bluuebunny/crossref_metadata_2025 huggingface dataset:
WHOLE-GENOME SEQUENCING ANDDE NOVOASSEMBLY OF A 2019 NOVEL CORONAVIRUS (SARS-COV-2) STRAIN ISOLATED IN VIETNAM
Authors: Lam Le Tung , Hieu Nguyen Trung , Trang Nguyen Hong , Thuong Ho Thi , Linh Tran Huyen , Tien Luu Thuy , Thao Nguyen Thi Ngoc , Loan Huynh Thi Kim , Quang Pham Duy , Quang Luong Chan , Thang Cao Minh , Thuong Nguyen Vu , Ha Hoang , Ha Chu Hoang , Lan Phan Trong , Hai Truong Nam
Published: June 2020

The pandemic COVID-19 caused by the zoonotic virus SARS-CoV-2 has devastated countries worldwide, infecting more than 4.5 million people and leading to more than 300,000 deaths. Whole genome sequencing (WGS) is an effective tool to monitor emerging strains and provide information for intervention, thus help to inform outbreak control decisions. Here, we reported the first effort to sequence andde novoassemble the whole genome of SARS-CoV-2 using PacBio’s SMRT sequencing technology in Vietnam. We also presented the annotation results and a brief analysis of the variants found in our SARS-CoV-2 strain, which was isolated from a Vietnamese patient. The sequencing was successfully completed andde novoassembled in less than 30 hours, resulting in one contig with no gap and a length of 29,766 bp. All detected variants as compared to the NCBI reference were highly accurate as confirmed by Sanger sequencing. The results have shown the potential of long read sequencing to provide high quality WGS data to support public health responses, and advance understanding of this and future pandemics.
Cellular and Cytokine Responses in the Granulomas of Asymptomatic Cattle naturally infected withMycobacterium bovisin Ethiopia
Authors: Tulu Begna , Martineau Henny M , Zewude Aboma , Desta Fekadu , Jolliffe David A , Abebe Markos , Tolera Taye , Belay Mulugeta , Martineau Adrian R , Ameni Gobena
Published: June 2020

Cellular (CD3+ T cell and CD68+ macrophages), cytokines (IFN-γ+ and TNF-α+) and effector molecule (iNOS+) responses were evaluated in the lymph nodes and tissue of cattle naturally infected withMycobacterium bovis. Detailed post mortem and immunonohistochemical examinations of lesions were performed on 16 cows positive for single intradermal cervical comparative tuberculin test (SICCTT) and identified from dairy farms located around the Addis Ababa City. The severity of the gross lesion was significantly higher (p=0.003) inM. bovisculture positive (n=12) cows than in culture negative (n=4). Immunohistochemical techniques showed that the mean percentage labelling of CD3+ T cells decreased as the stage of granuloma increased from stage I to stage IV in culture positive cows (p<0.001). On the other hand, the proportional fraction of CD68+ macrophages and the concentrations of IFN-γ+, TNF-α+ and iNOS+ increased significantly from stage I to stage IV (p< 0.001) in culture positive cows. At the early stage of the granuloma, the culture negative cows showed significantly higher mean proportions of CD68+ macrophages (p=0.03) as well as the concentrations of iNOS+ (p=0.007) compared to culture positive cows. Similarly, at advanced granuloma stages, culture negative cows demonstrated significantly higher mean proportions of CD3+ T cells (p< 0.001) compared to culture positive cows. Thus, the present study demonstrated that following natural infection of cows withM. bovis, as the stage of granuloma increases from stage I to stage IV, the proportion of CD3+ cells decreases while the immunolabeling fraction of CD68+ macrophages, IFN-γ+, TNF-α and iNOS+ increases.
Group A Streptococcus Infection of the Nasopharynx Requires Proinflammatory Signaling Through the Interleukin-1 Receptor
Authors: LaRock Doris L. , Russell Raedeen , Johnson Anders F. , Wilde Shyra , LaRock Christopher N.
Published: June 2020

Group AStreptococcus(GAS) is the etiologic agent of numerous high morbidity and high mortality diseases which commonly have a highly proinflammatory pathology. One factor contributing to this inflammation is the GAS protease SpeB, which directly activates the proinflammatory cytokine interleukin-1β (IL-1β), independent of the canonical inflammasome pathway. IL-1β drives neutrophil activation and recruitment that limits bacterial growth and invasion during invasive skin and soft tissue infections like necrotizing fasciitis. GAS also causes pharyngitis (strep throat), and the upper respiratory tract is its primary nidus for growth and transmission. Since the fitness selection for the species is likely primarily for this site, we examined the process of IL-1β activation in the murine nasopharynx. SpeB still activated IL-1β, which was required for neutrophil migration, but this inflammation instead increased GAS replication. Inhibiting IL-1β or depleting neutrophils, which both promote invasive infection, prevented GAS infection of the nasopharynx. Prior antibiotic exposure increased GAS growth in the murine nasopharynx, and antibiotics were sufficient to reverse the attenuation previously observed when IL-1β, neutrophils, or SpeB were not present to drive inflammation. Therefore, the same fundamental mechanism has opposing effects on virulence at different body sites. Invasive disease may be limited in part due to specific adaptations for inducing host inflammation that are beneficial for pharyngitis.

