title: Pneumonia in patients with rheumatoid arthritis: effect of microbial airway colonization

abstract:
Rheumatoid arthritis frequently complicates airway diseases and is associated with high rates of pneumonia and mortality. The relationship between microorganisms colonizing the lower respiratory tract and the subsequent incidence of pneumonia in patients with rheumatoid arthritis is unclear. In this study, we aimed to identify microorganisms colonizing the lower respiratory tract in patients with rheumatoid arthritis related to the risk of developing subsequent pneumonia in these patients.

A retrospective cohort study was designed to include a total of 121 patients with rheumatoid arthritis (median age, 67 years; women, 78.5%) who underwent bronchoscopy at three hospitals from January 2008 to December 2017. The following information was extracted from their electronic medical records: patient characteristics, microorganisms detected by bronchoscopy, and subsequent incidences of pneumonia. The patients were divided into groups based on the microorganisms isolated from the lower respiratory tract and compared with control subjects. The cumulative incidence of pneumonia was assessed using the Kaplan-Meier method and log-rank test. Risk factors for pneumonia were analyzed using the Cox proportional-hazards analysis.

The most frequently isolated microbes from the lower respiratory tract in descending order were Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. The annual incidence rates of pneumonia per 1000 patients were 100, 62, 132, and 38, in the P. aeruginosa, S. aureus, H. influenzae, and control group, respectively. Patients colonized with P. aeruginosa had a higher frequency of macrolide use and a higher degree of bronchiectasis than patients in the control group. The rate of the subsequent incidence of pneumonia was higher in the P. aeruginosa group (P = 0.038), and P. aeruginosa was an independent risk factor for pneumonia (hazard ratio, 3.504; 95% confidence interval, 1.153-10.330).

The colonization of the lower respiratory tract by P. aeruginosa in patients with rheumatoid arthritis was associated with the subsequent incidence of pneumonia.


title: Dynamic changes in the CD163+ and CCR2+ peripheral monocytes during Parkinson's disease

abstract:
1.Alpha-synuclein pathology is associated with immune activation and neurodegeneration in Parkinsons disease. The immune activation involves not only microglia but also peripheral immune cells, such as mononuclear phagocytes found in blood and infiltrated in the brain. Understanding peripheral immune involvement is essential for developing immunomodulatory treatment. Therefore, we aimed to study circulating mononuclear phagocytes in early- and late-stage Parkinsons disease, defined by disease duration of less or more than five years, respectively, and analyze their association with clinical phenotypes. We performed a cross-sectional multi-color flow cytometry study on 78 sex-balanced individuals with sporadic Parkinsons disease, 28 controls, and longitudinal samples from seven patients and one control. Cell frequencies and surface marker expressions on natural killer cells, monocyte subtypes, and dendritic cells were compared between groups and correlated with standardized clinical scores. We found elevated frequencies and surface levels of migration-(CCR2, CD11b) and phagocytic-(CD163) markers, particularly on classical and intermediate monocytes in early Parkinsons disease. HLA-DR expression was increased in advanced stages of the disease, whereas TLR4 expression was decreased in women with Parkinsons Disease. The disease-associated immune changes on CCR2 and CD11b correlated with worse cognition. Increased TLR2 expression was related to worse motor symptoms. In conclusion, our data highlights the TLR2 relevance in the symptomatic motor presentation of the disease and a role for peripheral CD163+ and migration-competent monocytes in Parkinsons disease cognitive defects. Our study suggests that the peripheral immune system is dynamically altered in Parkinsons disease stages and directly related to both symptoms and the sex bias of the disease.

HighlightsO_LITLR2 expression increased in patients with worse motor symptoms.
C_LIO_LIIncreased CD163 and HLA-DR monocytic expression in patients with long PD duration.
C_LIO_LISexual-dimorphism for CCR2, CD11b, and TLR4 expression on PD monocytes.
C_LIO_LICCR2 and CD11b expression are associated with cognitive impairment in PD.
C_LI

category: neurology


title: Changes in CD163+ and CCR2+ peripheral monocytes relate to Parkinson's disease and cognition


title: Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson's disease and cognition


title: Can we predict antibody responses in SARS-CoV-2? A cohort analysis.

abstract:
BackgroundAfter infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.

MethodsWe recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.

Results281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR -0.3-1.7). Six participants with follow-up nAbs all had titers [≤] 1:80.

ConclusionsWhile age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.

category: infectious diseases


title: JAX-CNV: A whole genome sequencing-based algorithm for copy number detection at clinical grade level

abstract: We aimed to develop a whole genome sequencing (WGS)-based copy number variant (CNV) calling algorithm with the potential of replacing chromosomal microarray assay (CMA) for clinical diagnosis. JAX-CNV is thus developed for CNV detection from WGS. The performance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and compared to the results of clinically-validated CMAs. Comparing to 112 CNVs reported by clinically-validated CMAs of the 31 samples, JAX-CNV is 100% recalling them. Besides, JAX-CNV identified an average of 30 CNVs per individual that is an approximately seven-fold increase compared to calls of clinically-validated CMAs. Experimental validation of 24 randomly selected CNVs, showed one false positive (i.e., a false discovery rate of 4.17%). A robustness test on lower-coverage data revealed a 100% sensitivity for CNVs greater than 300 kb (the current threshold for College of American Pathologists) down to 10x coverage. For CNVs greater than 50 kb, sensitivities were 100% for coverages deeper than 20x, 97% for 15x, and 95% for 10x. We developed a WGS-based CNV pipeline, including this newly developed CNV caller JAX-CNV, and found it capable of detecting CMA reported CNVs at 100% sensitivity with about 4% false discovery rate. We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS. JAX-CNV is available on https://github.com/TheJacksonLaboratory/JAX-CNV.

category: genetic and genomic medicine


title: B.1.1.7 became the dominant variant in Lebanon.

abstract: Recently, a new variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) designated VOC 202012/01 (or B.1.1.7 lineage) has become highly prevalent in several countries, after first being described in the United Kingdom (UK). Its rate of transmission has been estimated to be increased compared to other lineages. In the present study, we show the emergence, dominance and the rapid spread of the B.1.1.7 lineage in Lebanon.


title: Machine-Learning Powered Optoacoustic Sensor for Diabetes Progression

abstract: The assessment of diabetes severity relies primarily on a count of clinical complications to empirically characterize disease. Disease staging based on clinical complications also employs a scoring system that may not be optimally suited for analysis of earlier stages of diabetes development or for monitoring smaller increments of disease progress with high precision. We propose a novel sensor, which goes beyond the abilities of current state-of-the-art approaches and introduces a new concept in the assessment of biomedical markers by means of ultra-broadband optoacoustic detection. Being insensitive to photon scattering, the new sensor can resolve optical biomarkers in fine detail and as a function of depth and relates epidermal and dermal morphological and micro-vascular density features to diabetes state. We demonstrate basic sensor characteristics in phantoms and examine the novel sensing concept presented in a pilot study using data from 86 participants (20 healthy and 66 diabetic) at an ultra-wide optoacoustic bandwidth of 120 MHz. Machine learning based on ensemble trees was developed and trained in a supervised fashion and subsequently used to examine the relation of sensor data to disease severity, in particular as it associates to diabetes without complications vs. diabetic neuropathy or atherosclerotic cardiovascular disease. We also investigated the sensor performance in relation to HbA1C values. The proposed method achieved statistically significant detection in all different patient groups. The effect of technical parameters, in particular sensor area size and the time window of optoacoustic signals used in data training were also examined in measurements from phantoms and humans. We discuss how optoacoustic sensors fundamentally solve limitations present in optical sensing and, empowered by machine learning, open a new chapter in non-invasive portable sensing for biomedical applications.

category: endocrinology


title: A feasible and more efficient SARS-Cov-2 vaccine allocation to states and counties in the USA

abstract: While discussion of vaccine allocation has centered around who should be prioritized (e.g., health care personnel and the elderly), we argue that vaccines should also be allocated to jurisdictions (e.g., counties within the USA) with the greatest immunization thresholds needed for ending the epidemic. At the current rate of vaccine distribution (March 15, 2021), universal herd immunity in the USA could be reached in roughly 4.5 months. However, distributing vaccines according to where the virus spreads more easily (dense counties with high R0 values), herd immunity would be reached simultaneously in all counties almost two months earlier and would require roughly 40% fewer vaccine doses. Furthermore, under the current distribution strategy densely populated counties would reach herd immunity last, with negative epidemiological and socio-economic consequences. In sum, it would be more fair and efficient to distribute vaccines to jurisdictions that need them most to reach herd immunity.

category: epidemiology


title: Estimating the increased transmissibility of the B.1.1.7 strain over previously circulating strains in England using fractions of GISAID sequences and the distribution of serial intervals

abstract: The B.1.1.7 strain, also referred to as Alpha variant, is a variant strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Alpha variant is considered to possess higher transmissibility compared to the strains previously circulating in England. This paper proposes a new method to estimate the selective advantage of a mutant strain over another strain using the time course of strain frequencies and the distribution of the serial interval of infections. This method allows the instantaneous reproduction numbers of infections to vary over calendar time. The proposed method also assumes that the selective advantage of a mutant strain over previously circulating strains is constant. Applying the method to SARS-CoV-2 sequence data from England, the instantaneous reproduction number of the B.1.1.7 strain was estimated to be 26.6-45.9% higher than previously circulating strains in England. This result indicates that control measures should be strengthened by 26.6-45.9% when the B.1.1.7 strain is newly introduced to a country where viruses with similar transmissibility to the preexisting strain in England are predominant.


title: Estimating the increased transmissibility of the B.1.1.7 strain over previously circulating strains in England using frequencies of GISAID sequences and the distribution of serial intervals


title: Estimating the elevated transmissibility of the B.1.1.7 strain over previously circulating strains in England using GISAID sequence frequencies


title: Causal associations between fatty acid measures and schizophrenia - a two-sample Mendelian randomization study

abstract:
ObjectiveAlthough studies suggest that erythrocyte concentrations of omega-3 and omega-6 fatty acids are lower in individuals with schizophrenia, evidence of beneficial effects of omega-3 fatty acid supplementation is limited. This study therefore aimed to determine whether omega-3 and omega-6 fatty acid levels are causally related to schizophrenia.

