bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19
Authors: Hasichaolu  , Zhang Xinri , Li Xin , Li Xin , Li Dongyan
Published: July 2020

To investigate the immune status of people who previously had COVID-19 infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%) and IL-17 (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.
Heat-based Decontamination of N95 Masks Using a Commercial Laundry Dryer
Authors: Lensky Yuri D. , Mazenc Edward A. , Ranard Daniel , Vilim Matthew , Prakash Manu , Brooks Bill , Bradley Amanda , Engelschenschilt Alain , Plutz Jason , Zellmer Todd
Published: July 2020

We propose a dry heat method for decontaminating N95 masks of SARS-CoV-2, designed around placing them in resealable plastic bags, packed in large cardboard boxes installed at the rear end of commercial laundry dryers. Our protocol rests on data collected in collaboration with Alliance Laundry Systems (ALS) and the CDC/NIOSH laboratories, under the “NPPTL Respirator Assessments to Support the COVID-19 Response” initiative. We test the two most widely available ALS tumbler models, the UTF75N and UT075N, and show that if our procedure is carefully followed, the masks will be subject to suitably high and stable temperatures for decontamination; in particular the masks will be heated to at least 80 °C for at least 65 min. For the mask models 3M 1860, 3M 8511, and Halyard 62126, we establish that they pass quantitative fit tests and retain sufficient filtration performance after three cycles of our decontamination procedure. All masks used in this study were new and uncontaminated: the evidence for the levels of biological inactivation of SARS-CoV-2 is provided by [1]. While the protocol outlined here is currently specific to certain tested dryer models, this equipment is widely available, with machines estimated to be within 15 minutes of most US hospitals. Models from other manufacturers may also be appropriate for this decontamination method, though we stress the need for explicit testing on alternative models before use.
High-Plex and High-throughput Digital Spatial Profiling of non-small-cell lung cancer (NSCLC)
Authors: Monkman James , Taheri Touraj , Warkiani Majid Ebrahimi , O’leary Connor , Ladwa Rahul , Richard Derek , O’ Byrne Ken , Kulasinghe Arutha
Published: July 2020

Profiling the tumour microenvironment(TME) has been informative in understanding the underlying tumour-immune interactions. Multiplex immunohistochemistry(mIHC) coupled with molecular barcoding technologies have revealed greater insights into the TME. In this study, we utilised the Nanostring GeoMX™ Digital Spatial Profiler (DSP) platform to profile a NSCLC tissue microarray for protein markers across immune cell profiling, immuno-oncology(IO) drug target, immune activation status, immune cell typing, and pan-tumour protein modules. Regions of interest(ROIs) were selected that described tumour, TME and normal adjacent tissue(NAT) compartments. Our data revealed that paired analysis (n=18) of patient matched compartments indicated that the TME was significantly enriched in CD27, CD3, CD4, CD44, CD45, CD45RO, CD68, CD163, and VISTA relative to tumour. Unmatched analysis indicated that the NAT(n=19) was significantly enriched in CD34, fibronectin, IDO1, LAG3, ARG1 and PTEN when compared to the TME(n=32). Univariate Cox proportional hazards indicated that the presence of cells expressing CD3(HR:0.5, p=0.018), CD34(HR:0.53, p=0.004) and ICOS (HR:0.6, p=0.047) in tumour compartments were significantly associated with improved overall survival(OS). We implemented both high-plex and high-throughput methodologies to the discovery of protein biomarkers and molecular phenotypes within biopsy samples and demonstrate the power of such tools for a new generation of pathology research.

Conflict of interest statement

The authors have declared that no conflict of interest exists.
The COVID-19 Pandemic Impact on Primary Health Care services: An Experience from Qatar
Authors: Abdulmalik Mariam , Al Kuwari Mohamed Ghaith , Abdulla Samya Al , Bakri Ahmad Haj , Gibb John , Kandy Mujeeb Chettiyam
Published: July 2020

Introduction

In March 2020, Qatar started reporting increased numbers of COVID-19 positive cases. The Ministry of Public Health in Qatar has developed an emergency action plan to respond to the outbreak with the Primary Health Care Corporation (PHCC) as a main component of that response.

Aim

The aim of this review is to understand and document the Impact of COVID 19 on PHCC in Qatar in terms of response, modifications of services and introduction of new alternatives

Methodology

A retrospective data analysis was conducted for all the COVID-19 swabbing activities and for all the utilization services volume across the PHCC health centers between January 2018 and May 2020.

