bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer Disease Clinical Trials Targeting Amyloid
Authors: Reiss Allison B. , Montufar Natalie , DeLeon Joshua , Pinkhasov Aaron , Gomolin Irving H. , Glass Amy D. , Arain Hirra A. , Stecker Mark M.
Published: March 2021

Background:

The goal of slowing or halting the development of Alzheimer disease (AD) has resulted in the huge allocation of resources by academic institutions and pharmaceutical companies to the development of new treatments. The etiology of AD is elusive, but the aggregation of amyloid-β and tau peptide and oxidative processes are considered critical pathologic mechanisms. The failure of drugs with multiple mechanisms to meet efficacy outcomes has caused several companies to decide not to pursue further AD studies and has left the field essentially where it has been for the past 15 years. Efforts are underway to develop biomarkers for detection and monitoring of AD using genetic, imaging, and biochemical technology, but this is of minimal use if no intervention can be offered.

Review Summary:

In this review, we consider the natural progression of AD and how it continues despite present attempts to modify the amyloid-related machinery to alter the disease trajectory. We describe the mechanisms and approaches to AD treatment targeting amyloid, including both passive and active immunotherapy as well as inhibitors of enzymes in the amyloidogenic pathway.

Conclusion:

Lessons learned from clinical trials of amyloid reduction strategies may prove crucial for the leap forward toward novel therapeutic targets to treat AD.
Creutzfeldt-Jakob Disease May Present Early With Unusual Bulbar Predominance
Authors: Ghannam Malik , Patel Roshni , Nichols Kent , Smith Andrew , Robertson Jetter , Berry Brent M.
Published: March 2021

Introduction:

Creutzfeldt-Jakob disease (CJD) is a prion protein disorder of significant consequence and currently incurable. Diagnosis can be challenging early in the disease course. CJD can present in many ways but often fits a pattern of cognitive problems, cerebellar disturbance, behavioral/psychological changes, and perhaps myoclonus.

Case Report:

We herein present the case of a 69-year-old White male with subacute progressive bulbar and limb weakness over ten weeks period. Early on, he was diagnosed with amyotrophic lateral sclerosis versus autoimmune-related bulbar neuropathy and treated as such. However, he continued to deteriorate clinically that prompted another admission, upon readmission, his cerebrospinal fluid RTQuick and 14-3-3 from the National Prion Disease Pathology Surveillance Center (NPDPSC) did eventually return positive. Hence he was diagnosed with CJD.

Conclusions:

CJD may present with progressive bulbar symptoms similar to acute inflammatory demyelinating polyradiculoneuropathy (MF variant), motor neuron disease, or autoimmune brainstem encephalitis. It becomes even higher on the differentials especially with no response to immunotherapy.
Recurrent Syncope Caused by a Dural Arteriovenous Fistula
Authors: Sheinberg Dallas L. , Luther Evan , Chen Stephanie , McCarthy David , Starke Robert M.
Published: March 2021

Background:

Dural arteriovenous fistulas (DAVFs) are pathologic vascular connections that shunt dural arterial flow directly to dural venous drainage. Only a few isolated case reports describe syncope on presentation. We report the first case of DAVF causing recurrent, progressive syncope in an otherwise asymptomatic patient.

Case Report:

A female in her late 20s presented with a 9-year history of syncopal episodes and was found to have a DAVF. Syncopal episodes were exacerbated by positional changes, strenuous activity and emotional stressors. Symptoms occurred upon wakening and lasted for 2 to 3 hours before she was able to regain functionality. Physical examination revealed no abnormalities. Magnetic resonance imaging of the brain showed no irregularities. Magnetic resonance angiography revealed abnormal serpiginous structures in the left jugular foramen which communicated with the ascending pharyngeal branch of the left external carotid artery. Cerebral angiogram disclosed a left jugular bulb DAVF supplied by the left ascending pharyngeal and left occipital arteries. The DAVF was successfully managed by progressive endovascular embolization with coils and Onyx 34. On clinical follow-up evaluation, the patient had no further episodes of dizziness or syncope.

Conclusion:

We present an atypical case of DAVF in a patient presenting with recurrent syncope. Only 4 cases of DAVF causing syncope have been reported, all in combination with other neurological symptoms. In comparison, we report a unique case of DAVF presenting solely with recurrent syncope, a previously undocumented finding in the literature. Our case adds to other reports of nonspecific DAVF presentations and highlights the importance of considering this etiology.
Identifying global favourable habitat for early juvenile loggerhead sea turtles
Authors: Harrison Cheryl S. , Luo Jessica Y. , Putman Nathan F. , Li Qingfeng , Sheevam Pooja , Krumhardt Kristen , Stevens Jessica , Long Matthew C.
Published: March 2021