MethodsCausality was evaluated using the inverse variance weighted (IVW) 2-sample Mendelian randomization (MR) method using fatty acid levels and schizophrenia genome-wide association study results. Weighted median, weighted mode, and MR Egger regression methods were used as sensitivity analyses. To address the mechanism, analyses were performed using instruments within the FADS and ELOVL2 genes. Multivariable MR (MVMR) was used to estimate direct effects of omega-3 fatty acids on schizophrenia, independent of omega-6 fatty acids, lipoproteins and triglycerides.

ResultsMR analyses indicated that long-chain omega-3 and omega-6 fatty acid levels were associated with lower risk of schizophrenia (docosahexaenoic acid [DHA] ORIVW: 0.83, 95% CI: 0.75-0.92). In contrast, short-chain fatty acids were associated with an increased risk of schizophrenia (alpha-linolenic acid ORIVW: 1.07, 95% CI: 0.98-1.18). Causal effects were consistent across sensitivity and FADS single-SNP analyses. MVMR indicated that the protective effect of DHA on schizophrenia persisted after conditioning on other lipids (ORIVW: 0.84, 95% CI: 0.71-1.01).

ConclusionsResults are consistent with protective effects of long-chain omega-3 and omega-6 fatty acids on schizophrenia suggesting that people with schizophrenia may have difficulty converting short-chain to long-chain PUFAs. Long-chain PUFA supplementation or diet enrichment, particularly in higher risk individuals, might help prevent onset of disorder.

category: psychiatry and clinical psychology


title: Metagenomic sequencing of municipal wastewater provides a near-complete SARS-CoV-2 genome sequence identified as the B.1.1.7 variant of concern from a Canadian municipality concurrent with an outbreak

abstract: Laboratory-based wastewater surveillance for SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, can be conducted using RT-qPCR-based screening of municipal wastewater samples. Although it provides rapid viral detection and can inform SARS-CoV-2 abundance in wastewater, this approach lacks the resolution required for viral genotyping and does not support tracking of viral genome evolution. The recent emergence of several variants of concern, a result of mutations across the genome including the accrual of important mutations within the viral spike glycoprotein, has highlighted the need for a method capable of detecting the cohort of mutations associated with these and newly emerging genotypes. Here we provide an innovative methodology for the recovery of a near-complete SARS-CoV-2 sequence from a wastewater sample collected from across Canadian municipalities including one that experienced a significant outbreak attributable to the SARS-CoV-2 B.1.1.7 variant of concern. Our results demonstrate that a combined interrogation of genome consensus-level sequences and alternative alleles enables the identification of a SARS-CoV-2 variant of concern and the detection of a new allele within a viral accessory gene that may be representative of a recently evolved B.1.1.7 sublineage.

category: public and global health


title: Post-stroke fatigue is linked to resting state posterior hypoactivity and prefrontal hyperactivity

abstract:
Background and PurposeFatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown.

MethodsThis observational study included 63 stroke survivors (22 women; age 30-89 years; mean 67.5{+/-}13.4 years) from the Cognition And Neocortical Volume After Stroke (CANVAS) study, a cohort study examining cognition, mood, and brain volume in stroke survivors following ischaemic stroke. Participants underwent brain imaging 3 months post-stroke, including a 7-minute resting state fMRI echoplanar sequence. We calculated the fractional amplitude of low-frequency fluctuations, a measure of resting state brain activity at the whole-brain level.

ResultsForty-five participants reported experiencing post-stroke fatigue as measured by an item on the Patient Health Questionnaire-9. A generalised linear regression model analysis with age, sex, and stroke severity covariates was conducted to compare resting state brain activity in the 0.01-0.08 Hz range, as well as its subcomponents - slow-5 (0.01-0.027 Hz), and slow-4 (0.027-0.073 Hz) frequency bands between fatigued and non-fatigued participants. We found no significant associations between post-stroke fatigue and ischaemic stroke lesion location or stroke volume. However, in the overall 0.01-0.08 Hz band, participants with post-stroke fatigue demonstrated significantly lower resting-state activity in the calcarine cortex (p<0.001, cluster-corrected pFDR=0.009, k=63) and lingual gyrus (p<0.001, cluster-corrected pFDR=0.025, k=42) and significantly higher activity in the medial prefrontal cortex (p<0.001, cluster-corrected pFDR=0.03, k=45), attributed to slow-4 and slow-5 oscillations, respectively.

ConclusionsPost-stroke fatigue is associated with posterior hypoactivity and prefrontal hyperactivity, reflecting dysfunction within large-scale brain systems such as fronto-striatal-thalamic and frontal-occipital networks. These systems in turn might reflect a relationship between post-stroke fatigue and abnormalities in executive and visual functioning. This first whole-brain resting-state study provides new targets for further investigation of post-stroke fatigue beyond the lesion approach.


title: On the protective role of the blood vessels in glaucomatous damage: a transversal study.

abstract:
PurposeTo corroborate whether vessels on the surface of the optic nerve head can provide protection against the loss of underlying axons in subjects with manifest glaucoma.

MethodsIn this pilot study, thirty-six glaucomatous eyes with a perimetric defect in the Bjerrum area were included. The retinal nerve fiber layer (RNFL) thickness was measured in each of the sectors of the clock-hour map obtained by Cirrus HD-OCT considering the presence or absence of blood vessels. These sectors were related with their corresponding areas of the retina examined in the visual field using a mathematical model of the retina introduced by Jansonius, in order to determine the values of threshold sensitivity in those areas in the presence or absence of vessels.

ResultsWe corroborated the protective role of the blood vessel for peripapillary RNFL thickness of clock-hour 12 despite obtaining a p-value (p = 0.023; w = 228.5) close to the acceptance zone (p [≥] 0.05). The mean {+/-} standard deviation with vessel and without vessel were 70.95 {+/-} 24.35 and 88.46 {+/-} 23.96, respectively. No differences were found between the mean values of threshold sensitivity to the presence or absence of blood vessels in each of the sectors considered.

ConclusionsOur findings do not allow us to affirm that there is an association between the presence of a vessel and protection against glaucomatous damage in subjects with an advanced manifestation of the disease. In the future, more extensive studies are needed to study this relationship in subjects with early glaucoma.

category: ophthalmology


title: THE EFFECTIVENESS OF ACB-IP 1.0 UNIVERSAL PATHOGEN FREE CONCENTRATED COCKTAIL CONVALESCENT PLASMA IN COVID-19 INFECTION

abstract:
IntroductionThe efficacy of SARS-CoV2 standard single donor convalescent plasma varied according to the application time and most importantly the amount of antibody that is administered. Single donor plasma has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the efficacy and safety of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled convalescent plasma was investigated.

MethodsIn this study, ACB-IP 1.0 convalescent plasma product was prepared as follows; first, convalescent plasma was collected from different donors, then pathogen-inactivation was carried-out, and isohemagglutinins were cryodepleted, respectively. Finally, concentrated convalescent plasma product was pooled and stored until use.

A total of sixteen patients were treated with two different convalescent plasma products. Nine patients were treated with standard single donor convalescent plasma and seven were treated with pathogen-free, concentrated, pooled convalescent plasma (ACB-IP 1.0) between 01 March 2020 and 31 December 2020.

The outcomes of these two plasma products were compared regarding SARS-CoV2 antibody titers, neutralizing antibody activities, length of hospitalization and mortality rates.

ResultsFive out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor plasma. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor plasma (0.9642) in 1:256 dilution ({rho}=0.0087)

The mortality rate of the patients treated with ACB-IP 1.0 plasma showed statistically lower (p: 0,033) than the patients treated with single donor plasma. The administration of either single donor plasma or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization compared to administration of either plasma to the patients later than eight days ({rho}= 0,0021)

DiscussionPathogen-free, concentrated, pooled convalescent plasma may resolve the bias in SARS-CoV2 antibody titers and neutralizing antibody activities, without requiring blood group compatibility that allows patient accessibility in a shorter time and has safe plasma characteristic. This study indicates that ACB-IP 1.0 may be a superior product compared to standard single donor plasma.


title: High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study

abstract:
BackgroundThere is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e. severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen.

ResultsSimulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0{+/-}0.3 cmH2O at baseline to 33.8{+/-}0.4 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2{+/-}0.5 cmH2O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7{+/-}0.1 cmH2O at baseline to 17.9{+/-}0.3 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2{+/-}0.3 cmH2O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29{+/-}0.006 at baseline to 0.65{+/-}0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6{+/-}0.1 J/min at baseline to 12.9{+/-}0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9{+/-}0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7{+/-}0.2 cmH2O at baseline to 19.6{+/-}0.2 at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9{+/-}0.3 cmH2O at 10 ml/kg/30 breaths/min.

ConclusionsOur results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.

category: intensive care and critical care medicine


title: Knowledge barriers in the symptomatic-COVID-19 testing programme in the UK: an observational study

abstract:
BackgroundSymptomatic testing programmes are crucial to the COVID-19 pandemic response. We sought to examine United Kingdom (UK) testing rates amongst individuals with test-qualifying symptoms, and factors associated with not testing.

