bluuebunny/crossref_metadata_2025 huggingface dataset:
Using HoloLens2™ to reduce staff exposure to aerosol generating procedures during a global pandemic
Authors: Cafferkey John J , Hampson Dominic O P , Ross Clare , Kooner Angad S , Martin Guy FJ , Kinross James M
Published: May 2020

RATIONALE

COVID-19 poses a unique challenge; caring for patients with a novel, infectious disease whilst protecting staff. Some interventions used to give oxygen therapy are aerosol generating procedures. Staff delivering such interventions require PPE and are exposed to a significant viral load resulting in sick days and even death. We aim to reduce this risk using an augmented-reality communication device: The HoloLens by Microsoft.

OBJECTIVES

In a tertiary centre in London we aim to implement HoloLens technology, allowing other medical staff to remotely join the consulting clinician when in a high-risk patient area delivering oxygen therapy. The study primary outcome was to reduce the exposure to staff and demonstrate non-inferiority staff satisfaction when compared to not using the device. Our secondary outcome was to reduce extrapolated PPE costs when using the device.

METHODS

Our study was conducted in March and April 2020, within a respiratory unit delivering aerosolising oxygen therapies (High flow nasal oxygen, Continuous positive airway pressure and non-invasive ventilation) to patients with suspected or confirmed COVID-19 infection.

MEASUREMENTS

Self-reported questionnaires to assess satisfaction in key areas of patient care. An infrared people counting device was also used to assess staff in and out of the unit.

MAIN RESULTS

Mean self-reported time in the high-risk zone was less when using HoloLens (2.69 hours) compared to usual practice (3.96 hours) although this difference was not statistically significant (p = 0.3657). HoloLens showed non-inferiority when compared to usual practice in staff satisfaction score for all domains. Furthermore, mean staff satisfaction score encouragingly improved when using HoloLens. Self-reported PPE counts from this study showed 12 staff members changing PPE 25.8 times per shift, almost double the 13.5 times in the HoloLens count.

CONCLUSIONS

We have demonstrated HoloLens can reduce the number of staff exposed to aerosol generating areas in a novel infectious disease. Our results show it did not impair communication, medical staff availability or end of life care. HoloLens technology may also reduce the use of PPE, which has equipment availability and cost benefits. This study provides grounding for further use of the HoloLens device by bringing a bedside experience to experts remote to the situation.
SARS-CoV-2 detection in nasopharyngeal throat swabs by metagenomics
Authors: Tan Le Van , Hong Nguyen Thi Thu , Ngoc Nghiem My , Thanh Tran Tan , Lam Vo Thanh , Nguyet Lam Anh , Nhu Le Nguyen Truc , Ny Nguyen Thi Han , Minh Ngo Ngoc Quang , Man Dinh Nguyen Huy , Hang Vu Thi Ty , Khanh Phan Nguyen Quoc , Xuan Tran Chanh , Phong Nguyen Thanh , Tu Tran Nguyen Hoang , Hien Tran Tinh , Hung Le Manh , Truong Nguyen Thanh , Yen Lam Minh , Dung Nguyen Thanh , Thwaites Guy , Chau Nguyen Van Vinh ,   for OUCRU COVID-19 research group
Published: May 2020

Metagenomics could detect SARS-CoV-2 in all eight nasopharyngeal/throat swabs with high/low viral loads, and rhinovirus in a co-infected patient. The sequenced viruses belonged to lineage B1. Because metagenomics could detect novel pathogen and co-infection, and generate sequence data for epidemiological investigation, it is an attractive approach for infectious-disease diagnosis.
Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London
Authors: Zhou Jie , Otter Jonathan A. , Price James R. , Cimpeanu Cristina , Garcia Danel Meno , Kinross James , Boshier Piers R , Mason Sam , Bolt Frances , Holmes Alison H. , Barclay Wendy S.
Published: May 2020

Background

Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London.

Methods

We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined.

Results

Viral RNA was detected on 114/218 (52.3%) of surfaces and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces i and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus would not be culturable.

Conclusions

Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.
IgG serology in health care and administrative staff populations from 7 hospitals representative of different exposures to SARS-CoV-2 in Lombardy, Italy
Authors: Sandri Maria Teresa , Azzolini Elena , Torri Valter , Carloni Sara , Tedeschi Michele , Castoldi Massimo , Mantovani Alberto , Rescigno Maria
Published: May 2020

Lombardy is one of the regions in Italy most affected by COVID-19. We assessed the diffusion of the virus via testing plasma anti-SARS-CoV-2 IgG antibodies in 3985 employees of 7 different hospitals, located across the Lombardy region in areas with different exposure to the epidemic. Subjects filled an anamnestic questionnaire to self-report on COVID-19 symptoms, co-morbidities, smoking, regular or smart-working, and the exposure to COVID-19-infected individuals. We show that the number of individuals exposed to the virus depended on the geographical area where the hospital was located and ranged between 3 to 43% which correlated with the incidence of COVID-19 in Lombardy. There was a higher prevalence of females than males positive for IgG, however the level of antibodies was similar, suggesting a comparable magnitude of the response. We observed 10% of IgG positive asymptomatic individuals and another 20% with one or two symptoms. 81% of individuals presenting both anosmia/ageusia and fever resulted SARS-CoV-2 infected. IgG positivity correlated with family contacts.

