic. The distributed model is designed to account for a spread of initiation times of hot spots across a country; it does especially well at capturing the initial and linear phases of epidemics. The adaptive model accounts for the development of social mitigation factors, and does especially well at capturing the declining phases of epidemics. The historical data for the U.S., Italy, and the U.K. are analyzed in detail. The parameters of the fits to the two models provide complementary information about the pandemic. The initial infection rate constant was r0 {approx} 0.29 per day for each country, and the effective infection rate constants evolved with time in essentially the same way for each. This suggests that mitigation effects were equally effective in all three countries. Analysis with the distributed model suggests that it took somewhat different times T for the epidemic to spread across each country, with T(US) {approx} 50 days significantly greater than the T's of Italy or the U.K. The mortality ratio in the U.S. was about 0.061 while in Italy and U.K. it was much larger at about 0.15.


title: Association between environmental pollution and prevalence of coronavirus disease 2019 (COVID-19) in Italy

text: The novel coronavirus disease 2019 (COVID-19) has recently been upgraded to a pandemic by the World Health Organization due to the alarming levels of spread and severity. Since several lines of evidence also attest that Lombardy region has an extraordinarily high level of environmental pollution, we aimed to explore the potential epidemiological association between the number of cases of COVID-19 and environmental pollution in Italy. Data on environmental pollution in Italy were retrieved from the 2019 annual report of the organization Legambiente (League for the Ambient). The adjusted correlation between the number of days in which environmental pollutants exceeded established limits and the overall number of COVID-19 cases reveals the existence of a highly significant positive association (r=0.66; 95% CI, 0.48-0.79; p<0.001). The association remained statistically significant even when the number of days above pollutant limits was correlated with the number of COVID-19 cases per 1000 inhabitants (r=0.43; 95% CI, 0.18-0.62; p=0.001). Living in a province with over 100 days per year in which environmental pollutants were exceeded was found to be associated with a nearly 3-fold higher risk of being positive for COVID-19 (0.014 vs. 0.005 COVID-19 cases per 1000 inhabitants; OR, 2.96; 95% 2.12-4.13; p<0.001). Reinforced restrictive measures shall be considered in areas with higher air pollution, where the virus is more likely to find a fertile biological or environmental setting.


title: How high and long will the COVID-19 wave be? A data-driven approach to model and predict the COVID-19 epidemic and the required capacity for the German health system

text: Background an objective: In March 2020 the SARS-CoV-2 outbreak has been declared as global pandemic. Most countries have implemented numerous social distancing measures in order to limit its transmission and control the outbreak. This study aims to describe the impact of these control measures on the spread of the disease for Italy and Germany, forecast the epidemic trend of COVID-19 in both countries and estimate the medical capacity requirements in terms of hospital beds and intensive care units (ICUs) for optimal clinical treatment of severe and critical COVID-19 patients, for the Germany health system. Methods: We used an exponential decline function to model the trajectory of the daily growth rate of infections in Italy and Germany. A linear regression of the logarithmic growth rate functions of different stages allowed to describe the impact of the social distancing measures leading to a faster decline of the growth rate in both countries. We used the linear model to predict the number of diagnosed and fatal COVID-19 cases from April 10th until May 31st. For Germany we estimated the required daily number of hospital beds and intensive care units (ICU) using clinical observations on the average lengths of a hospital stay for the severe and critical COVID-19 patients. Results: Analyzing the data from Germany and Italy allowed us to identify changes in the trajectory of the growth rate of infection most likely resulted from the various social distancing measures implemented. In Italy a stronger decline in the growth rate was observed around the week of March 17th, whereas for Germany the stronger decline occurred approximately a week later (the week of March 23rd). Under the assumption that the impact of the measures will last, the total size of the outbreak can be estimated to 155,000 cases in Germany (range 140,000-180,000) and to 185,000 cases in Italy (range 175,000-200,000). For Germany the total number of deaths until May 31st is calculated to 3,850 (range 3,500-4,450). Based on the projected number of new COVID-19 cases we expect that the hospital capacity requirements for severe and critical cases in Germany will decline from the 2nd week of April onwards from 13,500 to ~2500 hospital beds (range 1500-4300) and from 2500 to ~500 ICU beds in early May (range 300-800). Conclusion: The modeling effort presented here provides a valuable framework to capture the impact of the social distancing measures on the COVID-19 epidemic in European countries and to forecast the future trend of daily COVID-19 cases. It provides a tool for medical authorities in Germany and other countries to help inform the required hospital capacity of the health care system. Germany appears to be in the middle of the (first) COVID-19 outbreak wave and the German health system is well prepared to handle it with the available capacities.


