title: Vaccine Rollout Strategies: The Case for Vaccinating Essential Workers Early

abstract: In planning for upcoming mass vaccinations against COVID-19, many jurisdictions have proposed using primarily age-based rollout strategies, where the oldest are vaccinated first and the youngest last. In the wake of growing evidence that approved vaccines are effective at preventing not only adverse outcomes, but also infection (and hence transmission of SARS-CoV-2), we propose that such age-based rollouts are both less equitable and less effective than strategies that prioritize essential workers. We demonstrate that strategies that target essential workers earlier consistently outperform those that do not, and that prioritizing essential work-ers provides a significant level of indirect protection for older adults. This conclusion holds across numerous outcomes, including cases, hospitalizations, Long COVID, deaths and net monetary benefit, and over a range of possible values for the efficacy of vaccination against infection. Our analysis focuses on regimes where the pandemic continues to be controlled with distancing and other measures as vaccination proceeds, and where the vaccination strategy is expected to last for over the coming 6-8 months -- for example British Columbia, Canada. In such a setting with a total population of 5M, vaccinating essential workers sooner is expected to prevent over 200,000 infections, over 600 deaths, and to produce a net monetary benefit of over $500M.


title: Evaluation of COVID-19 as a risk factor for maternal-fetal and neonatal complications: protocol of a systematic review and meta-analysis of cohort and case-control studies.

abstract:
BackgroundCOVID-19 in pregnant women has been suggested to impair maternal-fetal and neonatal outcomes. We then designed the present systematic review with meta-analysis to evaluate the repercussion of such disease over maternal fetal and neonatal mortality, need for intensive care, way of delivery, premature delivery, birth weight, Apgar score, presence of intrauterine growth restriction (IGR), and presence of amniotic fluid change.

MethodsWe will conduct a computerized search through MEDLINE/PubMed, LILACS/BIREME, Web of science, Biorxiv, Medrxiv, and Embase on July 23, 2020. We will include cohort and case-control studies fully reported comparing pregnant women with COVID-19 with those not affected by the disease for maternal fetal and neonatal mortality, need for intensive care, way of delivery, premature delivery occurrence, birth weight, Apgar scores, presence of intrauterine growth restriction, and presence of amniotic fluid change. Three doubles of reviewers will perform in duplicate and independently all steps on screening, risk of bias judgments, and data extraction with ability to discuss disagreements with supervising authors. Pooled effects will be estimated by both fixed and random-effects models and presented according to qualitative and quantitative heterogeneity assessment. Sensitivity analyses will be performed as well as a priori subgroup, meta-regression and multiple meta-regression analyses. Well also evaluate the risk of selective publication by assessing funnel plot asymmetry and the quality of the evidence by the application of the GRADE recommendations.

DiscussionThis systematic review with meta-analysis aims to assess the repercussion of COVID-19 in pregnant women over maternal-fetal and neonatal outcomes and to help clinicians and health systems improve such population outcomes throughout the current pandemic.

Systematic review registrationThis review protocol was also submitted to PROSPERO registration on February 9, 2021.

category: obstetrics and gynecology


title: Study protocol for an inception cohort investigating possible predictors of systemic steroids effectiveness in treatment of acute sciatic pain

abstract:
IntroductionSciatic pain secondary to nerve root compression occurs in approximately 1% of the general population in the United States, which represents enormous costs related to the treatment and loss of function of symptomatic individuals.

Acute radicular pain is predominantly caused by herniation of the intervertebral disc but can also be caused by degenerative changes. Compressive and inflammatory mechanical factors are interrelated in the pathophysiology of symptoms.

Although radiculopathy is self-limited in most cases, in its acute stage it is associated with painful symptoms and loss of essential function. The first-line treatment usually employed is a conservative approach, including a short rest period and use of common analgesics and nonsteroidal anti-inflammatory drugs.

As an alternative to the conservative approach, the systemic administration of oral corticosteroids, such as prednisone, are widely used. However, the current literature shows contradictory results for this treatment in terms of improvement of pain and function.

The present study hypothesizes that treatment with prednisone is effective in the treatment of acute sciatic pain in patients with social, clinical, and demographic characteristics favorable to this treatment.

Objectivesthe main objective of the present study is to identify predictors, both clinical and imaging, of a positive response, in terms of both function and pain intensity, to prednisone treatment in patients with acute sciatic pain.

Methods and analysisthe present study will include a cohort of patients, with a diagnosis of acute sciatica, who will receive treatment with oral prednisone. The pain and functional scores before and after treatment will be compared. Thereafter, the social, clinical, and radiographic characteristics of responsive patients will be compared to those of patients who did not respond well to the treatment.

Ethics and disseminationthe study received the approval of Federal University of Sao Paulo Research Committee (4.232.193) and Research Ethics National Committee (CONEP).

ARTICLE SUMMARYStrengths and limitations of this study

O_LIThe study is based on samples from a large population recruited from a reference facility for the treatment of acute sciatic pain.
C_LIO_LIThere is potential for optimization of treatment response with oral corticosteroids.
C_LIO_LIThe study will be conducted with a population with defined clinical characteristics.
C_LIO_LIDue to the relatively short follow-up period, the project will not evaluate alternative treatments, such as surgery.
C_LI

category: orthopedics


title: Effect of in-hospital treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on mortality and complications in patients hospitalized for COVID-19: a large Spanish cohort study.

abstract:
BackgroundThe use of ACEI (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin II Receptor Blocker) in COVID-19 remains controversial. Our main aim was to describe the effect of ACEI/ARB treatment during COVID-19 hospitalization on mortality and complications.

