bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraspecies strain exclusion, antibiotic pretreatment, and donor selection control microbiota engraftment after fecal transplantation
Authors: Podlesny Daniel , Durdevic Marija , Paramsothy Sudarshan , Kaakoush Nadeem O. , Högenauer Christoph , Gorkiewicz Gregor , Walter Jens , Fricke W. Florian
Published: August 2021

Fecal microbiota transplantation (FMT) is both a promising therapeutic approach to treat microbiota-associated pathologies and an experimental tool to establish a causal role of microbiome dysbiosis in human pathologies. Although clearly efficacious in resolving recurrent Clostridioides difficile infection (rCDI), the therapeutic value of FMT in other pathologies is not yet established, and our mechanistic and ecological understanding of how FMT alters the microbiome in patients is incomplete. Here, we assembled the most comprehensive FMT trial microbiota dataset to date, including new and previously generated fecal metagenomes from FMT trials in rCDI, inflammatory bowel disease (IBD), metabolic syndrome (MetS), drug-resistant pathogen colonization (MDR), and resistance to immune checkpoint inhibitor anti-tumor therapy (ICI). We characterized post-FMT microbiota assembly in the recipients by establishing the origin of the detected strains, and we identified the clinical and ecological factors that determine the engraftment of donor strains. Our findings showed little coexistence of donor and recipient strains and linked the magnitude of donor strain engraftment to dysbiosis of the recipient microbiome. Dysbiosis and strain engraftment were low in pathologies other than rCDI but could be enhanced through pretreatment with antibiotics and lavage. Using generalized linear mixed-effects models, we demonstrate that both ecological (low recipient and high donor ɑ-diversity and relative species abundance) and clinical (antibiotic pretreatment, bowel lavage, multiple rounds of FMT) variables are associated with increased donor microbiota engraftment, and that donor strain engraftment events are predictable for individual patients and strains. Overall donor strain engraftment was not linked to FMT outcome in IBD patients but was higher in ICI patients that responded to immunotherapy after FMT. Our findings provide an ecological framework for post-FMT microbiota assembly that can predict donor strain engraftment and determine its importance for clinical outcomes, informing more targeted and personalized approaches to increase the therapeutic benefits of FMTs.
Modeling SARS-CoV-2 transmission at a winter destination resort region with high outside visitation
Authors: Wu E.J. , Bayham J. , Carlton E. , Samet J. , Buchwald A.G.
Published: August 2021

Travel destinations, particularly large resorts in otherwise small communities, risk infectious disease outbreaks from an influx of visitors who may import infections during peak seasons. The COVID-19 pandemic highlighted this risk in the context of global travel and has raised questions about appropriate interventions to curb the potential spread of infectious disease at tourist destinations. In Colorado, the initial outbreaks of SARS-CoV-2 in the state occurred in ski communities, leading to large economic losses from closures and visitor restrictions. In this study, we modeled SARS-CoV-2 transmission during the 2020-21 season in a ski region of Colorado to determine optimal combinations of intervention strategies that would keep the region below a predetermined threshold of SARS-CoV-2 infection density. This analysis used an age-stratified, deterministic SEIR compartmental model of disease transmission, calibrated to cellphone-based mobility data, to simulate infection trajectories during the winter ski season. Under three national infection levels corresponding to high, medium, and low viral importation risk, we estimated the potential impact of interventions including policy and behavior changes, visitor restriction strategies, and case investigation/contact tracing, in order to quantify the relative and absolute impacts of these interventions in the context of the COVID-19 pandemic. Our results suggest that, in the context of low viral importation risk, case investigation/contact tracing and policy and behavior changes may be sufficient to stay below predetermined infection thresholds without visitor restrictions. However, if viral importation risk is high, visitor restrictions and/or screening for infected visitors would be needed to avoid lockdown-like control scenarios and large outbreaks in tourist communities. These findings provide important guidance to tourist destinations for balancing policy impact in future infectious disease outbreaks.
Interventions designed to improve vaccination uptake: Scoping review of systematic reviews and meta-analyses - protocol (version 1)
Authors: Heneghan CJ , Plüddemann A , Spencer EA , Brassey J , Rosca EC , Onakpoya IJ , Evans DH , Conly JM , Brewer NT , Jefferson T
Published: August 2021

Background

Vaccine uptake varies substantially, and resources to promote the uptake of vaccines differ widely by country and income level. As a result, immunization rates are often suboptimal. There is a need to understand what works, particularly in low- and middle-income countries and other settings where resources are scarce.

Methods

We plan to conduct a scoping review of interventions designed to increase vaccination uptake

We will include systematic reviews and meta-analyses of interventional studies that address the question of vaccine uptake. We will search the following electronic databases: MEDLINE, Cochrane Database of Systematic Reviews, EMBASE, Epistemonikos, Google Scholar, LILACs and TRIP database (which covers guidelines and the grey literature) until 01 July 2021 and hand-search the reference lists of included articles. We will include systematic reviews that comprise studies of all ages if they report quantitative data on the impact on vaccine uptake. To assess the quality, we will use a modified AMSTAR score and ate the quality of the evidence in included reviews using the “Grade of Recommendations Assessment, Development and Evaluation” (GRADE).

