bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and human milk: SARS-CoV-2, antibodies, and neutralizing capacity
Authors: Pace Ryan M. , Williams Janet E. , Järvinen Kirsi M. , Belfort Mandy B. , Pace Christina D.W. , Lackey Kimberly A. , Gogel Alexandra C. , Nguyen-Contant Phuong , Kanagaiah Preshetha , Fitzgerald Theresa , Ferri Rita , Young Bridget , Rosen-Carole Casey , Diaz Nichole , Meehan Courtney L. , Caffe Beatrice , Sangster Mark Y. , Topham David , McGuire Mark A. , Seppo Antti , McGuire Michelle K.
Published: September 2020

Background

It is not known whether SARS-CoV-2 can be transmitted from mother to infant during breastfeeding, and if so whether the benefits of breastfeeding outweigh this risk. This study was designed to evaluate 1) if SARS-CoV-2 RNA can be detected in milk and on the breast of infected women, 2) concentrations of milk-borne anti-SARS-CoV-2 antibodies, and 3) the capacity of milk to neutralize SARS-CoV-2 infectivity.

Methods

We collected 37 milk samples and 70 breast swabs (before and after breast washing) from 18 women recently diagnosed with COVID-19. Samples were analyzed for SARS-CoV-2 RNA using RT-qPCR. Milk was also analyzed for IgA and IgG specific for the nucleocapsid protein, receptor binding domain (RBD), S2 subunit of the spike protein of SARS-CoV-2, as well as 2 seasonal coronaviruses using ELISA; and for its ability to neutralize SARS-CoV-2.

Results

We did not detect SARS-CoV-2 RNA in any milk sample. In contrast, SARS-CoV-2 RNA was detected on several breast swabs, although only one was considered conclusive. All milk contained SARS-CoV-2-specific IgA and IgG, and levels of anti-RBD IgA correlated with SARS-CoV-2 neutralization. Strong correlations between levels of IgA and IgG to SARS-CoV-2 and seasonal coronaviruses were noted.

Conclusions

Our data do not support maternal-to-child transmission of SARS-CoV-2 via milk; however, risk of transmission via breast skin should be further evaluated. Importantly, milk produced by infected mothers is a source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness.
SARS-CoV-2 antibody signatures robustly predict diverse antiviral functions relevant for convalescent plasma therapy
Authors: Natarajan Harini , Crowley Andrew R. , Butler Savannah E. , Xu Shiwei , Weiner Joshua A. , Bloch Evan M. , Littlefield Kirsten , Wieland-Alter Wendy , Connor Ruth I. , Wright Peter F. , Benner Sarah E. , Bonny Tania S. , Laeyendecker Oliver , Sullivan David , Shoham Shmuel , Quinn Thomas C. , Larman H. Benjamin , Casadevall Arturo , Pekosz Andrew , Redd Andrew D. , Tobian Aaron A.R. , Ackerman Margaret E.
Published: September 2020

Convalescent plasma has emerged as a promising COVID-19 treatment. However, the humoral factors that contribute to efficacy are poorly understood. This study functionally and phenotypically profiled plasma from eligible convalescent donors. In addition to viral neutralization, convalescent plasma contained antibodies capable of mediating such Fc-dependent functions as complement activation, phagocytosis and antibody-dependent cellular cytotoxicity against SARS-CoV-2. These activities expand the antiviral functions associated with convalescent plasma and together with neutralization efficacy, could be accurately and robustly from antibody phenotypes. These results suggest that high-throughput profiling could be used to screen donors and plasma may provide benefits beyond neutralization.
Multifractal behavior of SARS-CoV2 COVID-19 pandemic spread, case of: Algeria, Russia, USA and Italy
Authors: Ouadfeul Sid-Ali
Published: September 2020

Here, the multifractal behavior SARS-CoV2 COVID-19 pandemic daily and death cases is investigated through the so-called Wavelet Transform Modulus Maxima lines (WTMM) method, data of daily and death cases available via the World Health Organization (WHO) database of Algeria, Russia, USA and Italy is analyzed. The obtained results show the multifractal behavior of the COVID-19 pandemic spread data with different spectra of singularities.
Ranking the relative importance of COVID-19 immunisation strategies: a survey of expert stakeholders in Canada
Authors: Zhao Linlu , Ismail Shainoor J. , Tunis Matthew C.
Published: September 2020

Background

In the face of anticipated limited COVID-19 vaccine supply necessitating the vaccination of certain groups earlier than others, the assessment of values and preferences of stakeholders is an important component of an ethically sound vaccine prioritisation framework.

Objective

To establish a preliminary expert stakeholder perspective on the relative importance of pandemic immunisation strategies for different COVID-19 pandemic scenarios at the time of initial COVID-19 vaccine availability.

Methods

A survey was conducted by an email process from July 22 to August 14, 2020. Stakeholders included clinical and public health expert groups, provincial and territorial committees and national Indigenous groups, patient and community advocacy representatives and experts, health professional associations, and federal government departments in Canada. Survey results were analysed using descriptive statistics.