MethodsRetrospective, observational, multicenter study, part of the SEMI-COVID-19 Registry, comparing patients with COVID-19 treated with ACEI/ARB during hospitalization to those not treated. The primary endpoint was incidence of the composite outcome of prognosis (IMV [Invasive Mechanical Ventilation], NIMV [Non-Invasive Mechanical Ventilation], ICU admission [Intensive Care Unit], and/or all-cause mortality). The secondary endpoint was incidence of MACE (Major Adverse Cardiovascular Events). We evaluated both outcomes in patients whose treatment with ACEI/ARB continued or was withdrawn during hospitalization.

ResultsBetween February and June 2020, 11,205 patients were included, with mean age 67 years (SD=16.3) and 43.1% female; 2,162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed a protective effect on all-cause mortality (p<.0001). In hypertensive patients it was also protective in terms of IMV, ICU admission, and the composite outcome of prognosis (p<.0001 for all). No differences were found in incidence of MACE. Patients previously treated with ACEI/ARB who continued treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB had a more beneficial effect on survival than ACEI (HR 0.77, 95%CI 0.62-0.96).

ConclusionACEI/ARB treatment during COVID-19 hospitalization had a protective effect on mortality. The benefits were greater in hypertensive patients, those who continued treatment during hospitalization, and those taking ARB.

SummaryTreatment with ACEI/ARB during COVID-19 hospitalization showed a beneficial effect on mortality in the general population. The benefit was greater in hypertensive patients, in those who maintained treatment during hospitalization and those taking ARB.

category: cardiovascular medicine


title: A scoping review exploring the impact of digital systems on processes and outcomes in the care management of acute kidney injury and progress towards establishing learning healthcare systems

abstract:
BackgroundDigital systems have long been used to improve the quality and safety of care when managing Acute Kidney Injury (AKI). The availability of digitised clinical data can also turn organisations and their networks into Learning Healthcare Systems (LHSs) if used across all levels of health and care. This review explores the impact of digital systems on AKI patient care to gauge progress towards establishing LHSs and to identify existing gaps in the research.

MethodEmbase, PubMed, Medline, Cochrane, Scopus and Web of Science databases were searched. Studies of real-time or near real-time digital AKI management systems which reported process and outcome measures were included.

ResultsThematic analysis of 43 studies showed that most interventions used real-time serum creatinine (SCr) levels to trigger responses to enable risk prediction, early recognition of AKI or harm prevention by individual clinicians (micro level) or specialist teams (meso level). Interventions at system (macro level) were rare. There was limited evidence of change in outcomes.

ConclusionWhilst the benefits of real time digital clinical data at micro level for AKI management have been evident for some time, their application at meso and macro levels is emergent therefore limiting progress towards establishing LHSs. Lack of progress is due to digital maturity, system design, human factors and policy levers. Future approaches need to harness the potential of interoperability and data analytic advances and include multiple stakeholder perspectives to overcome these factors.

category: health informatics


title: Use of WATCH antibiotics prior to presentation to the hospital in rural Burkina Faso

abstract:
BackgroundIn low- and middle-income countries (LMIC), the prevalence of antimicrobial resistance (AMR) is increasing. WHO recommends monitoring antibiotic use, in particular Watch antibiotics, clinical important but at risk of becoming ineffective due to increasing AMR. We investigated antibiotic use at primary care or community-level in rural Burkina Faso.

MethodsDuring 2016-2017, patients aged >3 months admitted with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, reported antibiotic use in the two weeks prior to consultation or hospitalization, which we analysed using the WHO Access, Watch, Reserve (AWaRe) classification. Most Watch antibiotics, e.g. ceftriaxone, are not recommended at primary health center level, as is also the case for ciprofloxacin in children.

ResultsOf 920 participants (63.0% [≤]14 years), pre-admission antibiotic use was reported by 363 (39.5%) of whom 58 (16.0%) reported more than one antibiotic. Use was more frequent among health center referrals (231, 54.0%) than among self-referred patients (131, 26.7%, p<0.001). Of 424 antibiotics, 261 (61.6%) were Access and 159 (37.5%) Watch antibiotics. Watch antibiotics use was more frequent among >14 year olds (72, 51.1%) than 0-14 year olds (87, 30.7%) and among referrals (41, 28.1%) compared to self-referred patients (117, 42.2%). Most frequently used Watch antibiotics were ceftriaxone (114, 26.9%) and ciprofloxacin (32, 7.5%). Among antibiotics reported by referral patients, ceftriaxone and ciprofloxacin were respectively recorded 100 (36.1%) and 12 times (4.3%).

ConclusionThe frequent use of Watch group antibiotics prior to presentation to the hospital in rural Burkina Faso highlights the need to address primary care, over-the-counter and informal community-level antibiotic use as part of antibiotic stewardship in LMIC, facilitating referral, access to qualified prescribers, or improving diagnostic tools in health centers.

category: public and global health


title: Non-pharmaceutical interventions and inoculation rate shape SARS-COV-2 vaccination campaign success

abstract: Nearly one year into the COVID-19 pandemic, the first SARS-COV-2 vaccines received emergency use authorization and vaccination campaigns began. A number of factors can reduce the averted burden of cases and deaths due to vaccination. Here, we use a dynamic model, parametrized with Bayesian inference methods, to assess the effects of non-pharmaceutical interventions, and vaccine administration and uptake rates on infections and deaths averted in the United States. We estimate that high compliance with non-pharmaceutical interventions could avert more than 60% of infections and 70% of deaths during the period of vaccine administration, and that increasing the vaccination rate from 5 to 11 million people per week could increase the averted burden by more than one third. These findings underscore the importance of maintaining non-pharmaceutical interventions and increasing vaccine administration rates.


