bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Environmental Chemicals on the Gut Microbiome
Authors: Chiu Karen , Warner Genoa , Nowak Romana A , Flaws Jodi A , Mei Wenyan
Published: May 2020

Since the surge of microbiome research in the last decade, many studies have provided insight into the causes and consequences of changes in the gut microbiota. Among the multiple factors involved in regulating the microbiome, exogenous factors such as diet and environmental chemicals have been shown to alter the gut microbiome significantly. Although diet substantially contributes to changes in the gut microbiome, environmental chemicals are major contaminants in our food and are often overlooked. Herein, we summarize the current knowledge on major classes of environmental chemicals (bisphenols, phthalates, persistent organic pollutants, heavy metals, and pesticides) and their impact on the gut microbiome, which includes alterations in microbial composition, gene expression, function, and health effects in the host. We then discuss health-related implications of gut microbial changes, which include changes in metabolism, immunity, and neurological function.
Successful treatment of a unique chronic multi-bacterial scalp infection with N-chlorotaurine, N-bromotaurine and bromamine T
Authors: Kyriakopoulos Anthony M. , Nagl Markus , Orth-Höller Dorothea , Marcinkiewicz Janusz , Baliou Stella , Zoumbourlis Vassilis
Published: May 2020

Microbial species can act in synergy to circumvent environmental stress conditions and survive. In addition, biofilms are a serious public-health issue globally and constitute a clinical emergency. Infection persistence, increased morbidity and mortality, and antibiotic resistance are consequences of poly-microbial synergy. Due to inherited complexity and synergy between numerous species, newer antimicrobial agents of increased efficacy and tolerability are needed. In this unique medical case, a chronic (9 year) multi-bacterial scalp infection was differentially diagnosed from other inflammatory skin disorders by prolonged microbiological culture. The bacterial species found seem to have caused lesions of visible biofilm not documented previously in the medical literature. This complicated infection was treated successfully and rapidly with the combined topical application of the active halogen compounds N-chlorotaurine, N-bromotaurine and bromamine T, which is in contrast to the previous failed systemic and topical therapeutic approaches. This study strengthens the case for the use of active halogen compounds against multi-bacterial infections of the skin in the future, without the occurrence of resistance.
Corynebacterium silvaticum sp. nov., a unique group of NTTB corynebacteria in wild boar and roe deer
Authors: Dangel Alexandra , Berger Anja , Rau Jörg , Eisenberg Tobias , Kämpfer Peter , Margos Gabriele , Contzen Matthias , Busse Hans-Jürgen , Konrad Regina , Peters Martin , Sting Reinhard , Sing Andreas
Published: May 2020

A total of 34

Corynebacterium

sp. strains were isolated from caseous lymph node abscesses of wild boar and roe deer in different regions of Germany. They showed slow growth on Columbia sheep blood agar and sparse growth on Hoyle’s tellurite agar. Cellular fatty acid analysis allocated them in the

C. diphtheriae

group of genus

Corynebacterium

. MALDI-TOF MS using specific database extensions and rpoB sequencing resulted in classification as

C. ulcerans

. Their quinone system is similar to

C. ulcerans

, with major menaquinone MK-8(H2). Their complex polar lipid profile includes major lipids phosphatidylinositol, phosphatidylinositol-mannoside, diphosphatidylglycerol, but also unidentified glycolipids, distinguishing them clearly from

C. ulcerans

. They ferment glucose, ribose and maltose (like

C. ulcerans

), but do not utilise d-xylose, mannitol, lactose, sucrose and glycogen (like

C. pseudotuberculosis

). They showed activity of catalase, urease and phospholipase D, but variable results for alkaline phosphatase and alpha-glucosidase. All were non-toxigenic, tox gene bearing and susceptible to clindamycin, penicillin and erythromycin. In 16SrRNA gene and RpoB protein phylogenies the strains formed distinct brancheswith

C. ulcerans

as nearest relative.Whole genome sequencing revealed the unique sequence type 578, a distinctbranch in pangenomic core genome MLST, average nucleotide identities <91%, enhancedgenome sizes (2.55 Mbp) and G/C content (54.4 mol%) compared to related species.These results suggest that the strains represent a novel species, for which wepropose the name Corynebactriumsilvaticum sp. nov., based on their first isolation from forest-dwellinggame animals. The type strain isKL0182T (= CVUAS 4292T = DSM 109166T = LMG 31313T= CIP 111 672T).
A model showing the relative risk of viral aerosol infection from breathing and the benefit of wearing masks in different settings with implications for Covid-19
Authors: Barr Gerald D
Published: May 2020

Background

Widespread use of masks in the general population is being used in many countries for control of Covid-19. There has been reluctance on the part of the WHO and some governments to recommend this.

Methodology

A basic model has been constructed to show the relative risk of aerosol from normal breathing in various situations together with the relative benefit from use of different masks.