Results

Of 156 stakeholders contacted, 74 surveys were completed for a participation rate of 47.4%. During an anticipated period of initial vaccine scarcity for all pandemic scenarios, stakeholders generally considered the most important immunisation strategy to be protecting those who are most vulnerable to severe illness and death from COVID-19. This was followed in importance by the strategies to protect healthcare capacity, and to minimise transmission of COVID-19. In this supply constrained context, an immunisation strategy to protect critical infrastructure was considered the least important.

Conclusion

The findings of this study provide a timely, preliminary Canadian expert perspective on priority COVID-19 pandemic immunisation strategies to guide early public health planning for an eventual COVID-19 immunisation program. These results fill a gap in the literature and could help advisory groups around the world in their assessment of values and preferences for ethical guidelines for COVID-19 vaccine allocation.
A self-assembled protein nanoparticle serving as a one-shot vaccine carrier
Authors: Wong Ten-Tsao , Liou Gunn-Guang , Kan Ming-Chung
Published: September 2020

In this paper, we are exploring the role of an amphipathic helical peptide in mediating the self-assembly of a fusion protein into a protein nanoparticle and the application of the nanoparticle as a one-shot vaccine carrier. Out of several candidates, an amphipathic helical peptide derived from M2 protein of type A influenza virus is found to stimulate high antigenicity when fused to a fluorescent protein genetically. This fusion protein was found to form protein nanoparticle spontaneously when expressed and purified protein stimulates long-lasting antibody responses in single immunization. Through modeling peptide structure and nanoparticle assembly, we have improved this vaccine carrier in complex stability. The revised vaccine carrier is able to stimulate constant antibody titer to a heterologous antigen for at least six months in single immunization. The immune response against a heterologous antigen can be boosted further by additional immunization in spite of high immune responses to carrier protein.
Sexually dimorphic influence of the circadian clock geneBmal1in the striatum on alcohol intake
Authors: de Zavalia Nuria , Schoettner Konrad , Goldsmith Jory A. , Solis Pavel , Ferraro Sarah , Parent Gabrielle , Amir Shimon
Published: September 2020

The geneBmal1(brain and muscle Arnt-like 1) plays an obligatory role in the generation of circadian rhythms in the suprachiasmatic nucleus (SCN), the master circadian clock in mammals [1–5]. Notably,Bmal1is widely expressed in mammalian brain [6], and perturbations inBmal1expression in select forebrain regions cause behavioral disturbances that are independent of the SCN, such as disturbances in sleep architecture, and in cognitive and affective behaviors [1, 7–15]. Interestingly, gene association studies in humans and in animals suggest thatBmal1may influence the propensity to consume alcohol, and that polymorphisms inBmal1may confer risk for alcohol dependence and related disorders [16–20]. However, research has not yet provided evidence of a causal role ofBmal1in the control of alcohol intake. We investigated voluntary alcohol consumption in conditional knockout mice that lackBmal1exclusively in the striatum, which is an important structure in the control of alcohol intake and preference [21–26]. Experiments were carried out in both male and female mice in order to account for the known sex differences in alcohol consumption [27–31] and in striatal functioning [32–36], as well as in the expression of clock genes and in the impact of circadian clocks on behavior [37–44]. We found that, in both males and females, selective deletion ofBmal1from principal medium spiny neurons (MSNs) of the striatum significantly altered voluntary alcohol intake and preference. Strikingly, the effect ofBmal1deletion was sexually dimorphic. Whereas in males, deletion ofBmal1augmented alcohol intake and preference, in females, the same deletion suppressed alcohol intake and preference. Interestingly, striatal deletion of the clock genePer2,which interacts withBmal1in the generation of circadian rhythms [4], and which has been shown to affect alcohol consumption in male mice [45], mimicked the effect ofBmal1deletion, albeit only in males. These results show thatBmal1in MSNs of the striatum exerts a sexually dimorphic influence on alcohol intake in mice, moderating intake in males, possibly viaPer2,and promoting heightened intake in females, independently ofPer2. We propose that a sexually dimorphic mechanism in the function ofBmal1in the striatum contributes to sex differences in the propensity to consume alcohol in mice. Whether such mechanism contributes to sex differences in other striatum-dependent appetitive and consummatory behaviors remains to be investigated.
Subcortical Atlas of the Rhesus Macaque (SARM) for Magnetic Resonance Imaging
Authors: Hartig Renée , Glen Daniel , Jung Benjamin , Logothetis Nikos K. , Paxinos George , Garza-Villarreal Eduardo A. , Messinger Adam , Evrard Henry C.
Published: September 2020

Digitized neuroanatomical atlases are crucial for localizing brain structures and analyzing functional networks identified by magnetic resonance imaging (MRI). To aid in MRI data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. The structural scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (RMBSC4; Paxinos et al., in preparation). The SARM features six parcellation levels, arranged hierarchically from fine regions-of-interest (ROIs) to broader composite regions, suited for fMRI studies. As a test, we ran a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques and found significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MR data processing software, such as AFNI, where the atlas can be embedded into the software alongside cortical macaque atlases.

Highlights

We present the Subcortical Atlas of the Rhesus Macaque (SARM).