Loggerhead sea turtles (
Caretta caretta
) nest globally on sandy beaches, with hatchlings dispersing into the open ocean. Where these juveniles go and what habitat they rely on remains a critical research question for informing conservation priorities. Here a high-resolution Earth system model is used to determine the biophysical geography of favourable ocean habitat for loggerhead sea turtles globally during their first year of life on the basis of ocean current transport, thermal constraints and food availability (defined here as the summed lower trophic level carbon biomass). Dispersal is simulated from eight major nesting sites distributed across the globe in four representative years using particle tracking. Dispersal densities are identified for all turtles, and for the top 15% ‘best-fed’ turtles that have not encountered metabolically unfavourable temperatures. We find that, globally, rookeries are positioned to disperse to regions where the lower trophic biomass is greatest within loggerheads' thermal range. Six out of the eight nesting sites are associated with strong coastal boundary currents that rapidly transport hatchlings to subtropical–subpolar gyre boundaries; narrow spatial migratory corridors exist for ‘best-fed’ turtles associated with these sites. Two other rookeries are located in exceptionally high-biomass tropical regions fuelled by natural iron fertilization. ‘Best-fed’ turtles tend to be associated with lower temperatures, highlighting the inverse relationship between temperature and lower trophic biomass. The annual mean isotherms between 20°C and the thermal tolerance of juvenile loggerheads are a rough proxy for favourable habitat for loggerheads from rookeries associated with boundary currents. Our results can be used to constrain regions for conservation efforts for each subpopulation, and better identify foraging habitat for this critical early life stage.
Limosilactobacillus urinaemulieris sp. nov. and Limosilactobacillus portuensis sp. nov. isolated from urine of healthy women
Authors: Ksiezarek Magdalena , Ribeiro Teresa Gonçalves , Rocha Joana , Grosso Filipa , Perovic Svetlana Ugarcina , Peixe Luisa
Published: March 2021

Two Gram-stain-positive strains, c9Ua_26_MTand c11Ua_112_MT, were isolated from voided urine samples from two healthy women. Comparative 16S rRNA gene sequences demonstrated that these novel strains were members of the genusLimosilactobacillus. Phylogenetic analysis based onpheSgene sequences and core genomes showed that each strain formed a separated branch and are closest toLimosilactobacillus vaginalisDSM 5837T. The average nucleotide identity (ANI) and Genome-to-Genome Distance Calculator (GGDC) values between c9Ua_26_MTand the closest relative DSM 5837Twere 90.7 and 42.9 %, respectively. The ANI and GGDC values between c11Ua_112_MTand the closest relative DSM 5837Twere 91.2 and 45.0 %, and those among the strains were 92.9% and 51,0 %, respectively. The major fatty acids were C12 : 0(40.2 %), C16 : 0(26.7 %) and C18 : 1ω9c(17.7 %) for strain c9Ua_26_MT, and C18 : 1ω9c(38.0 %), C16 : 0(33.3 %) and C12 : 0(17.6 %) for strain c11Ua_112_MT. The genomic DNA G+C content of strains c9Ua_26_MTand c11Ua_112_MTwas 39.9 and 39.7 mol%, respectively. On the basis of the data presented here, strains c9Ua_26_MTand c11Ua_112_MTrepresent two novel species of the genusLimosilactobacillus, for which the namesLimosilactobacillus urinaemulierissp. nov. (c9Ua_26_MT=CECT 30144T=LMG 31899T) andLimosilactobacillus portuensissp. nov. (c11Ua_112_MT=CECT 30145T=LMG 31898T) are proposed.
A novel 5E training model and other methods implemented for rapid readiness at an ad-hoc COVID-19 facility in India
Authors: Singh Suhail , Singh Anchit Raj , Pathak Basant , Tilak TVSVGK , Kumar Aparajita , Bhatia IPS , Hasvi Jayraj
Published: March 2021

Background

A ad-hoc dedicated COVID-19 hospital was setup in New Delhi, India over a span of 12 days. At this time, new teaching modalities were employed to train the staff. This study aims to identify and quantify the effectiveness of these teaching models in terms of learning which was evaluated using case scenarios before and after the teaching session.

Objectives

To assess education methods and models for training of healthcare workers during rapid deployment at an ad-hoc dedicated COVID-19 hospital.

Methods

The 5E (Engage, Explore, Explain, Elaborate and Evaluate) teaching modality through peer group teaching methods was utilised in the situation. Statistical analysis was done using Mann Whitney U test.

Results

A total of 86 participants (43 doctors and 43 nurses) answered the pre and post test questionnaires. The number of correct responses per question in the pre test (Mean + SD;49.0+ 18.53) vs post test (Mean + SD;54.40+ 15.95) with stratification by the domain of learning was analysed. No significant difference was found in the pre and post test responses.

Conclusion

Further studies of this nature will contribute towards assessing efficacy of teaching modalities employed in rapid readiness for future pandemic scenarios.
Proteome profiling of Cryoglobulinemia
Authors: Liu Peng , Wu Jianqiang , Sun Dandan , Qi Zhihong , Qin Xuzhen , Su Wei
Published: March 2021

Objective

To better understand and identify candidate protein biomarkers of cryoglobulinemia (CGE) from healthy patients or benign brain disease control patients.

Methods

The tandem mass tag (TMT)-labeled quantitative proteomics approach was used to identify differential proteins in the serum proteome of 10 CGE patients and 10 disease control patients with negative cryoglobulin (CG), respectively. GO, KEGG and protein domain enrichment analysis was used for functional annotation of differential proteins. The biomarker candidates were validated by the parallel reaction monitoring (PRM) method in 20 samples (10 CGE patients, 5 healthy control patients, and 5 disease control patients).