Results

The benefit from mask use between individuals is multiplicative not additive and although social distancing at 2 meters appears beneficial with regards to aerosol infectivity, in confined areas this is time limited requiring additional measures such as masks. The model shows the relative benefit of masks when social distancing is not possible at all times, or when in confined areas which can also be aided by efficient ventilation. Where a person is in one place for a prolonged period there is more risk requiring protection.

Conclusions

Masks should be used in the above situations especially at an early stage of an outbreak. Public health planning requires stockpiling of masks and encouraging everyone to have suitable masks in their household when supplies are normalised. In the absence of widely available good quality masks the use of a cloth mask will be better than no protection at all.
Quantifying and mitigating the impact of the COVID-19 pandemic on outcomes in colorectal cancer
Authors: Sud Amit , Jones Michael , Broggio John , Scott Stephen , Loveday Chey , Torr Bethany , Garrett Alice , Nicol David L. , Jhanji Shaman , Boyce Stephen A. , Williams Matthew , Lyratzopoulos Georgios , Barry Claire , Riboli Elio , Kipps Emma , McFerran Ethna , Lawler Mark , Muller David C. , Abulafi Muti , Houlston Richard , Turnbull Clare
Published: May 2020

Background

The COVID-19 pandemic has caused disruption across cancer pathways for diagnosis and treatment. In England, 32% of colorectal cancer (CRC) is diagnosed via urgent symptomatic referral from primary care, the “2-week-wait” (2WW) pathway. Access to routine endoscopy is likely to be a critical bottleneck causing delays in CRC management due to chronic limitation in capacity, acute competition for physician time, and safety concerns.

Methods

We used age-specific, stage-specific 10 year CRC survival for England 2007–2017 and 2WW CRC cases volumes. We used per-day hazard ratios of CRC survival generated from observational studies of CRC diagnosis-to-treatment interval to model the effect of different durations of per-patient delay. We utilised data from a large London observational study of faecal immunochemical testing (FIT) in symptomatic patients to model FIT-triage to mitigate delay to colonoscopy.

Findings

Modest delays result in significant reduction in survival from CRC with a 4-month delay resulting across age groups in ≥20% reduction in survival in Stage 3 disease and in total over a year, 1,419 attributable deaths across the 11,266 CRC patients diagnosed via the 2WW pathway. FIT triage of >10 ug Hb/g would salvage 1,292/1,419 of the attributable deaths and reduce colonoscopy requirements by >80%. Diagnostic colonoscopy offers net survival in all age groups, providing nosocomial COVID-19 infection rates are kept low (<2·5%).

Interpretation

To avoid significant numbers of avoidable deaths from CRC, normal diagnostic and surgical throughput must be maintained. An accrued backlog of cases will present to primary care following release of lockdown, supranormal endoscopy capacity will be required to manage this without undue delays. FIT-triage of symptomatic cases provides a rational approach by which to avoid patient delay and mitigate pressure on capacity in endoscopy. This would also reduce exposure to nosocomial COVID-19 infection, relevant in particular to older patient groups.

Funding

Breast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR).
BRAZIL IS PROJECTED TO BE THE NEXT GLOBAL COVID-19 PANDEMIC EPICENTER
Authors: de Lemos Menezes Pedro , Garner David M. , Valenti Vitor E.
Published: May 2020

Coronavirus disease 2019 (COVID-19) is a disease triggered by SARS-CoV-2 infection, which is related in the most recent pandemic situation, significantly affecting health and economic systems. In this study we assessed the death rate associated to COVID-19 in Brazil and the United States of America (USA) to estimate the probability of Brazil becoming the next pandemic epicenter. We equated data between Brazil and USA obtained through the Worldometer website (www.worldometer.info). Epidemic curves from Brazil and USA were associated and regression analysis was undertaken to predict the Brazilian death rate regarding COVID-19 in June. In view of data from April 9th 2020, death rates in Brazil follow a similar exponential increase to USA (r=0.999; p<0.001), estimating 64,310 deaths by June 9th 2020. In brief, our results demonstrated that Brazil follows an analogous progression of COVID-19 deaths cases when compared to USA, signifying that Brazil could be the next global epicenter of COVID-19. We highlight public strategies to decrease the COVID-19 outbreak.
A Novel Multi-ventilation Technique to Split Ventilators
Authors: Lee Albert , Umar Soban , Hoftman Nir N.
Published: May 2020

Background

Despite efforts to initially contain Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), it has spread worldwide and has strained international healthcare systems to the point where advanced respiratory resources and ventilators are depleted. This study aims to explore splitting ventilators, or “multi-ventilation,” as a viable alternative in these demanding times. We investigated whether individualized tidal volume and positive end expiratory pressure (PEEP) delivery is possible to lungs of different compliances that are being simultaneously ventilated from one anesthesia ventilator.

Methods

We performed a controlled experiment in an operating room environment without animal or human participants. Two “test lungs” were connected to distinct modified Y-pieces that were ventilated in parallel from a single anesthesia ventilator.