title: Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL Study

abstract: Central obesity is a leading health concern with a great burden carried by ethnic minority populations, and especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aim to: 1) identify novel loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC), and hip circumference (HIP), all adjusted for body mass index (adjBMI), using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); 2) determine if differences in genetic associations differ by background group within HCHS/SOL; 3) determine whether previously reported association regions generalize to HCHS/SOL. Our analyses included 7,472 women and 5,200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban, and Dominican) background residing in the US, with genome-wide array data imputed to the 1000 genomes Phase I multiethnic reference panel. We analyzed associations stratified by sex in addition to sexes combined using linear mixed-model regression. We identified 16 variants for WHRadjBMI, 22 for WCadjBMI, and 28 for HIPadjBMI that reached suggestive significance (P<1x10-6). Many of the loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in nine cohort studies (N=34,161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (ancestry-specific P<0.05 in replication, consistent direction of effect with HCHS/SOL, and P<5x10-8 after meta-analysis with HCHS/SOL), including rs13301996 in the sexes-combined analysis, and rs79478137 for women-only for WHRadjBMI; rs28692724 in women-only for HIPadjBMI; and rs3168072 in the sexes combined analysis for WCadjBMI. Also, a total of eight previously reported WHRadjBMI association regions, 12 for HIPadjBMI, and 10 for WCadjBMI generalized to HCHS/SOL. Our study findings highlight the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity-susceptibility that may be ancestry-specific.

category: genetic and genomic medicine


title: Health impact and cost-effectiveness of COVID-19 vaccination in Sindh Province, Pakistan

abstract:
BackgroundMultiple COVID-19 vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh province, Pakistan (population: 48 million).

Methods and FindingsWe fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalization outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario.

We project that one-year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5 year duration of protection is likely to avert around 0.9 (95% Credible Interval: 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Varying these assumptions, we generally find that prioritizing the older (65+) population prevents more deaths, but broad distribution from the outset is economically comparable in many scenarios, and either scheme can be cost-effective for low per-dose costs. However, high vaccine prices ($10/dose) may not be cost-effective.

The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses.

These projections are limited by the mechanisms present in the model. Because the model is a single-population compartmental model, detailed impacts of non-pharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritizing groups like healthcare or other essential workers. Additionally, because the future impact and implementation cost of NPIs is uncertain, how these would interact with vaccination remains an open question.

ConclusionsCOVID-19 vaccination can have a considerable health impact, and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact, but the advantage of focusing initially on older, high-risk populations may be smaller in generally younger populations where many people have already been infected, typical of many low- and -middle income countries, as long as vaccination gives good protection against infection as well as disease.

Author SummaryO_ST_ABSWhy Was This Study Done?C_ST_ABS- The evidence base for health and economic impact of COVID-19 vaccination in low- and middle-income settings is limited.
- Searching PubMed, medRxiv, and econLit using the search term ("coronavirus" OR "covid" OR "ncov") AND ("vaccination" OR "immunisation") AND ("model" OR "cost" OR "economic") for full text articles published in any language between 1 January 2020 and 20 January 2021, returned 29 (PubMed), 1,167 (medRxiv) and 0 (econLit) studies: 20 overall were relevant, with only 4 exclusively focused on low- or middle-income countries (India, China, Mexico), while 3 multi-country analyses also included low- or middle-income settings,
- However only three of these studies are considered economic outcomes, all of them comparing the costs of vaccination to the costs of non-pharmaceutical interventions and concluding that both are necessary to reduce infections and maximise economic benefit.
- The majority of studies are set in high-income settings and conclude that targeting COVID-19 vaccination to older age groups is the preferred strategy to minimise mortality, particularly when vaccine supplies are constrained, while other age- or occupational risk groups should be priorities when vaccine availability increases or when other policy objectives are pursued.

What Did the Researchers Do and Find?- We combined epidemiological and economic analysis of COVID-19 vaccination based on real-world disease and programmatic information in the Sindh province of Pakistan.
- We found vaccination in this setting is likely to be highly cost-effective, and even cost saving, as long as the vaccine is reasonably priced and efficacy is high.
- Unlike studies in high-income settings, we also found that vaccination programmes targeting all adults may have almost as much benefit as those initially targeted at older populations, likely reflecting the higher previous infection rates and different demography in these settings.

What Do These Findings Mean?- Lower- and middle-income countries (LMICs) and international bodies providing guidance for LMICs need to consider evidence specific to these settings when making recommendations about COVID-19 vaccination.
- Further data and model-based analyses in such settings are urgently needed in order to ensure that vaccination decisions are appropriate to these contexts.

category: health economics


title: COVID-19 vaccination in Sindh Province, Pakistan: a modelling study of health impact and cost-effectiveness


title: Evaluation of a surrogate virus neutralization test for high-throughput serosurveillance of SARS-CoV-2

abstract: High-throughput serological tests that can detect neutralizing antibodies against SARS-CoV-2 are desirable for serosurveillance and vaccine efficacy evaluation. Although the conventional neutralization test (cVNT) remains the gold standard to confirm the presence of neutralizing antibodies in sera, the test is too labour-intensive for massive screening programs and less reproducible as live virus and cell culture is involved. Here, we performed an independent evaluation of a commercially available surrogate virus neutralization test (sVNT, GenScript cPass) that can be done without biosafety level 3 containment in less than 2 hours. When using the cVNT and a Luminex multiplex immunoassay (MIA) as reference, the sVNT obtained a sensitivity of 94% (CI 90-96%) on a panel of 317 immune sera that were obtained from hospitalized and mild COVID-19 cases from Belgium and a sensitivity of 89% (CI 81-93%) on a panel of 184 healthcare workers from the Democratic Republic of Congo. We also found strong antibody titer correlations (rs>0.8) among the different techniques used. In conclusion, our evaluation suggests that the sVNT could be a powerful tool to monitor/detect neutralising antibodies in cohort and population studies. The technique could be especially useful for vaccine evaluation studies in sub-Saharan Africa where the basic infrastructure to perform cVNTs is lacking.