IMPORTANCE

Our previous reports showed that Group AStreptococcus(GAS) protease SpeB directly activates the host proinflammatory cytokine IL-1β and this restricts invasive skin infection. The upper respiratory tract is the primary site of GAS colonization and infection, but the host-pathogen interactions at this site are still largely unknown. We provide the first evidence that IL-1β-mediated inflammation promotes upper respiratory tract infection. This provides experimental evidence that the notable inflammation of strep throat, which presents with significant swelling, pain, and neutrophil influx, is not an ineffectual immune response, but rather is a GAS-directed remodeling of this niche for its pathogenic benefit.
Structure of the cysteine-rich domain ofPlasmodium falciparumP113 identifies the location of the RH5 binding site
Authors: Campeotto Ivan , Galaway Francis , Mehmood Shahid , Barfod Lea K. , Quinkert Doris , Kotraiah Vinayaka , Phares Timothy W. , Wright Katherine E. , Snijders Ambrosius P. , Draper Simon J. , Higgins Matthew. K. , Wright Gavin J.
Published: June 2020

Plasmodium falciparumRH5 is a secreted parasite ligand that is essential for erythrocyte invasion through direct interaction with the host erythrocyte receptor basigin. RH5 forms a tripartite complex with two other secreted parasite proteins: CyRPA and RIPR, and is tethered to the surface of the parasite through membrane-anchored P113. Antibodies against RH5, CyRPA and RIPR inhibit parasite invasion, suggesting that vaccines containing these three components have the potential to prevent blood-stage malaria. To further explore the role of the P113-RH5 interaction, we selected monoclonal antibodies against P113 that were either inhibitory or non-inhibitory for RH5 binding. Using a Fab fragment as a crystallisation chaperone, we determined the crystal structure of the RH5-binding region of P113 and showed that it is composed of two domains with structural similarities to rhamnose-binding lectins. We identified the RH5 binding site on P113 by using a combination of hydrogen-deuterium exchange mass spectrometry and site directed mutagenesis. We found that a monoclonal antibody to P113 that bound to this interface and inhibited the RH5-P113 interaction did not inhibit parasite blood-stage growth. These findings provide further structural information on the protein interactions of RH5 and will be helpful in the development of blood-stage malaria vaccines that target RH5.

Importance

Malaria is a deadly infectious disease primarily caused by the parasitePlasmodium falciparum.It remains a major global health problem and there is no highly effective vaccine. A parasite protein called RH5 is centrally involved in the invasion of host red blood cells, making it – and the other parasite proteins it interacts with – promising vaccine targets. We recently identified a protein called P113 that binds RH5 suggesting that it anchors RH5 to the parasite surface. In this paper, we use structural biology to locate and characterize the RH5 binding region on P113. These findings will be important to guide the development of new anti-malarial vaccines to ultimately prevent this disease which affects some of the poorest people on the planet.
Covariation of Zinc Deficiency with COVID-19 Infections and Mortality in European Countries: Is Zinc Deficiency a Risk Factor for COVID-19?
Authors: Singh Samer
Published: June 2020

Variables responsible for the differential COVID-19 pandemic severity among countries remain undefined. Zinc, a micronutrient required for immunocompetence, is found deficient in populations. We hypothesized the differential COVID-19 severity observed among European countries could be associated with the Zn-deficiency prevalence. The COVID-19 data from different stages of pandemic, i.e., 8 April, 12 and 26 May 2020, were analyzed for covariation with the estimated Zn-deficiency. A significant, relatively stable, but negative correlation of Zn-deficiency with cases per million for the time period [r(20): -0.4930 to -0.5335, p-value: 0.02720 to 0.0154] and a steady improvement of covariation with deaths per million [r(20): -0.4056; p-value: 0.0760 on 26 May 2020] was observed. Considering, Zinc’s key immunomodulatory role, widespread deficiency along with the self- and prescribed intervention in different target groups, e.g. children, women, elderly, carefully planned dedicated exploratory studies to understand the basis of the observed association are advisable.
Model-based spatial-temporal mapping of opisthorchiasis in endemic countries of Southeast Asia
Authors: Zhao Ting-Ting , Feng Yi-Jing , Doanh Pham Ngoc , Sayasone Somphou , Khieu Virak , Nithikathkul Choosak , Qian Men-Bao , Hao Yuan-Tao , Lai Ying-Si
Published: June 2020

Opisthorchiasis is an overlooked danger to Southeast Asia. High-resolution disease risk maps are critical but haven’t been available for Southeast Asia. Georeferenced disease data and potential influencing factor data were collected through a systematic review of literatures and open-access databases, respectively. Bayesian spatial-temporal joint models were developed to analyze both point- and area-level disease data, within a logit regression in combination of potential influencing factors and spatial-temporal random effects. The model-based risk mapping identified areas of low, moderate and high prevalence across the study region. Even though the overall population-adjusted estimated prevalence presented a trend down, a total of 12.39 million (95% BCI: 10.10-15.06) people were estimated infected with O. viverrini in 2018 in four major endemic countries (i.e., Thailand, Laos, Cambodia, and Vietnam), highlighting the public health importance of the disease in the study region. The high-resolution risk maps provide valuable information for spatial targeting of opisthorchiasis control interventions.
Brief report: social media as a tool for scientific updating at the time of COVID pandemic
Authors: Murri Rita , Segala Francesco Vladimiro , Del Vecchio Pierluigi , Cingolani Antonella , Taddei Eleonora , Micheli Giulia , Fantoni Massimo ,   COVID II Columbus Group
Published: June 2020

In the face of the rapid evolution of the COVID-19 pandemic, healthcare professionals on the frontline are in urgent need of frequent updates in the accomplishment of their practice. Hence, clinicians started to search for prompt, valid information on sources parallel to academic journals publications. Aim of this work is to investigate the extent of this phenomenon.