In conclusion, the frequency of IgG positivity and SARS-CoV-2 infection is dependent on the geographical exposure to the virus and to extra-hospital exposure.
Serum responses of children with Kawasaki Disease against SARS-CoV-2 proteins
Authors: Chang Arthur J , Croix Michael , Kenney Patrick , Baron Sarah , Hicar Mark D
Published: May 2020

Recently, numerous reports have suggested association of pediatric Coronavirus Disease 2019 (COVID-19) cases and Kawasaki Disease (KD). KD is a major cause of childhood acquired heart disease and vasculitis in the pediatric population. Epidemiological patterns suggest KD is related to an infectious agent; however, the etiology remains unknown1. As past reports have considered other coronaviruses to be related to KD2,3, these reports of pediatric COVID-19 related inflammatory disorder cases leads to the hypothesis of potential cross-coronavirus reactivity that would account for the past controversial proposals of other coronaviruses and these new cases. We sought to address this hypothesis by assessing the antigen targeting of biobanked plasma samples of febrile children, including those with KD, against SARS-CoV-2 proteins.
Age, gender and COVID-19 infections
Authors: Sobotka Tomáš , Brzozowska Zuzanna , Muttarak Raya , Zeman Kryštof , di Lego Vanessa
Published: May 2020

Data for ten European countries which provide detailed distribution of COVID-19 cases by sex and age show that among people of working age, women diagnosed with COVID-19 substantially outnumber infected men. This pattern reverses around retirement: infection rates among women fall at age 60-69, resulting in a cross-over with infection rates among men. The relative disadvantage of women peaks at ages 20-29, whereas the male disadvantage in infection rates peaks at ages 70-79. The elevated infection rates among women of working age are likely tied to their higher share in health- and care-related occupations. Our examination also suggests a link between women’s employment profiles and infection rates in prime working ages. The same factors that determine women’s higher life expectancy account for their lower fatality and higher male disadvantage at older ages.
Effect of various treatment modalities on the novel coronavirus (nCOV-2019) infection in humans: a systematic review & meta-analysis
Authors: Misra Shubham , Nath Manabesh , Hadda Vijay , Vibha Deepti
Published: May 2020

Background and aim

Several therapeutic agents have been investigated for the treatment of novel Coronavirus-2019 (nCOV-2019). We aimed to conduct a systematic review and meta-analysis to assess the effect of various treatment modalities in nCOV-2019 patients.

Methods

An extensive literature search was conducted before 22 May 2020 in PubMed, Google Scholar, Cochrane library databases. Quality assessment was performed using Newcastle Ottawa Scale. A fixed-effect model was applied if I2<50%, else the results were combined using random-effect model. Risk Ratio (RR) or Standardized Mean Difference (SMD) along-with 95% Confidence Interval (95%CI) were used to pool the results. Between study heterogeneity was explored using influence and sensitivity analyses & publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.

Results

Eighty-one studies involving 44in vitroand 37 clinical studies including 8662 nCOV-2019 patients were included in the review. Lopinavir-Ritonavir compared to controls was significantly associated with shorter mean time to clinical improvement (SMD -0.32; 95%CI -0.57 to -0.06) and Remdesivir compared to placebo was significantly associated with better overall clinical improvement (RR 1.17; 95%CI 1.07 to 1.29). Hydroxychloroquine was associated with less overall clinical improvement (RR 0.88; 95%CI 0.79 to 0.98) and longer time to clinical improvement (SMD 0.64; 95%CI 0.33 to 0.94), It additionally had higher all-cause mortality (RR 1.6; 95%CI 1.26 to 2.03) and more total adverse events (RR 1.84; 95% CI 1.58 to 2.13).

Conclusion

Our meta-analysis suggests that exceptin vitrostudies, no treatment till now has shown clear-cut benefit on nCOV-2019 patients. Lopinavir-Ritonavir and Remdesivir have shown some benefits in terms less time to clinical improvement and better overall clinical improvement. Hydroxychloroquine use has a risk of higher mortality and adverse events. Results from upcoming large clinical trials must be awaited to draw any profound conclusions.
Serum SARS-COV-2 Nucleocapsid Protein: A Sensitivity and Specificity Early Diagnostic Marker for SARS-COV-2 Infection
Authors: Li Tao , Wang Li , Wang Huihui , Li Xuemei , Zhang Shubing , Xu Yuanhong , Wei Wei
Published: May 2020

Objective

This study aimed to explore the diagnostic value of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid(N) protein assay in the early stage of SARS-COV-2 infection.

Method

Serum N protein in SARS-COV-2 infected patients and non-SARS-COV-2 infected population was measured by enzyme-linked immunosorbent assay (ELISA) double antibody sandwich assay. Colloidal gold immunochromatography assay is used to detect serum N protein antibodies in the above population.