Results

A total of 1004 proteins were quantitatively identified. Among these, 62 proteins were upregulated, and 56 proteins were downregulated. 25 candidate biomarkers were validated by PRM. 5 upregulated proteins of A2M, MMP2, VCAM1, MCAM, and PCSK9, and 4 downregulated proteins of C3, IGHG2, PROZ, PPBP were consistent with TMT results. Upregulated proteins mostly related with cholesterol metabolism, while downregulated proteins were associated with immune regulation.

Conclusion

This study is the first proteomic study of cryoglobulinemia in China These findings might contribute to the application of proteomics for detecting and monitoring CGE. And our findings indicated cholesterol metabolism accelerates the development of CGE.
High-intensity exercise is a risk factor for renal medullary carcinoma in individuals with sickle cell trait
Authors: Shapiro Daniel D. , Soeung Melinda , Perelli Luigi , Dondossola Eleonora , Surasi Devaki Shilpa , Tripathi Durga N. , Bertocchio Jean-Philippe , Xia Ruohan , Starbuck Michael W. , Van Alstine Michael L. , Rao Priya , Katz Matthew H. G. , Parker Nathan H. , Shah Amishi Y. , Carugo Alessandro , Heffernan Timothy P. , Schadler Keri L. , Logothetis Christopher , Walker Cheryl L. , Wood Christopher G. , Karam Jose A. , Draetta Giulio F. , Tannir Nizar M. , Genovese Giannicola , Msaouel Pavlos
Published: March 2021

Renal medullary carcinoma (RMC) predominantly occurs in individuals with sickle cell trait (SCT). We found that patients with RMC more frequently participated in high-intensity exercise than matched controls, and renal medullary hypoxia significantly increased predominantly in the right kidney of mice with SCT following high-but not moderate-intensity exercise, consistent with the distinct predilection of RMC toward the right kidney. These results establish high-intensity exercise as a risk factor for RMC in individuals with SCT.
Characterizing an epidemiological geography of the United States: influenza as a case study
Authors: Rosensteel Grant E. , Lee Elizabeth C. , Colizza Vittoria , Bansal Shweta
Published: March 2021

The prediction, prevention, and management of infectious diseases in the United States is either geographically homogeneous or is coordinated through ad-hoc administrative regions, ignoring the intense spatio-temporal heterogeneity displayed by most outbreaks. Using influenza as a case study, we characterize a regionalization of the United States. Based on influenza time series constructed from fine-scale insurance claims data from 2002-2009, we apply a complex network approach to characterize regions of the U.S. which experience comparable influenza dynamics. Our results identify three to five epidemiologically distinct regions for each flu season, with all locations within each region experiencing synchronous epidemics, and with an average of a two week delay in peak timing between regions. We find that there is significant heterogeneity across seasons in the identity of the regions and the relative timing across regions, making predictability from one season to the next challenging. Within a given season, however, our approach shows the potential to inform on the shaping of regions over time, to improve resources mobilization and targeted communication. Our epidemiologically-driven regionalization approach could allow for disease monitoring and control based on epidemiological risk rather than geopolitical boundaries, and provides a tractable public health approach to account for vast heterogeneity that exists in respiratory disease dynamics.
Impact of a new SARS-CoV-2 variant on the population: A mathematical modeling approach
Authors: Gonzalez-Parra Gilberto , Martínez-Rodríguez David , Villanueva-Micó Rafael-J.
Published: March 2021

Several SARS-CoV-2 variants have emerged around the world and the appearance of other variants depends on many factors. These new variants might have different characteristics that can affect the transmissibility and death rate. The administration of vaccines against the coronavirus disease 2019 (COVID-19) started in early December of 2020 and in some countries the vaccines will not soon be widely available. In this article, we study the impact of a new more transmissible SARS-CoV-2 strain on prevalence, hospitalizations, and deaths related to the SARS-CoV-2 virus. We study different scenarios regarding the transmissibility in order to provide a scientific support for public health policies and bring awareness of potential future situations related to the COVID-19 pandemic. We construct a compartmental mathematical model based on differential equations to study these different scenarios. In this way, we are able to understand how a new, more infectious strain of the virus can impact the dynamics of the COVID-19 pandemic. We study several metrics related to the possible outcomes of the COVID-19 pandemic in order to assess the impact of a higher transmissibility of a new SARS-CoV-2 strain on these metrics. We found that, even if the new variant has the same death rate, its high transmissibility can increase the number of infected people, those hospitalized, and deaths. The simulation results show that health institutions need to focus on increasing non-pharmaceutical interventions and the pace of vaccine inoculation since a new variant with higher transmissibility as, for example, VOC-202012/01 of lineage B.1.1.7, may cause more devastating outcomes in the population.
Racial and ethnic differences in COVID-19 vaccine hesitancy and uptake
Authors: Nguyen Long H. , Joshi Amit D. , Drew David A. , Merino Jordi , Ma Wenjie , Lo Chun-Han , Kwon Sohee , Wang Kai , Graham Mark S. , Polidori Lorenzo , Menni Cristina , Sudre Carole H. , Anyane-Yeboa Adjoa , Astley Christina M. , Warner Erica T. , Hu Christina Y. , Selvachandran Somesh , Davies Richard , Nash Denis , Franks Paul W. , Wolf Jonathan , Ourselin Sebastien , Steves Claire J. , Spector Tim D. , Chan Andrew T.
Published: March 2021

Background

Racial and ethnic minorities have been disproportionately impacted by COVID-19. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy and limited access may result in disparities in uptake.