title: Scirpy: A Scanpy extension for analyzing single-cell T-cell receptor sequencing data

text: Summary Advances in single-cell technologies have enabled the investigation of T cell phenotypes and repertoires at unprecedented resolution and scale. Bioinformatic methods for the efficient analysis of these large-scale datasets are instrumental for advancing our understanding of adaptive immune responses in cancer, but also in infectious diseases like COVID-19. However, while well-established solutions are accessible for the processing of single-cell transcriptomes, no streamlined pipelines are available for the comprehensive characterization of T cell receptors. Here we propose Scirpy, a scalable Python toolkit that provides simplified access to the analysis and visualization of immune repertoires from single cells and seamless integration with transcriptomic data. Availability and implementation Scirpy source code and documentation are available at https://github.com/icbi-lab/scirpy.


title: Reproducibility and reporting practices in COVID-19 preprint manuscripts

text: The novel coronavirus, COVID-19, has sparked an outflow of scientific research seeking to understand the virus, its spread, and best practices in prevention and treatment. If this international research effort is going to be as swift and effective as possible, it will need to rely on a principle of open science. When researchers share data, code, and software and generally make their work as transparent as possible, it allows other researchers to verify and expand upon their work. Furthermore, it allows public officials to make informed decisions. In this study, we analyzed 535 preprint articles related to COVID-19 for eight transparency criteria and recorded study location and funding information. We found that individual researchers have lined up to help during this crisis, quickly tackling important public health questions, often without funding or support from outside organizations. However, most authors could improve their data sharing and scientific reporting practices. The contrast between the commitment of researchers to doing important research and their reporting practices reveals underlying weaknesses in reporting habits, but not necessarily their science.


title: Sub-epidemic model forecasts for COVID-19 pandemic spread in the USA and European hotspots, February-May 2020

text: Mathematical models have been widely used to understand the dynamics of the ongoing coronavirus disease 2019 (COVID-19) pandemic as well as to predict future trends and assess intervention strategies. The asynchronicity of infection patterns during this pandemic illustrates the need for models that can capture dynamics beyond a single-peak trajectory to forecast the worldwide spread and for the spread within nations and within other sub-regions at various geographic scales. Here, we demonstrate a five-parameter sub-epidemic wave modeling framework that provides a simple characterization of unfolding trajectories of COVID-19 epidemics that are progressing across the world at different spatial scales. We calibrate the model to daily reported COVID-19 incidence data to generate six sequential weekly forecasts for five European countries and five hotspot states within the United States. The sub-epidemic approach captures the rise to an initial peak followed by a wide range of post-peak behavior, ranging from a typical decline to a steady incidence level to repeated small waves for sub-epidemic outbreaks. We show that the sub-epidemic model outperforms a three-parameter Richards model, in terms of calibration and forecasting performance, and yields excellent short- and intermediate-term forecasts that are not attainable with other single-peak transmission models of similar complexity. Overall, this approach predicts that a relaxation of social distancing measures would result in continuing sub-epidemics and ongoing endemic transmission. We illustrate how this view of the epidemic could help data scientists and policymakers better understand and predict the underlying transmission dynamics of COVID-19, as early detection of potential sub-epidemics can inform model-based decisions for tighter distancing controls.