We administered an anonymous online cross-sectional survey to 645 Italian clinicians. 369 questionnaires were returned. 19,5% (n=72) of respondents were younger than 30 years-old; 49,3% (n=182) worked in Infectious Diseases, Internal Medicine or Respiratory Medicine departments, 11.5% (n=42) in Intensive Care Unit and 7.4% (n=27) were general practitioner. 70% (n=261) of respondents reported that their use of social media to seek medical information increased during the pandemic. 39.3% (n = 145) consistently consulted Facebook groups and 53.1% (n = 196) Whatsapp chats. 47% (n = 174) of respondents reported that information shared on social media had a consistent impact on their daily practice. In the present study, we found no difference in social media usage between age groups or medical specialties.

Given the urgent need for scientific update in face of the present health emergency, these findings may help understanding how clinicians access new evidences and implement them in their daily practice.
Nasal-Swab Testing Misses Patients with Low SARS-CoV-2 Viral Loads
Authors: Callahan Cody , Lee Rose A. , Lee Ghee Rye , Zulauf Kate , Kirby James E. , Arnaout Ramy
Published: June 2020

The urgent need for large-scale diagnostic testing for SARS-CoV-2 has prompted pursuit of sample-collection methods of sufficient sensitivity to replace sampling of the nasopharynx (NP). Among these alternatives is collection of nasal-swab samples, which can be performed by the patient, avoiding the need for healthcare personnel and personal protective equipment.

Previous studies have reached opposing conclusions regarding whether nasal sampling is concordant or discordant with NP. To resolve this disagreement, we compared nasal and NP specimens collected by healthcare workers in a cohort consisting of individuals clinically suspected of COVID-19 and outpatients known to be SARS-CoV-2 RT-PCR positive undergoing follow-up. We investigated three different transport conditions, including traditional viral transport media (VTM) and dry swabs, for each of two different nasal-swab collection protocols on a total of 308 study participants, and compared categorical results and Ct values to those from standard NP swabs collected at the same time from the same patients. All testing was performed by RT-PCR on the Abbott SARS-CoV-2 RealTime EUA (limit of detection [LoD], 100 copies viral genomic RNA/mL transport medium). We found high concordance (Cohen’s kappa >0.8) only for patients with viral loads above 1,000 copies/mL. Those with viral loads below 1,000 copies/mL, the majority in our cohort, exhibited low concordance (Cohen’s kappa = 0.49); most of these would have been missed by nasal testing alone. Previous reports of high concordance may have resulted from use of assays with higher LoD (≥1,000 copies/mL). These findings counsel caution in use of nasal testing in healthcare settings and contact-tracing efforts, as opposed to screening of asymptomatic, low-prevalence, low-risk populations. Nasal testing is an adjunct, not a replacement, for NP.
Deep learning applications for the classification of psychiatric disorders using neuroimaging data: systematic review and meta-analysis
Authors: Quaak Mirjam , van de Mortel Laurens , Thomas Rajat Mani , van Wingen Guido
Published: June 2020

Deep learning (DL) methods have been increasingly applied to neuroimaging data to identify patients with psychiatric and neurological disorders. This review provides an overview of the different DL applications within psychiatry and compares DL model accuracy to conventional machine learning (ML). Fifty-three articles were included for qualitative analysis, primarily investigating autism spectrum disorder (ASD; n=22), schizophrenia (SZ; n=22) and attention-deficit/hyperactivity disorder (ADHD; n=9). Thirty-two of the thirty-five studies that directly compared DL to ML reported a higher accuracy for DL. Only sixteen studies could be included in a meta-regression to quantitatively compare DL and ML performance. This showed a higher odds ratio for DL models, though the comparison attained significance only for ASD. These results suggest that deep learning of neuroimaging data is a promising tool for the classification of individual psychiatric patients. The current evaluation is limited by minimal reporting of performance measures to enable quantitative comparisons, and the restriction to ADHD, SZ and ASD as current research focusses on large publicly available datasets.
COVID-19 Spread in India: Dynamics, Modeling, and Future Projections
Authors: Ranjan Rajesh
Published: June 2020