Results

50 cases of SARS-CoV-2 nucleic acid positive and SARS-CoV-2 antibody negative patients had a serum N protein positive rate of 76%, including 2% with a concentration of 10.00-49.99 pg / mL, 8% with a concentration of 50.00-99.99 pg / mL, 22% with a concentration of 100.00 - 299.99 pg/mL, and 44% with a concentration≥ 300.00 pg / mL. 37 samples of patients with serum SARS-CoV-2 antibody positive after infection had a serum SARS-CoV-2 N protein positive rate of 2.7%, of which 2.7% had the concentration of 10.00-49.99 pg / mL and 0% had the concentration of 50.00-99.99 pg / mL, 100.00 −299.99 pg / mL, and >300.00 pg / mL. Serum N protein test results of 633 non-SARS-COV-2 infected patients including pregnant women, other respiratory infections, and increased rheumatoid factor were all negative, having a serum N protein concentration less than 10.00 pg/mL, with a specificity of 100%. Using SPSS 19.0 to calculate the receiver operating characteristic curve, the area under the curve was 0.9756 (95% confidence interval 0.9485-1.000, p <0.0001), sensitivity and specificity were 92% (95% confidence interval 81.16% to 96.85%) and 96.84% (95% confidence interval 95.17% to 97.15%). The best CUTOFF value is 1.850 pg / mL.

Conclusion

The measurement of SARS-COV-2 serum N protein has a high diagnostic value for the infected patients before the antibody appears, and shortens the window period of serological diagnosis. The laboratory needs to establish an individual CUTOFF value according to purpose of the application.
Predicting COVID-19 Pandemic in Saudi Arabia Using Modified Singular Spectrum Analysis
Authors: Alharbi Nader
Published: May 2020

This research presents a modified Singular Spectrum Analysis (SSA) approach for the analysis of COVID-19 in Saudi Arabia. We have proposed this approach and developed it in [1–3] for separability and grouping step in SSA, which plays an important role for reconstruction and forecasting in the SSA. The modified SSA mainly enables us to identify the number of the interpretable components required for separability, signal extraction and noise reduction. The approach was examined using different number of simulated and real data with different structures and signal to noise ratio. In this study we examine its capability in analysing COVID-19 data. Then, we use Vector SSA for predicting new data points and the peak of this pandemic. The results shows that the approach can be used as a promising one in decomposing and forecasting the daily cases of COVID-19 in Saudi Arabia.
COVID-19: Effects of environmental conditions on the propagation of respiratory droplets
Authors: Zhao Lei , Qi Yuhang , Luzzatto-Fegiz Paolo , Cui Yi , Zhu Yangying
Published: May 2020

As Coronavirus disease 2019 (COVID-19) continues to spread, a detailed understanding on the transmission mechanisms is of paramount importance. The disease transmits mainly through respiratory droplets and aerosol. Although models for the evaporation and trajectory of respiratory droplets have been developed, how the environment impacts the transmission of COVID-19 is still unclear. In this study, we investigate the propagation of respiratory droplets and aerosol particles generated by speech under a wide range of temperature (0 °C to 40 °C) and relative humidity (0% to 92%) conditions. We show that droplets can travel three times farther in low temperature and high humidity environment, while the amount of aerosol increases in high temperature and low humidity environment. The results also underscore the importance of proper ventilation, as droplets and aerosol spread significantly farther in airstreams. This study contributes to the understanding of the environmental impact on COVID-19 transmission.
Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Network
Authors: Rojo José Manuel Casas , Santos Juan Miguel Antón , Núñez-Cortés Jesús Millán , Lumbreras Carlos , Rincón José Manuel Ramos , Roy-Vallejo Emilia , Artero Arturo , Fernández Francisco Arnalich , Bruñén Jose Miguel García , Núñez Juan Antonio Vargas , Castro Santiago J. Freire , Manzano Luis , Fraile Isabel Perales , Vieitez Anxela Crestelo , Puchades Francesc , Rodilla Enrique , Marquínez Marta Nataya Solís , Tur David Bonet , del Pilar Fidalgo Moreno María , Aizpuru Eva M Fonseca , Sánchez Francisco Javier Carrasco , Pejenaute Elisa Rabadán , Rubio-Rivas Manuel , Peña José David Torres , Huelgas Ricardo Gómez ,   for the SEMI-COVID-19 Network
Published: May 2020

Background

Spain has been one of the countries most affected by the COVID-19 pandemic.

Objective

To create a registry of patients with COVID-19 hospitalized in Spain in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease.

Methods

A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records.

Results

Up to April 30th 2020, 6,424 patients from 109 hospitals were included. Their median age was 69.1 years (range: 18-102 years) and 56.9% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.2%, 39.7%, and 18.7%, respectively. The most frequent symptoms were fever (86.2%) and cough (76.5%). High values of ferritin (72.4%), lactate dehydrogenase (70.2%), and D-dimer (61.5%), as well as lymphopenia (52.6%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.7%) and lopinavir/ritonavir (62.4%). 31.5% developed respiratory distress. Overall mortality rate was 21.1%, with a marked increase with age (50-59 years: 4.2%, 60-69 years: 9.1%, 70-79 years: 21.4%, 80-89 years: 42.5%, ≥ 90 years: 51.1%).