title: Spatial Network based model forecasting transmission and control of COVID-19

text: The SARS-CoV-2 driven infectious novel coronavirus disease (COVID-19) has been declared a pandemic by virtue of its brutal impact on the world in terms of loss on human life, health, economy, and other crucial resources. With the aim to explore more about its aspects, we adopted the SEIQRD (Susceptible-Exposed-Infected-Quarantine-Recovered-Death) pandemic spread with a time delay on the heterogeneous population and geography in this work. Focusing on the spatial heterogeneity, the entire population of interest in a region is divided into small distinct geographical sub regions, which interact by means of migration networks across boundaries. Utilizing the estimations of the time delay differential equations based model, we analyzed the spread dynamics of disease in a region and its sub regions. The model based numerical outcomes are validated from real time available data for India. We computed the approximate peak infection in forward time and relative timespan when disease outspread halts. To further evaluate the influence of the delay on the long term system dynamics, the sensitivity analysis is performed on time delay. The most crucial parameter, basic reproduction number R0 and its time-dependent generalization, has been estimated at both regional and sub regional levels. The impact of the most significant lockdown measure that has been implemented in India to contain the pandemic spread has been extensively studied by considering no lockdown scenario. A suggestion based on outcomes, for a bit relaxed lockdown, followed by an extended period of strict social distancing as one of the most effective control measures to manage COVID-19 spread is provided for India.


title: New approximations, and policy implications, from a delayed dynamic model of a fast pandemic

text: We study an SEIQR (Susceptible-Exposed-Infectious-Quarantined-Recovered) model for an infectious disease, with time delays for latency and an asymptomatic phase. For fast pandemics where nobody has prior immunity and everyone has immunity after recovery, the SEIQR model decouples into two nonlinear delay differential equations (DDEs) with five parameters. One parameter is set to unity by scaling time. The subcase of perfect quarantining and zero self-recovery before quarantine, with two free parameters, is examined first. The method of multiple scales yields a hyperbolic tangent solution; and a long-wave approximation yields a first order ordinary differential equation (ODE). With imperfect quarantining and nonzero self-recovery, the long-wave approximation is a second order ODE. These three approximations each capture the full outbreak, from infinitesimal initiation to final saturation. Low-dimensional dynamics in the DDEs is demonstrated using a six state non-delayed reduced order model obtained by Galerkin projection. Numerical solutions from the reduced order model match the DDE over a range of parameter choices and initial conditions. Finally, stability analysis and numerics show how correctly executed time-varying social distancing, within the present model, can cut the number of affected people by almost half. Alternatively, faster detection followed by near-certain quarantining can potentially be even more effective.


title: UV light influences covid-19 activity through big data: trade offs between northern subtropical, tropical, and southern subtropical countries

text: UV (ultraviolet) light is an important factor should be considered to predict coronavirus epidemic growth pace. UV is different from weather temperature since UV is electromagnetic wavelength from 10 nm to 400 nm in size, shorter than of visible lights. For some people, UV light can lead to cancer from unprotected sun exposure, however, for tropical people, which have been used to live in such condition, have resisted from negative effect high UV index. Moreover, UV has the capability to inactivate virus. This conclusion has been discussed deeply with biological experts. Although UV light has the ability to inactivate viruses, it may be meaningless in areas with high air pollution where UV light turns into heat.


title: COVID-19 transmission in Mainland China is associated with temperature and humidity: a time-series analysis

text: COVID-19 has become a pandemic. The influence of meteorological factors on the transmission and spread of COVID-19 if of interest. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the daily count of COVID-19 cases in 30 Chinese provinces (in Hubei from December 1, 2019 to February 11, 2020 and in other provinces from January 20, 2020 to Februarys 11, 2020). A Generalized Additive Model (GAM) was fitted to quantify the province-specific associations between meteorological variables and the daily cases of COVID-19 during the study periods. In the model, the 14-day exponential moving averages (EMAs) of AT and ARH, and their interaction were included with time trend and health-seeking behavior adjusted. Their spatial distributions were visualized. AT and ARH showed significantly negative associations with COVID-19 with a significant interaction between them (0.04, 95% confidence interval: 0.004-0.07) in Hubei. Every 1°C increase in the AT led to a decrease in the daily confirmed cases by 36% to 57% when ARH was in the range from 67% to 85.5%. Every 1% increase in ARH led to a decrease in the daily confirmed cases by 11% to 22% when AT was in the range from 5.04°C to 8.2°C. However, these associations were not consistent throughout Mainland China.