category: infectious diseases


title: A prospective evaluation of the analytical performance of GENECUBE(R) HQ SARS-CoV-2 and GENECUBE(R) FLU A/B

abstract:
BackgroundMolecular tests are the mainstay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, their accessibility can be limited by the long examination time and inability to evaluate multiple samples at once. This study evaluated the analytical performance of the newly developed rapid molecular assays GENECUBE(R) HQ SARS-CoV-2 and the GENECUBE(R) FLU A/B.

MethodThis prospective study was conducted between December 14, 2020, and January 9, 2021, at a polymerase chain reaction (PCR) center. Samples were collected from the nasopharynx with flocked swabs. Molecular tests were performed with the GENECUBE(R) system and reference reverse transcription (RT)-PCR, and the results of the two assays were compared.

ResultAmong 1065 samples, 81 (7.6%) were positive for SARS-CoV-2 on the reference RT-PCR. Three showed discordance between GENECUBE(R) HQ SARS-CoV-2 and the reference RT-PCR; the total, positive and negative samples of concordance for the two assays were 99.7%, 100%, and 99.7%, respectively. All discordant cases were positive for GENECUBE(R) HQ SARS-CoV-2 and negative for the reference RT-PCR. SARS-CoV-2 was detected from all three samples by another molecular assay for SARS-CoV-2. For the GENECUBE(R) FLU A/B, the total, positive and negative samples of concordance for the two assays were 99.5%, 100%, and 99.1%.

ConclusionThe GENECUBE(R) HQ SARS-CoV-2 and GENECUBE(R) FLU A/B demonstrated sufficient analytical performance to detect SARS-CoV-2 and influenza virus A/B.

Key pointsWe prospectively evaluated the analytical performance of the newly developed rapid molecular assays GENECUBE(R) HQ SARS-CoV-2 and the GENECUBE(R) FLU A/B. The two assays showed >99% concordance rate compared with a reference PCR, which indicated their sufficient analytical performance to detect SARS-CoV-2 and influenza virus A/B.


title: Genetic predisposition to psychiatric disorders and risk of COVID-19

abstract:
BackgroundPre-pandemic psychiatric disorders have been associated with an increased risk of COVID-19. However, the underlying mechanisms remain unknown, e.g. to what extent genetic predisposition to psychiatric disorders contributes to the observed association.

MethodsThe analytic sample consisted of white British participants of UK Biobank registered in England, with available genetic data, and alive on Jan 31, 2020 (i.e., the start of the COVID-19 outbreak in the UK) (n=346,554). We assessed individuals genetic predisposition to different psychiatric disorders, including substance misuse, depression, anxiety, and psychotic disorder, using polygenic risk score (PRS). Diagnoses of psychiatric disorders were identified through the UK Biobank hospital inpatient data. We performed a GWAS analysis for each psychiatric disorder in a randomly selected half of the study population who were free of COVID-19 (i.e., the base dataset). For the other half (i.e., the target dataset), PRS was calculated for each psychiatric disorder using the discovered genetic variants from the base dataset. We then examined the association between PRS of each psychiatric disorder and risk of COVID-19, or severe COVID-19 (i.e., hospitalization and death), using logistic regression models. The ascertainment of COVID-19 was through the Public Health England dataset, the UK Biobank hospital inpatient data and death registers, updated until July 26, 2020. For validation, we repeated the PRS analyses based on publicly available GWAS summary statistics.

Results155,988 participants (including 1,451 COVID-19 cases), with a mean age of 68.50 years at COVID-19 outbreak, were included for PRS analysis. Higher genetic liability forwards psychiatric disorders was associated with increased risk of both any COVID-19 and severe COVID-19, especially genetic risk for substance misuse and depression. The adjusted odds ratios (ORs) for any COVID-19 were 1.15 (95% confidence interval [CI] 1.02-1.31) and 1.26 (1.11-1.42) among individuals with a high genetic risk (above the upper tertile of PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Largely similar ORs were noted for severe COVID-19 and similar albeit slightly lower estimates using PRSs generated from GWAS summary statistics from independent samples.

ConclusionIn the UK Biobank, genetic predisposition to psychiatric disorders was associated with an increased risk of COVID-19, including severe course of the disease. These findings suggest the potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19, underscoring the need of increased medical surveillance of for this vulnerable population during the pandemic.

category: epidemiology


title: Detection and stability of SARS-CoV-2 fragments in wastewater: Impact of storage temperature

abstract:
SARS-CoV-2 wastewater epidemiology suffers from uncertainties concerning sample storage. We show the effect of storage of wastewater on the detectable SARS-CoV-2 load. Storage at 4 {degrees}C up to 9 days had no significant effect, while storage at -20 {degrees}C led to a significant reduction in gene copy numbers.