Expected results

We intend to present the evidence using summary tables to present the evidence stratified by vaccine coverage, the specific population, e.g., children, adolescents and older adults, and by setting, e.g. healthcare, community. We will also present when low middle-income subgroups are reported.
Effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) Program on Depression and Neural Structural Connectivity
Authors: Polcari Justin J. , Cali Ryan J. , Nephew Benjamin C. , Lu Senbao , Rashkovskii Mikhail , Wu Julianne , Saadeh Frances , Loucks Eric , King Jean A.
Published: August 2021

Hypertension-related illnesses are a leading cause of disability and death in the United States, where 46% of adults have hypertension and only half have it controlled. It is critical to reduce hypertension, and either new classes of interventions are required, or we need to develop enhanced approaches to improve medical regimen adherence. The Mindfulness-Based Blood Pressure Reduction program (MB-BP) is showing novel mechanisms and early evidence of efficacy, but the neural correlates are unknown. The objectives of this study were to identify structural neural correlates of MB-BP using diffusion tensor magnetic resonance imaging (DTI) and assess potential correlations with key clinical outcomes. In a subset of participants from a larger randomized controlled trial, MB-BP participants exhibited increased interoception and decreased depressive symptoms compared to controls. Analyses of DTI data revealed significant group differences in several white matter neural tracts associated with the limbic system and/or hypertension. Specific changes in neural structural connectivity were significantly associated with measures of blood pressure, depression anxiety and symptoms, mindfulness, and emotional regulation. It is concluded that MB-BP has extensive and substantial effects on brain structural connectivity which could mediate beneficial changes in depression, interoceptive awareness, blood pressure, and related measures in individuals with hypertension.
Tissue damage detected by quantitative gradient echo MRI correlates with clinical progression in non-relapsing progressive MS
Authors: Xiang Biao , Brier Matthew R. , Kanthamneni Manasa , Wen Jie , Snyder Abraham Z. , Yablonskiy Dmitriy A. , Cross Anne H.
Published: August 2021

Background

Imaging biomarkers of progressive MS are needed. Quantitative gradient recalled echo (qGRE) MRI technique allows evaluation of tissue damage associated with microstructural damage in multiple sclerosis (MS).

Objective

To evaluate qGRE-derived R2t* as an imaging biomarker of MS disease progression as compared to atrophy and lesion burden.

Methods

Twenty-three non-relapsing progressive MS (PMS), twenty-two relapsing-remitting MS (RRMS) and eighteen healthy control participants were imaged with qGRE at 3T. PMS subjects were imaged and neurologically assessed every nine months over five sessions. In each imaging session, lesion burden, atrophy and R2t* in cortical grey matter (GM), deep GM, normal-appearing white matter (NAWM) were measured.

Results

R2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression showed significantly faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group. Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period.

Conclusion

Clinical impairment and progression correlated with accumulating R2t*-defined microstructural tissue damage in deep GM and NAWM. qGRE-derived R2t* is a potential imaging biomarker of MS progression.
Can a vaccine-led approach end the NSW outbreak in 100 days, or at least substantially reduce morbidity and mortality?
Authors: Bablani Laxman , Wilson Tim , Andrabi Hassan , Sundararajan Vijaya , Ait Oukarim Driss , Abraham Patrick , Thompson Jason , Blakely Tony
Published: August 2021

Abstract
Background and Aims
The New South Wales (NSW) COVID-19 outbreak is at 478 daily cases on August 16, 2021.
Our aims were to:
1) estimate the time required to reach ≤5 cases per day under three lockdown strengths (weak, moderate, strong), and four vaccination rollouts: (a) per the original plan, (b) prioritizing essential workers, (c) b plus rapid vaccination of 25% of <60-year-olds with AstraZeneca (AZ25), and (d) b plus rapid vaccination of 50% of <60-year-olds with AstraZeneca (AZ50).
2) estimate the number of cases, hospitalizations, and deaths in the 100 days after 1/August for the 12 scenarios.
Methods
An agent-based model was adapted to NSW and the Delta variant. Hospitalization and mortality rates for unvaccinated COVID-19 infections were doubled given the virulence of Delta.
Results
The business-as-usual rollout fully vaccinates 50%, 70% and 80% of >16-year-olds by 10/Oct, 21/Nov, and 28/Dec, respectively. This reduced to 1/Oct, 30/Oct, and 22/Nov for the fastest (AZ50) rollout.
A strong lockdown with a rapid vaccine rollout was the fastest to reach ≤5 cases (14-day average), with a median of 78 days (90% Uncertainty interval 61 - 103) or 18/Oct, compared to 207 days (166 - 254) or 24/Feb for a weak lockdown with no rollout acceleration. Increased lockdown strength had more impact than rollout acceleration.
Under the AZ25 vaccination scenario, there were 1,440 (90% UI 262 - 10,600 deaths in the first 100 days of cases under a weak lockdown, compared to 71 (90% UI 26 - 178) under a strong lockdown scenario.
Conclusion
NSW will likely achieve 70% vaccination of >16-year-olds before reaching ≤5 daily cases. Accelerating the vaccine rollout is important for the medium-term, but in the short-term increased restriction strength was more effective at reducing caseload (and subsequently mortality and hospitalisation) than accelerating the vaccine rollout.
Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection
Authors: Israel Ariel , Shenhar Yotam , Green Ilan , Merzon Eugene , Golan-Cohen Avivit , Schäffer Alejandro A , Ruppin Eytan , Vinker Shlomo , Magen Eli
Published: August 2021

Background

Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time.