MethodsWe analysed a cohort of untested symptomatic app users (N=1,237), nested in the Zoe COVID Symptom Study (Zoe, N= 4,394,948); and symptomatic survey respondents who wanted, but did not have a test (N=1,956), drawn from the University of Maryland-Facebook Covid-19 Symptom Survey (UMD-Facebook, N=775,746).

FindingsThe proportion tested among individuals with incident test-qualifying symptoms rose from [~]20% to [~]75% from April to December 2020 in Zoe. Testing was lower with one vs more symptoms (73.0% vs 85.0%), or short vs long symptom duration (72.6% vs 87.8%). 40.4% of survey respondents did not identify all three test-qualifying symptoms. Symptom identification decreased for every decade older (OR=0.908 [95% CI 0.883-0.933]). Amongst symptomatic UMD-Facebook respondents who wanted but did not have a test, not knowing where to go was the most cited factor (32.4%); this increased for each decade older (OR=1.207 [1.129-1.292]) and for every 4-years fewer in education (OR=0.685 [0.599-0.783]).

InterpretationDespite current UK messaging on COVID-19 testing, there is a knowledge gap about when and where to test, and this may be contributing to the [~]25% testing gap. Risk factors, including older age and less education, highlight potential opportunities to tailor public health messages.

FundingZoe Global Limited, Department of Health, Wellcome Trust, EPSRC, NIHR, MRC, Alzheimers Society, Facebook Sponsored Research Agreement.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTo assess current evidence on test uptake in symptomatic testing programmes, and the reasons for not testing, we searched PubMed from database inception for research using the keywords (COVID-19) AND (testing) AND ((access) OR (uptake)). We did not find any work reporting on levels of test uptake amongst symptomatic individuals. We found three papers investigating geographic barriers to testing. We found one US based survey reporting on knowledge barriers to testing, and one UK based survey reporting on barriers in the period March - August 2020. Neither of these studies were able to combine testing behaviour with prospectively collected symptom reports from the users surveyed.

Added value of this studyThrough prospective collection of symptom and test reports, we were able to estimate testing uptake amongst individuals with test-qualifying symptoms in the UK. Our results indicate that whilst testing has improved since the start of the pandemic, there remains a considerable testing gap. Investigating this gap we find that individuals with just one test-qualifying symptom or short symptom duration are less likely to get tested. We also find knowledge barriers to testing: a substantial proportion of individuals do not know which symptoms qualify them for a COVID-19 test, and do not know where to seek testing. We find a larger knowledge gap in individuals with older age and fewer years of education.

Implications of all the available evidenceDespite the UK having a simple set of symptom-based testing criteria, with tests made freely available through nationalised healthcare, a quarter of individuals with qualifying symptoms do not get tested. Our findings suggest testing uptake may be limited by individuals not acting on mild or transient symptoms, not recognising the testing criteria, and not knowing where to get tested. Improved messaging may help address this testing gap, with opportunities to target individuals of older age or fewer years of education. Messaging may prove even more valuable in countries with more fragmented testing infrastructure or more nuanced testing criteria, where knowledge barriers are likely to be greater.


title: Interim results of the safety and immune-efficacy of 1 versus 2 doses of COVID-19 vaccine BNT162b2 for cancer patients in the context of the UK vaccine priority guidelines

abstract:
BackgroundThe efficacy and safety profile of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been definitively established in immunocompromised patient populations. Patients with a known cancer diagnosis were hitherto excluded from trials of the vaccines currently in clinical use.

MethodsThis study presents data on the safety and immune efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine in 54 healthy controls and 151 mostly elderly patients with solid and haematological malignancies, respectively, and compares results for patients who were boosted with BNT162b2 at 3 weeks versus those who were not. Immune efficacy was measured as antibody seroconversion, T cell responses, and neutralisation of SARS-CoV-2 Wuhan strain and of a variant of concern (VOC) (B.1.1.7). We also collected safety data for the BNT162b2 vaccine up to 5 weeks following first dose.

FindingsThe vaccine was largely well tolerated. However, in contrast to its very high performance in healthy controls (>90% efficacious), immune efficacy of a single inoculum in solid cancer patients was strikingly low (below 40%) and very low in haematological cancer patients (below 15%). Of note, efficacy in solid cancer patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer patients were boosted for clear conclusions to be drawn.

ConclusionsDelayed boosting potentially leaves most solid and haematological cancer patients wholly or partially unprotected, with implications for their own health; their environment and the evolution of VOC strains. Prompt boosting of solid cancer patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer patients.

RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSSome cancer patients have been shown to exhibit sustained immune dysregulation, inefficient seroconversion and prolonged viral shedding as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, their exclusion and, in particular, the exclusion of patients receiving systemic anti-cancer therapies, from the registry trials of the 5 approved COVID-19 vaccines raises questions about the efficacy and safety of SARS-CoV-2 vaccination in this patient population. In addition, whilst the change in the UKs dosing interval to 12-weeks aimed to maximise population coverage, it is unclear whether this strategy is appropriate for cancer patients and those on systemic anti-cancer therapies.

Added value of this studyWe report that the RNA-based SARS-CoV-2 BNT162b2 vaccine administered in cancer patients was well tolerated, and we provide first insights into both antibody and T cell responses to the vaccine in an immunocompromised patient population.

Implications of all the available evidenceIn cancer patients, one dose of 30ug of BNT162b2 yields poor vaccine efficacy, as measured by seroconversion rates, viral neutralisation capacity and T cell responses, at 3- and 5-weeks following the first inoculum. Patients with solid cancers exhibited a significantly greater response following a booster at 21-days. These data support prioritisation of cancer patients for an early (21-day) second dose of the BNT162b2 vaccine. Given the globally poor responses to vaccination in patients with haematological cancers, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of  ring vaccination, and careful follow-up should be prioritised.

category: oncology


title: In vivo evaluation of the virucidal efficacy of Chlorhexidine and Povidone-iodine mouthwashes against salivary SARS-CoV-2.

abstract:
BackgroundThe oral cavity is potentially high-risk transmitter of COVID-19. Antimicrobial mouthrinses are used in many clinical pre procedural situations for prophylactic purposes. An evident-based investigation for an effective mouthwash solution against salivary SARS-CoV-2 is urgently required for the exposure reduction during dental procedures.

AimsThis study aimed to evaluate in vivo virucidal efficacy of 2 mouthwashes: 1% Povidoneiodine and 0.2% Chlorhexidine as a dental preprocedural oral disinfection against salivary SARS-CoV-2.

Materials and MethodsIn this randomized-controlled clinical trial, studied group comprised laboratory-confirmed COVID-19 positive patients through nasopharyngeal swabs. Participants were divided into 3 groups. For 30 seconds, group A gargled with 1% Povidone-iodine, group B mouthrinsed with 0.2% Chlorhexidine and control group C mouthrinsed with distilled water. Saliva samples were collected before and 5 minutes after mouthwash. SARS-CoV-2 rRT-PCR was then performed for each sample. Evaluation of the efficacy was based on difference in Ct value. The analysis of data was carried out using GraphPad Prism version 5 for Windows. Paired t test and unpaired t test were used. A probability value of less than 0.05 was regarded as statistically significant.

ResultsSixty-one compliant participants (36 female and 25 male) with a mean age 45.3 {+/-} 16.7 years-old were enrolled. A significant mean Ct value difference (p < 0.0001) between the paired samples in group A (n = 25) and also in group B (n = 27) (p < 0.0001) was found. In contrast, no significant difference (p = 0.566) existed before and after the experiment in the control group C (n = 9). Moreover, a significant difference was noted between the delta Ct of distilled water wash and each of the 2 solutions 1 % Povidone-iodine (p = 0.012) and Chlorhexidine 0.2% (p = 0.0024). No significant difference was found between the delta Ct of patients using 1% Povidone-iodine and Chlorhexidine 0.2% solutions (p = 0.24).

ConclusionChlorhexidine 0.2% and 1% Povidone-iodine oral solutions are effective preprocedural mouthwashes against salivary SARS-COV-2 in dental treatments. Their use as a preventive strategy to reduce the spread of COVID-19 during dental practice should be systematically implemented.


title: Show us the Data: Global COVID-19 Wastewater Monitoring Efforts, Equity, and Gaps

abstract: A year since the declaration of the global coronavirus disease 2019 (COVID-19) pandemic there were over 110 million cases and 2.5 million deaths. Learning from methods to track community spread of other viruses such as poliovirus, environmental virologists and those in the wastewater based epidemiology (WBE) field quickly adapted their existing methods to detect SARS-CoV-2 RNA in wastewater. Unlike COVID-19 case and mortality data, there was not a global dashboard to track wastewater monitoring of SARS-CoV-2 RNA worldwide. This study provides a one year review of the "COVIDPoops19" global dashboard of universities, sites, and countries monitoring SARS-CoV-2 RNA in wastewater. Methods to assemble the dashboard combined standard literature review, direct submissions, and daily, social media keyword searches. Over 200 universities, 1,000 sites, and 55 countries with 59 dashboards monitor wastewater for SARS-CoV-2 RNA. However, monitoring is primarily in high-income countries (65%) with less access to this valuable tool in low and middle income countries (35%). Data are not widely shared publicly or accessible to researchers to further inform public health actions, perform meta-analysis, better coordinate, and determine equitable distribution of monitoring sites. For WBE to be used to its full potential during COVID-19 and beyond, show us the data.


title: The Influence of Covid-19 Vaccine on Daily Cases, Hospitalization, and Death Rate in Tennessee: A Case Study in the United States

abstract: The COVID-19 outbreak highlights the vulnerability to novel infections, and vaccination remains a foreseeable method to return to normal life. However, infrastructure is inadequate for the whole population to be vaccinated immediately. Therefore, policies have adopted a strategy to vaccinate the elderly and vulnerable population while delaying others. This study uses the Tennessee official statistic from the onset of COVID vaccination (17th of December 2021) to understand how age-specific vaccination strategies reduce daily cases, hospitalization, and death rate. The result shows that vaccination strategy can significantly influence the numbers of patients with COVID-19 in all age groups and lower hospitalization and death rates just in older age groups. The Elderly had a 95% lower death rate from December to March; however, and no change in the death rate in other age groups. The Hospitalization rate was reduced by 80% in this study cohort for people aged 80 or older, while people who were between 50 to 70 had almost the same hospitalization rate. The study indicates that vaccination targeting older age groups is the optimal way to avoid higher transmissions and reduce hospitalization and death rate for older groups.

category: health policy


title: Epigenetic drift association with cancer risk and survival, and modification by sex

abstract:
To investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case-control studies of colorectal (N=835), gastric (N=170), kidney (N=143), lung (N=332), prostate (N=869) and urothelial (N=428) cancers, and mature B-cell lymphoma (N=438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls) - replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios [HR]), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates (GS summary data) for these CpGs were 94%, 86% and 91%, respectively. Significant signals for cancer risk and survival were identified at some individual age-related CpGs. There was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Two CpGs overlapping TMEM49 and ARX genes were associated with survival of overall (HR=0.91, P=7.7x10-4) and colorectal (HR=1.52, P=1.8x10-4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.