SARM provides a neuroanatomical reference frame for neuroimaging analysis.

The entire subcortex is mapped, including the thalamus, basal ganglia, and brainstem.

ROIs are grouped hierarchically, making SARM useful at multiple spatial resolutions.

SARM is in the NMT v2 template space and complements the CHARM atlas for the cortex.
Genome-wide analysis of retinal transcriptome reveals common genetic network underlying perception of contrast and optical defocus detection
Authors: Tkatchenko Tatiana V. , Tkatchenko Andrei V.
Published: September 2020

Refractive eye development is regulated by optical defocus in a process of emmetropization. Excessive exposure to negative optical defocus often leads to the development of myopia. However, it is still largely unknown how optical defocus is detected by the retina. Here, we used genome-wide RNA-sequencing (RNA-seq) to conduct analysis of the retinal genetic networks underlying contrast perception and refractive eye development. We report that the genetic network subserving contrast perception plays an important role in optical defocus detection and emmetropization. Our results demonstrate an interaction between contrast perception, the retinal circadian clock pathway and the signaling pathway underlying optical defocus detection. We also observe that the relative majority of genes causing human myopia are involved in the processing of optical defocus. Together, our results support the hypothesis that optical defocus is perceived by the retina using contrast as a proxy and provide new insights into molecular signaling underlying refractive eye development.
Data-driven multiplexed microtomography of endogenous subcellular dynamics
Authors: Jo YoungJu , Cho Hyungjoo , Park Wei Sun , Kim Geon , Ryu Donghun , Kim Young Seo , Lee Moosung , Joo Hosung , Jo HangHun , Lee Sumin , Min Hyun-seok , Heo Won Do , Park YongKeun
Published: September 2020

Simultaneous imaging of various facets of intact biological systems across multiple spatiotemporal scales would be an invaluable tool in biomedicine. However, conventional imaging modalities have stark tradeoffs precluding the fulfilment of all functional requirements. Here we propose the refractive index (RI), an intrinsic quantity governing light-matter interaction, as a means for such measurement. We show that major endogenous subcellular structures, which are conventionally accessed via exogenous fluorescence labeling, are encoded in 3D RI tomograms. We decode this information in a data-driven manner, thereby achieving multiplexed microtomography. This approach inherits the advantages of both high-specificity fluorescence imaging and label-free RI imaging. The performance, reliability, and scalability of this technology have been extensively characterized, and its application within single-cell profiling at unprecedented scales has been demonstrated.
Quantitative Molecular Imaging of Breast Microcalcification Composition using Photon-Counting Spectral Computed Tomography
Authors: Curtis Tyler E. , Roeder Ryan K.
Published: September 2020

Mammographic screening for breast cancer is unable to distinguish molecular differences between hydroxyapatite (HA) microcalcifications (μcals) that are associated with malignancy and calcium oxalate (CaOx) μcals that are benign. Therefore, the objective of this study was to investigate quantitative material decomposition of model breast μcals of clinically-relevant composition and size using spectral photon-counting computed tomography (PCCT). Model μcals composed of HA, CaOx, and dicalcium phosphate (DCP) were treated as materials containing spatially coincident elemental compositions of calcium (Ca), phosphorus (P), and oxygen (O). Elemental decomposition was performed using constrained maximum-likelihood estimation in the image domain. Images were acquired with a commercial, preclinical PCCT system (MARS Bioimaging) with five energy bins selected to maximize counts at low photon energies and spectral differences between Ca and P. Elemental concentrations of Ca and P within the each μcal composition were accurately identified and quantified with a root-mean-squared error < 12%. HA and CaOx μcals, < 1 mm is size, were accurately discriminated by the measured P content with an area under the receiver operating characteristic curve (AUC) > 0.9. The mole fraction of P, P/(Ca+P), was able to discriminate all three μcal compositions with AUC > 0.8 for μcals < 1 mm is size and AUC = 1 for μcals > 2 mm in size. The overall accuracy for the classification of μcal types and quantification of P was robust against different assumptions in the elemental decomposition calibration, but quantification of Ca was improved with assumptions that most accurately accounted for the molar volume of each element within μcal compositions. Thus, PCCT enabled quantitative molecular imaging of breast μcal composition, which is not possible with current clinical molecular imaging modalities.
Non-additive biotic interactions improve predictions of tropical tree growth and impact community size structure
Authors: Lai Hao Ran , Chong Kwek Yan , Yee Alex Thiam Koon , Mayfield Margaret M. , Stouffer Daniel B.
Published: September 2020

