bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature
Authors: LoPresti Marissa , Beck David B. , Duggal Priya , Cummings Derek A. T. , Solomon Benjamin D. 
Published: June 2020

AbstractBackgroundThe recent SARS-CoV-2 pandemic raises many scientific and clinical questions. One set of questions involves host genetic factors that may affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work on other coronaviruses in humans or other host species may be relevant.ObjectivesTo review existing literature on host genetic factors and their association with infection and disease with coronaviruses in humans and in other host species.MethodsWe conducted a systematic review of literature on host genetic factors in humans associated with coronavirus outcomes. We also reviewed studies of host genetic factors associated with coronavirus outcomes in non-human species. We categorized articles, summarized themes related to animal studies, and extracted data from human studies for analyses.ResultsWe identified 1,187 articles of potential relevance. Forty-five studies examined human host genetic factors related to coronavirus, of which 35 involved analysis of specific genes or loci; aside from one meta-analysis on respiratory infections, all were candidate-driven studies, typically investigating small numbers of research subjects and loci. Multiple significant loci were identified, including 16 related to susceptibility to coronavirus (of which 7 identified protective alleles), and 16 related to outcomes or clinical variables (of which 3 identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Of the other studies, 28 involved both human and non-human host genetic factors related to coronavirus, and 174 involved study of non-human (animal) host genetic factors related to coronavirus.Key findingsWe have outlined key genes and loci from animal and human host genetic studies that may bear investigation in the nascent host genetic factor studies of COVID-19. Previous human studies have been limited by relatively low numbers of eligible participants and limited availability of advanced genomic methods. These limitations may be less important to studies of SARS-CoV-2.
Repurposed prophylaxis strategies for COVID-19: a review
Authors: Sallard Erwan , Lescure François-Xavier , Burdet Charles , Guedj Jérémie , Yazdanpanah Yazdan , Peiffer-Smadja Nathan 
Published: June 2020

AbstractIntroductionEfficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARSCoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis.MethodsWe screened several clinical trials repositories and platforms in search of the prophylactic strategies that are investigated against COVID-19 in late April 2020.ResultsUp to April 27, 2020, we found 68 clinical trials targeting medical workers (n = 43, 63%), patients relatives (n = 16, 24%) or individuals at risk of severe COVID-19 (n = 5, 7%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n = 46, 68%), before BCG vaccine (n = 5, 7%). Sixty-one (90%) clinical trials were randomized with a median of planned inclusions of 600 (IQR 255–1515).ConclusionThe investigated prophylaxis strategies cover both pre- and post-exposure prophylaxis and study numerous immune enhancers and antivirals, although most research efforts are focused on (hydroxy)chloroquine.
Development and Prospective Validation of a Transparent Deep Learning Algorithm for Predicting Need for Mechanical Ventilation
Authors: Shashikumar Supreeth P. , Wardi Gabriel , Paul Paulina , Paul Paulina , Carlile Morgan , Brenner Laura N , Hibbert Kathryn A , North Crystal M. , Mukerji Shibani S. , Robbins Gregory K. , Shao Yu-Ping , Malhotra Atul , Brandon Westover M. , Nemati Shamim 
Published: June 2020

ABSTRACTIMPORTANCEObjective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation is of great importance and may aid in delivering timely treatment.OBJECTIVETo develop, externally validate and prospectively test a transparent deep learning algorithm for predicting 24 hours in advance the need for mechanical ventilation in hospitalized patients and those with COVID-19.DESIGNObservational cohort studySETTINGTwo academic medical centers from January 01, 2016 to December 31, 2019 (Retrospective cohorts) and February 10, 2020 to May 4, 2020 (Prospective cohorts).PARTICIPANTSOver 31,000 admissions to the intensive care units (ICUs) at two hospitals. Additionally, 777 patients with COVID-19 patients were used for prospective validation. Patients who were placed on mechanical ventilation within four hours of their admission were excluded.MAIN OUTCOME(S) and MEASURE(S)Electronic health record (EHR) data were extracted on an hourly basis, and a set of 40 features were calculated and passed to an interpretable deep-learning algorithm to predict the future need for mechanical ventilation 24 hours in advance. Additionally, commonly used clinical criteria (based on heart rate, oxygen saturation, respiratory rate, FiO2and pH) was used to assess future need for mechanical ventilation. Performance of the algorithms were evaluated using the area under receiver-operating characteristic curve (AUC), sensitivity, specificity and positive predictive value.RESULTSAfter applying exclusion criteria, the external validation cohort included 3,888 general ICU and 402 COVID-19 patients. The performance of the model (AUC) with a 24-hour prediction horizon at the validation site was 0.882 for the general ICU population and 0.918 for patients with COVID-19. In comparison, commonly used clinical criteria and the ROX score achieved AUCs in the range of 0.773 – 0.782 and 0.768 – 0.810 for the general ICU population and patients with COVID-19, respectively.CONCLUSIONS and RELEVANCEA generalizable and transparent deep-learning algorithm improves on traditional clinical criteria to predict the need for mechanical ventilation in hospitalized patients, including those with COVID-19. Such an algorithm may help clinicians with optimizing timing of tracheal intubation, better allocation of mechanical ventilation resources and staff, and improve patient care.
Reduction in stroke patients’ referral to the ED in the COVID-19 era: A four-year comparative study
Authors: Mor Saban , Anna Reznik , Tal Shachar , Roten Sivan-Hoffmann 
Published: June 2020