Results

PHCC allocated testing sites for COVID-19 resulted in conducting 54824 swabs with 11455 positive cases and positivity rate of 20.8% between 14th of March and 15th of June 2020. The overall PHCC services utilization declined with overall reduction of 50% in April 2020. Alternative virtual and remote services were provided, telemedicine was introduced, and it made up 50% of the consultation volumes for April 2020. Home refill delivery medications managed to provide a total of 20920 delivered prescriptions by end of May 2020.

Conclusion and recommendations

To decrease the risk of infection to the patients and health care workers, PHCC in Qatar cancelled the appointments for some high-risk population. However, PHCC introduced virtual remote services that managed to make up for the in-person utilization volume and reflected acceptance in patients’ behaviours. PHCC continued in detecting positive COVID-19 cases among its targeted communities.
Soap versus sanitiser for preventing the transmission of acute respiratory infections: a systematic review with meta-analysis and dose-response analysis
Authors: Hoffmann Tammy , Bakhit Mina , Krzyzaniak Natalia , Mar Chris Del , Scott Anna , Glasziou Paul
Published: July 2020

Objective

To compare the effectiveness of hand hygiene using alcohol-based hand sanitiser to soap and water for preventing the transmission of acute respiratory infections (ARIs), and assess the relationship between the dose of hand hygiene and the number of ARI, influenza-like illness (ILI), or influenza events.

Methods

Systematic review of randomised trials that compared a community-based hand hygiene intervention (soap and water, or sanitiser) with a control, or trials that compared sanitiser with soap and water, and measured outcomes of ARI, ILI, or laboratory-confirmed influenza or related consequences. Searches were conducted in CENTRAL, PubMed, Embase, CINAHL and trial registries (April 2020) and data extraction completed by independent pairs of reviewers.

Results

Eighteen trials were included. When meta-analysed, three trials of soap and water versus control found a non-significant increase in ARI events (Risk Ratio (RR) 1.23, 95%CI 0.78-1.93); six trials of sanitiser versus control found a significant reduction in ARI events (RR 0.80, 95%CI 0.71-0.89). When hand hygiene dose was plotted against ARI relative risk, no clear dose-response relationship was observable. Four trials were head-to-head comparisons of sanitiser and soap and water but too heterogeneous to pool: two found a significantly greater reduction in the sanitiser group compared to the soap group; two found no significant difference between the intervention arms.

Conclusion

Adequately performed hand hygiene, with either soap or sanitiser, reduces the risk of ARI virus transmission, however direct and indirect evidence suggest sanitiser might be more effective in practice.
Coronavirus-related online web search desire amidst the rising novel coronavirus incidence in Ethiopia: Google Trends-based infodemiology
Authors: Terefe Behailu , Rovetta Alessandro , Rajan Asha K , Awoke Mengist
Published: July 2020

Background

During disease outbreaks, social communication and behaviors are very important to contain the outbreak. Under such circumstances, individual activities on online platforms will increase tremendously. This will result in the circulation useful or misleading/misinformation (infodemic monikers) in the community. Thus, exploring the online trending information is highly crucial in the process of containing disease outbreak. Therefore, this study aimed to explore users’ concerns towards coronavirus-related online web search activities and to investigate the extent of misleading terms adopted for identifying the virus in the early stage of COVID-19 spread in Ethiopia.

Methods

Google Trends was employed in exploring the tendency towards coronavirus-related web search activities in Ethiopia from March 13 to May 8, 2020. Keywords of the different names of COVID-19 and health-related issues were used to investigate the trends of public interest in searching from Google over time. Relative search volume (RSV) and Average peak comparison (APC) were used to compare the trends of online search interests. Pearson correlation coefficient was calculated to check for the presence of correlation.

Result

During the study period, “corona,” “virus,” “coronavirus,” “corona virus”, “China coronavirus,” and “COVID-19”, were the top names users adopted to identify the virus. In almost all search activities, the users’ employed infodemic monikers to identify the virus (99%). “Updates” related issues (APC=60, 95% CI, 55 – 66) were the most commonly trending health-related searches on Google followed by mortality (APC=27, 95% CI, 24 – 30) and symptoms (APC=55, 95% CI, 50 – 60) related issues. The regional comparison showed the highest cumulative peak for the Oromia region on querying health-related information from Google.