Objective

To determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals.

Methods

Antibody titers were measured between January 31, 2021, and July 31, 2021 in two mutually exclusive groups: i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and ii) SARS-CoV-2 convalescents who had not received the vaccine.

Results

A total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection.

Conclusions

This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.

Funding

This research was internally funded by Leumit Health Services (LHS) and was supported in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research.

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Impact statement

Large scale study display the kinetics of SARS-CoV-2 IgG antibodies present in individuals vaccinated with two doses of mRNA vaccine vs. unvaccinated patients who had recovered from the disease: initial levels of antibody are much higher in vaccinated patients, but decrease faster.
Intention to receive a COVID-19 vaccine by HIV status among a population-based sample of women and gender diverse individuals in British Columbia, Canada
Authors: Kaida Angela , Brotto Lori A. , Murray Melanie C.M. , Côté Hélène C. F. , Albert Arianne Y. , Nicholson Valerie , Gormley Rebecca , Gordon Shanlea , Booth Amy , Smith Laurie W. , Baaske Ally , Galea Liisa A. M. , Sadarangani Manish , Ogilvie Gina S.
Published: August 2021

Introduction

COVID-19 vaccination is recommended for people living with HIV (PLWH), among whom social inequities and co-morbidities may drive risks of COVID-19 infection and outcome severity. Among a provincial (British Columbia) sample, we determined the prevalence of COVID-19 vaccine intention by HIV status and assessed socio-demographic, vaccine hesitancy, and psychological predictors of vaccine intention.

Methods

Individuals (25-69y) recruited from province-wide research cohorts completed an online survey examining COVID-19 impacts (August/2020-March/2021). Among women and gender diverse participants, we compared intention to receive a recommended COVID-19 vaccine (Very likely/Likely vs Neutral/Unlikely/Very Unlikely) by self-reported HIV status. Logistic regression models assessed the independent effect of HIV status and other factors on vaccine intention.

Results

Of 5,588 participants, 69 (1.2%) were PLWH, of whom 79.7% were on antiretroviral therapy. Intention to vaccinate was significantly lower among PLWH compared to participants not living with HIV (65.2% vs 79.6%; OR: 0.44; 95%CI: 0.32-0.60). However, this association was attenuated after adjustment for social disparities (aOR:0.85; 95%CI: 0.48-1.55). Among PLWH, those with greater vaccine confidence, positive attitudes towards the COVID-19 vaccine, and more strongly influenced by direct and indirect social norms to vaccinate had significantly higher odds of vaccine intention.

Discussion

Tailored messaging is needed to build vaccine confidence, address questions about vaccine benefits, and support informed vaccination decision-making to promote COVID-19 vaccine uptake among women and gender diverse PLWH.
Is the BioNTech-Pfizer COVID-19 vaccination effective in elderly populations? Results from population data from Bavaria, Germany
Authors: Gomes Delphina , Beyerlein Andreas , Katz Katharina , Hoelscher Gabriele , Nennstiel Uta , Liebl Bernhard , Überla Klaus , von Kries Rüdiger
Published: August 2021

Background

The effect of the BioNTech-Pfizer BNT162b2 vaccination in the elderly (≥80 years) could not be fully assessed in the BioNTech-Pfizer trial due to low numbers in this age group. We aimed to evaluate the effectiveness of the BioNTech-Pfizer (BNT162b2) vaccine to prevent SARS-CoV-2 infection and severe outcomes in octo- and novo-generians in a German state setting.

Methods and Findings

A prospective observational study of 708,187 persons aged ≥80 years living in Bavaria, Germany, was conducted between Jan 9 to Apr 11, 2021. We assessed the vaccine efficacy (VE) for two doses of the BNT162b2 vaccine with respect to SARS-CoV-2 infection and related hospitalisations and mortality. Additionally, differences in VE by age groups ≥80 to ≤89 years and ≥90 years were studied. Analyses were adjusted by sex.

By the end of follow-up, 63.8% of the Bavarian population ≥80 years had received one dose, and 52.7% two doses, of the BNT162b2 vaccine. Two doses of the BNT162b2 vaccine lowered the proportion of SARS-CoV-2 infections and related outcomes, resulting in VE estimates of 68.3% (95% confidence interval (CI) 65.5%, 70.9%) for infection, 73.2% (95% CI 65.3%, 79.3%) for hospitalisation, and 80.1% (95% CI 80.0%, 89.0%) for mortality. Sex differences in the risk of COVID-19 outcomes observed among unvaccinated persons disappeared after two BNT162b2 vaccine doses. Overall, the BNT162b2 vaccine was equally efficacious in octo- and novo-genarians.