Conclusions

The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.
Bayesian modeling of COVID-19 cases with a correction to account for under-reported cases
Authors: Oliveira Anderson Castro Soares de , Morita Lia Hanna Martins , Silva Eveliny Barroso da , Granzotto Daniele Cristina Tita , Zardo Luiz André Ribeiro , Fontes Cor Jesus Fernandes
Published: May 2020

The novel of COVID-19 disease started in late 2019 making the worldwide governments came across a high number of critical and death cases, beyond constant fear of the collapse in their health systems. Since the beginning of the pandemic, researchers and authorities are mainly concerned with carrying out quantitative studies (modeling and predictions) overcoming the scarcity of tests that lead us to under-reporting cases. To address these issues, we introduce a Bayesian approach to the SIR model with correction for under-reporting in the analysis of COVID-19 cases in Brazil. The proposed model was enforced to obtain estimates of important quantities such as the reproductive rate and the average infection period, along with the more likely date when the pandemic peak may occur. Several under-reporting scenarios were considered in the simulation study, showing how impacting is the lack of information in the modeling.
Sociodemographic predictors of outcomes in COVID-19: examining the impact of ethnic disparities in Northern Nevada
Authors: Antwi-Amoabeng Daniel , Beutler Bryce D. , Awad Munadel , Kanji Zahara , Mahboob Sumaiya , Ghuman Jasmine , Boppana Sri Harsha , Sheikh Mohammad S. , Ulanja Mark B. , Gullapalli Nageshwara
Published: May 2020

Background

On March 11, 2020, the World Health Organization declared coronavirus disease-19 (COVID-19) a pandemic. Nearly five million individuals have since been diagnosed with this increasingly common and potentially lethal viral infection. Emerging evidence suggests a disproportionate burden of illness and death among minority communities. We aimed to evaluate the effect of ethnicity on outcomes among patients diagnosed with COVID-19 in Northern Nevada.

Design

Single-center, retrospective observational study

Materials and methods

The electronic health records of 172 patients diagnosed with COVID-19 were obtained from a 946-bed tertiary referral center serving Northern Nevada. Demographic and clinical characteristics were compared by ethnic group (Hispanic versus non-Hispanic). Logistic regression was used to determine predictors of mortality.

Results

Among 172 patients who were diagnosed with COVID-19 between March 12th and May 8th, 2020, 87 (50.6%) identified as Hispanic and 81 (47.1%) as non-Hispanic. The mean age was 46.0 among Hispanics and 55.8 among non-Hispanics. Comorbidities linked to increased COVID-19-related mortality – hypertension, obesity, and chronic obstructive pulmonary disease – were more common among the non-Hispanic population. Hispanic individuals were significantly more likely to be uninsured and to live in low-income communities as compared to their non-Hispanic counterparts (27.6% versus 8.2% and 52.9% versus 30.6%, respectively). Hispanic patients were also less likely than non-Hispanics to have a primary care provider (42.5% versus 61.2%). However, mortality was significantly higher among the non-Hispanic population (15.3% versus 5.8%).

Conclusion

The COVID-19 pandemic has disproportionately affected Hispanic individuals in Northern Nevada, who account for only 25.7% of the population but over half of the confirmed cases. Hispanic individuals were younger and had fewer comorbidities than their non-Hispanic counterparts; consequently, despite considerable socioeconomic disadvantage, mortality was lower among the Hispanic population. The underlying causes of ethnic disparities in COVID-19 incidence remain to be established, but further investigation may lead to more effective community- and systems-based interventions.
Estimation and monitoring of COVID-19’s transmissibility from publicly available data
Authors: Silveira Antonio , Pereira Antonio
Published: May 2020

The COVID-19 pandemic began in the city of Wuhan, China, at the end of 2019 and quickly spread worldwide. The disease is caused by contact with the SARS-CoV-2 virus, which probably jumped from an animal host to humans. SARS-CoV-2 infects various tissues in the body, notably the lungs, and patients usually die from respiratory complications. Mathematical models of the disease have been instrumental to guide the implementation of mitigation strategies aimed at slowing the spread of the disease. One of the key parameters of mathematical models is the basic reproduction ratioR0, which measures the degree of infectivity of affected individuals. The goal of mitigation is to reduceR0as close or below 1 as possible, as it means that new infections are in decline. In the present work, we use the recursive least-squares algorithm to establish the stochastic variability of a time-varyingR0(t) from eight different countries: Argentina, Belgium, Brazil, Germany, Italy, New Zealand, Spain, and the United States of America. The proposed system can be implemented as an online tracking application providing information about the dynamics of the pandemic to health officials and the public at large.
The effect of calcium and vitamin D on bone mineral density in patients taking glucocorticoid therapies: Protocol for a systematic review and network meta-analysis
Authors: Deng Jiawen
Published: May 2020

Glucocorticoid (GC) administration is an effective therapy commonly used in the treatment of autoimmune and inflammatory diseases. However, the use of GC can give rise to serious complications. The main detrimental side effect of GC therapy is significant bone loss, resulting in glucocorticoid-induced osteoporosis (GIOP).