Conclusion

This study revealed an initial increase in the public interest of COVID-19 related Google search, but this interest was declined over time. Tremendous circulation of infodemic monikers for the identification of the virus was also noticed in the country. The authors recommend concerned stakeholders to work immensely to keep the public alert on coronavirus-related issues and to promote the official names of the virus to decrease the circulation of misleading and misinformation amid the outbreak.
Prevalence of mask wearing in northern Vermont in response to SARS-CoV-2
Authors: Beckage Brian , Buckley Thomas E. , Beckage Maegan E.
Published: July 2020

Objectives

Information on prevalence of face mask usage in response to SARS-CoV-2 is required to both model disease spread and to improve compliance with mask usage. We sought to (1) estimate the prevalence of mask usage in northern Vermont and to (2) assess the effect of age and sex on mask usage.

Methods

We monitored the entrances to businesses and visually assessed individuals’ age, sex, and mask usage from a distance. We collected 1004 observations from 16 May through 30 May 2020 as businesses began to reopen following an extended state-wide lockdown. We analyzed these data using Bayesian random effects logistic regression.

Results

75.5% of individuals used a mask with significant effects of age and sex on mask usage. Females were more likely than males to wear masks (83.8%, n=488 vs. 67.6%, n=516); the odds of mask usage in males were 53% of those for females. Elders were most likely to wear a mask (91.4%, n=209) followed by young adults (74.8%, n=246), middle-aged adults (70.7%, n=519) and children (53.3%, n=30). The odds of an elder wearing a mask were 16.7 times that of a child, while the odds for young adults and middle-aged adults were ∼3 times greater than for a child. Highest mask usage was in elder females (96.3%, n=109) and lowest mask usage was in male children (43.8%, n=16).

Conclusions

We found high prevalence of mask usage overall, but also large differences in mask usage with age and sex. Females and elders had the highest use of face masks.
Geographic reconstruction of the SARS-CoV-2 outbreak in Lombardy (Italy) during the early phase
Authors: Valeria Micheli , Giordana Rimoldi Sara , Francesca Romeri , Francesco Comandatore , Alessandro Mancon , Anna Gigantiello , Matteo Brilli , Davide Mileto , Cristina Pagani , Alessandra Lombardi , Rita Gismondo Maria ,   Laboratory of Clinical Microbiology, Virology and Diagnostic of Bioemergencies group
Published: July 2020

The circulation of SARS-CoV-2 in Italy has been dominated by two large clusters of outbreaks in Northern part of the peninsula, source of alarming and prolonged infections in Lombardy region, in Codogno and Bergamo areas especially.

The aim of the study was to expand understanding on the circulation of SARS-CoV-2 in the affected Lombardy areas. To this purpose, twenty full length genomes were collected from patients addressing to several Lombard hospitals from February 20th to April 4th, 2020.

The obtained genome assemblies, available on the GISAD database and performed at the Referral Center for COVID-19 diagnosis, identified 2 main monophyletic clades, containing 9 and 52 isolates, respectively.

The molecular clock analysis estimated a clusters divergence approximately one month before the first patient identification, supporting the hypothesis that different SARS-CoV-2 strains spread all over the world at different time, but their presence became evident only in late February along with Italian epidemic emergence.

Therefore, the epidemiological reconstruction carried out by this work highlights multiple inputs of the virus into its initial circulation in Lombardy Region.

However, a phylogenetic reconstruction robustness will be improved when other genomic sequences will be available, in order to guarantee a complete epidemiological surveillance.
What factors influence symptom reporting during an emerging infectious disease outbreak? A rapid review of the evidence
Authors: Carter Patrice , Megnin-Viggars Odette , Rubin G James
Published: July 2020

Introduction

During any emerging infectious disease outbreak, people with symptoms of the illness are often asked to report their symptoms to the health service in a timely manner, to facilitate contact tracing. Numerous factors may influence an individual’s willingness to report these symptoms. Understanding these factors has become urgent during the COVID-19 pandemic.

Objective

To determine which factors influence symptom reporting during an emerging infectious disease outbreak.

Methods

We conducted a rapid review of the evidence. We included papers based on primary research; published in a peer-reviewed journal; written in English; included factors associated with symptom reporting or accessing healthcare; and related to a major public health incident involving an infectious disease outbreak.

Main results

Five themes were identified as facilitators of symptom reporting or accessing healthcare: accurate and informative communication; symptom severity; concern about exposure; ease of access; and relationship with the healthcare provider. Seven themes were identified as barriers of symptom reporting or accessing healthcare: lack of knowledge; fear; stigmatization; invasion of privacy; low concern about symptoms; economics; and practicalities of attending a healthcare facility.