Abstract

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

Abstract

A key parameter in epidemiological modeling which characterizes the spread of an infectious disease is the mean serial interval. There is increasing evidence supporting a prolonged viral shedding window for COVID-19, but the transmissibility in this phase is unclear. Based on this, we build a model including an additional compartment of infectious individuals who stay infectious for a longer duration than the reported serial interval, but with infectivity reduced to varying degrees. We find that such an assumption also yields a plausible model in explaining the data observed so far, but has different implications for the future predictions in case of a gradual easing on the lockdown measures. Considering the role of modeling in important decisions such as easing lockdown measures and adjusting hospital capacity, we believe that it is critically important to consider a chronically infectious population as an alternative modeling approach to better interpret the transmission dynamics of COVID-19.
Assessment of spread of SARS-CoV-2 by RT-PCR and concomitant serology in children in a region heavily affected by COVID-19 pandemic
Authors: Cohen Robert , Jung Camille , Ouldali Naim , Sellam Aurélie , Batard Christophe , Cahn-Sellem Fabienne , Elbez Annie , Wollner Alain , Romain Olivier , Corrard François , Aberrane Said , Soismier Nathalie , Creidy Rita , Smati-Lafarge Mounira , Launay Odile , Béchet Stéphane , Varon Emmanuelle , Levy Corinne
Published: June 2020

Background

Several studies indicated that children seem to be less frequently infected with SARS-CoV-2 and potentially less contagious. To examine the spread of SARS-CoV-2 we combined both RT-PCR testing and serology in children in the most affected region in France, during the COVID-19 epidemic.

Methods

From April 14, 2020 to May 12, 2020, we conducted a cross-sectional prospective, multicenter study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory pediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by RT-PCR and a microsample of blood for micro-method serology.

Results

Among the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) symptomatic. RT-PCR testing and serology were positive for 11 (1.8%) and 65 (10.7%) of all children, respectively. Only 3 children were RT-PCR–positive without any antibody response have been detected. The frequency of positivity on RT-PCR for SARS-CoV-2 was significantly higher in children with positive serology than those with a negative one (12.3% vs 0.6%, p<0.001). Contact with a person with proven COVID-19 increased the odds of positivity on RT-PCR (OR 7.8, 95% confidence interval [1.5; 40.7]) and serology (15.1 [6.6;34.6]).

Conclusion

In area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with positive SARS-CoV-2 RT-PCR was very low (1.8%), but the rate of positive on serology was higher (10.7%). Most of PCR positive children had at the same time positive serology.

What is already known on this topic?

-

As compared with adults, children seem to be less frequently infected with SARS-CoV-2 and potentially less contagious according to several studies.

-

Most of the studies were based on RT-PCR SARS-CoV-2 testing, without antibody assays.

What this study adds?

-

This study combining RT-PCR and serologic testing, assessed the spread of SARS-CoV-2 infection in children in area heavily affected by COVID-19 pandemic.

-

Among a large cohort of children (>600), 11 (1.8%) were positive on RT-PCR for SARS-CoV-2 and 65 (10.7%) were positive on serology.

-

The only factor affecting positivity of RT-PCR for SARS-CoV-2 or serology was the household contact COVID-19.
Upper-room ultraviolet air disinfection might help to reduce COVID-19 transmission in buildings
Authors: Beggs Clive B. , Avital Eldad J.
Published: June 2020

As the world economies get out of the lockdown imposed by the COVID-19 pandemic, there is an urgent need to assess the suitability of known technologies to mitigate COVID-19 transmission in confined spaces such as buildings. This feasibility study looks at the method of upper-room ultraviolet (UV) air disinfection that has already proven its efficacy in preventing the transmission of airborne diseases such as measles and tuberculosis.

Using published data from various sources it is shown that the SARS-CoV-2 virus, which causes COVID-19, is highly likely to be susceptible to UV damage while suspended in air irradiated by UV-C at levels that are acceptable and safe for upper-room applications. This is while humans are present in the room. Both the expected and worst-case scenarios are investigated to show the efficacy of the upper-room UV-C approach to reduce COVID-19 air transmission in a confined space with moderate but sufficient height. Discussion is given on the methods of analysis and the differences between virus susceptibility to UV-C when aerosolised or in liquid or on a surface.
Contribution of genetic and environmental factors to the onset of preclinical Alzheimer’s disease - a monozygotic twin study
Authors: Konijnenberg Elles , Tomassen Jori , den Braber Anouk , ten Kate Mara , Yaqub Maqsood M. , Mulder Sandra D. , Nivard Michel G. , Vanderstichele Hugo , Lammertsma Adriaan A. , Teunissen Charlotte E. , van Berckel Bart N.M. , Boomsma Dorret I. , Scheltens Philip , Tijms Betty M. , Visser Pieter Jelle
Published: June 2020

Objective

To study the genetic contribution to the start of Alzheimer’s disease as signified by abnormalities in amyloid and tau biomarkers in cognitively intact older identical twins.

Methods

We studied in 96 monozygotic twin-pairs relationships between Aβ aggregation as measured by the ratio Aβ1-42/1-40 in cerebrospinal fluid (CSF) and positron emission tomography (PET), and CSF markers for Aβ production (BACE1, Aβ1-40 and 1-38) and tau. Associations amongst markers were tested with Generalized Estimating Equations including a random effect for twin status, adjusted for age, gender, and APOE ε4 genotype. We used twin analyses to determine relative contributions of genetic and/or environmental factors to AD pathophysiological processes.