AbstractIntroductionCurrent reports indicate that the increased use of social distancing for preventive COID-19 distribution may have a negative effect on patients who suffering from acute medical conditions.AimWe examined the effect of social distancing on acute ischemic stroke (AIS) patients’ referral to the emergency department (ED)MethodA retrospective archive study was conducted between January 2017 and April 2020 in a comprehensive stroke center. We compare the number of neurologic consultations, time from symptoms onset to ED arrival, patients diagnosis with AIS, number of patients receiving treatment (tPA, endovascular thrombectomy (EVT) or combine) and in-hospital death.ResultsThe analysis included a total of 14,626 neurological consultations from the years 2017 to 2020. A significant decrease of 58.6% was noted during the months of January-April of the year 2020 compared to the parallel period of 2017. Percent of final AIS diagnosis for the year of 2020 represent 24.8% of suspected cases, with the highest diagnosis rate demarcated for the year of 2019 with 25.6% of confirmed patients. The most remarkable increase was noted in EVT performance through the examined years (2017, n=21; 2018, n=32; 2019, n=42; 2020, n=47).ConclusionCOVID-19 pandemic resulted in routing constraints on health care system resources that were dedicated for treating COVID-19 patients.The healthcare system must develop and offer complementary solutions that will enable access to health services even during these difficult times.
Evaluating post-vaccine expansion patterns of pneumococcal serotypes
Authors: Phillips Maile T. , Warren Joshua L. , Givon-Lavi Noga , Tothpal Adrienn , Regev-Yochay Gili , Dagan Ron , Weinberger Daniel M. 
Published: June 2020

ABSTRACTStreptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. Understanding of serotype replacement is important as higher-valency vaccines are introduced.
Sensitivity and specificity of prediction models based on gustatory disorders in diagnosing COVID-19 patients: a case-control study
Authors: Adamczyk Kamil , Herman Michał , Frączek Janusz , Piec Robert , Szykuła-Piec Barbara , Zaczyński Artur , Wójtowicz Rafał , Bojanowski Krzysztof , Rusyan Ewa , Król Zbigniew , Wierzba Waldemar , Franek Edward 
Published: June 2020

AbstractObjectiveto quantitatively assess disturbances of sweet, sour and salty and bitter tastes in a group of young, asymptomatic or oligosymptomatic COVID-19 patients; establish a reliable, sensitive and specific test that can diagnose COVID-19 on the basis of taste disorders and publish the results according to STARD 2015 statement (Standards for Reporting Diagnostic Accuracy).Designcase-control studySettingisolated rooms in the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw (which had been transformed into an infectious hospital) and a dormitory in one of Warsaw universities.Participants52 SARS-CoV-2 positive (51 men, mean age 21.7 years) and 36 negative students (34 men, mean age 20.8 years).Main outcome measuresa gustatory function assessment (sweet, salty, sour and bitter taste), with flavour concentrations established previously in healthy subjects was conducted for all subjects. Each participant received one tasteless reference and nine flavour tablets with sucrose concentrations of 40, 80 and 106.4 mg/ml; NaCl at 13.5, 17 and 27 mg/ml; ascorbic acid at 6.25 and 12.5 mg/ml and grapefruit extract at 40 mg/ml.Resultsthe only taste that was impaired significantly more frequently in COVID-19 patients was the sweet taste at the lowest flavour concentration (40 mg/ml, p = 0.002). Different screening and diagnostic models were constructed using the examined variables. The highest accuracy screening test consisted of the positive result of a three-question questionnaire (self-reported loss of taste, self-reported loss of smell, or fever within the last month (positive if at least one present) and/or ageusia of sweet taste at a sucrose concentration of 40 mg/ml. The sensitivity of the model was 94% with a specificity of 55%. The highest accuracy diagnostic test consisted of ageusia of sweet taste at a sucrose concentration of 106.4 mg/ml or/and ageusia of salty taste at an NaCl concentration of 13.5 or 17 mg/ml. The specificity of the test was found to be 100%, and the sensitivity was 34%.Conclusionas the most effective way of controlling the present pandemic involves testing the wider population for symptomatic, oligosymptomatic and asymptomatic carriers of SARSCoV-2 and isolating or hospitalising infected subjects, in the present study, an inexpensive, simple, fast and sensitive (94%) screening test that can be used for such a purpose is proposed. In addition, a specific (100%) diagnostic test that could be used to refer patients to quarantine in the case of limited availability of genetic or serological tests is proposed.
Meta-analysis of several epidemic characteristics of COVID-19
Authors: Zhang Panpan , Wang Tiandong , Xie Sharon X. 
Published: June 2020