We performed a systematic review and network meta-analysis (NMA) to evaluate whether the use of calcium supplementation, with or without vitamin D, vitamin D metabolites and vitamin D analogues is capable of increasing bone mineral density (BMD) at the lumbar spine, femoral neck, and hip in adult patients undergoing glucocorticoid therapies compared to no treatment.
Covid19 Surveillance in Peru on April using Text Mining
Authors: Saire Josimar Edinson Chire , Cruz Jimy Frank Oblitas
Published: May 2020

The present outbreak as consequence by coronavirus covid19 has generated an big impact over the world. South American countries had their own limitations, challengues and pandemic has highlighted what needs to improve. Peru is a country with good start with quarantine, social distancing policies but the policies was not enough during the weeks. So, the analysis over April is performed through infoveillance using posts from different cities to analyze what population was living or worried during this month. Results presents a high concern about international context, and national situation, besides Economy and Politics are issues to solve. By constrast, Religion and Transport are not very important for peruvian citizens.
Early life modifiable risk factors for the development of knee osteoarthritis: protocol for a systematic review
Authors: Singh Ambrish , Jones Graeme , Ding Changhai , Winzenberg Tania , Cicuttini Flavia , Lavekar Swati , Molina-Garcia Pablo , Otahal Petr , Antony Benny
Published: May 2020

Knee osteoarthritis (OA) is the most common form of OA which affects knee joints and there is currently no disease-modifying treatment available for OA. Therefore, an ideal strategy to prevent the development of OA is to identify and intervene at the modifiable risk factors for the development and progression of OA. Early-life factors such as obesity and malalignment may affect the mechanical aspect of the knee (i.e. alterations in normal knee kinematics) and could be the risk factor for the development of knee OA in later life. Identifying early-life (gestational factors, congenital defects, childhood, adolescence, early adulthood) factors which affect the development of knee OA in later stages of the life may help to develop targeted prevention programs in early-life itself to prevent the development of knee OA. Hence, this systematic review protocol provides the method to be used to comprehensively summarise the existing evidence on early life modifiable risk factors associated with the development and progression of knee OA.
COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva
Authors: Randad Pranay R. , Pisanic Nora , Kruczynski Kate , Manabe Yukari C. , Thomas David , Pekosz Andrew , Klein Sabra L. , Betenbaugh Michael J. , Clarke William A. , Laeyendecker Oliver , Caturegli Patrizio P. , Larman H. Benjamin , Detrick Barbara , Fairley Jessica K. , Sherman Amy C. , Rouphael Nadine , Edupuganti Srilatha , Granger Douglas A. , Granger Steve W. , Collins Matthew , Heaney Christopher D.
Published: May 2020

Non-invasive SARS-CoV-2 antibody testing is urgently needed to estimate the incidence and prevalence of SARS-CoV-2 infection at the general population level. Precise knowledge of population immunity could allow government bodies to make informed decisions about how and when to relax stay-at-home directives and to reopen the economy. We hypothesized that salivary antibodies to SARS-CoV-2 could serve as a non-invasive alternative to serological testing for widespread monitoring of SARS-CoV-2 infection throughout the population. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology and tested 167 saliva and 324 serum samples, including 134 and 118 negative saliva and serum samples, respectively, collected before the COVID-19 pandemic, and 33 saliva and 206 serum samples from participants with RT-PCR-confirmed SARS-CoV-2 infection. We evaluated the correlation of results obtained in saliva vs. serum and determined the sensitivity and specificity for each diagnostic media, stratified by antibody isotype, for detection of SARS-CoV-2 infection based on COVID-19 case designation for all specimens. Matched serum and saliva SARS-CoV-2 antigen-specific IgG responses were significantly correlated. Within the 10-plex SARS-CoV-2 panel, the salivary anti-nucleocapsid (N) protein IgG response resulted in the highest sensitivity for detecting prior SARS-CoV-2 infection (100% sensitivity at ≥10 days post-SARS-CoV-2 symptom onset). The salivary anti-receptor binding domain (RBD) IgG response resulted in 100% specificity. Among individuals with SARS-CoV-2 infection confirmed with RT-PCR, the temporal kinetics of IgG, IgA, and IgM in saliva were consistent with those observed in serum. SARS-CoV-2 appears to trigger a humoral immune response resulting in the almost simultaneous rise of IgG, IgM and IgA levels both in serum and in saliva, mirroring responses consistent with the stimulation of existing, cross-reactive B cells. SARS-CoV-2 antibody testing in saliva can play a critically important role in large-scale “sero”-surveillance to address key public health priorities and guide policy and decision-making for COVID-19.

40-word summary

A multiplex immunoassay to detect SARS-CoV-2-specific antibodies in saliva performs with high diagnostic accuracy as early as ten days post-COVID-19 symptom onset. Highly sensitive and specific salivary COVID-19 antibody assays could advance broad immuno-surveillance goals in the USA and globally.
Utility of Pan-Family Assays for Rapid Viral Screening: Reducing Delays in Public Health Responses During Pandemics
Authors: Erlichster Michael , Chana Gursharan , Zantomio Daniela , Goudey Benjamin , Skafidas Efstratios
Published: May 2020

Background

The SARS-CoV-2 pandemic has highlighted deficiencies in the testing capacity of many developed countries during the early stages of emerging pandemics. Here we describe the potential for pan-family viral assays to improve early accessibility of large-scale nucleic acid testing.

Methods

Coronaviruses and SARS-CoV-2 were used as a case-study for investigating the utility of pan-family viral assays during the early stages of a novel pandemic. Specificity of a pan-coronavirus (Pan-CoV) assay for viral detection was assessed using the frequency of common human coronavirus (HCoV) species in key populations. A reported Pan-CoV assay was assessed to determine sensitivity to SARS-CoV-2 and 59 other coronavirus species. The resilience of the primer target regions of this assay to mutation was assessed in 8893 high quality SARS-CoV-2 genomes to predict ongoing utility during pandemic progression.