Results

Twenty-seven individuals (14%) had an abnormal amyloid-PET, and 14 twin-pairs (15%) showed discordant amyloid status. Within twin-pairs, Aβ production markers and total-tau (t-tau) levels strongly correlated (r range 0.76, 0.88; all p<0.0001), and Aβ aggregation markers and 181-phosphorylated-tau (p-tau) levels correlated moderately strong (r range 0.49, 0.52; all p<0.0001). Cross-twin cross-trait analysis showed that Aβ1-38 in one twin correlated with Aβ1-42/1-40 ratios, t-tau and p-tau levels in their co-twins (r range 0.18, 0.58; all p<.07). Within-pair differences in Aβ production markers related to differences in tau levels (r range 0.49, 0.61; all p<0.0001). Twin discordance analyses suggest that Aβ production and tau levels show coordinated increases in very early AD.

Interpretation

Our results suggest a substantial genetic/shared environmental background contributes to both Aβ and tau increases, suggesting that modulation of environmental risk factors may aid in delaying the onset of AD pathophysiological processes.
Analysis of the time evolution of SARS-CoV-2 lethality rate in Italy: Evidence of an unaltered virus potency
Authors: Balasco Nicole , d’Alessandro Vincenzo , Smaldone Giovanni , Vitagliano Luigi
Published: June 2020

In recent months, the entire world is facing a dramatic health emergency caused by the diffusion of a hitherto unknown coronavirus (SARS-CoV-2). Despite the efforts, the understanding of the many facets of the pandemic is still rather limited. In the present manuscript, we have monitored the evolution of the lethality rate in Italy by using the data collected over the last three months. Our data indicate that there is a striking correlation between the number of infected people of a certain week and the deaths of the following one. Despite the overall simplicity of the applied approach and its many approximations, the analysis of the Italian scenario provides some interesting insights into the pandemic. Indeed, we have found that the lethality rate is virtually unchanged over the last two months. This implies that the reduction of the deaths is strictly connected to the decrease of cases. Unfortunately, the present study does not support the idea that the virus potency has lowered in the last weeks, as our data demonstrate that the likelihood of a fatal outcome after the infection has not decreased in the recent outbreak evolution. Moreover, we show that the lethality rate is still very high in the country (≈13.5%). Since this number is remarkably higher if compared to the actual lethality estimates made worldwide, this finding suggests that the number of detected cases may be a gross underestimation of the actual infected people, likely due to the presence of a significant number of non-symptomatic or paucisymptomatic individuals in the population.
Evaluating COVID-19 screening strategies based on serological tests
Authors: Baccini Michela , Mattei Alessandra , Rocco Emilia , Vannucci Giulia , Mealli Fabrizia
Published: June 2020

Background

Facing the SARS-CoV-2 epidemic requires intensive testing on the population to early identify and isolate infected subjects. Although RT-PCR is the most reliable technique to detect ongoing infections, serological tests are frequently proposed as tools in heterogeneous screening strategies. We analyze the performance of a screening strategy proposed in Tuscany (Italy), which first uses qualitative rapid tests for antibody detection, and then RT-PCR tests on the positive subjects.

Methods

We simulate the number of RT-PCR tests required by the screening strategy and the undetected ongoing infections in a pseudo-population of 500’000 subjects, under different prevalence scenarios and assuming a sensitivity of the serological test ranging from 0.50 to 0.80 (specificity=0.98). A compartmental model is used to predict the number of new infections generated by the false negatives two months after the screening, under different values of the infection reproduction number.

Results

Assuming a sensitivity equal to 0.80 and a prevalence of 0.3%, the screening procedure would require on average 11167.6 RT-PCR tests and would produce 300 false negatives, responsible after two months of a number of contagions ranging from 526 to 1132, under the optimistic scenario of a reproduction number between 0.5 to 1. Costs and false negatives increase with the prevalence.

Conclusions

The analyzed screening procedure should be avoided unless the prevalence and the rate of contagion are very low. The cost and effectiveness of the screening strategies should be evaluated in the actual context of the epidemic, accounting for the fact that it may change over time.
Modelling of the second (and subsequent) waves of the coronavirus epidemic. Spain and Germany as case studies
Authors: de Castro Francisco
Published: June 2020

The first wave of the coronavirus pandemic is waning in many countries. Some of them are starting to lift the confinement measures adopted to control it, but there is considerable uncertainty about if it is too soon and it may cause a second wave of the epidemic. To explore this issue, I fitted a SEIR model with time-dependent transmission and mortality rates to data from Spain and Germany as contrasting case studies. The model reached an excellent fit to the data. I then simulated the post-confinement epidemic under several scenarios. The model shows that (in the absence of a vaccine) a second wave is likely inevitable and will arrive soon, and that a strategy of adaptive confinement may be effective to control it. The model also shows that just a few days delay in starting the confinement may have caused and excess of thousands of deaths in Spain.
Cross-reactivity of neutralizing antibody and its correlation with circulating T follicular cells in recovered COVID-19 individuals
Authors: Zhang Jian , Wu Qian , Liu Ziyan , Wang Qijie , Wu Jiajing , Hu Yabin , Bai Tingting , Xie Ting , Huang Mincheng , Wu Tiantian , Peng Danhong , Huang Weijin , Jin Kun , Niu Ling , Guo Wangyuan , Luo Dixian , Lei Dongzhu , Wu Zhijian , Li Guicheng , Huang Renbin , Lin Yingbiao , Xie Xiangping , He Shuangyan , Deng Yunfan , Liu Jianghua , Li Weilang , Lu Zhongyi , Chen Haifu , Zeng Ting , Luo Qingting , Li Yi-Ping , Wang Youchun , Liu Wenpei , Qu Xiaowang
Published: June 2020