Conclusions

Two doses of BioNTech-Pfizer’s BNT162b2 vaccine is highly effective against COVID-19 outcomes in elderly persons.
The burden of isolation to the individual: a comparison between isolation for COVID-19 and for other influenza-like illnesses in Japan
Authors: Tsuzuki Shinya , Ohmagari Norio , Beutels Philippe
Published: August 2021

At present, there is scarce evidence about how much burden the isolation of COVID-19 patients is. We aimed to assess the differences between COVID-19 and other influenza like illnesses in disease burden brought by isolation. We conducted an online questionnaire survey of 302 people who had COVID-19 or other influenza-like illnesses (ILIs) and compared the burden of isolation due to sickness with one-to-one propensity score matching. The primary outcomes are the duration and productivity losses of isolation, the secondary outcome is quality of life (QOL) valuation on the day of the survey. Acute symptoms of outpatient COVID-19 and other ILIs lasted 17 (interquartile range [IQR] 9-32) and 7 (IQR 4-10) days, respectively. The length of isolation due to COVID-19 was 18 (IQR 10-33) days and that due to other ILIs was 7 (IQR 4-11) days, respectively. The monetary productivity loss of isolation due to COVID-19 was 1424.3 (IQR 825.6-2545.5) USD and that due to other ILIs was 606.1 (IQR 297.0-1090.9) USD, respectively. QOL at the time of the survey was lower in the COVID-19 group than in the “other ILIs” group (0.89 and 0.96, p = 0.001). COVID-19 infection imposes a substantial disease burden, even in patients with non-severe disease. This burden is larger for COVID-19 than other ILIs, mainly because the required isolation period is longer.
Childhood malnutrition and bacteraemia at a tertiary hospital in Malawi
Authors: Mukhula Victoria Temwanani , Harawa Philliness Prisca , Phiri Chisomo , Khoswe Stanley , Chaziya Jessica , Mbale Emmie , Tigoi Caroline , Tam Pui-Ying Iroh , Bandsma Robert , Voskuijl Wieger
Published: August 2021

Background

Malnutrition increases risk of acquiring infections but clinical characteristics and hospital outcomes among children in low resource settings with high rates of antimicrobial resistance have not been clearly described.

Aim

Our main aim was to ascertain prevalence of bacteraemia in hospitalised children at Queen Elizabeth Central Hospital, Malawi.

Methods

We conducted a secondary analysis of a prospective study of children who had a blood culture collected during hospitalisation.

Results

Out of 175 children who had blood cultures collected during hospitalisation, 75 had severe acute malnutrition (SAM), 31 moderate acute malnutrition (MAM), and 69 no acute malnutrition (NAM). Twelve (7%) had bacteraemia (8 SAM, 1 MAM, 3 NAM) and seventeen (10%) died (14 SAM, 2 MAM, 1 NAM). Fever, vomiting and convulsions were least common in SAM (69%, 37%, 1%) compared to MAM (90%, 81%, 10%) and NAM (99%, 46%, 29%; p<0.001) children. Mortality was significantly higher in those with than without bacteraemia (33% vs 8%, p=0.004). Most common isolates were Salmonella Typhimurium (31%) and Escherichia coli (23%). High rates of bacterial resistance were noted to gentamicin (58%), a first-line antibiotic, and ceftriaxone (33%), a second-line antibiotic.

Conclusions

Mortality and bacteraemia rates are highest in hospitalised children with SAM. Despite this, SAM children do not present with typical clinical features, including fever, vomiting and convulsions. Given the high rate of antimicrobial resistance in this setting, a high index of infection clinical suspicion, awareness of local susceptibility patterns and evidence-based antibiotic guidelines are needed to optimise clinical care and antimicrobial stewardship.

Lay Summary

Malnutrition increases the risk of having an infection but symptoms and hospital outcomes among children with malnutrition, in countries like Malawi with high rates of antimicrobial resistance, have not been clearly described. This study describes a study of children who had a blood culture collected during admission to Queen Elizabeth Central Hospital, Malawi. Of 175 children who had blood cultures collected, 12 (7%) had a bacteria found (‘bactaeriemia’) and 17 (10%) died. Fever, vomiting and convulsions were significantly less common in severe malnutrition compared to children with moderate malnutrition and those with no malnutrition. Mortality was significantly higher in those with bacteraemia than without. High rates of bacterial resistance were noted to first- and second-line antibiotics. Mortality and bacteraemia rates are highest in hospitalised children with SAM even though they do not present with typical features of bacteraemia.
Gut microbiota affects prostate cancer risk through steroid hormone biosynthesis
Authors: Kalinen Sofia , Kallonen Teemu , Gunell Marianne , Ettala Otto , Jambor Ivan , Knaapila Juha , Syvänen Kari T. , Taimen Pekka , Poutanen Matti , Ohlsson Claes , Aronen Hannu J. , Ollila Helena , Pietilä Sami , Elo Laura L. , Lamminen Tarja , Hakanen Antti J. , Munukka Eveliina , Boström Peter J. ,   the Multi-IMPROD Study group
Published: August 2021

Purpose

Although prostate cancer is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies or differences in lifestyle. Gut microbiota has been recently associated with cancer progression, but its role in prostate cancer is unclear.