Results

Ventilation can be manipulated to qualitatively deliver individually tailored tidal volumes in the setting of varying PEEP and compliance requirements in pressure control mode.

Conclusions

Splitting ventilators, or “multi-ventilation,” is a viable alternative to acute ventilator shortage during a pandemic. Ventilators can be split for individualized tidal volume and positive end-expiratory pressure delivery in multiple subjects of differing compliances and demographics.
A Method to Identify the Missing COVID-19 Cases in the U.S. and Results for mid-April 2020
Authors: Breton Theodore R.
Published: May 2020

I use the COVID-19 death rate in South Korea and a method relating the ratio of death rates in a U.S. state to its share of cumulative positive tests to estimate the total cases of COVID-19 in the U.S. and to estimate the extent of infection and the unidentified share of the infected population in each of the lower-48 states and in New York City in mid-April, 2020. I identify a logarithmic relationship between the cumulative death rate in a state and its cumulative positive share of tests. Using this relationship, I find that 4.3-5.4 million people, 1.4-1.7% of the U.S. population, were infected, with rates of infection that ranged from 0.1% in more rural states to 8-10% in New York state and 11-13% in New York City. Only 16-20% of these infected individuals were identified later through testing.
Effect of ethanol cleaning on the permeability of FFP2 mask
Authors: Lenormand Roland , Lenormand Guillaume
Published: May 2020

In this study we assessed the effect of ethanol on the filtering properties of FFP2 masks. The permeability of parts of a FFP2 mask was measured before and after six cleanings with ethanol. As for any porous medium, the filtering properties of a mask are related to the size and tortuosity of the pores of the filter, and are quantified by its permeability. Any damage to the filter will change its permeability. We show here that after six cleaning cycles, the permeability remains very close to the permeability before cleaning. Amid the COVID-19 pandemic and the shortage of protective masks, this study suggests that ethanol could be used to sanitize a FFP2 mask without significantly altering its filtering properties. Additional measurements on FFP2 and N95 masks from different manufacturers need to be performed to validate this study.
Rapid development of COVID-19 rapid diagnostics for low resource settings: accelerating delivery through transparency, responsiveness, and open collaboration
Authors: Adams Emily R , Augustin Yolanda , Byrne Rachel L , Clark David J , Cocozza Michael , Cubas-Atienzar Ana I , Cuevas Luis E. , Cusinato Martina , Davies Benedict M O , Davis Mark , Davis Paul , Duvoix Annelyse , Eckersley Nicholas M , Edwards Thomas , Fletcher Tom , Fraser Alice J , Garrod Gala , Hadcocks Linda , Hu Qinxue , Johnson Michael , Kay Grant A , Keymer Katherine , Kirwan Daniela , Klekotko Kesja , Lewis Zawditu , Mason Jenifer , Mensah-Kane Josie , Menzies Stefanie , Monahan Irene , Moore Catherine M , Nebe-von-Caron Gerhard , Owen Sophie I , Planche Tim , Sainter Chris , Schouten James , Staines Henry M , Turtle Lance , Williams Chris , Wilkins John , Woolston Kevin , Sall Amadou Alpha , Fitchett Joseph R A , Krishna Sanjeev
Published: May 2020

Here we describe an open and transparent consortium for the rapid development of COVID-19 rapid diagnostics tests. We report diagnostic accuracy data on the Mologic manufactured IgG COVID-19 ELISA on known positive serum samples and on a panel of known negative respiratory and viral serum samples pre-December 2019.

In January, Mologic, embarked on a product development pathway for COVID-19 diagnostics focusing on ELISA and rapid diagnostic tests (RDTs), with anticipated funding from Wellcome Trust and DFID.

834 clinical samples from known COVID-19 patients and hospital negative controls were tested on Mologic’s IgG ELISA. The reported sensitivity on 270 clinical samples from 124 prospectively enrolled patients was 94% (95% CI: 89.60% - 96.81%) on day 10 or more post laboratory diagnosis, and 96% (95% CI: 84.85% - 99.46%) between 14–21 days post symptom onset. A specificity panel comprising 564 samples collected pre-December 2019 were tested to include most common respiratory pathogens, other types of coronavirus, and flaviviruses. Specificity in this panel was 97% (95% CI: 95.65% - 98.50%).