AbstractAs the COVID-19 pandemic has strongly disrupted people’s daily work and life, a great amount of scientific research has been conducted to understand the key characteristics of this new epidemic. In this manuscript, we focus on four crucial epidemic metrics with regard to the COVID-19, namely the basic reproduction number, the incubation period, the serial interval and the epidemic doubling time. We collect relevant studies based on the COVID-19 data in China and conduct a meta-analysis to obtain pooled estimates on the four metrics. From the summary results, we conclude that the COVID-19 has stronger transmissibility than SARS, implying that stringent public health strategies are necessary.
Hospital readmissions of discharged patients with COVID-19
Authors: Ramírez Lina Marcela Parra , Caballero Mireia Cantero , de la Torre Ignacio Morrás , Plaza Alberto Vallejo , Yagüe Itziar Diego , Tejero Elena Jimenez , Rubio Elena Múñez , Asensio Ángel , Cruz Ana Fernández , Martínez Antonio Ramos 
Published: June 2020

AbstractBackgroundCOVID-19 infection has led to an overwhelming effort by health institutions to meet the high demand for hospital admissions.AimTo analyse the clinical variables associated with readmission of patients who had previously been discharged after admission for COVID-19.Design and methodsWe studied a retrospective cohort of patients with laboratory-confirmed SARS-CoV-2 infection who were admitted and subsequently discharged alive. We then conducted a nested case-control study paired (1:1 ratio) by age, sex and period of admission.ResultsOut of 1368 patients who were discharged during the study period, 61 patients (4.4%) were readmitted. Immunocompromised patients were at increased risk for readmission. There was also a trend towards a higher probability of readmission in hypertensive patients (p=0.07). Cases had had a shorter hospital stay and a higher prevalence of fever during the 48 hours prior to discharge. There were no significant differences in oxygen levels measured at admission and discharge by pulse oximetry intra-subject or between the groups. Neutrophil/lymphocyte ratio at hospital admission tended to be higher in cases than in controls (p=0.06). The motive for readmission in 10 patients (16.4%), was a thrombotic event in venous or arterial territory (p<0.001). Neither glucocorticoids nor anticoagulants prescribed at hospital discharge were associated with a lower readmission rate.ConclusionsThe rate of readmission after discharge from hospital for COVID-19 was low. Immunocompromised patients and those presenting with fever during the 48 hours prior to discharge are at greater risk of readmission to hospital.
COVID-19 trend in Bangladesh: deviation from epidemiological model and critical analysis of the possible factors
Authors: Ahmed Asif , Rahman Mohammad Mahmudur 
Published: June 2020