HighlightsO_LIRaw wastewater samples can be stored up to 9 days at 4{degrees}C for SARS-CoV-2 wastewater surveillance
C_LIO_LIFreezing of wastewater sample dramatically decreases RT-qPCR signal of SARS-CoV-2 from wastewater.
C_LI


title: Impact of COVID-19 on Mental Health: A Longitudinal Study Using Penalized Logistic Regression

abstract: The COVID-19 pandemic has posed significant influence on the public mental health in a stealthy manner. Current efforts focus on alleviating the impacts of the disease on public health and economy, with the psychological effects due to COVID-19 largely ignored. In this paper, we analyze a mental health related dataset from the US to enhance our understanding of human reactions to the pandemic. We are particularly interested in providing quantitative characterization of the pandemic impact on the public mental health, on top of qualitative explorations. We employ the multiple imputation by chained equations (MICE) method to deal with missing values and take the logistic regression with least absolute shrinkage and selection operator (Lasso) method to identify risk factors for mental health. The analyses are conducted to a large scale of online survey data from 12 consecutive weeks, so that the longitudinal trend of the risk factors can be investigated. Our analysis results unveil evidence-based findings to identify the groups who are psychologically vulnerable to COVID-19. This study is useful to assist healthcare providers and policy makers to take steps for mitigating the pandemic effects on public mental health.


title: ARTIFICIAL INTELLIGENCE BASED PERSONALIZED DIET: A PILOT CLINICAL STUDY FOR IBS

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackground and aimsC_ST_ABSCertain diets often used to manage functional gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). Personalized diet-induced microbiome modulation is being preferred method for symptom improvement in IBS. Although personalized nutritional therapies targeting gut microbiota using artificial intelligence (AI) promises a great potential, this approach has not been studied in patients with IBS. Therefore, in this study we investigated the efficacy of AI-based personalized microbiome diet in patients with IBS-Mix (M).

MethodsThis study was designed as a pilot, open-labelled study. We enrolled consecutive IBS-M patients (n=25, 19 females, 46.06 {+/-} 13.11 years) according to Rome IV criteria. Fecal samples were obtained from all patients twice (pre- and post-intervention) and high-througput 16S rRNA sequencing was performed. Patients were divided into two groups based on age, gender and microbiome matched. Six weeks of AI-based microbiome diet (n=14) for group 1 and standard IBS diet (Control group, n=11) for group 2 were followed. AI-based diet was designed based on optimizing a personalized nutritional strategy by an algorithm regarding individual gut microbiome features. An algorithm assessing an IBS index score using microbiome composition attempted to design the optimized diets based on modulating microbiome towards the healthy scores. Baseline and post-intervention IBS-SSS (symptom severity scale) scores and fecal microbiome analyses were compared.

ResultsThe IBS-SSS evaluation for both pre- and post-intervention exhibited significant improvement (p<0.02 and p<0.001 for the control and intervention groups, respectively). While the IBS-SSS evaluation changed to moderate from severe in 82% (14 out of 17) of the intervention group, no such change was observed in the control group. After 6-weeks of intervention, a major shift in microbiota profiles in terms of alfa- or beta-diversity was not observed in both groups. A trend of decrease in Ruminococcaceae family for the intervention group was observed (p=0.17). A statistically significant increase in Faecalibacterium genus was observed in the intervention group (p = 0.04). Bacteroides and putatively probiotic genus Propionibacterium were increased in the intervention group, however Prevotella was increased in the control group. The change (delta) values in IBS-SSS scores (before-after) intervention and control groups are significantly higher in the intervention group.

ConclusionAI-based personalized microbiome modulation through diet significantly improves IBS-related symptoms in patients with IBS-M. Further large scale, randomized placebo-controlled trials with long-term follow-up (durability) are needed.

category: gastroenterology


title: Specific Thoracic Pain: Red flag screening pathway for Physiotherapists. A Systematic Review.

abstract: The lifetime prevalence of isolated pain in the thoracic spine is relatively low, approximately 13-17%, compared to neck and low back pain, 40% and 57% respectively. However a patient with thoracic or chest pain is more likely to mask a serious pathology, such as spinal fracture, spinal tumor or metastasis, myocardial ischemia, pneumonia, etc.. A physical therapist is a primary healthcare professional and it is his responsibility to screen and identify serious pathologies outside the scope of practice. That is, differential diagnosis may help in excluding medical pain sources and, most importantly, recognize emergencys scenarios. An in-depth subjective and objective examination are the two pillars for the clinical evaluation that may help clinicians to determine if the pain is of musculoskeletal origin or not. In the literature, there is a lack of knowledge about the red flags (i.e. warning symptoms and signs) that can be useful for the screening for referral, not medical diagnosis, in the thoracic and chest wall pain. The aim of our systematic review is to investigate which findings form the subjective (symptoms and red flags) and objective examination (signs and tests) are valid tools for the differential diagnosis for thoracic pain or chest pain suspected to be caused by a serious pathology.

category: rehabilitation medicine and physical therapy


title: Epidemiological and Genomic analysis of a Sydney Hospital COVID-19 Outbreak

abstract: Australias early COVID-19 experience involved clusters in northern Sydney, including hospital and aged-care facility (ACF) outbreaks. We explore transmission dynamics, drivers and outcomes of a metropolitan hospital COVID-19 outbreak that occurred in the context of established local community transmission. A retrospective cohort analysis is presented, with integration of viral genome sequencing, clinical and epidemiological data. We demonstrate using genomic epidemiology that the hospital outbreak (n=23) was linked to a concurrent outbreak at a local aged care facility, but was phylogenetically distinct from other community clusters. Thirty day survival was 50% for hospitalised patients (an elderly cohort with significant comorbidities) and 100% for staff. Staff who acquired infection were unable to attend work for a median of 26.5 days (range 14-191); an additional 140 staff were furloughed for quarantine. Transmission from index cases showed a wide dispersion (mean 3.5 persons infected for every patient case and 0.6 persons infected for every staff case). One patient, who received regular nebulised medication prior to their diagnosis being known, acted as an apparent superspreader. No secondary transmissions occurred from isolated cases or contacts who were quarantined prior to becoming infectious. This analysis elaborates the wide-ranging impacts on patients and staff of nosocomial COVID-19 transmission and highlights the utility of genomic analysis as an adjunct to traditional epidemiological investigations. Delayed case recognition resulted in nosocomial transmission but once recognised, prompt action by the outbreak management team and isolation with contact and droplet (without airborne) precautions were sufficient to prevent transmission within this cohort. Our findings support current PPE recommendations in Australia but demonstrate the risk of administering nebulised medications when COVID-19 is circulating locally.