This is the first in a series of Mologic products for COVID-19, which will be deployed for COVID-19 diagnosis, contact tracing and sero-epidemiological studies to estimate disease burden and transmission with a focus on ensuring access, affordability, and availability to low-resource settings.
Paucity and disparity of publicly available sex-disaggregated data for the COVID-19 epidemic hamper evidence-based decision-making
Authors: Kocher Kristen , Délot-Vilain Arthur , Spencer D’Andre , LoTempio Jonathan , Délot Emmanuèle C.
Published: May 2020

COVID-19 has joined the long list of human disorders with sexually dimorphic expression. Increased lethality in men was evident in the first large reports from ChinaCDC and WHO-China, and the gender gap appeared even wider in the early Italian outbreak. Newspapers and scientific journals alike have commented on this finding and the preexisting conditions, biological processes, and gender role behavior differences that may underlie it. However, as for other diseases, and in spite of years of advocating for the collection of raw epidemiological data and the analysis of clinical trial data sets by sex, very little appeared to be released about sex differences in characteristics of the epidemics beyond infection and death rates, such as severity of disease, comorbidities, rate of recovery, length of hospital stay, or number of tests for the SARS-CoV-2 coronavirus. These data are critical not only for scientists to understand the pathophysiology of disease, but also to inform decision-making by countries and healthcare systems on how to prioritize testing and best allocate scarce resources and relief funds.

Systematic analysis of official websites for the 20 countries and 6 US states reporting the highest number of cases on March 21, 2020, revealed a wide disparity in sex-disaggregated data made available to the public and scholars. Only a handful of the countries reported cases by sex separately. None of the other characteristics, including fatality rates, were stratified by sex at the time. Beyond suboptimal sex disaggregation, our analysis found a paucity of usable raw data sets and a generalized lack of standardization of captured data, making comparisons difficult. A second round of data capture in April found more complete, but even more disparate, information.

Our analysis revealed a wide range of sex ratios among confirmed cases, which changed over time. In countries where a male-biased sex ratio was initially reported, the reported proportion of women among cases dramatically increased in under 3 weeks. In contrast, men were consistently over-represented in severe cases, intensive care admissions, and deaths. We also show that the sex ratio varies with age, with a complex pattern, reproduced across the 6 countries for which data were found.

Accurate, peer-reviewed, statistical analysis of harmonized, sex-disaggregated data for other characteristics of epidemics, such as availability of testing, suspected source of infection, or comorbidities will be critical to understand where the observed disparities come from and to generate evidence-based recommendations for decision-making by institutions and governments around the world.
THE G-FORCE CONUNDRUM IN PRF GENERATION- MANAGEMENT OF A PROBLEM HIDDEN IN PLAIN SIGHT
Authors: Sneha Kidambi , Ajmera Jhansi Rani , Chandra Rampalli Viswa
Published: May 2020

Aim

A force of 400g at 2700 RPM results in an optimum leucocyte and platelet-rich fibrin (L-PRF). Most of centrifuges with varying characteristics generate a g-force in excess of 700g at 2700 RPM. In this context, the study explores the effect of the original centrifugation protocol and a modified protocol tailor-made to lower the RPM to generate a g-force of ~400g on platelet concentration, clot size and growth factors release in L-PRF prepared in two different commercially available centrifuges.

Materials and Methods

25 subjects each were assigned to the following groups; R1and R2where L-PRF was obtained from two laboratory swing-out centrifuges (Remi 8C® & Remi C854®, Mumbai, India) respectively. PRF was obtained from each subject within a group using two protocols; Original (O) protocol: conforming to the original centrifugation cycle (2700 RPM for 12 min) and Modified (M) protocol. Clot size, growth factor estimation and platelet counts were measured at 20, 40 and 60 mins from all the L-PRF clots.

Results

At the third time period (40–60min), there were no significant differences in clot sizes with the original protocol (p=0.09), but a highly significant difference was noticed with the modified protocol in both the centrifuges (p=0.001). Our results showed an increased concentration of VEGF and EGF with modified protocol than with original protocol with both the centrifuges (p=0.001). By the end of second and third time periods, more platelet concentration was observed with modified protocol than with the original protocol in both the centrifuges (p=0.001)

Conclusion

This study infers that the centrifuge type and RCF can affect the quality and quantity of cells and growth factors and an optimum relationship between g-force and RPM should be maintained in order to obtain L-PRF with adequate cell viability and optimum growth factor release.
News from the front: Estimation of excess mortality and life expectancy in the major epicenters of the COVID-19 pandemic in Italy
Authors: Ghislandi Simone , Muttarak Raya , Sauerberg Markus , Scotti Benedetta
Published: May 2020

Existing studies on the mortality impacts of the COVID-19 pandemic commonly rely on national official reports. However, in a pandemic, deaths from COVID-19 can be miscounted due to under-reporting and inaccurate death registration. Official statistics on COVID-19 mortality are sensitive to classification, estimation and reporting practice which are not consistent across countries. Likewise, the reported mortality is often provided at the national level which results in underestimation of the true scale of the human life impact given that the outbreaks are localised.

This study overcomes the problem of under-reporting of COVID-19-related deaths by using all cause daily death registrations data provided by the Italian Statistical Office (ISTAT) from January 1 to April 30, 2020 in comparison with official figures reported by the Civil Protection Department. The study focuses on the five most severely hit provinces in Italy (Bergamo, Brescia, Cremona, Lodi and Piacenza) and Lombardy region. We calculate excess mortality in 2020 compared to the average of the years 2015 to 2019 and estimate life expectancy for the first wave of the epidemic and for the rest of the year 2020. Not only is life expectancy a reliable measure of a country’s health status and development, it also allows us to quantify the impact of COVID-19 on human life.