title: Evolution of behavioral resistance in host-pathogen systems

text: Behavioral resistance to parasites is widespread in animals, yet little is known about the evolutionary dynamics that have shaped these strategies. We show that theory developed for the evolution of physiological parasite resistance can only be applied to behavioral resistance under limited circumstances. We find that accounting explicitly for the behavioral processes, including the detectability of infected individuals, leads to novel dynamics that are strongly dependent on the nature of the costs and benefits of social interactions. As with physiological resistance, the evolutionary dynamics can also lead to mixed strategies that balance the costs of disease risk and the benefits of social interaction, with implications for understanding avoidance strategies in human disease outbreaks.


title: Electrocardiographic safety of daily Hydroxychloroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon.

text: Objective : To determine the early electrocardiographic changes in a cohort of ambulatory cameroonian COVID-19 patients treated with hydroxychloroquine and Azithromycin. Design : Prospective study. Setting : Treatment centres of the city of Yaounde, Cameroon, from May 7th to 24th 2020. Participants : We enrolled 51 consecutive confirmed COVID-19 on RT-PCR who having mild forms of COVID-19 and treated by hydroxychloroquine 200mg twice daily during seven days plus Azithromycin 500 mg the first day and 250 mg the remaining 4 days as per national standard. Main outcomes measures : The primary end-point was the change in QTc interval between day 0 (D0), day 3 (D3) and day 7 (D7). Secondary endpoints were changes in all other cardiac electrical conductivity patterns and the occurrence of clinical arrhythmic events during the course of treatment. Results: The population (29 men and 22 women) was aged 39 +/- 11 years (range 17 to 61 years). Mean Tisdale score was 3.35 +/- 0.48. No significant change from baseline (D0) of QTc was observed at D7 (429 +/- 27 ms at D0 versus 396 +/- 26 ms at D7; p = 0.27). A reduction of heart rate was observed between the D0 and D7 (75 +/- 13 bpm versus 70 +/- 13 bpm, p = 0.02) with increased QRS duration between D0 and D7 (95 +/- 10 ms versus 102 +/- 17 ms, p = 0.004). No symptomatic arrhythmic events occurred during the treatment course. Conclusions: No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with hydroxychloroquine and azithromycin. Studies are needed in critical-ill and older patients.


title: EVALUATION OF THE ABBOTT SARS-COV-2 IG-G ASSAY.

text: Introduction: Antibodies to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase as soon as 10-13 days after infection. We describe our evaluation of the Abbott SARS-CoV-2 IgG assay on the Architect immunoassay analyser. Methods: We assessed the precision, sensitivity, and specificity of the Abbott SARS-CoV-2 IgG assay in samples from polymerase chain reaction (PCR) positive patients and healthy healthcare workers. The manufacturer cut-off index (COI) of 1.4 was adopted to identify positive results. We examined the assay cross-reactivity with other viral antibodies (influenza/dengue/hepatitis C/hepatitis B) and rheumatoid factor (RF). The sample throughput of the Abbott assay was also assessed. Results: The Abbott assay showed excellent precision, with a CV of 3.4% for the negative control (COI = 0.06) and 1.6% for a high positive serum sample (COI = 8.6). Residual serum was available from 57 inpatients not initially suspected of having COVID-19, 29 of whom tested positive for SARS-CoV-2 IgG. The Abbott assay has a sensitivity of 90.9-100% when tested in 54 subjects [≥]14 days post PCR positive, and a specificity of 100% (N = 358). There was no cross-reactivity with other viral antibodies (influenza/dengue/hepatitis C/hepatitis B) and RF. The Architect Abbott assay has a throughput of 100 samples in 70 minutes. Conclusion: The Abbott SARS-CoV-2 IgG assay shows excellent performance that is well within FDA and CDC guidelines when testing patients [≥]14 days POS with little cross-reactivity from other viral antibodies. There is some evidence that SARS-CoV-2 IgG develops early in the disease process.