Methods

In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of prostate cancer were assessed utilizing 16S rRNA gene sequencing. Sequences were assigned to operational taxonomic units, and differential abundance analysis, α- and β-diversities, and predictive functional (PICRUSt) analyses were performed. Additionally, plasma steroid hormone levels were correlated with the predicted microbiota functions.

Results

Several differences in the gut microbiota between the subjects with and without prostate cancer were noted. Prevotella 9, members of the Erysipelotrichaceae family and Escherichia-Shigella were higher, and Jonquetella, Moryella, Anaeroglobus, Corynebacterium and CAG-352 were lower in the cancer group. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinal metabolism in the prostate cancer associated microbiome. Plasma testosterone associated negatively with the microbial 5-α-reductase activity (p=0.030). In a subgroup of men taking 5-α-reductase inhibitors (n=17), plasma estrone (p=0.027) and estradiol (p=0.059) levels were lower in men with predicted elevation of the microbial 5-α-reductase function.

Conclusions

Gut microbiota of the prostate cancer patients differed significantly compared to benign subjects. Microbial 5-α-reductase, copper absorption and retinol metabolism are potential mechanisms of action. These findings could explain the observed association of lifestyle, geography, and prostate cancer incidence.
SARS-CoV-2 specific T cells and antibodies in COVID-19 protection: a prospective study
Authors: Molodtsov Ivan A. , Kegeles Evgenii , Mitin Alexander N. , Mityaeva Olga , Musatova Oksana E. , Panova Anna E. , Pashenkov Mikhail V. , Peshkova Iuliia O. , Almaqdad Alsalloum , Asaad Walaa , Budikhina Anna S. , Deryabin Aleksander S. , Dolzhikova Inna V. , Filimonova Ioanna N. , Gracheva Alexandra N. , Ivanova Oxana I. , Kizilova Anastasia , Komogorova Viktoria V. , Komova Anastasia , Kompantseva Natalia I. , Lagutkin Denis A. , Lomakin Yakov A. , Maleeva Alexandra V. , Maryukhnich Elena V. , Mohammad Afraa , Murugin Vladimir V. , Murugina Nina E. , Navoikova Anna , Nikonova Margarita F. , Ovchinnikova Leyla A. , Pinegina Natalia V. , Potashnikova Daria M. , Romanova Elizaveta V. , Saidova Aleena A. , Sakr Nawar , Samoilova Anastasia G. , Serdyuk Yana , Shakirova Naina T. , Sharova Nina I. , Sheetikov Savely A. , Shemetova Anastasia F. , Shevkova Liudmila , Shpektor Alexander V. , Trufanova Anna , Tvorogova Anna V. , Ukrainskaya Valeria M. , Vinokurov Anatoliy S. , Vorobyeva Daria A. , Zornikova Ksenia V. , Efimov Grigory A. , Khaitov Musa R. , Kofiadi Ilya A. , Komissarov Alexey A. , Logunov Denis Y. , Naigovzina Nelli B. , Rubtsov Yury P. , Vasilyeva Irina A. , Volchkov Pavel , Vasilieva Elena
Published: August 2021

Rapid spread of COVID-19 pandemic made a substantial share of the world population immunised by SARS-CoV-2 antigens. Infection induces the development of virus-specific antibodies and T cells. Ample evidence on the antibody-mediated protection is contrasted by the elusive role of T cells in preventing infection. To explore the impact of T cells and to quantify the protective levels of the immune responses we conducted a large prospective study: 5,340 Moscow residents were evaluated for the antibody and cellular immune responses to SARS-CoV-2 and monitored for COVID-19 up to 300 days. The antibody and cellular responses were tightly interconnected, their magnitude inversely correlated with infection probability. Similar maximal level of protection was reached by individuals positive for both types of responses and by individuals with antibodies alone. Meanwhile, T cells in the absence of antibodies provided an intermediate level of protection. The real-world data on the protective effects of T cells have important implications for T cell immunology and development of the strategies to fight the pandemic.
Anticipating the hospital burden of future COVID-19 epidemic waves
Authors: Boennec Corentin , Alizon Samuel , Sofonea Mircea T
Published: August 2021

Forecasting SARS-CoV-2 epidemic trends with confidence more than a few weeks ahead is almost impossible as these entirely depend on political decisions. We address this problem by investigating the consequences for the health system of an epidemic wave of a given size. This approach yields semi-quantitative results that depend on the proportion of the population already infected and vaccinated. We introduce the COVimpact software, which allows users to visualise estimated numbers of ICU admissions, deaths, and infections stratified by age class at the French departmental, regional, or national level caused by the wave. We illustrate the usefulness of our approach by showing that for France, even with a 95% vaccination coverage, the current vaccine efficiency against the delta variant would make a large epidemic wave infecting 25% of the population difficult to sustain for the current hospital bed occupancy capacity. Overall, using the final epidemic wave size and ignoring detailed epidemiological dynamics yields valuable and practical insights to optimise public health response to epidemics.
Health status and cancer related mortality among nuclear plant workers exposed to ionizing radiation
Authors: Javinaani Ali , Abolghasemi Hasan , Hamidi Hadi
Published: August 2021

medRxiv has withdrawn this manuscript because it was not submitted by the named authors and has been deemed to be fraudulent
The social media response to twice-weekly mass asymptomatic testing in England
Authors: Dennis Amelia , Robin Charlotte , Carter Holly
Published: August 2021