The estimated excess deaths show significantly higher mortality than COVID-19 official mortality statistics, particularly during the peak of the epidemic and amongst people aged 60 years and over. We find that for the first wave of the epidemic, life expectancy in the five provinces reduced by 5.1 to 7.8 and 3.2 to 5.8 years for men and women, respectively. For annual life expectancy for the year 2020, in a scenario with no harvesting effect i.e. mortality rates resume to an average level of the years 2015-2019 after the end of the first epidemic wave, the years of life lost is equivalent to 2 to 3.5 years for men and 1.1. to 2.5 years for women in the five provinces.

The COVID-19 pandemic posed a substantial impact on population health in Italy as it represents the largest decline in life expectancy after the 1918 influenza pandemic and the Second World War.
Preliminary Results of Seroprevalence of SARS-CoV-2 at Community Clinics in Tokyo
Authors: Takita Morihito , Matsumura Tomoko , Yamamoto Kana , Yamashita Erika , Hosoda Kazutaka , Hamaki Tamae , Kusumi Eiji
Published: May 2020

Serological evaluation with SARS-CoV-2 specific IgG antibody will be an alternative way to know the pandemic of novel coronavirus disease (COVID-19) if the capacity for diagnostic PCR test is limited. The point-of-care test to detect SARS-CoV-2 specific IgG antibody in peripheral blood (n=202) was performed in two community clinics in Tokyo, Japan. The overall positive rate of SRAS-CoV-2 IgG antibody was 5.9% (95% confidence interval[CI]: 3.1-10.1). Higher rate was observed for healthcare workers (n=55, 9.1 [3.0-20.0]). The limitation on antibody tests includes low sensitivity and potent cross-reactivity with the previous coronavirus. Robust healthcare policy to efficiently monitor COVID-19 spread is warranted in Tokyo.
Differential effects of voclosporin and tacrolimus on insulin secretion from human islets
Authors: Kolic Jelena , Beet Leanne , Overby Peter , Cen Haoning Howard , Panzhinskiy Evgeniy , Ure Daren R. , Cross Jennifer L. , Huizinga Robert B. , Johnson James D.
Published: May 2020

Context

The incidence of new onset diabetes after transplant (NODAT) has increased over the past decade, likely due to calcineurin inhibitor-based immunosuppressants, including tacrolimus (TAC) and cyclosporin (CsA). Voclosporin (VCS), a next generation calcineurin inhibitor is reported to cause fewer incidences of NODAT but the reason is unclear.

Objective

Whilst calcineurin signaling plays important roles in pancreatic β-cell survival, proliferation, and function, its effects on human β-cells remain understudied. In particular, we do not understand why some calcineurin inhibitors have more profound effects on the incidence of NODAT.

Methods

We compared the effects of TAC and VCS on the dynamics of insulin secretory function, programmed cell death rate, and the transcriptomic profile of human islets. We studied two clinically relevant doses of TAC (10 ng/ml, 30 ng/ml) and VCS (20 ng/ml, 60 ng/ml), meant to approximate the clinical trough and peak concentrations.

Results

TAC, but not VCS, caused a significant impairment of 15 mM glucose-stimulated and 30 mM KCl-stimulated insulin secretion. This points to molecular defects in the distal stages of exocytosis after voltage-gated Ca2+entry. No significant effects on islet cell survival or total insulin content were identified. RNA sequencing showed that TAC significantly decreased the expression of 17 genes, including direct and indirect regulators of exocytosis (SYT16,TBC1D30,PCK1,SMOC1,SYT5, PDK4, andCREM), whereas VCS has less broad and milder effects on gene expression.

Conclusions

Clinically relevant doses of TAC, but not VCS, directly inhibit insulin secretion from human islets, likely via transcriptional control of exocytosis machinery.
Geospatial Correlation Between COVID-19 Health Misinformation and Poisoning with Household Cleaners in the Greater Boston Area
Authors: Chary Michael , Overbeek Daniel , Papadimoulis Alexandria , Sheroff Adina , Burns Michele
Published: May 2020

Objective

To determine the relationship between health misinformation on social media and adverse health outcomes.

Methods

We analyzed 16,729 calls to the Regional Center for Poison Control and Prevention serving Massachusetts and Rhode Island (MARI PCC) and 25,231 tweets discussing treating COVID-19 with house cleaners.

Results

Half of the spikes in calls to MARI PCC about exposures to cleaners were preceded 2–3 days earlier by tweets advocating ingesting or insufflating bleach to cure COVID-19. The relationship was only statistically significant for tweets in the Greater Boston Area and calls to MARI PCC. [Results of network analysis].