Discussion & Conclusion

If contract tracing services are to be effective, members of the public need to have the capability, opportunity and motivation to use them. The themes identified should be used to evaluate the information provided to the public about such a service, the routes of access, and the underlying policies relating to the service, in order to ensure that as many people as possible with relevant symptoms will make contact.
Effective Contact Tracing for COVID-19: A Systematic Review
Authors: Juneau Carl-Etienne , Briand Anne-Sara , Pueyo Tomas , Collazzo Pablo , Potvin Louise
Published: July 2020

Background

Contact tracing is commonly recommended to control outbreaks of COVID-19, but its effectiveness is unclear. This systematic review aimed to examine contact tracing effectiveness in the context of COVID-19.

Methods

Following PRISMA guidelines, MEDLINE, Embase, Global Health, and All EBM Reviews were searched using a range of terms related to contact tracing for COVID-19. Articles were included if they reported on the ability of contact tracing to slow or stop the spread of COVID-19 or on characteristics of effective tracing efforts. Two investigators screened all studies.

Results

A total of 32 articles were found. All were observational or modelling studies, so the quality of the evidence was low. Observational studies (n=14) all reported that contact tracing (alone or in combination with other interventions) was associated with better control of COVID-19. Results of modelling studies (n=18) depended on their assumptions. Under assumptions of prompt and thorough tracing with no further transmission, they found that contact tracing could stop an outbreak (e.g. by reducing the reproduction number from 2.2 to 0.57) or that it could reduce infections (e.g. by 24%-71% with a mobile tracing app). Under assumptions of slower, less efficient tracing, modelling studies suggested that tracing could slow, but not stop COVID-19.

Conclusions

Observational and modelling studies suggest that contact tracing is associated with better control of COVID-19. Its effectiveness likely depends on a number of factors, including how many and how fast contacts are traced and quarantined, and how effective quarantines are at preventing further transmission. A cautious interpretation suggests that to stop the spread of COVID-19, public health practitioners have 2-3 days from the time a new case develops symptoms to isolate the case and quarantine at least 80% of its contacts, and that once isolated, cases and contacts should infect zero new cases. Less efficient tracing may slow, but not stop, the spread of COVID-19. Inefficient tracing (with delays of 4-5+ days or less than 60% of contacts quarantined with no further transmission) may not contribute meaningfully to control of COVID-19.

Funding

LP holds the Canada Research Chair in Community Approaches and Health Inequalities (CRC 950-232541). This funding source had no role in the design, conduct, or reporting of the study.

Competing interests

CEJ has contractual agreements with the Centre intégré universitaire de santé et de services sociaux du Centre-Sud-de-l’Île-de-Montréal and is founder of Dr. Muscle and the COVID-19 Science Updates (https://covid1.substack.com/).

Registration

PROSPERO CRD42020198462
Regional differences in time off work after injury: a comparison of Australian states and territories within a single workers’ compensation system
Authors: Lane Tyler J , Sheehan Luke , Gray Shannon , Collie Alex
Published: July 2020

Background

Time off work after workplace injury varies by compensation system. While often attributed to features of the compensation system, unaccounted regional factors may drive much of the effect. In this study, we compare disability durations by state and territory of residence within a single national workers’ compensation system. Large differences would indicate that factors other than compensation system settings are responsible for system effects observed in previous studies.

Methods

We applied crude and adjusted Cox proportional hazards models to compare disability durations by state and territory of residence. Confounders included factors known to influence disability duration. Durations were left-censored at two weeks and right-censored at 104 weeks.

Results

We analysedN= 38,686 claims. In both crude and adjusted models, three of the seven states and territories significantly differed from the reference group, New South Wales. However, two of the three were different between crude and adjusted models. Regional effects were relatively small compared to other factors including insurer type, age, and type of injury.