Growth in individual size or biomass is a key demographic component in population models, with wide-ranging applications from quantifying species performance across abiotic or biotic conditions to assessing landscape-level dynamics under global change. In forest ecology, the responses of tree growth to biotic interactions are widely held to be crucial for understanding forest diversity, function, and structure. To date, most studies on plant–plant interactions only examine the additive competitive or facilitative interactions between species pairs; however, there is increasing evidence of non-additive, higher-order interactions (HOIs) impacting species demographic rates. When HOIs are present, the dynamics of a multi-species community cannot be fully understood or accurately predicted solely from pairwise outcomes because of how additional species ‘interfere’ with the direct, pairwise interactions. Such HOIs should be particularly prevalent where species show nonlinear functional responses to resource availability and resource-acquisition traits themselves are density dependent. With this in mind, we used data from a tropical secondary forest—a system that fulfills both of these conditions—to build a ontogenetic diameter-growth model for individuals across ten woody-plant species. We allowed both direct and indirect interactions within communities to influence the species-specific growth parameters in a generalized Lotka–Volterra model. Specifically, indirect interactions entered the model as higher-order quadratic terms, i.e. non-additive effects of conspecific and heterospecific neighbour size on the focal individual’s growth. For the whole community and for four out of ten focal species, the model that included HOIs had more statistical support than the model that included only direct interactions, despite the former containing a far greater number of parameters. HOIs had comparable effect sizes to direct interactions, and tended to further reduce the diameter growth rates of most species beyond what direct interactions had already reduced. In a simulation of successional stand dynamics, the inclusion of HOIs lead to rank swaps in species’ diameter hierarchies, even when community-level size distributions remained qualitatively similar. Our study highlights the implications, and discusses possible mechanisms, of non-additive density dependence in highly diverse and light-competitive tropical forests.
Single-cell immune landscape of human recurrent spontaneous abortion
Authors: Wang Feiyang , Jia Wentong , Fan Mengjie , Li Zhilang , Liu Yongjie , Ma Yeling , Shao Xuan , Li Yu-xia , Li Rong , Tu Qiang , Wang Yan-Ling
Published: September 2020

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent spontaneous abortion (RSA). However, an in-depth understanding of the disorders from the aspect of systematic and decidual immune environment in RSA remains largely lacking. In this study, we utilized single-cell RNA-sequencing to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and RSA pregnancies at the early stage of gestation. Integrative analysis identified 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RSA cases was revealed. Specifically, the cytotoxic properties of CD8T effector, NK, and MAIT cells in peripheral blood indicated apparently enhanced immune inflammatory status, and the subpopulation proportions and ligand-receptor interactions of the decidual leukocyte subsets demonstrated preferential immune activation in RSA patients. The molecular features, spatial distribution and the developmental trajectories of five decidual NK (dNK) subsets were illustrated. The proportion of a dNK subset responsible for fetal protection was reduced, while the ratio of another dNK subset with cytotoxic and immune-active signature was significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subpopulation was substantially accumulated in RSA decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy, which provides an in-depth insight into the immune pathogenesis for early pregnancy loss.
Disparities in COVID-19 Related Mortality in U.S. Prisons and the General Population
Authors: Nowotny Kathryn M. , Cloud David , Wurcel Alysse G. , Brinkley-Rubinstein Lauren
Published: September 2020

We provide an analysis of COVID-19 mortality data to assess the potential magnitude of COVID-19 among prison residents. Data were pooled from Covid Prison Project and multiple publicly available national and state level sources. Data analyses consisted of standard epidemiologic and demographic estimates. A single case study was included to generate a more in-depth and multi-faceted understanding of COVID-19 mortality in prisons. The increase in crude COVID-19 mortality rates for the prison population has outpaced the rates for the general population. People in prison experienced a significantly higher mortality burden compared to the general population (standardized mortality ratio (SMR) = 2.75; 95% confidence interval = 2.54, 2.96). For a handful of states (n = 5), these disparities were more extreme, with SMRs ranging from 5.55 to 10.56. Four states reported COVID-19 related death counts that are more than 50% of expected deaths from all-causes in a calendar year. The case study suggested there was also variation in mortality among units within prison systems, with geriatric facilities potentially at highest risk. Understanding the dynamic trends in COVID-19 mortality in prisons as they move in and out of “hotspot” status is critical.
The “Great Lockdown”: Inactive Workers and Mortality by Covid-19
Authors: Borri Nicola , Drago Francesco , Santantonio Chiara , Sobbrio Francesco
Published: September 2020

In response to the Covid-19 outbreak the Italian Government imposed an economic lockdown on March 22, 2020 and ordered the closing of all non-essential economic activities. This paper estimates the causal effects of this measure on mortality by Covid-19 and on mobility patterns. The identification of the causal effects exploits the variation in the active population across municipalities induced by the economic lockdown. The difference-in-differences empirical design compares outcomes in municipalities above and below the median variation in the share of active population before and after the lockdown within a province, also controlling for municipality-specific dynamics, daily-shocks at the provincial level and municipal unobserved characteristics. Our results show that the intensity of the economic lockdown is associated with a statistically significant reduction in mortality by Covid-19 and, in particular, for age groups between 40-64 and older (with larger and more significant effects for individuals above 50). Back of the envelope calculations indicate that 4,793 deaths were avoided, in the 26 days between April 5 to April 30, in the 3,518 municipalities which experienced a more intense lockdown. Several robustness checks corroborate our empirical findings.
The impact of the SARS-CoV-2 pandemic on healthcare provision in Italy to non-COVID patients: a systematic review
Authors: Gianmarco Lugli , Maria Ottaviani Matteo , Annarita Botta , Guido Ascione , Alessandro Bruschi , Federico Cagnazzo , Lorenzo Zammarchi , Paola Romagnani , Tommaso Portaluri
Published: September 2020

Background

Italy has been one of the countries most affected by the SARS-CoV-2 pandemic and the regional healthcare system has had to quickly adapt its organization to meet the needs of infected patients. This has led to a drastic change in the routine management of non-communicable diseases with a potential long-term impact on patient health care. We investigated the management of non-COVID-19 patients across all medical specialties during the pandemic in Italy.