Background

From 9th April 2021, everyone in England has been encouraged to take two COVID-19 tests per week. This is the first time that national mass asymptomatic testing has been introduced in the UK and the effectiveness of the policy depends on uptake with testing and willingness to self-isolate following a positive test result. This paper examines attitudes towards twice-weekly testing, as well as barriers and facilitators to engaging in testing.

Methods

Between 5th April and 28th May 2021 we searched Twitter, Facebook, and online news articles with publicly available comment sections to identify comments relating to twice-weekly testing. We identified 5783 comments which were then analysed using a framework analysis.

Results

We identified nine main themes. Five themes related to barriers to engaging in testing: low perceived risk from COVID-19; mistrust in the government; concern about taking a test; perceived ineffectiveness of twice-weekly testing policy; and perceived negative impact of twice-weekly testing policy. Four themes related to facilitators to engaging in testing: wanting to protect others; positive perceptions of tests; a desire to return to normal; and perceived efficacy for reducing asymptomatic transmission.

Conclusions

Overall, the comments identified indicated predominately negative attitudes towards the twice weekly testing policy. Several recommendations can be made to improve engagement with twice weekly testing, including: 1) communicate openly and honestly about the purpose of testing; 2) provide information about the accuracy of tests; 3) provide financial support for those required to self-isolate, and; 4) emphasise accessibility of testing.
Seroresponse to SARS-CoV-2 vaccines among maintenance dialysis patients
Authors: Hsu Caroline M. , Weiner Daniel E. , Aweh Gideon N. , Manley Harold J. , Ladik Vladimir , Frament Jill , Miskulin Dana , Agyropoulos Christos , Abreo Kenneth , Chin Andrew , Gladish Reginald , Salman Loay , Johnson Doug , Lacson Eduardo K.
Published: August 2021

Importance

Vaccines against SARS-CoV-2 are highly effective in the general population; however, their efficacy may be diminished in maintenance dialysis patients, a population particularly vulnerable to COVID-19 infection and morbidity.

Objective

We assessed vaccine response in a national sample of maintenance dialysis patients and identified predictors of response.

Design

Retrospective cohort study

Setting

130 Dialysis Clinic, Inc (DCI) facilities

Participants

Maintenance dialysis patients without known prior COVID-19 or a positive baseline antibody titer

Exposure(s)

Vaccine type and clinical characteristics

Main Outcome(s)

Using a semi-quantitative assay for antibodies against SARS-CoV-2 spike antigen, vaccine response was defined as at least one titer ≥1 U/L between 14 and 74 days after completion of a SARS-CoV-2 vaccine series. Regression analysis was used to identify characteristics associated with response.

Results

Among 1528 patients, 437 received BNT162b2/Pfizer vaccine, 766 received mRNA-1273/Moderna, and 325 received Ad26.COV2.S/Janssen. Serologic response differed significantly by vaccine type: 381/437 (87%) among BNT162b2/Pfizer recipients, 736/766 (96%) among mRNA-1273/Moderna recipients, and 119/325 (37%) among Ad26.COV2.S/Janssen recipients. Vaccine type, older age, immune-modulating medication, history of transplantation, and lower serum albumin were associated with vaccine non-response.

Conclusions and Relevance

Serologic response to mRNA vaccines is robust among maintenance dialysis patients. Future research should evaluate durability of this response, correlation between seroresponse and protection from COVID-19, and the role of the AD26.COV2.S/Janssen vaccine in this vulnerable population.
Assessment of inter-laboratory differences in SARS-CoV-2 consensus genome assemblies between public health laboratories in Australia
Authors: Foster Charles S.P. , Stelzer-Braid Sacha , Deveson Ira W. , Bull Rowena A. , Yeang Malinna , Phan-Au Jane , Silva Mariana Ruiz , van Hal Sebastiaan J. , Rockett Rebecca J. , Sintchenko Vitali , Kim Ki Wook , Rawlinson William D.
Published: August 2021