Conclusions

Regional factors influence disability duration, which persist with adjustment for demographic, work, insurer type, and injury confounders. However, the effects are inconsistently significant and fairly small, especially when compared to the effect of confounders and system effects found in previous studies. Regional factors likely only account for a small share of the difference in disability duration between compensation systems.
Mathematical Modeling and Optimal Control Analysis of COVID-19 in Ethiopia
Authors: Alemneh Haileyesus Tessema , Tilahun Getachew Teshome
Published: July 2020

In this paper we developed a deterministic mathematical model of the pandemic COVID-19 transmission in Ethiopia, which allows transmission by exposed humans. We proposed an SEIR model using system of ordinary differential equations. First the major qualitative analysis, like the disease free equilibruim point, endemic equilibruim point, basic reproduction number, stability analysis of equilibrium points and sensitivity analysis was rigorously analysed. Second, we introduced time dependent controls to the basic model and extended to an optimal control model of the disease. We then analysed using Pontryagin’s Maximum Principle to derive necessary conditions for the optimal control of the pandemic. The numerical simulation indicated that, an integrated strategy effective in controling the epidemic and the gvernment must apply all control strategies in combating COVID-19 at short period of time.
Superspreaders and lockdown timing explain the power law dynamics of COVID-19
Authors: Vazquez Alexei
Published: July 2020

Infectious disease outbreaks are expected to grow exponentially in time, when left unchecked Measures such as lockdown and social distancing can drastically alter the growth dynamics of the outbreak. Indeed the 2019-2020 COVID-19 outbreak is characterized by a power law growth 1. Strikingly however, the power law exponent is different across countries 2. Here I illustrate the relationship between these two extreme scenarios, exponential and power law growth, based on the impact of superspreaders and lockdown strategies to contain the outbreak. The theory predicts an inverse relationship between the power law exponent and the speed of the lockdown that is validated by the observed COVID-19 data across different countries.
Segmental Signs and Spontaneous Pain in Acute Visceral Disease - Lateralization and Bodily Patterns
Authors: Shaballout Nour , Aloumar Anas , Manuel Jorge , May Marcus , Beissner Florian
Published: July 2020

The differential diagnosis of acute visceral diseases is a challenging clinical problem. The older literature suggests that patients with acute visceral problems show segmental signs, such as hyperalgesia, skin resistance, or muscular defence, whose lateralization and segmental distribution may be used for differential diagnosis.

This study aimed to investigate the lateralization and segmental distribution of spontaneous pain and segmental signs in acute visceral diseases.

We recruited 208 emergency room patients that were presenting for acute medical problems. All patients underwent a structured 10-minute bodily examination to test for various segmental signs and were asked for spontaneous pain and segmental symptoms, such as nausea, meteorism, and urinary retention. We collected all findings as digital drawings on a tablet-PC. After the final diagnosis, patients were divided into groups according to the organ affected. Using statistical image analysis, we calculated average distributions of pain and segmental signs for the heart, lungs, stomach, liver/gallbladder, and kidneys/ureters analyzing their segmental distribution and lateralization.

85 of 110 patients with a single-organ problem reported pain, while 81 had at least one segmental sign, the most frequent being hyperalgesia (n=46), and muscle resistance (n=39). While the pain was distributed along the body midline, segmental signs for the heart, stomach and liver/gallbladder appeared mostly ipsilateral to the affected organ. An unexpectedly high number of patients (n=37) further showed ipsilateral mydriasis.

The present study underlines the usefulness of including segmental signs in the bodily examination of patients with acute medical problems.
Dose-dependent volume loss in subcortical deep grey matter structures after cranial radiotherapy
Authors: Nagtegaal Steven H.J , David Szabolcs , Philippens Marielle E.P. , Snijders Tom J. , Leemans Alexander , Verhoeff Joost J.C.
Published: July 2020

Background and purpose

The relation between radiotherapy (RT) dose to the brain and morphological changes in healthy tissue has seen recent increased interest. There already is evidence for changes in the cerebral cortex and white matter, as well as selected subcortical grey matter (GM) structures. We studied this relation in all deep GM structures, to help understand the aetiology of post-RT neurocognitive symptoms.

Materials and methods

We selected 31 patients treated with RT for glioma. Pre-RT and post-RT 3D T1 MRIs were automatically segmented, and the changes in volume of the following structures were assessed: amygdala, nucleus accumbens, caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus. The volumetric changes were related to the mean RT dose received by each structure. Hippocampal volumes were entered into a population-based nomogram to estimate hippocampal age.

Results

A significant relation between RT dose and volume loss was seen in all examined structures, except the caudate nucleus. The volume loss rates ranged from 0.16-1.37 %/Gy, corresponding to 4.9-41.2% per 30 Gy. Hippocampal age, as derived from the nomogram, was seen to increase by a median of 11 years.