title: Early Antibody Responses Associated with Survival in COVID19 Patients

abstract:
Neutralizing antibodies to the SARS CoV-2 spike proteins have been issued Emergency Use Authorizations and are a likely mechanism of vaccines to prevent COVID-19. However, benefit of treatment with monoclonal antibodies has only been observed in clinical trials in outpatients with mild to moderate COVID-19 but not in patients who are hospitalized and/or have advanced disease. To address this observation, we evaluated the timing of anti SARS-CoV-2 antibody production in hospitalized patients with the use of a highly sensitive multiplexed bead-based immunoassay allowing for early detection of antibodies to SARS-CoV-2. We found that significantly lower levels of antibodies to the SARS-CoV-2 spike protein in the first week after symptom onset were associated with patients who expired as compared to patients who were discharged. We also developed a model, based on antibody level trajectory, to predict COVID 19 outcome that is compatible with greater antibody benefit earlier in COVID 19 disease.

Author SummaryWe evaluated antibodies to SARS-CoV-2 over time in patients that were hospitalized with COVID 19. Early detection of Anti-SARS-CoV-2 antibodies was associated with survival in patients hospitalized with COVID 19. Early antibody levels predicted outcome in our study. This result is consistent with the benefit of therapeutic antibodies early in the course of COVID 19 disease. With additional study, early antibody levels may be helpful in deciding on appropriate therapies.


title: Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial

abstract:
BackgroundOlder patients are at risk of increased morbidity and mortality from COVID-19 disease due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There are few effective treatments for outpatients with COVID-19.

ObjectiveTo evaluate the efficacy of hydroxychloroquine to reduce time in quarantine for symptomatic [≥]40 years-old COVID-19 patients.

DesignA randomized, double-blind, placebo-controlled clinical trial.

SettingOutpatients with polymerase chain reaction confirmed COVID-19 at a University of Pennsylvania affiliated testing center between April 15, 2020 and, July 14, 2020.

ParticipantsOut of 5511 SARS-CoV-2 positive patients, 1072 met initial eligibility criteria for telephone-based recruitment, but only 34 subjects were able to be randomized.

InterventionsHydroxychloroquine 400 mg per twice daily (n=17) or matching placebo (n=17), taken orally for up to 14 days.

MeasurementsThe primary outcome was the time to release from quarantine. Secondary outcomes included the participant-reported secondary infection of co-inhabitants, hospitalization, treatment-related adverse events, time to symptom improvement, and incidence of cardiac arrhythmia.

ResultsThe median time to release from quarantine for HCQ-treated vs. placebo-treated participants was 8 days (range 4-19 days) vs. 11 days (4-18 days); z-score +0.58, p=n.s. This did not meet the pre-specified criteria for early termination, however, this study was terminated early due to lack of feasibility. There was no mortality in either study arm.

LimitationSince this study was terminated early due to a lack of feasibility, no conclusion can be made about the efficacy of hydroxychloroquine as a treatment for COVID-19 patients 40 years of age or older quarantined at home.

ConclusionThe design of this remotely conducted study could guide testing of other more promising agents during the COVID-19 pandemic.

Trial registrationClinicaltrials.gov identifier: NCT04329923


title: Laboratory-Developed Test for SARS-CoV-2 Using Saliva Samples at the University of California, Riverside

abstract: Here we describe a relatively quick, simple, economical and accurate laboratory developed test (LDT) for detection of SARS-CoV-2 in heated and diluted saliva samples without RNA extraction. Our protocol is a variation of the University of Illinois Urbana-Champaign SHIELD LDT. Differences include chilling of the samples during dilution and using a reduced volume for the qRT-PCR reactions. The level of detection for our LDT is 3125 copies/ml, which compares favorably with other saliva-based tests. Initial validation studies with a limited number of patient samples have demonstrated excellent agreement between results using our LDT and those obtained from external laboratories. The cost of consumables for our test is under $8 and a throughput of 1000 tests/day can be achieved with 3-4 personnel.


title: Association between Functional Inhibitors of Acid Sphingomyelinase and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: results from an observational multicenter study

abstract: Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter retrospective study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) who were taking a FIASMA medication, and 1,060 patients (41.4%) who were not. Taking a FIASMA medication was associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p<0.001) and the primary IPW (HR=0.58; 95%CI=0.46-0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one FIASMA class or medication. These results show the potential importance of the ASM/ceramide system as a treatment target in COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.


title: Risk of death among teachers in England and Wales during the Covid19 pandemic

abstract:
ObjectivesTo estimate occupation risk from Covid19 among teachers and others working in schools using publicly available data on mortality in England and Wales.

DesignAnalysis of national death registration data from the Office for National Statistics.

SettingEngland and Wales, March 20th to 28th December 2020, during the Covid19 pandemic.

ParticipantsThe total working age population in England and Wales plus those still working aged over 65.

Primary and Secondary outcomesDeath with Covid19 as a primary outcome and death from all causes as a secondary outcome.