Whole-genome sequencing of viral isolates is critical for informing transmission patterns and ongoing evolution of pathogens, especially during a pandemic. However, when genomes have low variability in the early stages of a pandemic, the impact of technical and/or sequencing errors increases. We quantitatively assessed inter-laboratory differences in consensus genome assemblies of 72 matched SARS-CoV-2-positive specimens sequenced at different laboratories in Sydney, Australia. Raw sequence data were assembled using two different bioinformatics pipelines in parallel, and resulting consensus genomes were compared to detect laboratory-specific differences. Matched genome sequences were predominantly concordant, with a median pairwise identity of 99.997%. Identified differences were predominantly driven by ambiguous site content. Ignoring these produced differences in only 2.3% (5/216) of pairwise comparisons, each differing by a single nucleotide. Matched samples were assigned the same Pango lineage in 98.2% (212/216) of pairwise comparisons, and were mostly assigned to the same phylogenetic clade. However, epidemiological inference based only on single nucleotide variant distances may lead to significant differences in the number of defined clusters if variant allele frequency thresholds for consensus genome generation differ between laboratories. These results underscore the need for a unified, best-practices approach to bioinformatics between laboratories working on a common outbreak problem.
Using routine emergency department data for syndromic surveillance of acute respiratory illness in Germany, week 10-2017 to 10-2021
Authors: Boender T. Sonia , Cai Wei , Schranz Madlen , Kocher Theresa , Wagner Birte , Ullrich Alexander , Buda Silke , Zöllner Rebecca , Greiner Felix , Diercke Michaela , Grabenhenrich Linus
Published: August 2021

Background

The Coronavirus disease 2019 (COVID-19) pandemic expanded the need for timely information on acute respiratory illness on the population level.

Aim

We explored the potential of routine emergency department data for syndromic surveillance of acute respiratory illness in Germany.

Methods

We included routine attendance data from emergency departments who continuously transferred data between week 10-2017 and 10-2021, with ICD-10 codes available for >75% of the attendances. Case definitions for acute respiratory illness (ARI), severe ARI (SARI), influenza-like illness (ILI), respiratory syncytial virus disease (RSV) and COVID-19 were based on a combination of ICD-10 codes, and/or chief complaints, sometimes combined with information on hospitalisation and age.

Results

We included 1,372,958 attendances from eight emergency departments. The number of attendances dropped in March 2020, increased during summer, and declined again during the resurge of COVID-19 cases in autumn and winter of 2020/2021. A pattern of seasonality of acute respiratory infections could be observed. By using different case definitions (i.e. for ARI, SARI, ILI, RSV) both the annual influenza seasons in the years 2017-2020 and the dynamics of the COVID-19 pandemic in 2020-2021 were apparent. The absence of the 2020/2021 flu season was visible, parallel to the resurge of COVID-19 cases. The percentage SARI among ARI cases peaked in April-May 2020 (17%) and November 2020-January 2021 (14%).

Conclusion

Syndromic surveillance using routine emergency department data has the potential to monitor the trends, timing, duration, magnitude and severity of illness caused by respiratory viruses, including both influenza and SARS-CoV-2.
Bias as a source of inconsistency in ivermectin trials for COVID-19: A systematic review
Authors: Izcovich Ariel , Peiris Sasha , Ragusa Martín , Tortosa Fernando , Rada Gabriel , Aldighieri Sylvain , Reveiz Ludovic
Published: August 2021

Background and purpose

The objective of this systematic review is to summarize the effects of ivermectin for the prevention and treatment of patients with COVID-19 and to assess inconsistencies in results from individual studies with focus on risk of bias due to methodological limitations.

Evidence review

We searched the L.OVE platform through July 6, 2021 and included randomized trials (RCTs) comparing ivermectin to standard or other active treatments. We conducted random-effects pairwise meta-analysis, assessed the certainty of evidence using the GRADE approach and performed sensitivity analysis excluding trials with risk of bias.

Results

We included 29 RCTs which enrolled 5592 cases. Overall, the certainty of the evidence was very low to low. Compared to standard of care, ivermectin may reduce mortality, may increase symptom resolution or improvement, may increase viral clearance, may reduce infections in exposed individuals and may decrease hospitalizations (Risk difference (RD) 21 fewer per 1000, 95%CI: 35 fewer to 4 more). However, after excluding trials classified as “high risk” or “some concerns” in the risk of bias assessment, most estimates of effect changed substantially: Compared to standard of care, low certainty evidence suggests that ivermectin may not significantly reduce mortality (RD 7 fewer per 1000, 95%CI: 77 fewer to 108 more) nor mechanical ventilation (RD 6 more per 1000, 95%CI: 43 fewer to 86 more), and moderate certainty evidence shows that it probably does not significantly increase symptom resolution or improvement (RD 14 more per 1000, 95%CI: 29 fewer to 71 more) nor viral clearance (RD 12 fewer per 1000, 95%CI: 84 fewer to 76 more). It is uncertain if ivermectin increases or decreases severe adverse events and symptomatic infections in exposed individuals.

Conclusions and Relevance

Ivermectin may not improve clinically important outcomes in patients with COVID-19 and its effects as a prophylactic intervention in exposed individuals are uncertain. Previous reports concluding significant benefits associated with ivermectin are based on potentially biased results reported by studies with substantial methodological limitations. Further research is needed.
Feasibility of Continuous Distal Body Temperature for Passive, Early Pregnancy Detection
Authors: Grant Azure , Smarr Benjamin
Published: August 2021