Methods

We performed a cohort study among U.S. and U.K. participants in the smartphone-based COVID Symptom Study (March 24, 2020-February 16, 2021). We used logistic regression to estimate odds ratios (ORs) of COVID-19 vaccine hesitancy (unsure/not willing) and receipt.

Results

In the U.S. (n=87,388), compared to White non-Hispanic participants, the multivariable ORs of vaccine hesitancy were 3.15 (95% CI: 2.86 to 3.47) for Black participants, 1.42 (1.28 to 1.58) for Hispanic participants, 1.34 (1.18 to 1.52) for Asian participants, and 2.02 (1.70 to 2.39) for participants reporting more than one race/other. In the U.K. (n=1,254,294), racial and ethnic minorities had similarly elevated hesitancy: compared to White participants, their corresponding ORs were 2.84 (95% CI: 2.69 to 2.99) for Black participants, 1.66 (1.57 to 1.76) for South Asian participants, 1.84 (1.70 to 1.98) for Middle East/East Asian participants, and 1.48 (1.39 to 1.57) for participants reporting more than one race/other. Among U.S. participants, the OR of vaccine receipt was 0.71 (0.64 to 0.79) for Black participants, a disparity that persisted among individuals who specifically endorsed a willingness to obtain a vaccine. In contrast, disparities in uptake were not observed in the U.K.

Conclusions

COVID-19 vaccine hesitancy was greater among racial and ethnic minorities, and Black participants living in the U.S. were less likely to receive a vaccine than White participants. Lower uptake among Black participants in the U.S. during the initial vaccine rollout is attributable to both hesitancy and disparities in access.
COVID-19 International Border Surveillance Cohort Study at Toronto’s Pearson Airport
Authors: Goel Vivek , Bulir David , De Propetis Eric , Jamil Munaza , Rosella Laura , Mertz Dominik , Regehr Cheryl , Smieja Marek
Published: March 2021

Objectives

The primary objective was to estimate the positivity rate of air travelers coming to Toronto, Canada in September and October, 2020, at arrival, day 7 and day 14. Secondary objectives were to estimate degree of risk based on country of origin; to assess knowledge and attitudes towards COVID-19 control measures; and subjective well-being during the quarantine period.

Design

Prospective cohort of arriving international travelers.

Setting

Toronto Pearson Airport Terminal 1, Toronto, Canada.

Participants

Passengers arriving on international flights. Inclusion criteria were those aged 18 or older who had a final destination within 100 km of the airport; spoke English or French; and provided consent. Excluded were those taking a connecting flight; who had no internet access; who exhibited symptoms of COVID-19 on arrival; or who were exempted from quarantine.

Main outcome measures

Positive for SARS-CoV-2 virus on RT-PCR with self-administered nasal-oral swab, and general well-being using the WHO-5 index.

Results

Of 16,361 passengers enrolled, 248 (1·5%, 95% CI 1.3%,1.5%) tested positive. Of these, 167 (67%) were identified on arrival, 67 (27%) on day 7, and 14 (6%) on day 14. The positivity rate increased from 1% in September to 2% in October. Average well-being score declined from 19.8 (out of a maximum of 25) to 15.5 between arrival and day 7 (p<0.001).

Conclusions

A single arrival test will pick up two-thirds of individuals who will become positive, with most of the rest detected on the second test at day 7. These results support strategies identified through mathematical models that a reduced quarantine combined with testing can be as effective as a 14 day quarantine.

Article Summary

Strengths and limitations of this study

Decisions regarding border restrictions have been based on trial and error and mathematical models with limited empirical data to support such decision-making.

This study assessed the prevalence of SARS-CoV-2 in a cohort of international travellers at arrival, day 7 and 14 of quarantine.

It is limited to one airport and there is the potential from bias due to non-participation and loss to follow-up.

Self-collected nasal-oral swabs were used which facilitated participation but may have reduced sensitivity.
Predicting COVID-19 related death using the OpenSAFELY platform
Authors:   The OpenSAFELY Collaborative, Williamson Elizabeth J , Tazare John , Bhaskaran Krishnan , McDonald Helen I , Walker Alex J , Tomlinson Laurie , Wing Kevin , Bacon Sebastian , Bates Chris , Curtis Helen J , Forbes Harriet , Minassian Caroline , Morton Caroline E , Nightingale Emily , Mehrkar Amir , Evans Dave , Nicholson Brian D , Leon Dave , Inglesby Peter , MacKenna Brian , Davies Nicholas G , DeVito Nicholas J , Drysdale Henry , Cockburn Jonathan , Hulme Will , Morley Jess , Douglas Ian , Rentsch Christopher T , Mathur Rohini , Wong Angel , Schultze Anna , Croker Richard , Parry John , Hester Frank , Harper Sam , Grieve Richard , Harrison David A , Steyerberg Ewout W. , Eggo Rosalind M , Diaz-Ordaz Karla , Keogh Ruth , Evans Stephen JW , Smeeth Liam , Goldacre Ben
Published: March 2021

Objectives

To compare approaches for obtaining relative and absolute estimates of risk of 28-day COVID-19 mortality for adults in the general population of England in the context of changing levels of circulating infection.