Conclusion

Almost all subcortical GM structures are susceptible to radiation-induced volume loss, with more volume loss being observed with increasing dose. Volume loss of these structures is associated with neurological deterioration, including cognitive decline, in neurodegenerative diseases. To support a causal relationship between radiation-induced deep GM loss and neurocognitive functioning in glioma patients, future studies are needed that directly correlate volumetrics to clinical outcomes.
Evolution of spray and aerosol from respiratory releases: theoretical estimates for insight on viral transmission
Authors: de Oliveira P. M. , Mesquita L. C. C. , Gkantonas S. , Giusti A. , Mastorakos E.
Published: July 2020

By modelling the evaporation and settling of droplets emitted during respiratory releases and using previous measurements of droplet size distributions and SARS-CoV-2 viral load, estimates of the evolution of the liquid mass and the number of viral copies suspended were performed as a function of time from the release. The settling times of a droplet cloud and its suspended viral dose are significantly affected by the droplet composition. The aerosol (defined as droplets smaller than 5 µm) resulting from 30 seconds of continued speech has o(1 h) settling time and a viable viral dose an order-of-magnitude higher than in a short cough. The time-of-flight to reach 2 m is only a few seconds resulting in a viral dose above the minimum required for infection, implying that physical distancing in the absence of ventilation is not sufficient to provide safety for long exposure times. The suspended aerosol emitted by continuous speaking for 1 hour in a poorly ventilated room gives 0.1–11% infection risk for initial viral loads of 108-1010 copies/mll, respectively, decreasing to 0.03–3% for 10 air changes per hour by ventilation. The present results provide quantitative estimates useful for the development of physical-distancing and ventilation controls.
Evidence of integrated health service delivery during COVID-19 in low- and middle-income countries: protocol for a scoping review
Authors: Neill Rachel , Hasan Md Zabir , Das Priyanka , Venugopal Vasuki , Jain Nishant , Arora Dinesh , Gupta Shivam
Published: July 2020

Introduction

The importance of integrated, people-centered health systems has been recognized as a central component of achieving Universal Health Coverage. Integration has also been highlighted as a critical element for building resilient health systems that can stand the shock of health emergencies. However, there is dearth of research and systematic synthesis of evidence on the synergistic relationship between integrated health services and pandemic preparedness in low- and low-middle income countries (LMICs). Thus, the authors are organizing a scoping review aiming to explore application of integrated health service delivery approaches during the emerging COVID-19 pandemic in LMICs.

Methods and analysis

This scoping review adheres to the six steps for scoping reviews from Arksey and O’Malley (2005). Peer reviewed scientific literature will be systematically assembled utilizing a standardized and replicable search strategy from seven electronic databases, including PubMed, Embase, Scopus, Web of Science, CINAHL Plus, the World Health Organization’s Global Research Database on COVID-19, and LitCovid. Initially, the title and abstract of the collected literature, published in English from December 2019 to June 2020, will be screened for inclusion which will be followed by a full text review by two independent reviewers. Data will be charted using a data extraction form and reported in narrative format with accompanying data matrixes.

Ethics and dissemination

No ethical approval is required for the review. The study will be conducted from June to December 2020. Results from this study will provide a snapshot of the evidence currently being generated related to integrated health service delivery in response to the COVID-19 pandemic. The findings will be developed into reports and a peer-reviewed articles and will assist policy makers in making pragmatic and evidence-based decisions for current and future pandemic response.

Article Summary

Strengths and limitations of this study

The scoping review aims to uncover new evidence in response to the evolving pandemic and will not assess the quality of existing evidence

The review will map a rapidly emerging evidence base in response to COVID-19 from seven different electronic databases that can be used to inform response and recovery strategies in LMICs

The early research and published evidence on the COVID-19 pandemic was focused in high-income and upper-middle income countries, thus, we expect evidence of from LMICs may be scarce

The scoping review is limited to peer review publications that were originally written in English or have translated versions
Herd immunity thresholds for SARS-CoV-2 estimated from unfolding epidemics
Authors: Aguas Ricardo , Gonçalves Guilherme , Ferreira Marcelo U. , M. Gomes M. Gabriela
Published: July 2020