Findings

Due to infection with common HCoV species, a Pan-CoV assay would return a false positive for as few as 1% of asymptomatic adults, but up to 30% of immunocompromised patients displaying symptoms of respiratory disease. Two of the four reported pan-coronavirus assays would have identified SARS-CoV-2 and we demonstrate that with small adjustments to the primers, these assays can accommodate novel variation observed in animal coronaviruses. The assay target region of one well established Pan-CoV assay is highly resistant to mutation compared to regions targeted by other widely applied SARS-CoV-2 RT-PCR assays.

Interpretation

Pan-family assays have the potential to greatly assist management of emerging public health emergencies through prioritization of high-resolution testing or isolation measures, despite limitations in test specificity due to cross-reactivity with common pathogens. Targeting highly conserved genomic regions make pan-family assays robust and resilient to mutation of a given virus. This approach may be applicable to other viral families and has utility as part of a strategic stockpile of tests maintained to better contain spread of novel diseases prior to the widespread availability of specific assays.
Cytoplasmic pool of spliceosome protein SNRNP70 regulates the axonal transcriptome and development of motor connectivity
Authors: Nikolaou Nikolas , Gordon Patricia M. , Hamid Fursham , Taylor Richard , Makeyev Eugene V. , Houart Corinne
Published: May 2020

Regulation of pre-mRNA splicing and polyadenylation plays a profound role in neurons by diversifying the proteome and modulating gene expression during development and in response to physiological cues. Although most pre-mRNA processing reactions are thought to occur in the nucleus, numerous splicing regulators are also found in neurites. Here, we show that U1-70K/SNRNP70, a major spliceosomal component, localizes in RNA-associated granules in axons. We identify the cytoplasmic pool of SNRNP70 as an important local regulator of motor axonal growth, nerve-dependent acetylcholine receptor (AChR) clustering and neuromuscular synaptogenesis. This cytoplasmic pool has a protective role for a limited number of axonal transcripts preventing them from degradation. Moreover, non-nuclear SNRNP70 is able to locally regulates splice variants of transcripts such asagrin, thereby locally controlling formation of synapses. Our results point to an unexpected, yet essential, function of local SNRNP70 in axonal development and indicate a role of splicing factors in local RNA metabolism during establishment and maintenance of neuronal connectivity.
The persistence of NontypeableHaemophilus influenzaefuels airway inflammation
Authors: Saliu Fabio , Rizzo Giulia , Bragonzi Alessandra , Cariani Lisa , Cirillo Daniela M. , Colombo Carla , Daccò Valeria , Girelli Daniela , Rizzetto Sara , Sipione Barbara , Cigana Cristina , Lorè Nicola I.
Published: May 2020

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NontypeableHaemophilus influenzae(NTHi) is commonly isolated from airway of cystic fibrosis (CF) patients. However, to what extent NTHi persistence contributes to the lung inflammatory burden during CF chronic airway disease is controversial. Here, we aimed at determining the pathological role of NTHi persistence in a cohort of CF patients and in a newly generated mouse model of NTHi persistence.

In our study cohort, we found that CF patients chronically colonized by NTHi had significantly higher levels of IL-8 and CXCL1 than those who were not colonized. To better define the impact of NTHi persistence in fuelling inflammatory response, we developed a new mouse model using both laboratory and CF clinical strains. NTHi persistence was associated with chronic inflammation of the lung, characterized by recruitment of neutrophils and cytokine release (KC, G-CFS, IL-6 and IL-17A) at 2 and 14 days postinfection. An increased burden of T cell mediated response (CD4+and γδ cells) and higher levels of matrix metalloproteinase 9, known to be associated with tissue remodelling, were observed at 14 days post-infection. Of note we found that both CD4+IL-17+cells and levels of IL-17 cytokine were enriched in mice at advanced stage of NTHi chronic infection. Moreover, by immunohistochemistry we found CD3+, B220+and CXCL-13+cells localized in bronchus-associated lymphoid tissue-like structures at day 14.

Our results demonstrate that NTHi persistence exerts a pro-inflammatory activity in the human and murine lung, and could therefore contribute to the exaggerated burden of lung inflammation in CF patients.
Structural Insights on Fusion Mechanisms of Extracellular Vesicles with Model Plasma Membrane
Authors: Perissinotto Fabio , Rondelli Valeria , Senigagliesi Beatrice , Brocca Paola , Almásy László , Bottyan Laszlo , Merkel Dániel Géza , Amenitsch Heinz , Sartori Barbara , Pachler Karin , Mayr Magdalena , Gimona Mario , Rohde Eva , Casalis Loredana , Parisse Pietro
Published: May 2020