Seroconversion appeared early after COVID-19 onset, and convalescent sera therapy benefit some critical patients. However, neutralizing antibody (nAb) in convalescents is largely unknown. We found that 97.01% (65/67) of COVID-19 convalescents maintained IgG antibodies with high binding and avidity to SARS-CoV-2 spike subunits S1 and S2, and 95.52% (64/67) had neutralization activity against SARS-CoV-2 pesudovirus, one month after discharge (median ID50, 2.75; IQR, 2.34-3.08). Some sera exhibited cross-neutralization against SARS-CoV (76.12%), MERS-CoV (17.91%), or both (10.45%). Interestingly, individuals recovered from severe disease (severe group) had nAbs with binding and neutralization titers higher than non-severe group. Severe group appeared a rapid increase of lymphocytes and a high proportion of circulating CXCR3+Tfh cells. Interestingly, the later were spike-specific and positively correlated with SARS-CoV-2 nAb titers. All subjects had no autoimmunity. Our findings provide novel insights into nAb responses in COVID-19 convalescents and facilitate treatment and vaccine development for SARS-CoV-2 infection.
Impact on mental health care and on mental health service users of the COVID-19 pandemic: a mixed methods survey of UK mental health care staff
Authors: Johnson Sonia , Dalton-Locke Christian , Vera San Juan Norha , Foye Una , Oram Sian , Papamichail Alexandra , Landau Sabine , Olive Rachel Rowan , Jeynes Tamar , Shah Prisha , Rains Luke Sheridan , Lloyd-Evans Brynmor , Carr Sarah , Killaspy Helen , Gillard Steve , Simpson Alan
Published: June 2020

Purpose

The COVID-19 pandemic has potential to disrupt and burden the mental health care system, and to magnify inequalities experienced by mental health service users.

Methods

We investigated staff reports regarding the impact of the COVID-19 pandemic in its early weeks on mental health care and mental health service users in the UK using a mixed methods online survey. Recruitment channels included professional associations and networks, charities and social media. Quantitative findings were reported with descriptive statistics, and content analysis conducted for qualitative data.

Results

2,180 staff from a range of sectors, professions and specialties participated. Immediate infection control concerns were highly salient for inpatient staff, new ways of working for community staff. Multiple rapid adaptations and innovations in response to the crisis were described, especially remote working. This was cautiously welcomed but found successful in only some clinical situations. Staff had specific concerns about many groups of service users, including people whose conditions are exacerbated by pandemic anxieties and social disruptions; people experiencing loneliness, domestic abuse and family conflict; those unable to understand and follow social distancing requirements; and those who cannot engage with remote care.

Conclusion

This overview of staff concerns and experiences in the early COVID-19 pandemic suggests directions for further research and service development: we suggest that how to combine infection control and a therapeutic environment in hospital, and how to achieve effective and targeted tele-health implementation in the community, should be priorities. The limitations of our convenience sample must be noted.
High Incidence of Venous Thrombosis in Patients with Moderate to Severe COVID-19
Authors: Kerbikov Oleg B. , Orekhov Pavel Yu. , Borskaya Ekaterina N. , Nosenko Natalia S.
Published: June 2020

COVID-19 predisposes to venous thromboembolism and there are multiple data regarding high incidence of venous thrombosis in critical COVID-19 patients, however reports on this complication in less severe patients are not widely available.

The aim of this study was to investigate the incidence of deep-vein thrombosis (DVT) in patients with moderate to severe COVID-19 and to assess the prevalence of DVT with lung computerized tomography (lung CT) exams, clinical information and lab data. This study examined 75 consecutive patients with moderate to severe COVID-19, with specific exclusions.

METHODS

Almost all patients (pts) admitted to our hospital in the first half of May underwent comprehensive vein ultrasonography. 75 pts (aged 27-92 y, median – 63 y, 36 males and 39 females) with moderate to severe COVID-19 were included in our study.

RESULTS

Spontaneous echo contrast (decreased blood velocity and blood stasis) was detected in common femoral veins in 53 pts (70.7%). DVT was found in 15 pts (20%). The vast majority of those with DVT (13 pts, 86.7%) had thrombi only in calf veins and ileofemoral thrombosis was detected in 2 pts with DVT (13.3%). There was no significant observed difference between DVT and non-DVT patients with respect to age, underlying diseases, lung CT scores and SpaO2 at admission. There was also no significant observed difference between DVT and non-DVT patients with respect to both “time from symptoms onset to admission” and with respect to the majority of lab data.

However, a significant difference was observed in D-dimer level (1.87 ± 1.62 vs 0.51 ± 0,4 mcg/mL p<0.0001) and C-reactive protein (116.9 ± 83,6 and 65.1 ± 64.98 mg/L, p = 0.014) for patients with DVT and patients without DVT respectably (Receiver operating characteristics (ROC) curve analysis revealed that the level of D-dimer ≥ 0.69 mcg/mL is the predictor of DVT with a sensitivity of 76.9%, a specificity of 77.6%, p < 0.001 (AUC area under curve = 0.7944). Logistic regression confirmed that D-dimer is an independent predictor of DVT and patients with D-dimer ≥ 0.69 mcg/mL have odds ratio (OR) of developing DVT = 5.1 (confidence interval [CI] 1.9 - 13.5)).