Variation in individual susceptibility or frequency of exposure to infection accelerates the rate at which populations acquire immunity by natural infection. Individuals that are more susceptible or more frequently exposed tend to be infected earlier and hence more quickly selected out of the susceptible pool, decelerating the incidence of new infections as the epidemic progresses. Eventually, susceptible numbers become low enough to prevent epidemic growth or, in other words, the herd immunity threshold (HIT) is reached. We have recently proposed a method whereby mathematical models, with gamma distributions of susceptibility or exposure to SARS-CoV-2, are fitted to epidemic curves to estimate coefficients of individual variation among epidemiological parameters of interest. In the initial study we estimated HIT around 25-29% for the original Wuhan virus in England and Scotland. Here we explore the limits of applicability of the method using Spain and Portugal as case studies. Results are robust and consistent with England and Scotland, in the case of Spain, but fail in Portugal due to particularities of the dataset. We describe failures, identify their causes, and propose methodological extensions.
Clinical Impact, Costs, and Cost-Effectiveness of Expanded SARS-CoV-2 Testing in Massachusetts
Authors: Neilan Anne M. , Losina Elena , Bangs Audrey C. , Flanagan Clare , Panella Christopher , Eskibozkurt G. Ege , Mohareb Amir , Hyle Emily P. , Scott Justine A. , Weinstein Milton C. , Siedner Mark J. , Reddy Krishna P. , Harling Guy , Freedberg Kenneth A. , Shebl Fatma M. , Kazemian Pooyan , Ciaranello Andrea L.
Published: July 2020

Background

We projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model.

Methods

We compared five testing strategies: 1) PCR-severe-only: PCR testing only patients with severe/critical symptoms; 2) Self-screen: PCR-severe-only plus self-assessment of COVID-19-consistent symptoms with self-isolation if positive; 3) PCR-any-symptom: PCR for any COVID-19-consistent symptoms with self-isolation if positive; 4) PCR-all: PCR-any-symptom and one-time PCR for the entire population; and, 5) PCR-all-repeat: PCR-all with monthly re-testing. We examined effective reproduction numbers (Re, 0.9-2.0) at which policy conclusions would change. We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70/100%) and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180-days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]).

Results

In all scenarios, PCR-all-repeat would lead to the best clinical outcomes and PCR-severe-only would lead to the worst; at Re 0.9, PCR-all-repeat vs. PCR-severe-only resulted in a 63% reduction in infections and a 44% reduction in deaths, but required >65-fold more tests/day with 4-fold higher costs. PCR-all-repeat had an ICER <$100,000/QALY only when Re ≥1.8. At all Re values, PCR-any-symptom was cost-saving compared to other strategies.

Conclusions

Testing people with any COVID-19-consistent symptoms would be cost-saving compared to restricting testing to only those with symptoms severe enough to warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Universal screening would be cost-effective when paired with monthly retesting in settings where the COVID-19 pandemic is surging.
Factors associated with psychological distress in health-care workers during an infectious disease outbreak: A rapid living systematic review
Authors: Sirois Fuschia M. , Owens Janine
Published: July 2020

Background

Health-care workers (HCW) are at risk for psychological distress during an infectious disease outbreak due to the demands of dealing with a public health emergency.

Aims

To examine the factors associated with psychological distress among HCW during an outbreak.

Method

We systematically reviewed literature on the factors associated with psychological distress (demographic characteristics, occupational, social, psychological, and infection-related factors) in HCW during an outbreak (COVID-19, SARS, MERS, H1N1, H7N9, Ebola). Four electronic databases were searched (2000 to 10 July 2020) for relevant peer-reviewed research according to a pre-registered protocol. A narrative synthesis was conducted to identify fixed, modifiable, and infection-related factors.

Results

From the 3335 records identified, 52 with data from 54,800 HCW were included. All but two studies were cross-sectional. Consistent evidence indicated that being female, a nurse, experiencing stigma, maladaptive coping, having contact or risk for contact with infected patients, and being quarantined, were risk factors for psychological distress among HCW. Personal and organisational social support, perceiving control, positive work attitudes, sufficient information about the outbreak and proper protection, training and resources, were associated with less psychological distress.

Conclusions

HCW who may be most at risk for psychological distress during an outbreak require early intervention and ongoing monitoring as there is some evidence that HCW distress can persist for years after an outbreak. Further research is needed to track the associations of risk factors with distress over time and the extent to which certain factors are inter-related and linked to sustained or transient distress.
Assessing the Age Specificity of Infection Fatality Rates for COVID-19: Systematic Review, Meta-Analysis, and Public Policy Implications
Authors: Levin Andrew T. , Hanage William P. , Owusu-Boaitey Nana , Cochran Kensington B. , Walsh Seamus P. , Meyerowitz-Katz Gideon
Published: July 2020

Structured Abstract

Objective

Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups.