Simple SummaryAgeing is the strongest cancer risk factor, and men and women exhibit disparate risk profiles in terms of incidence and survival. DNA methylation is known to strongly vary by age and sex. Epigenetic drift refers to age-related DNA methylation changes and the tendency for increasing discordance between epigenomes over time, but it remains unknown to what extent the epigenetic drift might contribute to cancer risk and survival. The aims of this study were to identify age-associated, sex-associated and sexually dimorphic age-associated (age-by-sex-associated) DNA methylation markers and investigate whether age- and age-by-sex-associated markers are associated with cancer risk and survival. Our study, which used a total of 3,215 matched case-control pairs with DNA methylation in pre-diagnostic blood, is the first large study to examine the association between sex-specific epigenetic drift and cancer development and progression. The results may be useful for cancer early diagnosis and prediction of prognosis.


title: The impact of policy timing on the spread of COVID-19

abstract: We model COVID-19 data for 89 nations and US states with a recently developed formalism that describes mathematically any pattern of growth with the minimum number of parameters. The results show that the disease has a typical duration of 18 days, with a significant increase in fatality when it lasts longer than about 4 months. Searching for correlations between "flattening of the curve" and preventive public policies, we find strong statistical evidence for the impact of the first implemented policy on decreasing the pandemic growth rate; a delay of one week in implementation nearly triples the size of the infected population, on average. Without any government action, the initial outburst still slows down after 36 days, possibly thanks to changes in public behavior in response to the pandemic toll. Stay-at-home (lockdown) was not the first policy of any sample member and we do not find statistically meaningful evidence for its added impact, similar to a recent study that employed an entirely different approach. However, lockdown was mostly imposed only shortly before the exponential rise was arrested. The possibility remains that lockdown might have shortened significantly the initial exponential rise had it been employed as first, rather than last resort.


title: Characteristics and risk factors for SARS-CoV-2 among children in Italy: a cross-sectional study in 20 pediatric centers

abstract:
BackgroundNo study has described factors associated with COVID-19 diagnosis in children.

AimDescribe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 pediatric centers across Italy.

MethodsCases aged 0-18 years tested for SARS-CoV-2 between February 23 and May 24 2020 were included. Our primary analysis focused on children tested because of COVID-19 suggestive symptoms.

ResultsAmong 2494 children tested for SARS-CoV-2, 2148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of SARS-CoV-2 included - beside fever (82.4%) and respiratory signs or symptoms (60.4%) - also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other flu-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 were: exposure history (adjusted OR 39.83 95%CI 17.52-90.55 p<0.0001), cardiac disease (adjusted OR 3.10 95%CI 1.19-5.02 p<0.0001), fever (adjusted OR 3.05 % 95% CI 1.67-5.58 p=0.0003), and anosmia/ageusia (OR 4.08 95%CI 1.69 -9.84 p=0.002). Among 190 (7.6%) children diagnosed with SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted in ICU, while 100% recovered.

ConclusionRecommendations for SARS-CoV-2 testing in children should be updated based on the evidence of broader clinical features. Exposure history, fever, and anosmia/ageusia are strong risk factors for COVID-19 in children, while other symptoms dont seem helping discriminating in between the SARS-CoV-2 positive and the negative cases. This study confirm that COVID-19 is a mild disease in the general population of children in Italy. Further studies are needed to understand the risk, clinical spectrum and outcomes of COVID-19 in children with specific preexisting conditions.

category: pediatrics


title: Evaluation of a new spike (S) protein based commercial immunoassay for the detection of anti-SARS-CoV-2 IgG

abstract:
BackgroundThe investigation of antibody response to SARS-CoV-2 represents a key aspect in facing the COVID-19 pandemic. In the present study, we compared one new and four widely used commercial serological assays for the detection of antibodies targeting S (spike) and NC (nucleocapsid) protein.

MethodsSerum samples from a group of apparently non-responders, from an unbiased group of convalescent patients and from a negative control group were sim-ultaneously analyzed by the LIAISON(R) SARS-CoV-2 S1/S2 IgG test, Euroimmun anti-SARS-CoV-2 S1 IgG ELISA and IDK(R) anti-SARS-CoV-2 S1 IgG assays. IgG binding NC were detected by the Abbott SARS-CoV-2 IgG assay and by the panimmunoglobulin immunoassay Elecsys(R) Anti-SARS-CoV-2. Additionally, samples were also tested by live virus and pseudovirus neutralization tests.

ResultsOverall, about 50% of convalescent patients with undetectable IgG antibodies using the commercial kit by Euroimmun were identified as IgG positive by Immundiagnostik and Roche. While both assays achieved similarly high sensitivities, Immundiagnostik correlated better with serum neutralizing activity than Roche.

ConclusionsAlthough the proportion of IgG seropositive individuals appears to be higher using more sensitive immunoassays, the protective ability and the potential to serve as indirect markers of other beneficial immune responses warrants for further research.


title: A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories

abstract: The determination of anti-SARS-CoV-2 neutralizing antibodies (NAbs) is of interest in many respects. High NAb titers, for example, are the most important criterion regarding the effectiveness of convalescent plasma therapy. However, common cell culture-based NAb assays are time-consuming and feasible only in special laboratories. Our data reveal the suitability of a novel ELISA-based surrogate virus neutralization test (sVNT) to easily measure the inhibition-capability of NAbs in the plasma of COVID-19 convalescents. We propose a combined strategy to detect plasma samples with high NAb titers ([≥] 1:160) reliably and to, simultaneously, reduce the risk of erroneously identifying low-titer specimens. For this approach, results of the sVNT assay are compared to and combined with those acquired from the Euroimmun anti-SARS-CoV-2 IgG assay. Both assays are appropriate for high-throughput screening in standard BSL-2 laboratories. Our measurements further show a long-lasting humoral immunity of at least 11 months after symptom onset.


title: Financial Incentives and Healthcare Provision: Evidence from an Experimental Aedes aegypti Control Programme in Brazil

abstract:
BackgroundMosquito control is the most effective means of reducing Aedes aegypti infections worldwide. In many developing countries, however, vector management programmes fail to reach their goals due to low worker productivity. Research suggests that financial incentives may increase the productivity of health personnel, yet there is little evidence about the impact of monetary rewards on A. aegypti-reduction strategies. We evaluated whether individual and collective financial incentives improve the performance of healthcare workers fighting A. aegypti, as well as their effect on city-level numbers of dengue hospitalisations.

Methodology/Principal findingsWe hired and trained subjects to visit households, find A. aegypti breeding sites, and eliminate mosquito larvae in the city of Rio Verde, Brazil. We randomly assigned workers into three groups. The control group received a flat compensation for their tasks, while workers in the two treatment groups received individual and collective monetary bonuses, respectively. Financial rewards increased the number of cleaned breeding sites in both treatment groups (individual and team bonuses), and the collective treatment also improved larvae extermination. The intervention lowered dengue hospitalisations in 10.3%, but the result was not consistent across all model specifications.

Conclusions/SignificanceA. aegypti control programmes may benefit from alternative compensation schemes, especially when provided to teams. For this strategy to succeed, financial incentives have to be distributed widely as their aggregate effect is limited. More research is needed to assess whether higher worker productivity decreases dengue hospitalisations.

Author SummaryDiseases transmitted by the Aedes aegypti mosquito, such as chikungunya, dengue, yellow fever, and Zika, continue to affect thousands of people per year. As there are no safe vaccines for most of these infections, insecticide spraying and breeding site elimination are the best means to fight the mosquito. In several developing countries, which host the majority of A. aegypti infections, anti-mosquito campaigns are carried out inconsistently, thus it is crucial to find ways to improve the productivity of healthcare workers in charge of these tasks. We designed a randomised field experiment that provided individual and collective financial incentives to healthcare agents in a Brazilian city, and we tested the effect of monetary rewards on their productivity and on city-level dengue hospitalisations. We find that financial bonuses improved the number of cleaned breeding sites in both treatment groups (individual and team incentives) and that the collective treatment also improved larvae extermination. The impact of our treatment on city-level hospitalisations was not consistent across all specifications. In sum, financial incentives may be used to boost field productivity in anti-A. aegypti programmes, but further research is required to evaluate how healthcare worker productivity impacts dengue outcomes.

category: health economics


title: Positioning zoonotic disease research in forced migration: a systematic literature review of theoretical frameworks and approaches

abstract:
BackgroundThe emergence and transmission of zoonotic diseases are driven by complex interactions between health, environmental, and socio-political systems. Human movement is considered a significant and increasing factor in these processes, yet forced migration remains an understudied area of zoonotic research - due in part to the complexity of conducting interdisciplinary research in these settings.