title: Understanding the Collective Responses of Populations to the COVID-19 Pandemic in Mainland China

text: Timely information acquisition and stay-at-home measures have been considered as two effective steps that every person could take to help contain the coronavirus (COVID-19) pandemic. From the perspectives of information and mobility, this work aims at evaluating to what degree the massive population has responded to the emergencies of the COVID- 19 pandemic in China. Using the real-time and historical data collected from the Baidu Maps and Baidu search engines, we confirm the strong correlation between the local pandemic situation in every major Chinese city and the population inflows from Wuhan between 1 January and 23 January 2020. We further evidence that, in cities under more critical situations, people are likely to engage COVID-19-related searches more frequently, while they are not likely to escape from the cities. Finally, the correlation analysis using search and mobility data shows that well-informed individuals are likely to travel less, even while the overall travel demands are low compared to the historical records. Partial correlation analysis has been conducted to test the significance of these observations with respect to other controlling factors.


title: Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis

text: Understanding the temporal dynamics of COVID-19 patient phenotypes is necessary to derive fine-grained resolution of the pathophysiology. Here we use state-of-the-art deep neural networks over an institution-wide machine intelligence platform for the augmented curation of 8.2 million clinical notes from 14,967 patients subjected to COVID-19 PCR diagnostic testing. By contrasting the Electronic Health Record (EHR)-derived clinical phenotypes of COVID-19-positive (COVIDpos, n=272) versus COVID-19-negative (COVIDneg, n=14,695) patients over each day of the week preceding the PCR testing date, we identify diarrhea (2.8-fold), change in appetite (2-fold), anosmia/dysgeusia (28.6-fold), and respiratory failure (2.1-fold) as significantly amplified in COVIDpos over COVIDneg patients. The specific combination of cough and diarrhea has a 4-fold amplification in COVIDpos patients during the week prior to PCR testing, and along with anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19 (4-7 days prior to typical PCR testing date). This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional knowledge captured in EHRs. The platform holds tremendous potential for scaling up curation throughput, with minimal need for training underlying neural networks, thus promising EHR-powered early diagnosis for a broad spectrum of diseases.


title: A Small interfering RNA lead targeting RNA-dependent RNA-polymerase effectively inhibit the SARS-CoV-2 infection in Golden Syrian hamster and Rhesus macaque

text: A small interfering RNA (siRNA) inhibitors have demonstrated the novel modality for suppressing infectious diseases. Sixty-one siRNA molecules, predicted by the bioinformatics programs, were screened for the possibility of treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in vitro plaque assay. Among six siRNA leads with the efficacy of reducing plaque number, the siRNA targeting RNA-dependent RNA polymerase (RdRp) showed a reduction in SARS-CoV-2 infection-induced fever and virus titer in the Golden Syrian hamster and rhesus macaque. These results suggest the potential for RdRp targeting siRNA as a new treatment for the coronavirus disease 2019 (COVID-19).


title: Systematic review of international guidelines for tracheostomy in COVID-19 patients.

text: At this moment, the world leaves under the SARS-CoV-2 outbreak pandemic. As Otolaryngologists - Head & Neck Surgeons, we need to perform and participate in examinations and procedures within the head and neck region and airway that are at particularly high risk of exposure and infection because of aerosol and droplet contamination. One of those surgical procedures on demand at this moment is tracheostomy, due the increasing admission in ICU departments and the increased need of ventilatory support secondary to respiratory distress syndrome. This review of international guidelines for tracheostomy in COVID-19 infected patients, aiming to summarize in a systematic way the available recommendations from 18 guidelines from all over the world.