Design

Three designs were compared. (A) case-cohort which does not explicitly account for the time-changing prevalence of COVID-19 infection, (B) 28-day landmarking, a series of sequential overlapping sub-studies incorporating time-updating proxy measures of the prevalence of infection, and (C) daily landmarking. Regression models were fitted to predict 28-day COVID-19 mortality.

Setting

Working on behalf of NHS England, we used clinical data from adult patients from all regions of England held in the TPP SystmOne electronic health record system, linked to Office for National Statistics (ONS) mortality data, using the OpenSAFELY platform.

Participants

Eligible participants were adults aged 18 or over, registered at a general practice using TPP software on 1stMarch 2020 with recorded sex, postcode and ethnicity. 11,972,947 individuals were included, and 7,999 participants experienced a COVID-19 related death. The study period lasted 100 days, ending 8thJune 2020.

Predictors

A range of demographic characteristics and comorbidities were used as potential predictors. Local infection prevalence was estimated with three proxies: modelled based on local prevalence and other key factors; rate of A&E COVID-19 related attendances; and rate of suspected COVID-19 cases in primary care.

Main outcome measures

COVID-19 related death.

Results

All models discriminated well between patients who did and did not experience COVID-19 related death, with C-statistics ranging from 0.92-0.94. Accurate estimates of absolute risk required data on local infection prevalence, with modelled estimates providing the best performance.

Conclusions

Reliable estimates of absolute risk need to incorporate changing local prevalence of infection. Simple models can provide very good discrimination and may simplify implementation of risk prediction tools in practice.
Muscle Strength Explains the Protective Effect of Physical Activity against COVID-19 Hospitalization among Adults aged 50 Years and Older
Authors: Maltagliati Silvio , Sieber Stephen , Sarrazin Philippe , Cullati Stéphane , Chalabaev Aïna , Millet Grégoire P. , Boisgontier Matthieu P. , Cheval Boris
Published: March 2021

Objectives

Physical activity has been proposed as a protective factor for COVID-19 hospitalization. However, the mechanisms underlying this association are unclear. Here, we examined the association between physical activity and COVID-19 hospitalization and whether this relationship was explained by other risk factors for severe COVID-19.

Method

We used data from adults aged 50 years and older from the Survey of Health, Ageing and Retirement in Europe. The outcome was self-reported hospitalization due to COVID-19 measured before August 2020. The main exposure was usual physical activity, self-reported between 2004 and 2017. Data were analyzed using logistic regression models.

Results

Among the 3139 participants included in the study (69.3 ± 8.5 years, 1763 women), 266 were tested positive for COVID-19 and 66 were hospitalized. Results showed that individuals who engaged in physical activity more than once a week had lower odds of COVID-19 hospitalization than individuals who hardly ever or never engaged in physical activity (odds ratios = 0.41, 95% confidence interval = 0.22–0.74, p = .004). This association between physical activity and COVID-19 hospitalization was explained by muscle strength, but not by other risk factors.

Conclusion

These findings suggest that, after 50 years of age, engaging in physical activity more than once a week is associated with lower odds of COVID-19 hospitalization. The protective effect of physical activity on COVID-19 hospitalization is explained by muscle strength.
RT-qPCR assay for detection of British (B.1.1.7) and South Africa (B.1.351) variants of SARS-CoV-2
Authors: Yaniv Karin , Ozer Eden , Plotkin Noam , Bhandarkar Nikhil Suresh , Kushmaro Ariel
Published: March 2021

Less than a year following the SARS-CoV-2 outbreak, variants of concern have emerged in the form of the British variant B.1.1.7 and the South Africa variant B.1.351. Due to their high infectivity and morbidity, it is crucial to quickly and effectively detect them. Current methods of detection are either time-consuming, expensive or indirect. Here, we report the development of a rapid, cost-effective and direct RT-qPCR method for detection of the two variants of concern. We developed and validate a detection system for the detection of the B.1.1.7 variant and another single detection set for the B.1.351 variant. The developed approach was characterized and tested on wastewater samples and illustrated that all primers and probes were sensitive and specific. The novel system presented here will allow proper response and pandemic containment with regard to these variants. In addition, it may provide a basis for developing tools for the detection of additional variants of concern.
Donor Anti-Spike Immunity is Related to Recipient Recovery and Can Predict the Efficacy of Convalescent Plasma Units
Authors: Janaka Sanath Kumar , Hartman William , Mou Huihui , Farzan Michael , Stramer Susan L. , Goodhue Erin , Weiss John , Evans David , Connor Joseph P.
Published: March 2021

Background

The novel coronavirus, SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.31 million people within the last year and yet no cure exists. Whereas passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable option, selection of optimal units for therapy and lack of clear therapeutic benefit from transfusion remain as barriers to the use of CCP.