Conclusions

Health misinformation on social media had a spatiotemporally specific relationship with increased calls to Poison Control and referrals to hospitals for cleaner ingestions. The spatiotemporal specificity of our results strengthens our conviction that the increased calls were driven in part by health misinformation on social media.

Public Health Implications

Health misinformation can directly lead to secondary harm. Thematically targeted messages at specific loci in the social network may stem this harm.
COVID-19 length of hospital stay: a systematic review and data synthesis
Authors: Rees Eleanor M , Nightingale Emily S , Jafari Yalda , Waterlow Naomi , Clifford Samuel , Pearson Carl A B ,   CMMID Working Group, Jombert Thibaut , Procter Simon R , Knight Gwenan M
Published: May 2020

Background The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.

Methods We performed a systematic review to gather data on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach we provide distributions for general hospital and ICU LoS from studies in China and elsewhere, for use by the community.

Results We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies - four each within and outside China - with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR: 10-19) days for China, compared with 5 (IQR: 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.

Conclusion Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.
Group testing for SARS-CoV-2 allows for up to 10-fold efficiency increase across realistic scenarios and testing strategies
Authors: Verdun Claudio M. , Fuchs Tim , Harar Pavol , Elbrächter Dennis , Fischer David S. , Berner Julius , Grohs Philipp , Theis Fabian J. , Krahmer Felix
Published: May 2020

We provide a comparison of general strategies for group testing in view of their application to medical diagnosis in the current COVID-19 pandemic. We find significant efficiency gaps between different group testing strategies in realistic scenarios for SARS-CoV-2 testing, highlighting the need for an informed decision of the pooling protocol depending on estimated prevalence, target specificity, and high- vs. low-risk population. For example, using one of the presented methods, all 1.47 million inhabitants of Munich, Germany, could be tested using only around 141 thousand tests if an infection rate up to 0.4% is assumed. Using 1 million tests, the 6.69 million inhabitants from the city of Rio de Janeiro, Brazil, could be tested as long as the infection rate does not exceed 1%. Altogether this work may help provide a basis for efficient upscaling of current testing procedures, fine grained towards the desired study population, e.g. cross-sectional versus health-care workers and adapted mixtures thereof. For comparative visualization and querying of the precomputed results we provide an interactive web application. The source code for computation is open and freely available.
Humoral immune response and prolonged PCR positivity in a cohort of 1343 SARS-CoV 2 patients in the New York City region
Authors: Wajnberg Ania , Mansour Mayce , Leven Emily , Bouvier Nicole M. , Patel Gopi , Firpo Adolfo , Mendu Rao , Jhang Jeffrey , Arinsburg Suzanne , Gitman Melissa , Houldsworth Jane , Baine Ian , Simon Viviana , Aberg Judith , Krammer Florian , Reich David , Cordon-Cardo Carlos
Published: May 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The percentage of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can still be detected at considerable time post symptom resolution. Here we investigated both seroconversion and PCR-positivity in a large cohort of convalescent serum donors in New York City.

Methods

Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via enzyme-linked immunosorbent assay for presence of anti SARS-CoV-2 spike antibodies.

Results

All but three confirmed SARS-CoV-2 patients seroconverted to the SARS-CoV-2 spike while only 37.4% of suspected SARS-CoV-2 patients seroconverted. PCR-positivity was detected up to 28 days from symptom resolution.

Conclusions

Here we show that the vast majority of confirmed COVID19 patients seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks post symptom resolution, but it is unclear if this signal represents infectious virus.
Determining county-level counterfactuals for evaluation of population health interventions: A novel application ofK-means cluster analysis
Authors: Strutz Kelly L. , Luo Zhehui , Raffo Jennifer E. , Meghea Cristian I. , Meulen Peggy Vander , Roman Lee Anne
Published: May 2020

Objectives

Evaluating population health initiatives at the community level necessitates valid counterfactual communities, which includes having similar complexity with respect to population composition, healthcare access, and health determinants. Estimating appropriate county counterfactuals is challenging in states with large inter-county variation. We present and discuss an application ofK-means cluster analysis for determining county-level counterfactuals in an evaluation of a county perinatal system of care for Medicaid-insured pregnant women.

Materials and Methods

Counties were described using indicators from the American Community Survey, Area Health Resources Files, University of Wisconsin Population Health Institute County Health Rankings, and vital records for Michigan Medicaid-insured births for the year intervention began (or the closest available year). We ran analyses of 1,000 iterations with random starting cluster values for each of a range of number of clusters from 3 to 10 and used standard variability and reliability measures to identify the optimal number of clusters.

Results

One county was grouped with the intervention county in all solutions for all iterations and thus considered most valid for 1:1 population county comparisons. Two additional counties were frequently grouped with the intervention county. However, no county was ideal for all subpopulation analyses.