Methods

Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports. A total of 111 studies were reviewed in depth and screened. Studies of 33 locations satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities four weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze IFR by age.

Results

Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFRs are very low for children and younger adults but increase progressively to 0.4% at age 55, 1.3% at age 65, 4.2% at age 75, and 14% at age 85. We find that differences in the age structure of the population and the age-specific prevalence of COVID-19 explain nearly 90% of the geographical variation in population IFR.

Discussion

These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.
A systematic review of utilisation of diurnal timing information in clinical trial design for Long QT syndrome
Authors: Seed Lydia M , Hearn Timothy J
Published: July 2020

Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 hours, and drug delivery. Despite guidelines having been issued around the analysis of 24-hour ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.
Time to SARS-CoV-2 Clearance Among Patients with Cancer and COVID-19
Authors: Xu Wenxin , Piper-Vallillo Andrew J. , Bindal Poorva , Wischhusen Jonathan , Patel Jaymin M. , Costa Daniel B , Peters Mary Linton B.
Published: July 2020

Key Points

Question

What is the median time to clearance of SARS-CoV-2 among cancer patients according to currently used criteria?

Findings

In this single-institution retrospective cohort study, the median time to SARS-CoV-2 clearance was 50 days using the ASCO/CDC criteria of 2 negative RT-PCR assays >24 hours apart. Using alternative criteria of 1 negative RT-PCR assay (UK-NICE) or CDC clinical criteria (10 days after first positive RT-PCR and 3 days after last symptoms), median clearance times were 31 days and 13 days, respectively.

Meaning

SARS-CoV-2 clearance times differ substantially depending on criteria used and may be prolonged in cancer patients.
A novel haplotype-based eQTL approach identifies genetic associations not detected through conventional SNP-based methods
Authors: Bkhetan Ziad Al , Chana Gursharan , Ong Cheng Soon , Goudey Benjamin , Ramamohanarao Kotagiri
Published: July 2020

Motivation

The high accuracy of current haplotype phasing tools has enabled the interrogation of haplotype (or phase) information more widely in genetic investigations. Including such information in eQTL analysis complements SNP-based approaches as it has the potential to detect associations that may otherwise be missed.

Results

We have developed a haplotype-based eQTL approach calledeQTLHapto investigate associations between gene expression and haplotype blocks. Using simulations, we demonstrate that eQTLHap significantly outperforms typical SNP-based eQTL methods when the causal genetic architecture involves multiple SNPs. We show that phasing errors slightly impact the sensitivity of the proposed method (< 4%). Finally, the application of eQTLHap to real GEUVADIS and GTEx datasets finds 22 associations that replicated in larger studies or other tissues and could not be detected using a single-SNP approach.

Availability

https://github.com/ziadbkh/eQTLHap.
Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function Following Chronic Traumatic Brain Injury
Authors: Badner Anna , Reinhardt Emily K. , Nguyen Theodore V. , Midani Nicole , Marshall Andrew T. , Lepe Cherie , Echeverria Karla , Lepe Javier , Torrecampo Vincent , Bertan Sara H. , Tran Serinee H. , Anderson Aileen J. , Cummings Brian J.
Published: July 2020

Human neural stem cells (hNSCs) have potential as a cell therapy following traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from on-going culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks – a more clinically-relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested following long-term cryostorage and thawing prior to transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At 4-weeks post-injury, 6×105freshly thawed hNSCs were transplanted into six injection sites (2 ipsi- and 4 contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk-taking behavior in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to restore function after TBI and demonstrate that long-term bio-banking of cells and thawing aliquots prior to use may be suitable for clinical deployment.

Significance Statement

There is no cure for chronic traumatic brain injury (TBI). While human neural stem cells (hNSCs) offer a potential treatment, no one has demonstrated efficacy of thawed hNSCs from long-term cryobanked stocks. Frozen aliquots are critical for multisite clinical trials, as this omission impacted the use of MSCs for graft versus host disease. This is the first study to demonstrate the efficacy of thawed hNSCs, while also providing support for novel mechanisms of action – linking meningeal and ventricular engraftment to reduced neuroinflammation and improved hippocampal neurogenesis. Importantly, these changes also led to clinically relevant effects on spatial learning/memory and risk-taking behavior. Together, this new understanding of hNSCs lays a foundation for future work and improved opportunities for patient care.