Study design and methods

To identify plasma that is expected to benefit recipients, we measured anti-SARS-CoV2 antibody levels using clinically available serological assays and correlated with the neutralizing activity of CCP from donors. Neutralizing titer of plasma samples was measured by assaying infectivity of SARS-CoV-2 spike protein pseudotyped retrovirus particles in the presence of dilutions of plasma samples. We also used this assay to identify evidence of passive transfusion of neutralizing activity in CCP recipients.

Results

Viral neutralization and anti-spike protein antibodies in 109 samples from 87 plasma donors were highly varied but modestly correlated with each other. Recipients who died of COVID-19 were found to have been transfused with units with lower anti-spike antibody levels and neutralizing activity. Passive transfer of neutralization activity was documented in 62% of antibody naive plasma recipients.

Conclusions

Since viral neutralization is the goal of CCP transfusion, our observations not only support the use of anti-spike SARS-CoV2 serology tests to identify beneficial CCP units, but also support the therapeutic value of convalescent plasma with high titers of anti-spike antibodies.
A Multilayer Model for Early Detection of COVID-19
Authors: Shmueli Erez , Mansuri Ronen , Porcilan Matan , Amir Tamar , Yosha Lior , Yechezkel Matan , Patalon Tal , Handelman-Gotlib Sharon , Gazit Sivan , Yamin Dan
Published: March 2021

Current efforts for COVID-19 screening mainly rely on reported symptoms and potential exposure to infected individuals. Here, we developed a machine-learning model for COVID-19 detection that utilizes four layers of information: 1) sociodemographic characteristics of the tested individual, 2) spatiotemporal patterns of the disease observed near the testing episode, 3) medical condition and general health consumption of the tested individual over the past five years, and 4) information reported by the tested individual during the testing episode. We evaluated our model on 140,682 members of Maccabi Health Services, tested for COVID-19 at least once between February and October 2020. These individuals had 264,516 COVID-19 PCR-tests, out of which 16,512 were found positive. Our multilayer model obtained an area under the curve (AUC) of 81.6% when tested over all individuals, and of 72.8% when tested over individuals who did not report any symptom. Furthermore, considering only information collected before the testing episode – that is, before the individual may had the chance to report on any symptom – our model could reach a considerably high AUC of 79.5%. Namely, most of the value contributed by the testing episode can be gained by earlier information. Our ability to predict early the outcomes of COVID-19 tests is pivotal for breaking transmission chains, and can be utilized for a more efficient testing policy.
Aberrant levels of cortical myelin distinguish individuals with unipolar depression from healthy controls
Authors: Baranger David A.A. , Halchenko Yaroslav O. , Satz Skye , Ragozzino Rachel , Iyengar Satish , Swartz Holly A. , Manelis Anna
Published: March 2021

The association of unipolar depression (UD), relative to healthy controls (HC), with cortical myelin is underexplored, despite growing evidence of associations with white matter tract integrity. We characterized cortical myelin in the 360 Glasser atlas regions using the T1w/T2w ratio in 39 UD and 47 HC participants (ages=19-44, 75% female). A logistic elastic net regularized regression with nested cross-validation and a subsequent linear discriminant analysis conducted on held-out samples were used to select brain regions and classify UD vs. HC. True-label model performance was compared against permuted-label model performance. Cortical myelin distinguished UD from HC with 68% accuracy (p<0.001; sensitivity=63.8%, specificity=71.5%). Brain regions contributing to this classification performance were located in the orbitofrontal cortex, anterior cingulate, extended visual, and auditory cortices, and showed statistically significant decreases and increases in myelin levels in UD vs. HC. The patterns of cortical myelin in these regions may be a biomarker of UD.
Excess deaths reveal the true spatial, temporal, and demographic impact of COVID-19 on mortality in Ecuador
Authors: Cuéllar Leticia , Torres Irene , Romero-Severson Ethan , Mahesh Riya , Ortega Nathaniel , Pungitore Sarah , Hengartner Nicolas , Ke Ruian
Published: March 2021

Background

In early 2020, Ecuador reported one of the highest surges of per capita deaths across the globe.

Methods

We collected a comprehensive dataset containing individual death records between 2015 and 2020 from the Ecuadorian National Institute of Statistics and Census and the Ecuadorian Ministry of Government. We computed the number of excess deaths across time, geographical locations and demographic groups using Poisson regression methods.

Results

Between January 1st and September 23rd, 2020, the number of excess deaths in Ecuador is 36,402 (95% CI: 35,762-36,827) or 208 per 105 population, which is 171% of the expected deaths in that period in a typical year. Only 20% of the excess deaths are attributable to confirmed COVID-19 deaths. Strikingly, in provinces that were most affected by COVID-19, such as Guayas and Santa Elena, the all-cause deaths are more than double the expected number of deaths that would have occurred in a normal year. The extent of excess deaths in men is higher than in women, and the number of excess deaths increases with age. Indigenous populations had the highest level of excess deaths among all ethnic groups.