Extracellular vesicles (EVs) represent a potent intercellular communication system. Within a lipid bilayer such small vesicles transport biomolecules between cells and throughout the body, strongly influencing the fate of recipient cells. Due to their specific biological functions they have been proposed as biomarkers for various diseases and as optimal candidates for therapeutic applications. Despite of their extreme biological relevance, the small size (30 to a few hundred nanometers in diameter) of EVs still poses a great challenge for their isolation, quantification and biophysical/biochemical characterization, therefore the complex network of EVs and cells as well as their interaction remains to be further revealed. Here we propose a multiscale platform based on Atomic Force Microscopy, Small Angle X-ray Scattering, Small Angle Neutron Scattering and Neutron Reflectometry to reveal structure-function correlations of purified EVs through the analysis of their interaction with model membrane systems, in form of both supported lipid bilayers and suspended unilamellar vesicles of variably complex composition. The analysis reveals a strong interaction of EVs with the model membranes and preferentially with liquid ordered raft-like lipid domains, and opens the way to understand uptake mechanisms in different vesicle to cell membrane relative compositions.
Population structure-guided profiling of antibiotic resistance patterns in clinicalListeria monocytogenesisolates from Germany identifiespbpB3alleles associated with low levels of cephalosporin resistance
Authors: Fischer Martin A. , Wamp Sabrina , Fruth Angelika , Allerberger Franz , Flieger Antje , Halbedel Sven
Published: May 2020

Abstract

Case numbers of listeriosis have been increasing in Germany and the European Union during the last decade. In addition reports on the occurrence of antibiotic resistance inListeria monocytogenesin clinical and environmental isolates are accumulating. The susceptibility towards 14 antibiotics was tested in a selection of clinicalL. monocytogenesisolates to get a more precise picture of the development and manifestation of antibiotic resistance in theL. monocytogenespopulation. Based on the population structure determined by core genome multi locus sequence typing (cgMLST) 544 out of 1,220 sequenced strains collected in Germany between 2009 and 2019 were selected to cover the phylogenetic diversity observed in the clinicalL. monocytogenespopulation. All isolates tested were susceptible towards ampicillin, penicillin and co-trimoxazole - the most relevant antibiotics in the treatment of listeriosis. Resistance to daptomycin and ciprofloxacin was observed in 493 (91%) and in 71 (13%) of 544 isolates, respectively. While all tested strains showed resistance towards ceftriaxone, the minimal inhibitory concentrations (MIC) observed varied widely between 4 mg/L up to >128 mg/L. An allelic variation of the penicillin binding protein genepbpB3could be identified as the cause of this difference in ceftriaxone resistance levels. This study is the first population structure-guided analysis of antimicrobial resistance in recent clinical isolates and confirms the importance of penicillin binding protein B3 (PBP B3) for the high level of intrinsic cephalosporin resistance ofL. monocytogeneson a population-wide scale.
COVID-Align: Accurate online alignment of hCoV-19 genomes using a profile HMM
Authors: Lemoine Frédéric , Blassel Luc , Voznica Jakub , Gascuel Olivier
Published: May 2020

Motivation

The first cases of the COVID-19 pandemic emerged in December 2019. Until the end of February 2020, the number of available genomes was below 1,000, and their multiple alignment was easily achieved using standard approaches. Subsequently, the availability of genomes has grown dramatically. Moreover, some genomes are of low quality with sequencing/assembly errors, making accurate re-alignment of all genomes nearly impossible on a daily basis. A more efficient, yet accurate approach was clearly required to pursue all subsequent bioinformatics analyses of this crucial data.

Results

hCoV-19 genomes are highly conserved, with very few indels and no recombination. This makes the profile HMM approach particularly well suited to align new genomes, add them to an existing alignment and filter problematic ones. Using a core of ∼2,500 high quality genomes, we estimated a profile using HMMER, and implemented this profile in COVID-Align, a user-friendly interface to be used online or as standalone via Docker. The alignment of 1,000 genomes requires less than 20mn on our cluster. Moreover, COVID-Align provides summary statistics, which can be used to determine the sequencing quality and evolutionary novelty of input genomes (e.g. number of new mutations and indels).

Availability

https://covalign.pasteur.cloud,hub.docker.com/r/evolbioinfo/covid-align

Contacts

olivier.gascuel@pasteur.fr,frederic.lemoine@pasteur.fr

Supplementary information

Supplementary information is available atBioinformaticsonline.
High-Efficiency Electroporation of Chytrid Fungi
Authors: Swafford Andrew J.M. , Hussey Shane P. , Fritz-Laylin Lillian K.
Published: May 2020

Two species of parasitic fungi from the phylum Chytridiomycota (chytrids) are annihilating global amphibian populations. These chytrid species—Batrachochytrium dendrobatidisandB. salamandrivorans—have high rates of mortality and transmission. Upon establishing infection in amphibians, chytrids rapidly multiply within the skin and disrupt their hosts’ vital homeostasis mechanisms. Current disease models suggest that chytrid fungi locate and infect their hosts during a motile, unicellular ‘zoospore’ life stage. Moreover, other chytrid species parasitize organisms from across the tree of life, making future epidemics in new hosts a likely possibility. Efforts to mitigate the damage and spread of chytrid disease have been stymied by the lack of knowledge about basic chytrid biology and tools with which to test molecular hypotheses about disease mechanisms. To overcome this bottleneck, we have developed high-efficiency delivery of molecular payloads into chytrid zoospores using electroporation. Our electroporation protocols result in payload delivery to between 75-97% of living cells of three species:B. dendrobatidis, B. salamandrivorans,and a non-pathogenic relative,S. punctatus. This method lays the foundation for molecular genetic tools needed to establish ecological mitigation strategies and answer broader questions in evolutionary and cell biology.
Single-cell growth inference ofCorynebacterium glutamicumreveals asymptotically linear growth
Authors: Messelink Joris , Meyer Fabian , Bramkamp Marc , Broedersz Chase P.
Published: May 2020