CONCLUSION

Patients with moderate to severe COVID-19 show high incidence of DVT, indicating that moderate to severe COVID-19 patients may require an early administration of anticoagulation therapy as part of their treatment. Such therapy may be continued after hospital discharge. Based on these findings, these patients may also require a follow-up with vein ultrasonography after recovery to rule out DVT.
Developing an automatic pipeline for analyzing chatter about health services from social media: A case study for Medicaid
Authors: Yang Yuan-Chi , Al-Garadi Mohammed Ali , Hogg-Bremer Whitney , Zhu Jane M. , Grande David , Sarker Abeed
Published: June 2020

Objective

Social media can be an effective but challenging resource for conducting close-to-real-time assessments of consumers’ perceptions about health services. Our objective was to develop and evaluate an automatic pipeline, involving natural language processing and machine learning, for automatically characterizing user-posted Twitter data about Medicaid.

Material and Methods

We collected Twitter data via the public API using Medicaid-related keywords (Corpus-1), and the website’s search option using agency-specific handles (Corpus-2). We manually labeled a sample of tweets into five pre-determined categories or other, and artificially increased the number of training posts from specific low-frequency categories. We trained and evaluated several supervised learning algorithms using manually-labeled data, and applied the best-performing classifier to collected tweets for post-classification analyses assessing the utility of our methods.

Results

We collected 628,411 and 27,377 tweets for Corpus-1 and -2, respectively. We manually annotated 9,571 (Corpus-1: 8,180; Corpus-2: 1,391) tweets, using 7,923 (82.8%) for training and 1,648 (17.2%) for evaluation. A BERT-based (bidirectional encoder representations from transformers) classifier obtained the highest accuracies (83.9%, Corpus-1; 86.4%, Corpus-2), outperforming the second-best classifier (SVMs: 79.6%; 76.4%). Post-classification analyses revealed differing inter-corpora distributions of tweet categories, with political (63%) and consumer-feedback (43%) tweets being most frequent for Corpus-1 and -2, respectively.

Discussion and Conclusion

The broad and variable content of Medicaid-related tweets necessitates automatic categorization to identify topic-relevant posts. Our proposed pipeline presents a feasible solution for automatic categorization, and can be deployed/generalized for health service programs other than Medicaid. Annotated data and methods are available for future studies (LINK_TO_BE_AVAILABLE).
Burnout among healthcare professionals during COVID-19 pandemic: a cross-sectional study
Authors: Jalili Mohammad , Niroomand Mahtab , Hadavand Fahimeh , Zeinali Kataun , Fotouhi Akbar
Published: June 2020

Background

The unpredictable nature of the new COVID-19 pandemic and the already alarming incidence of healthcare workers being affected can have a significant impact on the psychological well-being of the staff.

Objective

To describe the prevalence of burnout among healthcare professionals and the associated factors.

Design

Cross-sectional survey.

Setting

Eight university affiliated hospitals in the capital city of Tehran, Iran.

Participants

All healthcare workers at the study sites who had been taking care of COVID-19 patients.

Measurements

Age, gender, marital status, having children, hospital, job category, experience, and work load, as well as the level of burnout in each subscale.

Results

326 persons (53.0%) experienced high levels of burnout. The average score in emotional exhaustion, depersonalization and lack of personal accomplishment was 26.6, 10.2, and 27.3, respectively. The level of burnout in the three subscales varied based on the personal as well as work related factors and gender was the only variable that was associated with high levels of all three domains.

Limitations

There was no control group and thus we cannot claim a causal relationship between COVID-19 and the observed level of burnout. Not all confounding factors might have been accounted for.

Conclusions

Burnout is prevalent among healthcare workers caring for COVID-19 patients. Age, gender, job category, and site of practice contribute to the level of burnout that the staff experience.

Funding source

None
How much leeway is there to relax COVID-19 control measures?
Authors: Anderson Sean C. , Mulberry Nicola , Edwards Andrew M. , Stockdale Jessica E. , Iyaniwura Sarafa A. , Falcao Rebeca C. , Otterstatter Michael C. , Janjua Naveed Z. , Coombs Daniel , Colijn Caroline
Published: June 2020

Following successful widespread non-pharmaceutical interventions aiming to control COVID-19, many jurisdictions are moving towards reopening economies and borders. Given that little immunity has developed in most populations, re-establishing higher contact rates within and between populations carries substantial risks. Using a Bayesian epidemiological model, we estimate the leeway to reopen in a range of national and regional jurisdictions that have experienced different COVID-19 epidemics. We estimate the risks associated with different levels of reopening and the likely burden of new cases due to introductions from other jurisdictions. We find widely varying leeway to reopen, high risks of exceeding past peak sizes, and high possible burdens per introduced case per week, up to hundreds in some jurisdictions. We recommend a cautious approach to reopening economies and borders, coupled with strong monitoring for changes in transmission.
A Logistic Model for Age-Specific COVID-19 Case-Fatality Rates
Authors: Gao Xiang , Dong Qunfeng
Published: June 2020

Objectives

To develop a mathematical model to characterize age-specific case-fatality rates (CFR) of COVID-19.