AbstractBackgroundSince its first report on March 08, COVID-19 positive cases and number of deaths are increasing in Bangladesh. In the first month of COVID-19 infection, incidence of daily positive cases did follow the susceptible, infected and recovered (SIR) based predictions we reported in April, but started to deviate in the following months. COVID-19 transmission and disease progression depends on multifaceted determinants e.g. viral genetics, host immunity, social distancing, co-morbidity, socio-demographic and environmental parameters. Therefore deviation in confirmed cases from predicted model may appear and warrant thorough investigation.MethodsIn this short report, we compared real data with SIR model and analyzed the possible factors associated with the deviation which included preventive intervention strategies, socioeconomic capabilities, climatic and meteorological indexes, acquired immunity of Bangladeshi population, demographic characteristics, health indicators and food habits.ResultsThe key factor responsible for the observed deviation was found to be the number of tests performed. Having population with low median age, young age groups are being mostly infected. Low prevalence of non-communicable diseases among them and strong immunity compared to the elderly might have kept most of them asymptomatic with silent recovery. Warm temperature, humidity and UV index of Bangladesh during this summer period might have contributed to the slow progression of infection. Longer daylight mediated immunity, fresh air circulations and ventilation, less population density in rural areas and certain food habits perhaps helped the large number of populations to restrict the infection up to a level.ConclusionDespite all these helpful determinants in Bangladesh, person to person contact is still the leading risk factor for COVID-19 transmission. Infection may increase rapidly if safe distance and preventive measures are not strictly followed while resuming the normal social and work life. Expanding test capacity, strong collaborative action plans, strategies and implementation are needed immediately to prevent catastrophe.HighlightsLimited number of tests compared to large population was the key reason for possible low daily positive cases reported in Bangladesh.Controlled interventions viz. official leave; transport ban and social distancing had helped initially to slow down the transmission.Warm weather, high humidity and UV index, sunlight mediated immunity, fresh air circulations, low pollutions, food habit and heterologous immunity might have reduced the transmission capabilities of SARS-CoV-2.Having large number of young people with strong immunity might have kept most of the infected asymptomatic who recovered silently.Person to person contact still remain as key risk factor in COVID-19 transmission, so strict health measures should be in place even after reopening social activities to contain further transmission.
High-throughput Screening with Pluripotent Stem Cells Identifies CUDC-907 as an Effective Compound for Restoring the Proinflammatory Phenotype of Nakajo-Nishimura Syndrome
Authors: Kase Naoya , Terashima Madoka , Ohta Akira , Niwa Akira , Honda-Ozaki Fumiko , Kawasaki Yuri , Nakahata Tatsutoshi , Kanazawa Nobuo , Saito Megumu K. 
Published: June 2020

AbstractNakajo-Nishimura syndrome (NNS) is an autoinflammatory disorder caused by a homozygous mutations inPSMB8gene. The administration of systemic corticosteroids is partially effective, but continuous treatment causes severe side effects. We previously established a pluripotent stem cell (PSC)-derived NNS disease model that reproduces several inflammatory phenotypes including the overproduction of monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein-10 (IP-10). Here we performed high-throughput compound screening (HTS) using this PSC-derived NNS model to find potential therapeutic candidates and identified CUDC-907 as an effective inhibitor of the release of MCP-1 and IP-10. CUDC-907 did not induce cell death within therapeutic concentrations and was also effective on primary patient cells. Further analysis indicated that the inhibitory effect was post-transcriptional. These findings suggest that HTS with PSC-derived disease models is useful for finding drug candidates for autoinflammatory diseases.Significance statementIn this study, we identified a histone deacetylase inhibitor CUDC-907 as a potential effective compound for ameliorating overproduction of inflammatory chemokines in an autoinflammatory disease named Nakajo-Nishimura syndrome. We performed high-throughput screening using pluripotent stem cell-derived monocytic cell lines. Our data prove the validity of screening system as a versatile platform for seeking candidate compounds for the treatment of congenital immunological disorders associated with monocytic lineage cells.
INSIGHT: a population scale COVID-19 testing strategy combining point-of-care diagnosis with centralised high-throughput sequencing
Authors: Wu Qianxin , Suo Chenqu , Brown Tom , Wang Tengyao , Teichmann Sarah A. , Bassett Andrew R. 
Published: June 2020

AbstractWe present INSIGHT (Isothermal NASBA-Sequencing-based hIGH-througput Test): a two-stage COVID-19 testing strategy, using a barcoded isothermal NASBA reaction that combines point-of-care diagnosis with next generation sequencing, aiming to achieve population-scale COVID-19 testing. INSIGHT combines the advantages of near-patient with centralised testing. Stage 1 allows a quick decentralised readout for early isolation of pre-symptomatic or asymptomatic patients. The same reaction products can then be used in a highly multiplexed sequencing-based assay in Stage 2, confirming the near-patient testing results and facilitating centralised data collection. Based on experiments using commercially acquired human saliva with spiked-in viral RNA as input, the INSIGHT platform gives Stage 1 results within one to two hours, using either fluorescence detection or a lateral flow (dipstick) readout, whilst simultaneously incorporating sample-specific barcodes into the amplification product. INSIGHT Stage 2 can be performed by directly pooling and sequencing all post-amplification barcoded Stage 1 products from hundreds of thousands of samples with minimal sample preparation steps. The 95% limit of detection (LoD-95) for INSIGHT is estimated to be below 50 copies of viral RNA per 20 μl of reaction. Our two-stage testing strategy is suitable for further development into a rapid home-based and point-of-care assay, and is potentially scalable to the population level.