ObjectivesWe conducted a systematic review to identify and analyze theoretical frameworks and approaches used to study linkages between forced migration and zoonotic diseases.

MethodsWe searched within eight electronic databases: ProQuest, SCOPUS, Web of Science, PubMed, PLoSOne, Science Direct, JSTOR, and Google Scholar, to identify a) research articles focusing on zoonoses considering forced migrants in their study populations, and b) forced migration literature which engaged with zoonotic disease. Both authors conducted a full-text review, evaluating the quality of literature reviews and primary data using the Critical Appraisal Skills Programme (CASP) model, while theoretical papers were evaluated for quality using a theory synthesis adapted from Bonell and Fletcher (2013). Qualitative data were synthesized thematically according to the method suggested by Noblit and Hare (1988).

ResultsAnalyses of the 23 included articles showed the increasing use of interdisciplinary frameworks and approaches over time, the majority of which stemmed from political ecology. Approaches such as EcoHealth and One Health were increasingly popular, but were more often linked to program implementation and development than broader contextual research. The majority of research failed to acknowledge the heterogeneity of migrant populations, lacked contextual depth, and insufficient acknowledgement of migrant agency in responding to zoonotic threats.

ConclusionsAddressing the emergence and spread of zoonoses in forced migration contexts requires more careful consideration and use of interdisciplinary research to integrate the contributions of social and natural science approaches. Robust interdisciplinary theoretical frameworks are an important step for better understanding the complex health, environment, and socio-political drivers of zoonotic diseases in forced migration. Lessons can be learned from the application of these approaches in other hard-to-reach or seldom-heard populations.


title: Development of a Video-based Evidence Synthesis Knowledge Translation Resource: Applying a User-Centred Approach

abstract:
BackgroundPeople of all ages and walks of life are bombarded with health claims from an array of sources. An understanding of evidence synthesis is important for people to make truly informed healthcare decisions. There is an increasing focus on the use of knowledge translation resources within healthcare; however, the development of these resources has often been poorly described or studied.

ObjectivesThis study employs a user-centred approach to develop a video animation resource to explain the purpose, use and importance of evidence synthesis to the general public regarding healthcare decision-making.

MethodsWe employed a user-centred approach to developing a spoken animated video that could explain evidence synthesis to a public audience, conducting several cycles of idea generation, prototyping, user-testing, analysis and refinement. Six researchers with expertise in evidence synthesis and knowledge translation resource development gave input on the key messages of the video animation and informed the first draft of the storyboard and script. Seven members of the public provided feedback on this draft through Think-aloud interviews, which we used to develop a video animation prototype. Seven additional members of the public participated in Think-aloud interviews while watching the video prototype. In addition to interviews, participants completed a questionnaire that collected data on perceived usefulness, desirability, clarity and credibility. One experienced patient and public involvement (PPI) advocate also provided feedback on the script and prototype. At the end of each feedback cycle, we assimilated all data and made necessary changes, resulting in a final, rendered version of the animation video.

ResultsResearchers identified the initial key messages for the SAV as 1) the importance of evidence synthesis, 2) what an evidence synthesis is and 3) how evidence synthesis can impact healthcare decision-making. Using guidance and feedback from members of the public, we produced a three-and-a-half-minute video animation that members of the public rated 9/10 for usefulness, 8/10 for desirability, 8/10 for clarity and 9/10 for credibility. The video was uploaded on YouTube (https://www.youtube.com/watch?v=nZR0xQmZVQg) and has been viewed over 5500 times to date.

ConclusionsEmploying a user-centred approach, we developed a video animation knowledge translation resource to explain evidence synthesis to the general public that was assessed as useful, desirable and clear by its intended target audience. This study describes the structured and systematic development of this knowledge translation resource and how key stakeholders and end-users informed the final output.


title: Novel blood test for early biomarkers of preeclampsia and Alzheimer's disease

abstract: Non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimers disease (AD) and other proteinopathy diseases. However, a blood test based on a mechanistic link to pathologic protein aggregate complexes has not been yet elucidated. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE as well as AD in both dementia and prodromal mild cognitive impairment (MCI) stages. The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid {beta}-42, -synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Autophagy-proficient human trophoblasts failed to accumulate serum protein aggregates under similar culture conditions. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity. In conclusion, we have developed a novel noninvasive diagnostic and predictive assay for AD, MCI and PE.

category: obstetrics and gynecology


title: Cancer services during the COVID-19 pandemic: systematic review of patients' and caregivers' experiences

abstract:
BackgroundCancer patients have faced intersecting crises in the face of COVID-19 pandemic. This review aimed to examine patients and caregivers experiences of accessing cancer services during the COVID-19 pandemic and perceived impact of the pandemic on their psychological wellbeing.

MethodsA protocol-led (CRD42020214906) systematic review was conducted by searching six databases including EMBASE, MEDLINE and CINAHL for articles published in English-language between 1/2020-12/2020. Data were extracted using a pilot-tested, structured data extraction form. Thematic synthesis of data was undertaken and reported as per the PRISMA guideline.

ResultsA total of 1110 articles were screened of which 19 studies met the inclusion criteria. Studies originated from 10 different countries including the US, UK, India and China. Several themes were identified which were categorised into seven categories. Postponement and delays in cancer screening and treatment, drug shortages and inadequate nursing care were commonly experienced by patients. Hospital closures, resource constraints, national lockdowns and patient reluctance to use health services because of infection worries contributed to the delay. Financial and social distress, isolation; and spiritual distress due to the uncertainty of rites as well as fulfilment of last wishes were also commonly reported. Caregivers felt anxious about infecting cancer patients with COVID-19.

ConclusionsPatients and caregivers experienced extensive impact of COVID-19 on cancer screening, treatment and care, and their own psychological wellbeing. Patient and caregiver views and preferences should be incorporated in ensuring resilient cancer services that can minimise the impact of ongoing and future pandemic on cancer care and mitigate patient fears.

Protocol RegistrationPublished protocol registered with Centre for Review and Dissemination CRD42020214906 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=214906)


title: ExPheWas: a browser for gene-based pheWAS associations

abstract:
Structured AbstractO_ST_ABSMotivationC_ST_ABSThe relationship between protein coding genes and phenotypes has the potential to inform on the underlying molecular function in disease etiology. We conducted a phenome-wide association study (pheWAS) of protein coding genes using a principal components analysis-based approach in the UK Biobank.

ResultsWe tested the association between 19,114 protein coding gene regions and 1,210 phenotypes including anthropometric measurements, laboratory biomarkers, cancer registry data, hospitalization and death record codes and algorithmically-defined cardiovascular outcomes. We report the pheWAS results in a user-friendly web-based browser. Taking atrial fibrillation, a common cardiac arrhythmia, as an example, ExPheWas identified genes that are known drug targets for the treatment of arrhythmias and genes involved in biological processes implicated in cardiac muscle function. We also identified MYOT as a possible atrial fibrillation gene.

Availability and implementationThe ExPheWas browser and API are available at http://exphewas.statgen.org/

ContactMarie-Pierre.Dube@mhi-rc.org


title: The effects of physical distancing and lockdown to restrain SARS-CoV-2 outbreak in the Italian Municipality of Cogne

abstract: The outbreak of SARS-CoV-2 started in Wuhan, China, and is now a pandemic. An understanding of the prevalence and contagiousness of the disease, and of whether the strategies used to contain it to date have been successful, is important for understanding future containment strategies. One strategy for controlling the spread of SARS-CoV-2 is to adopt strong social distancing policies. The Municipality of Cogne (I), adopted strict lockdown rules from March 4, 2020 up to May 18, 2020. This first wave of the pandemic impressed by the extremely low impact of the SARS-CoV-2 on the locals, compared to the number accused on all the Italian territory. Starting from October 2020 up to the end of December, when the second wave hit Italy and Cogne territory, heavier effects were observed. In order to cast light on the effectiveness of the adopted strategy 74,5% of the local population underwent to a blood screening to detect IgM and IgG antibodies and after six months all the people tested positive were again investigated to establish the longitudinal changes in antibodies level. Moreover, within the context of this survey a rare and interesting case of secondary infection has been identified and here presented.


title: Human lipoproteins comprise at least 12 different classes that are 1 lognormally distributed.

abstract: Lipoproteins in medical samples have been measured by enzymatic methods that coincide with conventional ultracentrifugation. However, the high gravity and time required for ultracentrifugation can cause sample degradation. This study presents the results of HPLC, a gentler and rapid separation method, for 55 human serum samples. The elution patterns were analysed parametrically, and the attribute of each class was confirmed biochemically. Human samples contained 12 classes of lipoproteins, each of which may consist primarily of proteins. There are three classes of VLDLs. The level of each class was distributed lognormally, and the standard amount and the 95% range were estimated. Enzymatic methods measure the levels of several mixed classes. This lognormal character suggests that the levels are controlled by the synergy of multiple factors.

category: hematology


title: Human lipoproteins comprise at least 12 different classes that are lognormally distributed.


title: A Prospective Study of Long-Term Outcomes Among Hospitalized COVID-19 Patients with and without Neurological Complications

abstract:
BackgroundLittle is known regarding long-term outcomes of patients hospitalized with COVID-19.

MethodsWe conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep.