Conclusions

Overall, the exceptionally high level of excess deaths in Ecuador highlights the enormous burden and heterogeneous impact of COVID-19 on mortality especially in older age groups and indigenous populations in Ecuador that was not fully revealed by COVID-19 death counts. Together with the limited testing in Ecuador, our results suggest that the majority of the excess deaths were likely to be undocumented COVID-19 deaths.
Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration
Authors: Pita-Thomas Wolfgang , Gonçalves Tassia Mangetti , Zhao Guoyan , Cavalli Valeria
Published: March 2021

Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote RGC axon regeneration, we identified transcription factors (TF) and chromatin accessible sites enriched in embryonic RGCs (high axon growth capacity) compared to postnatal RGC (low axon growth capacity). Developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the differentially opened regions of the chromatin in embryonic RGCs and proteomic analysis confirmed their expression in RGC nuclei. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon growth. Consistently, overexpression of CREB fused to the VP64 transactivation domain in RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.
The localized rise of a B.1.526 SARS-CoV-2 variant containing an E484K mutation in New York State
Authors: Lasek-Nesselquist Erica , Lapierre Pascal , Schneider Erasmus , George Kirsten St. , Pata Janice
Published: March 2021

The E484K mutation in the spike protein of SARS CoV-2 contributes to immune escape from monoclonal antibodies as well as neutralizing antibodies in COVID-19 convalescent plasma. It appears in two variants of concern – B.1.351 and P.1 - but has evolved multiple times in different SARS-CoV-2 lineages, suggesting an adaptive advantage. Here we report on the emergence of a 484K variant in the B.1.526 lineage that has recently become prevalent in New York State, particularly in the New York City metropolitan area. In addition to the E484K mutation, these variants also harbor a D235G substitution in spike that might help to reduce the efficacy of neutralizing antibodies.
Long-Term SARS-CoV-2-Specific Immune and Inflammatory Responses Across a Clinically Diverse Cohort of Individuals Recovering from COVID-19
Authors: Peluso Michael J. , Deitchman Amelia N. , Torres Leonel , Iyer Nikita S. , Nixon Christopher C. , Munter Sadie E. , Donatelli Joanna , Thanh Cassandra , Takahashi Saki , Hakim Jill , Turcios Keirstinne , Janson Owen , Hoh Rebecca , Tai Viva , Hernandez Yanel , Fehrman Emily , Spinelli Matthew A. , Gandhi Monica , Trinh Lan , Wrin Terri , Petropoulos Christos J. , Aweeka Francesca T. , Rodriguez-Barraquer Isabel , Kelly J. Daniel , Martin Jeffrey N. , Deeks Steven G. , Greenhouse Bryan , Rutishauser Rachel L. , Henrich Timothy J.
Published: March 2021

A detailed understanding of long-term SARS-CoV-2-specific T cell responses and their relationship to humoral immunity and markers of inflammation in diverse groups of individuals representing the spectrum of COVID-19 illness and recovery is urgently needed. Data are also lacking as to whether and how adaptive immune and inflammatory responses differ in individuals that experience persistent symptomatic sequelae months following acute infection compared to those with complete, rapid recovery. We measured SARS-CoV-2-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally up to 9 months following infection in a diverse group of 70 individuals with PCR-confirmed SARS-CoV-2 infection. The participants had varying degrees of initial disease severity and were enrolled in the northern California Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort. Adaptive T cell responses remained remarkably stable in all participants across disease severity during the entire study interval. Whereas the magnitude of the early CD4+ T cell immune response is determined by the severity of initial infection (participants requiring hospitalization or intensive care), pre-existing lung disease was significantly associated with higher long-term SARS-CoV2-specific CD8+ T cell responses, independent of initial disease severity or age. Neutralizing antibody levels were strongly correlated with SARS-CoV-2-specific CD4+ T but not CD8+ T cell responses. Importantly, we did not identify substantial differences in long-term virus-specific T cell or antibody responses between participants with and without COVID-19-related symptoms that persist months after initial infection.
Mathematical modeling to inform vaccination strategies and testing approaches for COVID-19 in nursing homes
Authors: Kahn Rebecca , Holmdahl Inga , Reddy Sujan , Jernigan John , Mina Michael J. , Slayton Rachel B.
Published: March 2021

Background

Nursing home residents and staff were included in the first phase of COVID-19 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against SARS-CoV-2 infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for possible changes to infection prevention guidance for vaccinated populations, including testing strategies.

Methods

We use a stochastic agent-based SEIR model of a nursing home to simulate SARS-CoV-2 transmission. We model three scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario.

Results

Increasing vaccination coverage in staff decreases total symptomatic cases in each scenario. When there is low VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, but asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents through exposure to asymptomatic but infected staff. High frequency testing is needed to reduce total symptomatic cases if the vaccine has low efficacy against infection and infectiousness, or only protects against symptoms.

Conclusions

Encouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness.