The majority of American women become aware of pregnancy ~3-7 weeks after conception, and all must seek testing to confirm their pregnant status. The delay between conception and awareness is often a time in which contraindicated behaviors take place. However, there is long standing evidence that passive, early pregnancy detection may be possible using body temperature. To address this possibility, we analyzed 30 individuals’ continuous distal body temperature (DBT) in the 180 days surrounding self-reported conception in comparison to self-reported pregnancy confirmation. Features of DBT nightly maxima changed rapidly following self-reported conception, reaching uniquely elevated values after a median of 5.5 ± 3.5 days, whereas individuals reported a positive pregnancy test result at a median of 14.5 ± 4.2 days. Together, we were able to generate a retrospective, hypothetical alert a median of 9 ± 3.9 days prior to the date at which individuals received a positive pregnancy test. Continuous temperature-derived features can provide early, passive indication of pregnancy onset. We propose these features for testing and refinement in clinical settings, and for exploration in large, diverse cohorts. The development of pregnancy detection using DBT may reduce the delay from conception to awareness and increase the agency of pregnant individuals.
Linking Free Text Documentation of Functioning and Disability to the ICF with Natural Language Processing
Authors: Newman-Griffis Denis , Maldonado Jonathan Camacho , Ho Pei-Shu , Sacco Maryanne , Silva Rafael Jimenez , Porcino Julia , Chan Leighton
Published: August 2021

Background

Invaluable information on patient functioning and the complex interactions that define it is recorded in free text portions of the Electronic Health Record (EHR). Leveraging this information to improve clinical decision-making and conduct research requires natural language processing (NLP) technologies to identify and organize the information recorded in clinical documentation.

Methods

We used NLP methods to analyze information about patient functioning recorded in two collections of clinical documents pertaining to claims for federal disability benefits from the U.S. Social Security Administration (SSA). We grounded our analysis in the International Classification of Functioning, Disability and Health (ICF), and used the ICF’s Activities and Participation domain to classify information about functioning in three key areas: Mobility, Self-Care, and Domestic Life. After annotating functional status information in our datasets through expert clinical review, we trained machine learning-based NLP models to automatically assign ICF categories to mentions of functional activity.

Results

We found that rich and diverse information on patient functioning was documented in the free text records. Annotation of 289 documents for Mobility information yielded 2,455 mentions of Mobility activities and 3,176 specific actions corresponding to 13 ICF-based categories. Annotation of 329 documents for Self-Care and Domestic Life information yielded 3,990 activity mentions and 4,665 specific actions corresponding to 16 ICF-based categories. NLP systems for automated ICF coding achieved over 80% macro-averaged F-measure on both datasets, indicating strong performance across all ICF categories used.

Conclusions

NLP can help to navigate the tradeoff between flexible and expressive clinical documentation of functioning and standardizable data for comparability and learning. The ICF has practical limitations for classifying functional status information in clinical documentation, but presents a valuable framework for organizing the information recorded in health records about patient functioning. This study advances the development of robust, ICF-based NLP technologies to analyze information on patient functioning, and has significant implications for NLP-powered analysis of functional status information in disability benefits management, clinical care, and research.
StainedGlass: Interactive visualization of massive tandem repeat structures with identity heatmaps
Authors: Vollger Mitchell R. , Kerpedjiev Peter , Phillippy Adam M. , Eichler Evan E.
Published: August 2021

Visualization and analysis of genomic repeats is typically accomplished through the use of dot plots; however, the emergence of telomere-to-telomere assemblies with multi-megabase repeats requires new visualization strategies. Here, we introduce StainedGlass which can generate publication quality figures and interactive visualizations that depict the identity and orientation of multi-megabase repeat structures at a genome-wide scale. The tool can rapidly reveal higher-order structures and improve the inference of evolutionary history for some of the most complex regions of genomes.

Availability and implementation

StainedGlass is implemented using Snakemake and is available open source under the MIT license athttps://mrvollger.github.io/StainedGlass/.

Contact

mvollger@uw.edu
Using Natural Language Processing to Classify Serious Illness Communication with Oncology Patients
Authors: Davoudi Anahita , Tissot Hegler , Doucette Abigail , Gabriel Peter E. , Parikh Ravi , Mowery Danielle L. , Miranda Stephen
Published: August 2021

One core measure of healthcare quality set forth by the Institute of Medicine is whether care decisions match patient goals. High-quality “serious illness communication” about patient goals and prognosis is required to support patient-centered decision-making, however current methods are not sensitive enough to measure the quality of this communication or determine whether care delivered matches patient priorities. Natural language processing (NLP) offers an efficient method for identification and evaluation of documented serious illness communication, which could serve as the basis for future quality metrics in oncology and other forms of serious illness. In this study, we trained NLP algorithms to identify and characterize serious illness communication with oncology patients.
Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
Authors: Shamier Marc C. , Tostmann Alma , Bogers Susanne , de Wilde Janet , IJpelaar Jeroen , van der Kleij Willemijn A. , de Jager Herbert , Haagmans Bart L. , Molenkamp Richard , Oude Munnink Bas. B. , van Rossum Carsten , Rahamat-Langendoen Janette , van der Geest Nannet , Bleeker-Rovers Chantal P. , Wertheim Heiman , Koopmans Marion P.G. , GeurtsvanKessel Corine H.
Published: August 2021

Background

SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur.

Methods

We analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture.

Results

The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness.

Conclusions

We conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.