ResultsOf 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N=196 neurological patients and N=186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on [≥]1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 2.03, 95%CI 1.22-3.40, P=0.01), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P=0.01) and were less likely to return to work than controls (41% versus 64%, P=0.04). Cognitive and Neuro-QOL metrics were similar between groups.

ConclusionsAbnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.


title: Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality

abstract: Despite advances in COVID-19 management, it is unclear how to recognize patients who evolve towards death. This would allow for better risk stratification and targeting for early interventions. However, the explosive increase in correlates of COVID-19 severity complicates biomarker prioritisation. To identify early biological predictors of mortality, we performed an immunovirological assessment (SARS-CoV-2 viral RNA, cytokines and tissue injury markers, antibody responses) on plasma samples collected from 144 hospitalised COVID-19 patients 11 days after symptom onset and used to test models predicting mortality within 60 days of symptom onset. In the discovery cohort (n=61, 13 fatalities), high SARS-CoV-2 vRNA, low RBD-specific IgG levels, low SARS-CoV-2-specific antibody-dependent cellular cytotoxicity, and elevated levels of several cytokines and lung injury markers were strongly associated with increased mortality in the entire cohort and the subgroup on mechanical ventilation. Model selection revealed that a three-variable model of vRNA, age and sex was very robust at identifying patients who will succumb to COVID-19 (AUC=0.86, adjusted HR for log-transformed vRNA=3.5; 95% CI: 2.0-6.0). This model remained robust in an independent validation cohort (n=83, AUC=0.85). Quantification of plasma SARS-CoV-2 RNA can help understand the heterogeneity of disease trajectories and identify patients who may benefit from new therapies.


title: Heightened COVID-19 Vaccine Response following SARS-CoV-2 Infection

abstract:
BackgroundCurrent recommendations in the United States are that subjects with a previous history of COVID-19 disease receive the full 2 dose mRNA vaccine regimen. We tested the hypothesis that humoral immune responses and reactogenicity to a SARS-CoV-2 mRNA vaccine (BNT-162b2) differ qualitatively and quantitatively in subjects with prior SARS-CoV-2 infection versus infection-naive subjects.

MethodsHealth care workers (n=61) from a single academic institution with and without prior COVID-19 received two 30 {micro}g doses of BNT162b2 vaccine 3 weeks apart. The COVID group (n=30) received vaccine approximately 7 months post infection. IgG antibody against the Spike receptor-binding domain (RBD), serum neutralizing activity and vaccine adverse reactions were assessed every 2 weeks for 56 days after the 1st injection. A longitudinal design and long study duration allowed the onset, maximum response and initial decay rate of Spike IgG antibody to be assessed in each subject. In addition, Spike IgG antibody levels are expressed as {micro}g / mL to provide normal values for clinical decision making.

FindingsSpike IgG responses were highly variable in both groups. However, the COVID group manifested rapid increases in Spike IgG antibody and serum neutralizing activity post 1st vaccine dose but little or no increase in Spike IgG or serum neutralizing activity after the 2nd dose. In fact, Spike IgG was maximum prior to the 2nd dose in 36% of the COVID group and 0% of controls. Peak IgG antibody was lower but appeared to fall more slowly in the COVID than in the control group. Finally, adverse systemic reactions e.g., fever, headache and malaise, after both the 1st and 2nd injection were more frequent and lasted longer in the COVID group than in the control group.

ConclusionsHealth care workers with prior COVID-19 demonstrate a robust, accelerated humoral immune response to the 1st dose of the COVID-19 mRNA vaccine but attenuated response to the 2nd dose. They also experience greater reactogenicity than controls. Accordingly, subjects with prior COVID-19 may require only a single dose of vaccine.


title: A Longitudinal Study of BNT162b2 Vaccine-Induced Humoral Response and Reactogenicity in Health Care Workers with Prior COVID-19 Disease


title: Arresting Vertical Transmission of Hepatitis B Virus (AVERT-HBV) in the Democratic Republic of the Congo

abstract:
BackgroundHepatitis B virus (HBV) remains endemic throughout sub-Saharan Africa despite the widespread availability of effective vaccines. We evaluated the feasibility of adding HBV testing and treatment of pregnant women and birth-dose vaccination of HBV-exposed infants to the HIV prevention of MTCT (PMTCT) program infrastructure in the Democratic Republic of the Congo (DRC), where HBV treatment and birth-dose vaccination programs are not established.

MethodsAs part of the HIV PMTCT program at two maternity centers in Kinshasa, DRC, pregnant women were screened for HBV at routine prenatal care registration. Pregnant women with high viral load and/or HBeAg positivity were offered tenofovir disoproxil fumarate (TDF). HBV-exposed infants received a birth-dose of HBV vaccine within 24 hours of life. The primary endpoint was the feasibility and acceptability of the study.

FindingsOf 4,016 women screened, 109 (2.7%) were HBsAg-positive. Ten of 91 (11.1%) women evaluated had high-risk disease. Of 88 infants, 60 (68.2%) received a birth-dose vaccine; of these, 46 (76.7%) received a timely birth-dose. No cases of HBV MTCT were observed in our cohort. There were no serious adverse events associated with TDF nor with birth-dose vaccine. The study procedures were highly acceptable (>80%) among mothers.

InterpretationAdding HBV screening and treatment of pregnant women and infant birth-dose vaccination to existing HIV PMTCT platforms is feasible in countries like the DRC. Birth-dose vaccination against HBV integrated within the current Expanded Programme on Immunization (EPI) and HIV PMTCT program could accelerate progress toward HBV elimination in Africa.


title: Development and validation of the long covid symptom and impact tools, a set of patient-reported instruments constructed from patients' lived experience

abstract:
ObjectivesTo develop and validate patient-reported instruments, based on patients lived experiences, for monitoring the symptoms and impact of long covid.

DesignThe long covid Symptom and Impact Tools (ST and IT) were constructed from the answers to a survey with open-ended questions to 492 patients with long covid. Validation of the tools involved adult patients with suspected or confirmed covid-19 and symptoms extending over three weeks after onset. Construct validity was assessed by examining the relations of the ST and IT scores with health related quality of life (EQ-5D-5L), function (PCFS, post-covid functional scale), and perceived health (MYMOP2). Reliability was determined by a test-retest. The "patient acceptable symptomatic state" (PASS) was determined by the percentile method.

ResultsValidation involved 1022 participants (55% with confirmed covid-19, 79% female and 12.5% hospitalised for covid-19). The long covid ST and IT scores were strongly correlated with the EQ-5D-5L (rs = -0.45 and rs = -0.59 respectively), the PCFS (rs = -0.39 and rs = -0.55), and the MYMOP2 (rs = -0.40 and rs = -0.59). Reproducibility was excellent with an interclass correlation coefficient of 0.83 (95% confidence interval 0.80 to 0.86) for the ST score and 0.84 (0.80 to 0.87) for the IT score. In total, 793 (77.5%) patients reported an unacceptable symptomatic state, thereby setting the PASS for the long covid IT score at 30 (28 to 33).

ConclusionsThe long covid ST and IT tools, constructed from patients lived experiences, provide the first validated and reliable instruments for monitoring the symptoms and impact of long covid.

Short summaryWe developed the long covid Symptom and Impact Tools (ST and IT) from the experiences of 492 patients, captured during a survey with open-ended questions, and assessed their validity and reliability in a sample of 1022 patients with long covid.


title: Assessing the utility of lymphocyte count to diagnose COVID-19

abstract:
BackgroundCOronaVirus Disease 2019 (COVID-19) can be challenging to diagnose, because symptoms are non-specific, clinical presentations are heterogeneous, and false negative tests can occur. Our objective was to assess the utility of lymphocyte count to differentiate COVID-19 from influenza or community-acquired pneumonia (CAP).

MethodsWe conducted a cohort study of adults hospitalized with COVID-19 or another respiratory infection (i.e., influenza, CAP) at seven hospitals in Ontario, Canada.The first available lymphocyte count during the hospitalization was used. Standard test characteristics for lymphocyte count (x109/L) were calculated (i.e., sensitivity, specificity, area under the receiver operating curve [AUC]). All analyses were conducting using R.

ResultsThere were 869 hospitalizations for COVID-19, 669 for influenza, and 3009 for CAP. The mean age across the three groups was 67 and patients with pneumonia were older than those with influenza or COVID19, and approximately 46% were woman. The median lymphocyte count was nearly identical for the three groups of patients: 1.0 x109/L (interquartile range [IQR]:0.7,2.0) for COVID-19, 0.9 x109/L (IQR 0.6,1.0) for influenza, and 1.0 x109/L (IQR 0.6,2.0) for CAP. At a lymphocyte threshold of less than 2.0 x109/L, the sensitivity was 87% and the specificity was approximately 10%. As the lymphocyte threshold increased, the sensitivity of diagnosing COVID-19 increased while the specificity decreased. The AUC for lymphocyte count was approximately 50%.

InterpretationLymphocyte count has poor diagnostic discrimination to differentiate between COVID-19 and other respiratory illnesses. The lymphopenia we consistently observed across the three illnesses in our study may reflect a non-specific sign of illness severity. However, lymphocyte count above 2.0 x109/L may be useful in ruling out COVID-19 (sensitivity = 87%).


title: Comparing the efficacy of anti-infectious drugs for the treatment of mild to severe COVID-19 patients: a protocol for a systematic review and network meta-analysis of randomized clinical trials

abstract:
BackgroundCOVID-19 is a viral infection spreading at a great speed and has quickly caused an extensive burden to individuals, families, countries, and the world. No intervention has yet been proven highly effective for the treatment of COVID-19. Different drugs were being evaluated and reported through randomized clinical trials, and more are currently under trial. This review aimed to compare the efficacy of anti-infectious drugs with a comparator of the standard of care or placebo in patients with COVID-19.