Methods

A PRISMA guideline-based systematic review of the available literature was performed using PubMed, Embase, and Scopus, restricting the search to the main outbreak period in Italy (from 20 February to 25 June, 2020). We selected articles in English or Italian that detailed changes in the Italian hospital care for non-COVID-19 patients due to the pandemic. Our keywords included all medical specialties in combination with our geographical focus (Italy) and COVID-19.

Findings

Of the 4643 potentially eligible studies identified by the search, 247 studies were included in the systematic review. A decrease in the management of emergencies in non-COVID patients was found together with an increase in mortality. Similarly, non-deferrable conditions met a tendency toward decreased diagnosis. All specialties have been affected by the reorganization of healthcare provision in the hub-and-spoke system and have benefited from telemedicine during the pandemic.

Interpretation

Our work highlights the changes taking place in the Italian public healthcare system in order to tackle the developing health crisis due to the COVID-19 pandemic. The findings of our review may be useful to analyze future directions for the healthcare system in the case of new pandemic scenarios.
Anaemia Types and Severity in Patients aged 1 to 14 years at the Children’s Hospital of the University Teaching Hospitals in Zambia
Authors: Nkhoma Panji , Loti Patrick , Sinkala Musalula , Mantina Hamakwa , Mwaba Florence , Kafita Doris , Mwenechanya Oliver , Munsaka Sody
Published: September 2020

Anaemia is a condition in which either the number of red blood cells or their oxygen-carrying capacity is insufficient to meet physiologic needs, which vary by age, sex, altitude, smoking and pregnancy status. The global estimate of childhood anaemia indicates that 293.1 million children are anaemic, and 28.5% of these children reside in sub-Sahara Africa. Also, anaemia is a significant public health problem with a high age-standardised death rate of 11.18 per 100,000 in Zambia.

We conducted a cross-sectional study involving 392 anaemic children aged one year to 14 years. The study was conducted at the Children Hospital, University Teaching Hospitals, which is a third-level referral Hospital in Lusaka, Zambia. The aim was to determine the most common type of anaemia, it’s severity, and the most affected age groups among children aged 1–14 years.

Out of 392 participants, 219 (56%) were female. Maximum haemoglobin recorded was 10.9g/dl, a minimum of 2.0 g/dl, a mean of 7.8g/dl and a standard deviation of 1.86g/dl. 200 (51%) participants had severe anaemia, and 192 (49%) had moderate anaemia with none having mild anaemia. Microcytic hypochromic anaemia was the commonest (60%), followed by normochromic normocytic anaemia (26%) and the least was macrocytic anaemia in 14% of the participants. An analysis of variance (ANOVA) showed that the difference in mean haemoglobin concentration between age groups was not significant, F (7.94) = 0.83, p > 0.57. A Chi-squared test was used to determine the relationship between anaemia types (microcytic, hypochromic) and age groups. The interaction was not significant (Chi-Square (1) = 1.28, p-value = 0.73. Microcytic hypochromic anaemia was the most prevalent and all age groups were equally affected. We recommend the country’s National Food and Nutrition Commission to revisit the Zambian National Strategy and Plan of Action for the Prevention and Control of Vitamin A Deficiency and Anaemia of 1999 to 2004 and implement the measures stated in the strategic plan.
High-risk exposure without personal protective equipment and infection with SARS-CoV-2 in healthcare workers: results of the CoV-CONTACT prospective cohort
Authors: Tubiana Sarah , Burdet Charles , Houhou Nadhira , Thy Michael , Manchon Pauline , Blanquart François , Charpentier Charlotte , Guedj Jérémie , Alavoine Loubna , Behillil Sylvie , Leclercq Anne , Lucet Jean-Christophe , Yazdanpanah Yazdan , Attia Mikaël , Demeret Caroline , Rose Thierry , Bielicki Julia Anna , Bruijning-Verhagen Patricia , Goossens Herman , Descamps Diane , van der Werf Sylvie , Lina Bruno , Duval Xavier
Published: September 2020

Objective

We aimed to estimate the risk of infection in Healthcare workers (HCWs) following a high-risk exposure without personal protective equipment (PPE).

Methods

We conducted a prospective cohort in HCWs who had a high-risk exposure to SARS-CoV-2-infected subject without PPE. Daily symptoms were self-reported for 30 days, nasopharyngeal swabs for SARS-CoV-2 RT-PCR were performed at inclusion and at days 3, 5, 7 and 12, SARS-CoV-2 serology was assessed at inclusion and at day 30. Confirmed infection was defined by positive RT-PCR or seroconversion, and possible infection by one general and one specific symptom for two consecutive days.