Practice Implications

Although the K-means method was successful at identifying a comparison county, concerning intervention-comparison differences remained. This limitation of the method may be specific to this county and the constraints of a within-state study. This method could potentially be more useful when applied to other counties in and outside of Michigan.
Beyond predicting the number of infections: predicting who is likely to be COVID negative or positive
Authors: Zhang Stephen X. , Sun Shuhua , Jahanshahi Asghar Afshar , Wang Yifei , Madavani Abbas Nazarian , Dinani Maryam Mokhtari
Published: May 2020

This study provides the first attempt to identify people at greater risk of COVID-19 infection, enabling more targeted infectious disease prevention and control, which are especially important in the ongoing shortage of COVID-19 testing.

We conducted a primary survey of 521 adults on April 1-10, 2020 in Iran, where the official infection rate was 0·08%. In our sample, 3% reported being COVID-19 positive and 15% were unsure of their status. This relatively high positive rate enabled us to conduct the analysis at the 5% significance level.

At the time of the survey, 44% of the adults worked from home; 26% still went to work in their workplaces; 27% had stopped working due to the COVID-19 pandemic; and 3% were unemployed. Adults who exercised more were more likely to be COVID-19 negative. Each additional hour of exercise per day predicted a 78% increase in the likelihood of being COVID-19 negative. Adults with chronic medical illnesses were 48% more likely to be COVID-19 negative. In terms of work situation, those who worked from home were the most likely to be COVID-19 negative, and those who had stopped working were the most likely to be COVID-19 positive. Individuals in larger organizations were less likely to be COVID-19 positive.

Given the testing shortage in many countries, we identify a novel approach to predict the likelihood of COVID-19 infection by a set of personal and work situation characteristics, in order to help to identify individuals with more or less risk of contracting the virus. We hope this research opens a new research avenue to identify the individual risk factors of COVID-19 infection to enable more targeted infectious disease prevention, communication, testing, and control to complement the effort to expand testing capacity.
Evaluation of effects of public health interventions on COVID-19 transmission for Pakistan: A mathematical simulation study
Authors: Bhutta Zulfiqar A , Harari Ofir , Park Jay JH , Zannat Noor-E , Zoratti Michael , Churches Tim , Thorlund Kristian , Mills Edward J
Published: May 2020

Background

In an effort to contain the COVID-19 epidemic, many governments across the world have enforced lockdown or social distancing measures. Several outbreak models have been developed to investigate the effects of different public health strategies for COVID-19, but they have not been developed for Pakistan and other South East Asian countries, where a large proportion of global population resides.

Methods

We developed a stochastic individual contact model by extending the widely-used Susceptible-Infectious-Recovered (SIR) compartment model with additional compartments to model both anticipated mitigating effects of public health intervention strategies for Pakistan. We estimated the projected spread, number of hospitalizations, and case fatalities under no intervention and four increasingly stringent public health strategies of social distancing and self-isolation at the national and provincial levels of Pakistan.

Results

Our analysis shows that without any public health interventions the expected number of cumulative case fatalities is 671,596 in Pakistan with the virus is expected to peak in terms of the number of required ICU-hospitalizations at 198,593 persons by the end of the June 2020. The estimated total numbers of cumulative case fatalities are lower for other public health strategies with strict social distancing showing the lowest number of deaths at 1,588 (Self-isolation: n=341,359; Flexible social distancing strategy: n=3,995; and Exit strategy: n=28,214). The lowest number of required ICU-hospitalization is also estimated for strict social distancing strategy (n=266 persons at the end of May 2020). Generally, the simulated effects of the different public health strategies at the provincial-level were similar to the national-level with strict social distancing showing the fewest number of case fatalities and ICU-hospitalizations.

Conclusion

Our results indicate that case fatalities and ICU-hospitalizations for Pakistan will be high without any public health interventions. While strict social distancing can potentially prevent a large number of deaths and ICU-hospitalizations, the government faces an important dilemma of potentially severe economic downfall. Consideration of a temporary strict social distancing strategy with gradual return of the lower-risk Pakistani population, as simulated in our exit strategy scenario, may an effective compromise between public health and economy of Pakistani population.
AutoAudio: Deep Learning for Automatic Audiogram Interpretation
Authors: Crowson Matthew G. , Lee Jong Wook , Hamour Amr , Mahmood Rafid , Babier Aaron , Lin Vincent , Tucci Debara L. , Chan Timothy C.Y.
Published: May 2020

Objectives

Hearing loss is the leading human sensory system loss, and one of the leading causes for years lived with disability with significant effects on quality of life, social isolation, and overall health. Coupled with a forecast of increased hearing loss burden worldwide, national and international health organizations have urgently recommended that access to hearing evaluation be expanded to meet demand.

Methods

The objective of this study was to develop ‘AutoAudio’ – a novel deep learning proof-of-concept model that accurately and quickly interprets diagnostic audiograms. Adult audiogram reports representing normal, conductive, mixed and sensorineural morphologies were used to train different neural network architectures. Image augmentation techniques were used to increase the training image set size. Classification accuracy on a separate test set was used to assess model performance.