Methods and analysisTwo independent review authors will extract data and assess a risk of bias using RoB2. Randomized controlled trials (RCT) that evaluate single and/or combined antiviral drugs recommended by WHO latest guideline for the treatment of COVID-19 will be included. We will search for Pub Med, the Cochrane Center for Clinical Trial database (CENTRAL), clinicaltrials.gov, etc. databases for articles published in the English language between December 2019 to April 2021. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) involving Network Meta-analysis guidelines for the design and reporting of the results. The primary endpoints will be time to clinical recovery and time to RNA negativity. The certainty of evidence will be evaluated using the GRADE extension of NMA. Data analysis will be performed using the frequentist NMA approach with netmeta package implemented in R.

Ethics and disseminationThere are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open access peer-reviewed journals.

PROSPERO registration numberID=CRD42021230919.

Strengths and limitations of this studyO_LIThis will be the first systematic review and network meta-analysis to assess the efficacy specific to anti-infectious drugs category for for mild to severe patients of COVID-19.
C_LIO_LIIts compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA-P) involving network meta-analysis(NMA) will ensure the quality of reporting.
C_LIO_LIDoing both pairwise meta-analysis and network meta-analysis (NMA) can comprehensively analyse direct and indirect comparison results of different anti-infectious drugs for COVID 19 will give more reliable conclusions aswell as the rank of those drugs.
C_LIO_LIThere is risk of heterogeneity and inconsistency, given the different anti-infectious drugs that will be included; however, we try to control intransitivity by carefully identifying the eligibility criteria depending on PICOS strategy and assess inconsistency using local as well as global approaches.
C_LIO_LIThe limitation of this study is it will not explore the economic benefits of these drugs.
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title: Respiratory and Cardiovascular Health Effects of E-Cigarette Substitution: Protocol for Two Living Systematic Reviews

abstract:
BackgroundDespite the clear risks of tobacco use, millions of people continue to smoke. Electronic nicotine delivery systems (ENDS), commonly called e-cigarettes, have been proposed as a substitute for those who are unwilling or unable to quit. Current systematic and narrative reviews on the health effects of ENDS use, respiratory and cardiovascular effects in particular, have come to differing conclusions.

ObjectiveThe purpose of our two systematic reviews is to critically assess and synthesize the available human studies on the respiratory and cardiovascular health effects of ENDS substitution for people who smoke. The primary goal is to provide clinicians with evidence on the health effects of ENDS substitution to inform their treatment recommendations and plans. The twin goal is to promote the health literacy of ENDS users with facts on the health effects of ENDS. A secondary goal is to develop policy briefs to provide governmental bodies with a preliminary assessment of the potential public health impacts of ENDS.

MethodsThese two reviews will be living systematic reviews. The systematic reviews will be initiated with a baseline review. Studies will be evaluated with the JBI quality assessment tools and a checklist of biases drawn from the Centre for Evidence Based Medicines Catalogue of Bias. A narrative synthesis is planned due to the heterogeneity of data. A search for recently published studies will be conducted every three months, and an updated review published every six months for the duration of the project or possibly longer.

ResultsThe baseline and updated reviews will be published in a peer review journal. The review findings will be reported in a white paper for clinicians, a fact sheet for people who use ENDS, and country-specific policy briefs.

ConclusionsThe substitution of ENDS for cigarettes is one of the ways to potentially reduce the risks of smoking. Clinicians and their patients need to understand the potential benefits and possible risks of substituting ENDS for cigarettes. Our living systematic reviews seek to highlight the best and most up-to-date evidence in this highly contentious and fast-moving field of research.

category: addiction medicine


title: First wastewater surveillance-based city zonation for effective COVID-19 pandemic preparedness powered by early warning: A study of Ahmedabad, India

abstract:
Following the proven concept, capabilities, and limitations of detecting the RNA of Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) in wastewater, it is pertinent to understand the utility of wastewater surveillance data on various scale. In the present work, we put forward the first wastewater surveillance-based city zonation for effective COVID-19 pandemic preparedness. A three-month data of Surveillance of Wastewater for Early Epidemic Prediction (SWEEP) was generated for the world heritage city of Ahmedabad, Gujarat, India. In this expedition, one hundred sixteen wastewater samples were analyzed to detect SARS-CoV-2 RNA, from September 3rd to November 26th, 2020. A total of 111 samples were detected with at least two out of three SARS-CoV-2 genes (N, ORF 1ab, and S). Monthly variation depicted a significant decline in all three gene copies in October compared to September 2020, followed by a sharp increment in November 2020. Correspondingly, the descending order of average genome concentration was: November ([~]10729 copies/ L) > September ([~]3047 copies/ L) > October ([~]454 copies/ L). Monthly variation of SARS-CoV-2 RNA in the wastewater samples may be ascribed to a decline of 19.3% in the total number of active cases in October 2020 and a rise of 1.82% in November 2020. Also, the monthly recovery rate of patients was 16.61, 19.31, and 15.58% in September, October, and November 2020, respectively. The percentage change in the genome concentration was observed in the lead of 1-2 weeks with respect to the provisional figures of confirmed cases. SWEEP data-based city zonation was matched with the heat map of the overall COVID-19 infected population in Ahmedabad city, and month-wise effective RNA concentration variations are shown on the map. The results expound on the potential of WBE surveillance of COVID-19 as a city zonation tool that can be meaningfully interpreted, predicted, and propagated for community preparedness through advance identification of COVID-19 hotspots within a given city.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/21253898v1_ufig1.gif" ALT="Figure 1">
View larger version (47K):
org.highwire.dtl.DTLVardef@c1669org.highwire.dtl.DTLVardef@19358f5org.highwire.dtl.DTLVardef@b56189org.highwire.dtl.DTLVardef@167711_HPS_FORMAT_FIGEXP  M_FIG C_FIG Highlights{blacksquare} Wastewater surveillance-based city zonation is effective for COVID-19 pandemic preparedness.
{blacksquare}Three months variation of SARS-CoV-2 RNA in the wastewaters of Ahmedabad, India is presented.
{blacksquare}Wastewater monitoring offers a lead of [~]2 weeks to realize and manage the pandemic situation.
{blacksquare}Mapping powered by early warning can strengthen the preparedness of community.
{blacksquare}WBE based COVID-19 surveillance is a high end technique for identifying hotspots on city scale.


title: Underlying cardiovascular risk and major adverse cardiovascular events after acute respiratory infection: a population-based cohort study of over 4.2 million individuals in England, 2008-2018

abstract:
BackgroundWhile acute respiratory infections (ARIs) can lead to cardiovascular complications, the effect of underlying cardiovascular risk profile on ARI incidence and cardiovascular complications in those without established cardiovascular disease (CVD) is unknown. Whether to consider individuals at raised cardiovascular risk a priority group for vaccination against respiratory infections therefore remains unclear.

MethodsWe conducted a cohort study in individuals aged 40-64 years without established CVD or a chronic health condition eligible for influenza vaccination, using Clinical Practice Research Datalink GOLD and Aurum data from 01/09/2008-31/08/2018 linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England. We classified cardiovascular risk based on diagnosed hypertension and overall predicted cardiovascular risk estimated using QRISK2 score ([≥]10% compared with <10%). Using multivariable Poisson regression models, we obtained incidence rate ratios (IRR) for ARI. Among individuals who had an ARI, we then used multivariable Cox regression to obtain hazard ratios (HR) for the risk of major adverse cardiovascular events (MACE) within one year of infection.

Findings4,212,930 individuals were included; 12{middle dot}5% had hypertension and 14{middle dot}4% had a QRISK2 score [≥]10%. After adjusting for confounders, patients with hypertension (IRR 1{middle dot}04, 95% CI 1{middle dot}03-1{middle dot}05) or QRISK2 score [≥]10% (IRR 1{middle dot}39, 1{middle dot}37-1{middle dot}40) had a higher incidence of ARI. Of the 442,408 individuals with an ARI, 4,196 had a MACE within one year of infection. After adjustment, hypertension (HR 1{middle dot}98, 1{middle dot}83-2{middle dot}15) and QRISK2 score [≥]10% (HR 3{middle dot}65, 3{middle dot}42-3{middle dot}89) were associated with substantial increased risk of a MACE after infection.

InterpretationPeople without diagnosed CVD but who have raised cardiovascular risk, measured by diagnosed hypertension or, in particular, overall predicted cardiovascular risk, have increased incidence of both ARI and cardiovascular complications following an ARI.


title: Details of COVID-19 Disease Mitigation Strategies in 17 K-12 Schools in Wood County, Wisconsin

abstract:
ImportanceWith the current COVID-19 return-to-school guidelines, over half of Americas K-12 students are being denied access to full time in-person education, leading to harmful academic, emotional and health consequences.

ObjectiveTo describe the specific details of mitigation strategies employed at 17 K-12 schools in Wisconsin during a time of exceptionally high COVID-19 community disease prevalence where in-school transmission was minimal. The aim of this report is to assist school districts and governing bodies in developing full-time return to school plans.

DesignRetrospective cohort

SettingWood County, Wisconsin, August 31-November 29, 2020

Participants5,530 students and staff from 17 schools in 4 school districts

Main outcomes and measuresO_LIDistancing between primary and secondary students in school
C_LIO_LISchool ventilation details
C_LIO_LIMasking among teachers
C_LIO_LILunch, recess and bussing practices
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Results89.3% of elementary students included in our study did not maintain 6 feet of physical distancing in the classroom and 94.8% were within 6 feet in lunchrooms. The majority of secondary students (86.2%) were able to maintain 6 feet of distancing in the classroom but no students were greater than 6 feet in the hallways. 58.8% of schools did not install new ventilation systems prior to the school year. Students ate lunch indoors. Bussing of students continued and all elementary children were allowed to go without masks at recess.