Regulation of growth and cell size is crucial for the optimization of bacterial cellular function. So far, single bacterial cells have been found to grow exponentially, which implies the need for tight regulation to maintain cell size homeostasis. Here, we characterize the growth behavior of the apically growing bacteriumCorynebacterium glutamicumusing a novel broadly applicable inference method for single-cell growth dynamics. Using this approach, we find thatC. glutamicumexhibits asymptotically linear single-cell growth. To explain this growth mode, we model elongation as being rate-limited by the apical growth mechanism. Our model accurately reproduces the inferred cell growth dynamics and is validated with elongation measurements on a transglycosylase deficientΔrodAmutant. Finally, with simulations we show that the distribution of cell lengths is narrower for linear than exponential growth, suggesting that this asymptotically linear growth mode can act as a substitute for tight division length and division symmetry regulation.
A network linking scene perception and spatial memory systems in posterior cerebral cortex
Authors: Steel Adam , Billings Madeleine M. , Silson Edward H. , Robertson Caroline E.
Published: May 2020

Abstract

Here, we report a network of brain areas bridging the spatial-memory and scene-perception systems of the human brain. Using fine-grained individual-subject fMRI, we reveal three cortical areas of the human brain, each lying immediately anterior to a region of the scene perception network in posterior cerebral cortex, that selectively activate when recalling familiar real-world locations. Despite their close proximity to the scene-perception areas, network analyses show that these regions constitute a distinct functional network that interfaces with memory systems during naturalistic scene understanding. These “place-memory areas” offer a new framework for understanding how the brain implements memory-guided visual behaviors, including navigation.
Preliminary analysis of scRNA sequencing of children’s lung tissues excludes the expression of SARS-CoV-2 entry related genes as the key reason for the milder syndromes of COVID-19 in children
Authors: Tao Yue , Yang Ruwen , Wen Chen , Fan Jue , Ma Jing , He Qiao , Zhao Zhiguang , Song Xinyu , Chen Hao , Shi Guocheng , Yin Minzhi , Fang Nan , Zhang Hao , Chen Huiwen , Mo Xi
Published: May 2020

To explore whether the expression levels of viral-entry associated genes might contribute to the milder symptoms in children, we analyzed the expression of these genes in both children and adults’ lung tissues by single cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC). Both scRNA-seq and IHC analyses showed comparable levels of the key genes for SARS-CoV-2 entry in children and adults, includingACE2, TMPRSS2andFURIN, suggesting that instead of lower virus intrusion rate, other factors are more likely to be the key reasons for the milder symptoms of SARS-CoV-2 infected children.
Periodontal therapy on disease activity of Rheumatoid Arthritis. Systematic review and meta-analysis
Authors: Novillo Francisco , Lai Shuheng , Cárdenas Geovanna , Verdugo Francisca , Rada Gabriel
Published: May 2020

Objective

The objective of this systematic review is to assess the impact of periodontal therapy on disease activity of patients with Rheumatoid Arthritis

Data Sources

We will conduct a comprehensive search in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Lilacs, the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, US National Institutes of Health (NIH) and grey literature, to identify all relevant randomized controlled trials regardless of language or publication status (published, unpublished, in press and in progress).

Elegibility Criteria for Selecting Studies and Methods

We will include randomised trials evaluating the effect of periodontal therapy on disease activity of rheumatoid arthritis. Two reviewers will independently screen each study for eligibility, data extraction, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE system to assess the certainty of the evidence for each outcome.

Ethics and Dissemination

No ethics approval is considered necessary. The results of this review will be disseminated via peer-reviewed publications, social networks and traditional media.

PROSPERO Registration ID

CRD42020150286.
What Can We Learn from the Time Evolution of COVID-19 Epidemic in Slovenia?
Authors: Bâldea Ioan
Published: May 2020

A recent work (DOI 10.1101/2020.05.06.20093310) indicated that temporarily splitting larger populations into smaller groups can efficiently mitigate the spread of SARS-CoV-2 virus. The fact that, soon afterwards, on May 15, 2020, the two million people Slovenia was the first European country proclaiming the end of COVID-19 epidemic within national borders may be relevant from this perspective. Motivated by this evolution, in this paper we investigate the time dynamics of coronavirus cases in Slovenia with emphasis on how efficient various containment measures act to diminish the number of COVID-19 infections. Noteworthily, the present analysis does not rely on any speculative theoretical assumption; it is solely based on raw epidemiological data. Out of the results presented here, the most important one is perhaps the finding that, while imposing drastic curfews and travel restrictions reduce the infection rate k by a factor of four with respect to the unrestricted state, they only improve the κ-value by ~ 15% as compared to the much bearable state of social and economical life wherein (justifiable) wearing face masks and social distancing rules are enforced/followed. Significantly for behavioral and social science, our analysis of the time dependence κ = κ(t) may reveal an interesting self-protection instinct of the population, which became manifest even before the official lockdown enforcement.