Results

The architecture with the highest out-of-training set accuracy was ResNet-101 at 97.5%. Neural network training time varied between 2 to 7 hours depending on the depth of the neural network architecture. Each neural network architecture produced misclassifications that arose from failures of the model to correctly label the audiogram with the appropriate hearing loss type. The most commonly misclassified hearing loss type were mixed losses.

Conclusion

Re-engineering the process of hearing testing with a machine learning innovation may help enhance access to the growing worldwide population that is expected to require audiologist services. Our results suggest that deep learning may be a transformative technology that enables automatic and accurate audiogram interpretation.
Neutrophil extracellular traps and thrombosis in COVID-19
Authors: Zuo Yu , Zuo Melanie , Yalavarthi Srilakshmi , Gockman Kelsey , Madison Jacqueline A. , Shi Hui , Knight Jason S. , Kanthi Yogendra
Published: May 2020

Here, we report on four patients whose hospitalizations for COVID-19 were complicated by venous thromboembolism (VTE). All demonstrated high levels of D-dimer as well as high neutrophil-to-lymphocyte ratios. For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Neutrophil-derived S100A8/A9 (calprotectin) was also elevated. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19.
Risk Factors of the Severity of COVID-19: a Meta-Analysis
Authors: Rahman Abdur , Sathi Nusrat Jahan
Published: May 2020

BACKGROUND

Although the infection rate of COVID-19 is very high, all the patients getting infected don’t always die or go through brutal states. This indicates there may be some factors that possibly boost the severity of COVID-19.

OBJECTIVE

We intend to identify some probable risk factors that are responsible for the severity of COVID-19 using a meta-analysis.

METHODS

The literature exploration lasted up to 18 April 2020 and through PubMed, Google Scholar, EMBASE, and Cochrane Library we have identified 10 pertinent publications. To paraphrase the outcomes of autonomous researches, we have performed a random-effect meta-analysis.

RESULTS

A total of 2272 patients’ information was extracted from the selected literature. We have found sex (male) (Risk ratio [RR] =1.29 [1.07; 1.54]), hypertension (RR=1.79 [1.57; 2.04]), diabetes (RR=1.57 [1.25; 1.98]), fatigue or myalgia (RR=1.17 [1.02; 1.35]), and smoking history (RR=1.71 [1.25; 2.35]) are potential risk factors for the severity of COVID-19. We found fever (RR=1.21 [0.66; 2.22]), cough (1.13 [0.98; 1.30]), and diarrhea (RR=1.14 [0.93; 1.40]) as insignificant risk factors for COVID-19 severity.

CONCLUSION

The findings of this research may be beneficial to identify patients with higher risks to provide additional medical attention from the very beginning of the treatment.
A molecular atlas of proximal airway identifies subsets of known airway cell types revealing details of the unique molecular pathogenesis of Cystic Fibrosis
Authors: Carraro Gianni , Langerman Justin , Sabri Shan , Lorenzana Zareeb , Purkayastha Arunima , Konda Bindu , Aros Cody J. , Calvert Ben A. , Szymaniak Aleks , Wilson Emily , Mulligan Michael , Bhatt Priyanka , Vijayaraj Preethi , Yao Changfu , Shia David W. , Israely Edo , Rickabaugh Tammy M. , Mense Martin , Randell Scott H. , Vladar Eszter K. , Ryan Amy L. , Plath Kathrin , Mahoney John , Stripp Barry R. , Gomperts Brigitte N.
Published: May 2020

Introduction/Abstract

Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts in excess of 70,000 people globally. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most significant determinant of morbidity and mortality. In this study we report results from a multi-institute consortium in which single cell transcriptomics were applied to define disease-related changes to the proximal airway of CF donors (n=19) undergoing transplantation for end-stage lung disease compared to the proximal airway of previously healthy lung donors (n=19). We found that all major airway epithelial cell types were conserved between control and CF donors. Disease-dependent differences were observed, including an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subtypes coupled with an unexpected decrease in cycling basal cells. This study developed a molecular atlas of the proximal airway epithelium that will provide insights for the development of new targeted therapies for CF airway disease.
Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Authors: Jamal Alainna J. , Mozafarihashjin Mohammad , Coomes Eric , Powis Jeff , Liu Angel Xin , Paterson Aimee , Anceva-Sami Sofia , Barati Shiva , Crowl Gloria , Faheem Amna , Farooqi Lubna , Khan Saman , Prost Karren , Poutanen Susan , Yip Lily , Zhong Zoe , McGeer Allison J. , Mubareka Samira ,   for the Toronto Invasive Bacterial Diseases Network COVID-19 Investigators
Published: May 2020

We enrolled 53 consecutive in-patients with COVID-19 at six hospitals in Toronto, Canada, and tested one nasopharyngeal swab/saliva sample pair from each patient for SARS-CoV-2. Overall, sensitivity was 89% for nasopharyngeal swabs and 77% for saliva (p=NS); difference in sensitivity was greatest for sample pairs collected later in illness.