The extent of efficacy of SARS-CoV-2 vaccines against infection, infectiousness, or disease, impacts strategies for vaccination and testing in nursing homes. If vaccines confer some protection against infection or infectiousness, encouraging vaccination in staff may reduce symptomatic cases in residents.
Prioritizing the first doses of SARS-CoV-2 vaccine to save the elderly: the case study of Italy
Authors: Pontrelli Giuseppe , Cimini Giulio , Roversi Marco , Gabrielli Andrea , Salina Gaetano , Bernardi Stefania , Rocchi Francesca , Simonetti Alessandra , Giaquinto Carlo , Rossi Paolo , Labini Francesco Sylos
Published: March 2021

Many countries are currently facing high mortality caused by the circulation of SARS-CoV-2 among the elderly not yet vaccinated. Vaccine shortage poses relevant challenges to health authorities, called to act in a timely manner, and with scarcity of vaccine, and data. We have developed a model for estimating the impact of vaccination on the mortality of the elderly following a schedule of mRNA SARS-CoV-2 vaccine that prioritize first dose administration, as alternative to the standard schedule of two doses administered 3 to 4 weeks apart. We studied the Italian scenario, considering it representative of other Countries facing similar conditions in terms of virus circulation, mortality, and vaccine shortage, in the period from February, 10 to April, 14 2021. Under different conditions of quantity of vaccine administration, the schedule prioritizing first doses showed always significant increase of protected individuals, and a decrease of deaths, up to 19.8% less than the standard schedule. These findings support the vaccination option of prioritizing first dose in the elderly until vaccine supplies are adequate.
Covid-19 lockdown: Ethnic differences in children’s self-reported physical activity and the importance of leaving the home environment. A longitudinal and cross-sectional study from the Born in Bradford birth cohort study
Authors: Bingham Daniel D , Daly-Smith Andy , Hall Jennifer , Seims Amanda , Dogra Sufyan A. , Fairclough Stuart J , Ajebon Mildred , Kelly Brian , Hou Bo , Shire Katy A , Crossley Kirsty L , Mon-Williams Mark , Wright John , Pickett Kate , McEachan Rosemary , Dickerson Josie , Barber Sally E
Published: March 2021

Background

In England, the onset of COVID-19 and a rapidly increasing infection rate resulted in a lockdown (March-June 2020) which placed strict restrictions on movement of the public, including children. Using data collected from children living in a multi-ethnic city with high levels of deprivation, this study aimed to: (1) report childrens self-reported physical activity (PA) during the first COVID-19 UK lockdown and identify associated factors; (2) examine changes of childrens self-reported PA prior to and during the first UK lockdown.

Methods

This study is part of the Born in Bradford (BiB) COVID-19 Research Study. PA (amended Youth Activity Profile), sleep, sedentary behaviours, daily frequency/time/destination/activity when leaving the home, were self-reported by 949 children (9-13 years). A sub-sample (n=634) also self-reported PA (Physical Activity Questionnaire for Children) pre-pandemic (2017-February 2020). Univariate analysis assessed differences in PA between sex and ethnicity groups; multivariable logistic regression identified factors associated with children’s PA. Differences in children’s levels of being sufficiently active were examined using the McNemar test examined change in PA prior to and during the lockdown, and multivariable logistic regression to identify factors explaining change.

Results

During the pandemic, White British (WB) children were more sufficiently active (34.1%) compared to Pakistani Heritage children (PH) (22.8%) or ‘Other’ ethnicity children (O) (22.8%). WB children reported leaving the home more frequently and for longer periods than PH and O children. Modifiable variables related to being sufficiently active were frequency, duration, type of activity, and destination away from the home environment. There was a large reduction in children being sufficiently active during the first COVID-19 lockdown (28.9%) compared to pre-pandemic (69.4%).

Conclusions

Promoting safe extended periods of PA everyday outdoors is important for all children, in particular for children from ethnic minority groups. Children’s PA during the first COVID-19 UK lockdown has drastically reduced from before. Policy and decision makers, and practitioners should consider the findings in order to begin to understand the impact and consequences that COVID-19 has had upon children’s PA which is a key and vital behaviour for health and development.
The Charitable Feeding System helps Food Insecure Participants maintain Fruit and Vegetable intake during COVID-19
Authors: Bertmann Farryl , Rogomentich Katherine , Belarmino Emily H. , Niles Meredith T.
Published: March 2021

Charitable food services, including food banks and pantries, support individual and households’ food access, potentially maintaining food security and diet quality during emergencies. During the COVID-19 pandemic, the use of food banks and pantries has increased in the US. Here we examine perceptions of the charitable food system and its relationship to food security and dietary quality, specifically fruit and vegetable (FV) intake during the first six months of the COVID-19 pandemic, using a statewide representative survey (n=600) of residents of Vermont. We find that demand for charitable food services increased by 68%. The utilization of food pantries was more common among food insecure households and households with children. Among food insecure respondents, those who used the charitable food system were less likely to reduce their FV intake during the pandemic than those who did not use the charitable food system. Further, we find significant interactions between food pantry use and food insecure households, suggesting that, for food, insecure households, utilizing a food pantry since the onset of the COVID-19 pandemic was associated with higher fruit consumption. These results indicate that these services may support food access and diet quality for at-risk populations during emergencies.