Materials and Method

Based on two large-scale Chinese and Italian CFR data, a logistic model was derived to provide quantitative insight on the dynamics between CFR and age.

Results and Discussion

We inferred that CFR increased faster in Italy than in China, as well as in females over males. In addition, while CFR increased with age, the rate of growth eventually slowed down, with a predicted theoretical upper limit for males (32%), females (21%), and the general population (23%).

Conclusion

Our logistic model provided quantitative insight on the dynamics of CFR.

Lay Summary

Recently published studies have qualitatively shown that the COVID-19 case-fatality rates increased with age, with elder people at higher risk of fatality than younger ones. In our study, we presented a quantitative mathematical modeling approach to re-analyze those published data. Specifically, we were able to derive a logistic model to characterize age-specific CFRs. The derived mathematical model uncovered novel quantitative insights on the dynamics between CFR and age. Specifically, we inferred from the model that while CFR increased with age, the rate of growth eventually slowed down, with a predicted theoretical upper limit of 23% for the general population.
Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic
Authors: Zhang Wenjuan , Govindavari John Paul , Davis Brian , Chen Stephanie , Kim Jong Taek , Song Jianbo , Lopategui Jean , Plummer Jasmine T , Vail Eric
Published: June 2020

Given the higher mortality rate and widespread phenomenon of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) within the United States (US) population, understanding the mutational pattern of SARS CoV-2 has global implications for detection and therapy to prevent further escalation. Los Angeles has become an epicenter of the SARS-CoV-2 pandemic in the US. Efforts to contain the spread of SARS-CoV-2 require identifying its genetic and geographic variation and understanding the drivers of these differences. For the first time, we report genetic characterization of SARS-CoV-2 genome isolates in the Los Angeles population using targeted next generation sequencing (NGS). Samples collected at Cedars Sinai Medical Center were collected from patients with confirmed SARS-CoV-2 infection. We identified and diagnosed 192 patients by our in-house qPCR assay. In this population, the highest frequency variants were in known mutations in the 5’UTR, AA193 protein, RdRp and the spike glycoprotein. SARS-CoV-2 transmission within the local community was tracked by integrating mutation data with patient postal codes with two predominant community spread clusters being identified. Notably, significant viral genomic diversity was identified. Less than 10% of the Los Angeles community samples resembled published mutational profiles of SARS-CoV-2 genomes from China, while >50% of the isolates shared closely similarities to those from New York State. Based on these findings we conclude SARS-CoV-2 was likely introduced into the Los Angeles community predominantly from New York State but also via multiple other independent transmission routes including but not limited to Washington State and China.
Population density and basic reproductive number of COVID-19 across United States counties
Authors: Sy Karla Therese L. , White Laura F. , Nichols Brooke
Published: June 2020

The basic reproductive number (R0) is a function of contact rates among individuals, transmission probability, and duration of infectiousness. We sought to determine the association between population density and R0of SARS-CoV-2 across U.S. counties, and whether population density could be used as a proxy for contact rates. We conducted a cross-sectional analysis using linear mixed models with random intercept and fixed slopes to assess the association of population density and R0. We also assessed whether this association was differential across county-level main mode of transportation-to-work percentage. Counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density. The effect of population density and R0was not modified by private transportation use. Differential R0by population density can assist in more accurate predictions of the rate of spread of SARS-CoV-2 in areas that do not yet have active cases.

Article Summary Line

U.S. counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density.
Nr2e3functional domain ablation by CRISPR-Cas9D10A identifies a new isoform and generates Retinitis Pigmentosa and Enhanced S-cone Syndrome models
Authors: Aísa-Marín Izarbe , López-Iniesta M José , Milla Santiago , Lillo Jaume , Navarro Gemma , de la Villa Pedro , Marfany Gemma
Published: June 2020

Mutations inNR2E3cause retinitis pigmentosa (RP) and enhanced S-cone syndrome (ESCS) in humans. This gene produces a large isoform encoded in 8 exons and a previously unreported shorter isoform of 7 exons, whose function is unknown. We generated two mouse models by targeting exon 8 ofNr2e3using CRISPR/Cas9-D10A nickase. Allele Δ27 is an in-frame deletion of 27 bp that ablates the dimerization domain, whereas allele ΔE8 (full deletion of exon 8), produces only the short isoform that lacks the dimerization and repressor domains. The Δ27 mutant shows developmental alterations and a non-progressive electrophysiological dysfunction that resembles the ESCS phenotype. The ΔE8 mutant exhibits progressive retinal degeneration, as occurs in human RP patients. Interestingly, the mutant retinas show invaginations similar to fovea-like pits. Our mutants suggest a role ofNr2e3as a cone-patterning regulator and provide valuable models for studying mechanisms ofNR2E3-associated retinal dystrophies and evaluating potential therapies.

Abstract Figure

Highlights

-Nr2e3mouse models were generated by exon 8 deletion using CRISPR/Cas9 D10A nickase.

- NewNr2e3mRNA retaining intron 7 encodes a short protein expressed in adult retina.

- Deletion of 9 aa of the NR2E3 dimerization domain causes enhanced S-cone syndrome.

- Deletion of exon 8 produces a phenotype similar to Retinitis Pigmentosa in mouse.