Results

Between February 5thand May 30th, 2020, 154 HCWs were enrolled within 14 days following one high-risk exposure to either a hospital patient (70/154; 46.1%) and/or a colleague (95/154; 62.5%). At day 30, 25.0% had a confirmed infection (37/148; 95%CI, 18.4%; 32.9%), and 43.9% (65/148; 95%CI, 35.9%; 52.3%) had a confirmed or possible infection. Factors independently associated with confirmed or possible SARS-CoV-2 infection were being a pharmacist or administrative assistant rather than being from medical staff (adjusted OR (aOR)=3.8, CI95%=1.3;11.2, p=0.01), and exposure to a SARS-CoV-2-infected patient rather than exposure to a SARS-CoV-2-infected colleague (aOR=2.6, CI95%=1.2;5.9, p=0.02). Among the 26 HCWs with a SARS-CoV-2-positive nasopharyngeal swab, 7 (26.9%) had no symptom at the time of the RT-PCR positivity.

Conclusions

The proportion of HCWs with confirmed or possible SARS-CoV-2 infection was high. There were less occurrences of high-risk exposure with patients than with colleagues, but those were associated with an increased risk of infection.
Seroprevalence of Antibodies to SARS-CoV-2 in US Blood Donors
Authors: Vassallo Ralph R. , Bravo Marjorie D. , Dumont Larry J. , Hazegh Kelsey , Kamel Hany
Published: September 2020

Background

To identify blood donors eligible to donate Coronavirus Disease-2019 (COVID-19) Convalescent Plasma (CCP), a large blood center began testing for antibodies to SARS-CoV-2, the etiologic agent of COVID-19. We report the seroprevalence of total immunoglobulin directed against the S1 spike protein of SARS-CoV-2 in US blood donors.

Methods

Unique non-CCP donor sera from June 1–July 31, 2020 were tested with the Ortho VITROS Anti-SARS-CoV-2 total immunoglobulin assay (positive: signal-to-cutoff (S/C) ≥1). Donor age, sex, race/ethnicity, ABO/RhD, education, and experience were compared to June and July 2019. Multivariate regressions were conducted to identify demographics associated with the presence of antibodies and with S/C values.

Results

Unique donors (n=252,882) showed an overall seroprevalence of 1.83% in June (1.37%) and July (2.26%), with the highest prevalence in northern New Jersey (7.3%). In a subset of donors with demographic information (n=189,565), higher odds of antibody reactivity were associated with non-Hispanic Native American/Alaskan (NH-NAA/A) and Black (NH-B), and Hispanic (H) race/ethnicity, age 18-64, middle school or lesser education, blood Group A, and never or non-recent donor status. In positive donors (n=2,831), antibody signal was associated with male sex, race/ethnicity (NH-NAA/A, NH-B and H) and geographic location.

Conclusions

Seroprevalence remains low in US blood donors but varies significantly by region. Temporal trends in reactivity may be used to gauge the effectiveness of public health measures. Before generalizing these data from healthy donors to the general population however, rates must be corrected for false positive test results among low prevalence test subjects and adjusted to match the wider demography.
Intervention strategies for cystinuria: A systematic review
Authors: Bhatt Nirmal P. , Deshpande Aniruddh V. , Jones-Freeman Bernadette , Jiang Simon H. , Starkey Malcolm R.
Published: September 2020

Purpose

This systematic review evaluates the current intervention strategies for cystinuria and assesses their quality and efficacy in order to determine the need to identify new and improved strategies for treatment.

Materials and Methods

A literature search for interventions in cystinuria was conducted on key electronic databases for studies published between 1996 and 2019. Quality was assessed using Methodological Index for Non-Randomized Studies (MINORS). Studies meeting the inclusion criteria were assessed for study design, patient characteristics and outcomes of interventions, including urinary cystine levels, stone-free rate and stone recurrence rate. A qualitative and critical analysis was performed.

Results

Common treatment strategies for cystinuria include hydration and diuresis, alkali therapy and thiol-based therapeutics. Conservative therapies such as adequate hydration and urinary alkalization effectively increased urinary pH, decreased urinary cystine levels and the formation of cystine stones. Second line agents reported included thiols such as Tiopronin, D-penicillamine and captopril. Non-invasive surgical procedures were found to reduce operative trauma and preserved renal function. Combined treatment approaches with hydration and thiols after surgical procedures were associated with less stones and reduced stone recurrence rates. Patient compliance to interventions was often poor and contributed to recurrent cystine stones.

Conclusions

Despite existing pharmacological intervention strategies, cystinuria patients frequently require surgical procedures. A more detailed understanding of the mechanisms of pathogenesis of cystinuria as well as an evaluation of patients on an individual basis may be beneficial in reducing the severity of cystinuria, by reducing stone recurrence and associated renal complications.
Factors associated with the spatial heterogeneity of COVID-19 in France: a nationwide ecological study
Authors: Gaudart J , Landier J , Huiart L , Legendre E , Lehot L , Bendiane MK , Chiche L , Petitjean A , Mosnier E , Kirakoya-Samadoulougou F , Demongeot J , Piarroux R , Rebaudet S
Published: September 2020

Like in many countries and regions, spread of the COVID-19 pandemic has exhibited important spatial heterogeneity across France, one of the most affected countries so far.