Conclusion and relevanceIn the setting of high community COVID-19 disease transmission, 6 feet of distance between elementary students and major ventilation system renovations in primary or secondary schools do not appear to be necessary to minimize disease spread. Requiring masks at recess and prohibiting bussing also appears unnecessary. These findings may inform guidance on the safe reopening of schools and allow for more children to return to in-person schooling.


title: Sarcopenic obesity and the risk of hospitalisation or death from COVID-19: findings from UK Biobank

abstract:
BackgroundCoronavirus disease{square}2019 (COVID{square}19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS{square}CoV{square}2 virus). The role of skeletal muscle mass in modulating immune response is well documented. Whilst obesity is well-established as a key factor in COVID-19 infection and outcome, no study has examined the influence of both sarcopenia (low muscle mass) and obesity, termed  sarcopenic obesity on COVID-19 risk.

MethodsThis study uses data from UK Biobank. Probable sarcopenia was defined as low handgrip strength. Sarcopenic obesity was mutually exclusively defined as the presence of obesity and low muscle mass (based on two established criteria: appendicular lean mass (ALM) adjusted for either: 1) height and 2) body mass index (BMI)).  Severe COVID-19 was defined by a positive test result in a hospital setting or death with a primary cause reported as COVID-19. Fully adjusted logistic regression models were used to analyse the associations between sarcopenic status and severe COVID-19. This work was conducted under UK Biobank application number 52553.

ResultsWe analysed data from 490,301 UK Biobank participants. 2203 (0.4%) had severe COVID-19 infection. Individuals with probable sarcopenia were 64% more likely to have had severe COVID-19 infection (odds ratio (OR) 1.638; P<.001). Obesity increased the likelihood of severe COVID-19 infection by 76% (P<.001). Using either ALM index and ALM/BMI index to define low muscle mass, those with sarcopenic obesity were 2.6 times more likely to have severe COVID-19 (OR: 2.619; P<.001). Sarcopenia alone did not increase the risk of COVID-19.

ConclusionsSarcopenic obesity may increase the risk of severe COVID-19 infection, over that of obesity alone. The mechanisms for this are complex but could be a result of a reduction in respiratory functioning, immune response, and ability to respond to metabolic stress.


title: Effect of Increased Alcohol Consumption During COVID-19 Pandemic on Alcohol-related Liver Disease: A Modelling Study

abstract:
ObjectivesThe burden of alcohol-related liver disease (ALD) is surging in the US. There is evidence that alcohol consumption increased during the early periods of the coronavirus disease-2019 (COVID-19) pandemic. We describe the impact of increased alcohol consumption on alcohol-related liver disease.

DesignMicrosimulation model

SettingModel parameters estimated from publicly available data sources, including national surveys on drug and alcohol use and published studies informing the impact of alcohol consumption on ALD severity.

ParticipantsUS residents

MethodsWe extended a previously validated microsimulation model that estimated the short- and long-term effect of increased drinking during the COVID-19 pandemic in individuals in the US born between 1950-2012. We modelled short- and long-term outcomes of current drinking patterns during COVID-19 (status quo) using survey data of changes in alcohol consumption in a nationally representative sample between February and April 2020. We compared these outcomes with a counter-factual scenario wherein no COVID-19 occurs, and drinking patterns do not change. Reported outcomes are for individuals aged 18-65.

Main outcome measuresALD-related deaths inclusive of HCC mortality, the prevalence and incidence of decompensated cirrhosis and hepatocellular carcinoma, and disability-adjusted life-years (DALYs)

ResultsIncreases in alcohol consumption during 2020 due to the COVID-19 pandemic are estimated to result in to 8,200 [95% UI 7,700 - 8,700] additional ALD-related deaths (1% increase compared with the counter-factual scenario), 17,100 [95% UI 16,100 - 18,200] cases of decompensated cirrhosis (2% increase) and 1,100 [95% UI 1,100 - 1,200] cases of HCC (1% increase) between 2020 and 2040. Between 2020 and 2023, alcohol consumption changes due to COVID-19 will lead to 100 [100-200] additional deaths and 2,200 [2,200-2,300] additional decompensations in patients suffering from alcohol-related liver disease.

ConclusionsA short-term increase in alcohol consumption during the COVID-19 pandemic can substantially increase long-term ALD-related morbidity and mortality. Our findings highlight the need for individuals and policymakers to make informed decisions to mitigate the impact of high-risk alcohol drinking in the US.

Summary Box"O_ST_ABSWhat is already known on this topicC_ST_ABSO_LIThe impact of an increase in alcohol consumption during coronavirus disease 2019 (COVID-19) on drinking trajectory changes and alcohol-related liver diseases is not known.
C_LIO_LIStudies have reported increases in hospital admissions for alcohol-related liver disease or pancreatitis potentially related to COVID-19, increases in alcohol consumption, and exacerbation of pre-existing liver injury, though limited evidence exists for the long-term effect of increased drinking on alcohol-related liver cirrhosis and liver cancer in the USA.
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Added value of this studyO_LIOur study provides new data on liver disease morbidity and mortality associated with increased consumption of alcohol during the COVID-19 pandemic.
C_LIO_LIOur study suggests that drinking changes associated with the COVID-19 pandemic it is expected to lead to increases in both mortality and morbidity in the long term. to 8,200 additional ALD-related deaths, 17,100 cases of decompensated cirrhosis, and 1,100 cases of HCC between 2020 and 2040 2
C_LI

category: gastroenterology


title: Common Data Elements, Scalable Data Management Infrastructure and Analytics Workflows for Large-scale Neuroimaging Studies

abstract: 1.Neuroscience studies require considerable bioinformatic support and expertise. Numerous high-dimensional and multimodal datasets must be preprocessed and integrated to create robust and reproducible analysis pipelines. We describe a common data elements and scalable data management infrastructure that allows multiple analytics workflows to facilitate preprocessing, analysis and sharing of large-scale multi-level data. The process uses the Brain Imaging Data Structure (BIDS) format and supports MRI, fMRI, EEG, clinical and laboratory data. The infrastructure provides support for other datasets such as Fitbit and flexibility for developers to customize the integration of new types of data. Exemplar results from 200+ participants and 11 different pipelines demonstrate the utility of the infrastructure.


title: Transdiagnostic Neural Signatures in common Pediatric Psychiatric Disorders: a data-driven meta-analysis of functional neuroimaging studies

abstract:
BACKGROUNDIn the last decades, neuroimaging studies have attempted to unveil the neurobiological markers underlying pediatric psychiatric disorders. However, children diagnosed with such disorders are likely to receive an additional diagnosis in the following years. Yet, the vast majority of neuroimaging studies focus on a single nosological category, which limit our understanding of the shared/specific neural correlates between these disorders. Therefore, we aimed to investigate the transdiagnostic neural signatures through a novel meta-analytical method.

METHODA data-driven meta-analysis was carried out which grouped similar experiments topographic map together, irrespectively of nosological categories and task-characteristics. Then, activation likelihood estimation meta-analysis was performed on each group of experiments to extract spatially convergent brain regions.

RESULTSOne hundred forty-seven experiments were retrieved (3199 subjects): 79 attention-deficit/hyperactivity disorder, 32 conduct/oppositional defiant disorder, 14 anxiety disorders, 22 major depressive disorders. Four significant groups of experiments were observed. Functional characterization suggested that these groups of aberrant brain regions may be implicated internally/externally directed processes, attentional control of affect, somato-motor and visual processes. Furthermore, despite that some differences in rates of studies involving major depressive disorders were noticed, nosological categories were evenly distributed between these four sets of regions. Additionally, main effects of task characteristics were observed.

CONCLUSIONSBy using a data-driven meta-analytic method, we observed four significant groups of aberrant brain regions that may reflect transdiagnostic neural signature of pediatric psychiatric disorders. Overall, results of this study underscore the importance of studying pediatric psychiatric disorders simultaneously rather than independently.


title: Equitable Vaccine Access within an Age-Based Framework

abstract:
ObjectivesSeveral states have adopted age-based prioritization for COVID-19 vaccine eligibility (also prioritizing teachers and child care workers) because it is simple (especially when age is quantized by decade) and age is strongly associated with COVID-19 mortality. But this approach raises equity concerns based in law and ethics. This study proposes data-driven solutions for equitable policy that retains the advantages of an age-based approach.

MethodsUsing data from CDC and U.S. Census Bureau, I analyzed 507,227 COVID-19 deaths in the U.S. by age and race-ethnicity and compared the risk ratios to published data on risk ratios for other conditions.

ResultsCOVID-19 mortality in the U.S. rose 2.59-fold per decade of life [95% confidence interval (2.52, 2.66)]. Down syndrome, organ transplantation, and intellectual/developmental disability have risk ratios for COVID-19 mortality that exceed that.

ConclusionsPeople with specific conditions (including certain disabilities and certain medical conditions) associated with a risk ratio of 2.59 or 6.71 should be granted vaccine eligibility along with people 10 or 20 years older, respectively. Along with additional recommendations on data collection and reporting, this could help address equity within an age-based framework.

3-Question Summary BoxO_LISome states have adopted age-only prioritization for COVID-19 vaccine access, quantized by decade of life, because it is simple, and age has a strong association with COVID-19 mortality. But this raises concerns based in law and ethics.
C_LIO_LIThis study quantifies the age effect and documents that COVID-19 mortality increases 2.59-fold per decade of life--a smaller increase than some conditions.
C_LIO_LIPeople with conditions associated with at least 2.59-fold COVID-19 mortality should be granted vaccine eligibility along with people at least 10 years older.
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