ResultsAcross occupational groups there was a strong correlation between Covid19 mortality and both non-Covid19 and all-cause mortality. The absolute mortality rates for deaths with Covid19 were low amongst those working in schools (from 10 per 100,000 in female primary school teachers to 39 per 100,000 male secondary school teachers) relative to many other occupations (range: 10 to 143 per 100,000 in men; 9 to 50 per 100,000 in women).There was weak evidence that secondary school teachers had slightly higher risks of dying with Covid19 compared to the average for all working aged people, but stronger evidence of a higher risk compared to the average for all professionals; primary school teachers had a lower risk. All-cause mortality was also higher amongst all teachers compared to all professionals. Teaching and lunchtime assistants were not at higher risk of death from Covid19 compared with all working aged people.

ConclusionThere was weak evidence that Covid19 mortality risk for secondary school teachers was above expectation, but in general school staff had Covid19 mortality risks which were proportionate to their non-covid mortality risk.

Strengths and limitations of this studyO_LIWe used routinely collected data on all deaths in England and Wales;, which are near-complete and not susceptible to serious ascertainment biases.
C_LIO_LIWe were able to compare mortality data for teachers and other school workers with all other occupational groups and with the working-age population.
C_LIO_LIThe number of deaths due to Covid19 were small and thus differences between the specific occupational groups were imprecisely estimated.
C_LIO_LIWe did not have access to individual level mortality data so were not able to account for potential confounders such as comorbidities or household size.
C_LIO_LIFor those working in school aged over 65 we had neither mortality rates per 100,000 nor total numbers within the group; we only had number of deaths and a 5-year average and we do not know whether the denominators have changed for this group over the last 5 years.
C_LI


title: Young and invisible: an explanatory model for service engagement by people who inject drugs in India

abstract:
IntroductionThe HIV epidemic in India is concentrated in key populations such as people who inject drugs (PWID). New HIV infections are high among young PWID ([≤] 30 years of age), who are hard to engage in services. We assessed perspectives of young PWID across three Indian cities representing historic and emerging drug use epidemics to guide development of youth-specific services.

MethodsWe conducted focus group discussions (FGDs) with PWID (ages 18-35 years) and staff at venues offering services to PWID in three cities (Aizawl and Imphal, Northeast India and Amritsar, Northwest India). A semi-structured interview guide was used to elicit participants narratives on injection initiation experiences, motivating factors and barriers to seeking harm-reduction services, service-delivery gaps, and recommendations to promote engagement.

Thematic analysis was used to develop an explanatory model for engagement for each temporal stage across the injection continuum: (a) pre-injection initiation, (b) peri-injection initiation and (c) established injection behavior.

Results43 PWID (81% male, 19% female) and 10 staff members participated in FGDs. Injection initiation followed non-injection opioid dependence. Lack of services for non-injection opioid dependence was a key gap in the pre-injection initiation phase. Lack of knowledge and reliance on informal sources for injecting equipment were key reasons for non-engagement in the peri-injection phase. Additionally, low risk perception resulted in low motivation to seek services.

Psychosocial and structural factors shaped engagement after established injection. Housing and food insecurity, and stigma disproportionately affected female PWID while lack of confidential adolescent friendly services impeded engagement by adolescent PWID.

ConclusionsDevelopment of youth-specific services for young PWID in India will need to address unique vulnerabilities and service gaps along each stage of the injection continuum. Scaling-up of tailored services is needed for young female PWID and adolescents, including interventions that prevent injection initiation and provision of confidential harm-reduction services.

STRENGTHS AND LIMITATIONSO_LIThe findings in this study represent some of the first qualitative data to explore engagement with services, specifically among young PWID in India.
C_LIO_LIThe study was conducted in multiple cities representing older and emerging injection drug use epidemics. The inclusion of multiple cities adds strength to the findings.
C_LIO_LIWe did not recruit adolescent PWID due to constraints rendered by laws pertaining to informed consent in India.
C_LIO_LIAlthough all PWID we recruited had initiated injection in adolescence or young adulthood, the preponderance of older PWID in our study limits the conclusions we can draw about the needs of adolescent PWID.
C_LI


title: Effect of rearfoot strikes on the hip and knee rotational kinetic chain during the early phase of cuttings in female athletes

abstract:
PurposeBiomechanical factors affecting horizontal-plane hip and knee kinetic-chain and anterior cruciate ligament (ACL) injury risks during cutting maneuvers remains unclear. This study aimed to examine whether different foot strike patterns alter horizontal-plane hip and knee kinetics and kinematics during a cutting maneuver in female athletes and clarify the individual force contribution for producing high-risk hip and knee loadings.

MethodsTwenty-five healthy female athletes performed a 60{degrees} cutting task with forefoot and rearfoot first strike conditions. Horizontal-plane hip and knee moment components, angles, and angular velocities were calculated using synchronized data of the marker positions on the body landmarks and ground reaction forces (GRF) during the task. The one-dimensional statistical parametric mapping paired t-test was used to identify the significant difference in kinetic and kinematic time-series data between foot strike conditions.

ResultsIn the rearfoot strike condition, large hip and knee internal rotation loadings were produced during the first 5% of stance due to the application of GRFs, causing a significantly larger hip internal rotation excursion than that of the forefoot strike condition. Dissimilarly, neither initial hip internal rotation displacement nor knee internal rotation GRF loadings were observed in the forefoot strike condition.