To better understand factors associated with incidence, mortality and lethality heterogeneity across the 96 administrative departments of metropolitan France, we thus conducted a geo-epidemiological analysis based on publicly available data, using hierarchical ascendant classification (HAC) on principal component analysis (PCA) of multidimensional variables, and multivariate analyses with generalized additive models (GAM).

Our results confirm a marked spatial heterogeneity of in-hospital COVID-19 incidence and mortality, following the North East – South West diffusion of the epidemic. The delay elapsed between the first COVID-19 associated death and the onset of the national lockdown on March 17th, 2020, appeared positively associated with in-hospital incidence, mortality and lethality. Mortality was also strongly associated with incidence. Mortality and lethality rates were significantly higher in departments with older population, but they were not significantly associated with the number of intensive-care beds available in 2018. We did not find any significant association between incidence, mortality or lethality rates and incidence of new chloroquine and hydroxychloroquine dispensations in pharmacies either, nor between COVID-19 incidence and climate, nor between economic indicators and in-hospital COVID-19 incidence or mortality.

This ecological study highlights the impact of population age structure, epidemic spread and transmission mitigation policies in COVID-19 morbidity or mortality heterogeneity.
Impact of obesity on gastroenterological diseases: a protocol for umbrella review of systematic review and meta-analysis
Authors: Kim Min Seo , Lee Inhyeok , Kwon Yeongkeun , Park Sungsoo
Published: September 2020

The global prevalence of overweight and obesity among both men and women has risen as the global mean BMI has increased[1, 2]. As digestive diseases were known to have a close relation to metabolic and mechanical changes in obesity cohorts[3], several previous meta-analyses reported the association between obesity and gastroenterological diseases including cancers[4-9] and benign diseases[10-15] of the digestive system. Although some of the reported association between obesity and gastroenterological diseases might be causal, considerable heterogeneity, confounders, and bias could be included in the studies. We aim to conduct an umbrella review to evaluate the validity and strength of existing evidence for the impact of obesity on the risk and outcomes of gastroenterological (GI) diseases.
RPA-Based Method For The Detection Of SARS-COV2
Authors: Nassir Angus A. , Baptiste Mazarati Jean , Mwikarago Ivan , Habimana Majidi R. , Ndinkabandi Janvier , Murangwa Anthere , Nyatanyi Thierry , Muvunyi Claude Mambo , Nsanzimana Sabin , Leon Mutesa , Musanabaganwa Clarisse
Published: September 2020

Background

Coronavirus disease 2019 (COVID-19) is a highly infectious disease with significant mortality, morbidity, and far-reaching economic and social disruptions. Testing is key in the fight against COVID-19 disease. The gold standard for COVID-19 testing is the reverse transcription polymerase chain reaction (RT-PCR) test. RT-PCR requires highly specialized, expensive, and advanced bulky equipment that is difficult to use in the field or in a point of care setting. There is need for a simpler, inexpensive, convenient, portable and accurate test. Our aims were to: (i) design primer-probe pairs for use in isothermal amplification of the S1, ORF3 and ORF8 regions of the SARS-CoV2 virus; (ii) optimize the recombinase polymerase amplification (RPA) assay for the isothermal amplification of the named SARS-COV2 regions; (iii) detect amplification products on a lateral flow device. and (ii) perform a pilot field validation of RPA on RNA extracted from nasopharyngeal swabs.

Results

Assay validation was done at the National Reference Lab (NRL) at the Rwanda Biomedical Center (RBC) in Rwanda. Results were compared to an established, WHO-approved rRT-PCR laboratory protocol. The assay provides a faster and cheaper alternative to rRT-PCR with 100% sensitivity, 93% specificity, and positive and negative predictive agreements of 100% and 93% respectively.

Conclusion

To the best of our knowledge, this is the first in-field and comparative laboratory validation of RPA for COVID-19 disease in low resource settings. Further standardization will be required for deployment of the RPA assay in field settings.
Epidemiology of SARS-CoV-2 infection in Karnataka State, South India: Transmission dynamics of symptomatic vs. asymptomatic infections
Authors: Kumar Narendra , Hameed Shafeeq K Shahul , Babu Girdhara R , Venkataswamy Manjunatha M , Dinesh Prameela , Kumar Prakash BG , John Daisy A. , Desai Anita , Ravi Vasanthapuram
Published: September 2020

Background

In this report, we describe the epidemiology of SARS-CoV-2 infection, specifically examining how the symptomatic persons drove the transmission in the state of Karnataka, India, during the lockdown phase.

Methods

The study included all the cases reported from March 8 to May 31, 2020 in the state. Any person with history of international or domestic travel from high burden states, those presenting with Influenza-like or Severe Acute Respiratory Illness and high-risk contacts of COVID19 cases, who were SARS-CoV-2 RT-PCR positive were included. Detailed analysis based on contact tracing data available from line-list of the state surveillance unit was performed using cluster analysis software package.

Findings

Amongst the 3404 COVID-19 positive cases, 3096 (91%) were asymptomatic while 308 (9%) were symptomatic. Majority of the asymptomatic cases were in the age range of 16-50 years while symptomatic cases were between 31-65 years. Most of those affected were males. Cluster analysis of 822 cases indicated that the secondary attack rate, size of the cluster (dispersion) and occurrence of overt clinical illness is significantly higher when the index case in a cluster was symptomatic compared to an asymptomatic.

Interpretation

Our findings indicate that both asymptomatic and symptomatic SARS-CoV-2 cases transmit the infection; however, the main driving force behind the spread of infection within the state was significantly higher from symptomatic cases. This has major implications for policies related to testing. Active search for symptomatic cases, subjecting them to testing and treatment should be prioritized for containing the spread of COVID-19.

Funding

Intermediate Fellowship, Wellcome Trust-DBT India Alliance to Giridhara R Babu, Grant number: IA/CPHI/14/1/501499.
The impact of vital signs on the death of patients with new coronavirus pneumonia: A systematic review and meta-analysis
Authors: Du Meixia , Zhao Jie , Yin Xiaochun , Zhang Nadi , Zheng Guisen
Published: September 2020

Background

Assessing the impact of vital signs (blood pressure, body temperature, heart rate, respiratory rate, and oxygen saturation) on the death of patients with new coronavirus pneumonia would provide a simple and convenient method for the monitoring of subsequent illness, and therefore, in some degree reduce treatment costs and increase the cure rate clinically.

Methods

Six databases were retrieved. The software R 3.6.2 was used for meta-analysis of the included literature.

Results

12 studies were included, which comprise 8996 patients affected with COVID-19 infection. The meta-analysis study found that blood pressure (MAP, SBP and DBP), heart rate, respiration rate and SpO2 are the risk factors for disease progression in patients with COVID-19. Among them, the increase in MAP and the decrease in SpO2 have the greatest impact on the death of patients with COVID-19 [MAP: MD = 5.66, 95% CI (0.34, 10.98), SpO2: MD = −5.87, 95% CI (−9.17, −2.57), P = 0.0005]. However, comparing the body temperature of the death group and the survival group found that the body temperature was not statistically significant between the two groups [body temperature: MD = 0.21, 95% CI (−0.01, 0.43), P = 0.0661].

Conclusion

The increase in MAP, heart rate and respiratory rate, as well as the decrease in SBP, DBP and SpO2 are all independent risk factors for death in patients with COVID-19. These factors are simple and easy to monitor, and individualized treatment can be given to patients in time, reducing the mortality rate and improving treatment efficiency.
Anterior Knee Pain Risk Differs Between Male and Female Military Tactical Athletes
Authors: Glaviano Neal R. , Boling Michelle C. , Fraser John J.
Published: September 2020

Background

Anterior knee pain (AKP) is commonly diagnosed in military members and is a threat to operational readiness. AKP includes a range of conditions, with localized pain around the patella being a frequent location of pain and disability. Mechanical overuse is one suggested etiology for many of these conditions, suggesting occupational demands in the military may influence AKP frequency amongst the service members. Previous research suggests females are at a greater risk for AKP, however, it is unknown how occupation affects AKP risk.

Study Design

Epidemiological cohort.

Level of Evidence

Level 2.

Methods

The Defense Medical Epidemiology Database was queried for the number of individuals with ICD-9 diagnosis codes on their initial encounter from 2006 to 2015. Diagnoses were categorized into anterior or retropatellar pain, patellar instability, knee tendinopathy, as well the sum of the three groups which was defined as AKP. Relative risk (RR) and chi-square statistics were calculated in the assessment of sex and occupational category. Regressions were calculated to determine association between service branch, sex, and AKP across time.

Results

From 2006-2018, a total of 151, 263 enlisted and 14,335 officer services members were diagnosed with AKP. The incidence rate was 13.2 in enlisted members and 6.2 in in officers. Females were significantly at greater risk of developing AKP compared to males within both the enlisted (relative risk=1.32) and officer (relative risk=2.01) service members. Differences in risk were also noted across military occupation for both enlisted and officer service members, p<.05.

Conclusion

Sex and military occupation were salient factors for AKP risk. Evaluation of training requirements and developing interventions programs across military occupation could serve as a focus for future research aiming to decrease the incidence of chronic knee pain.
Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants
Authors: Pang Juanita , Slyker Jennifer A. , Roy Sunando , Bryant Josephine , Atkinson Claire , Cudini Juliana , Farquhar Carey , Griffiths Paul , Kiarie James , Morfopoulou Sofia , Roxby Alison C. , Tutil Helena , Williams Rachel , Gantt Soren , Goldstein Richard A. , Breuer Judith
Published: September 2020

Cytomegalovirus (CMV) is the most congenital infection (cCMVi), and is particularly common among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly-developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers, and identify the possibility of congenitally-transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally-infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally-transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue-tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.