ConclusionRearfoot strike during cutting appears to increase noncontact ACL injury risks as the GRF tend to produce combined hip and knee internal rotation moments and the high-risk lower limb configuration. Conversely, forefoot strike during cutting appears to be an ACL-protecting strategy as the ACL-harmful joint loadings and lower-extremity configurations do not tend to be produced. Thus, improving foot strike patterns during cutting should be incorporated into ACL injury prevention programs.

category: sports medicine


title: Impact of Systemic Arterial Pressure, Collateral Vascular Resistance and Degree of Carotid Stenosis on Cerebral Blood Flow, Reserve Blood Flow, Critical Carotid Stenosis, Cerebral Ischemia and Carotid Hemodynamics

abstract:
IntroductionCarotid artery stenosis related stroke is a major health care concern. Current risk management strategies for patients with asymptomatic carotid stenosis include ultrasound surveillance and occasionally an estimate of cerebral blood flow reserve. Other patient specific hemodynamic variables may be predictive of ischemic stroke risk. This study, based on a cerebral blood flow hemodynamic model, aims to investigate the impact of systemic arterial pressure, collateral vascular resistance and degree of carotid stenosis on cerebral ischemic risk, cerebrovascular blood flow reserve, critical carotid artery stenosis, carotid artery blood flow and carotid stenosis hemodynamics.

MethodsThis study uses a three-component (carotid, collateral, brain) energy conservation cerebrovascular fluid mechanics model in combination with the Lassen cerebral blood flow autoregulation model that predicts cerebral blood flow in patients with carotid stenosis. It is a two-phase model, zone A when regional cerebral blood flow is autoregulated at normal values and zone B when cerebral blood flow is below normal and dependent on collateral perfusion pressure. The model solution with carotid artery occlusion defines collateral vascular resistance, with patient specific values calculated from clinical pressure measurements. In addition to cerebral blood flow the model predicts critical stenosis values and carotid and collateral blood flows as a function of systemic arterial pressure and percent diameter stenosis. Carotid stenosis blood flow velocities and energy dissipation are predicted from carotid blood flow solutions.

ResultsThe model defines patient specific collateral vascular resistance, cerebral vascular resistance and critical carotid stenosis. It predicts carotid vascular resistance to be non-linearly proportional to area carotid stenosis. Solutions include reserve cerebral blood flow, the carotid and collateral components of cerebral blood flow, criteria for cerebral ischemia and carotid stenosis hemodynamics. Critical carotid stenosis is determined by mean systemic arterial pressure and the Lassen autoregulation threshold cerebral perfusion pressure. Critical stenosis values range from 61% to 76% diameter stenosis when mean systemic arterial pressures are 80mmHg to 120mmHg and the cerebral autoregulation pressure threshold is 50mmHg. When carotid stenosis is less than critical, cerebral blood flow is maintained normal and the ratios of carotid blood flow to collateral blood flow are inversely proportional to the carotid to collateral vascular resistance ratios. At stenosis greater than the critical, carotid blood flow is not adequate to maintain normal cerebral blood flow, cerebral blood flow is primarily collateral flow, all reserve blood flow is collateral and prevention of cerebral ischemia requires adequate collateral flow. Patient specific collateral vascular resistance values less than 1.0 predict normal cerebral blood flow at moderate to severe stenosis. Values greater than 1.0 predicts cerebral ischemia to be dependent on the magnitude of collateral vascular resistance. Systemic arterial pressure is a major determinant of carotid stenosis hemodynamics. Carotid blood flow velocities increase with carotid stenosis and have progressively higher variance depending on collateral blood flow as predicted by collateral vascular resistance. Turbulent flow energy dissipation intensity is similarly inversely proportional to collateral vascular resistance at severe carotid stenosis.

ConclusionsCerebral, collateral and carotid blood flow solutions are determined by systemic arterial pressure, collateral vascular resistance and degree of stenosis. Critical carotid stenosis, systemic arterial pressure and collateral vascular resistance are primary determinants of cerebral ischemic risk in patients with significant carotid stenosis.

category: surgery


title: Development of web-based quality-assurance tool for radiotherapy target delineation for head and neck cancer: quality evaluation of nasopharyngeal carcinoma

abstract:
PurposeWe developed QUANNOTATE, a new web-application for rapid review of radiotherapy (RT) target volumes, and used it to evaluate the relationship between target delineation compliance with the international guidelines and treatment outcomes in nasopharyngeal carcinoma (NPC) patients undergoing definitive RT.

Methods and MaterialsThe dataset used for this study consists of anonymized CT simulation scans, RT structures, and clinical data of 332 pathologically confirmed NPC patients treated with intensity-modulated RT between July 2005 and August 2017. We imported the contours of intermediate risk clinical target volumes of the primary tumor (IR-CTVp) receiving 56 Gy into QUANNOTATE. We determined inclusion of anatomic sites within IR-CTVp in accordance with 2018 International guideline for CTV delineation for NPC and correlated the results with time to local failure (TTLF) using Cox-regression.

ResultsAt a median follow-up of 5.6 years, 5-year TTLF and overall survival rates were 93.1% and 85.9% respectively. The most frequently non-guideline compliant anatomic sites were sphenoid sinus (n = 69, 20.8%), followed by cavernous sinus (n = 38, 19.3%), left and right petrous apices (n = 37 and 32, 11.1% and 9.6%), clivus (n = 14, 4.2%), and right and left foramen rotundum (n = 14 and 12, 4.2% and 3.6%). Among 23 patients with a local failure (6.9%), the number of non-compliant cases were 8 for sphenoid sinus, 7 cavernous sinus, 4 left and 3 right petrous apices, and 2 clivus. Compared to conforming cases, cases which did not contour the cavernous sinus had a higher local failure (LF) rate (89.1% vs 93.6%, p= 0.013). Multivariable analysis confirmed that lack of cavernous sinus contouring was prognostic for LF.

ConclusionsQUANNOTATE allowed rapid review of target volumes in a large patient cohort. Despite an overall high compliance with the international guidelines, undercoverage of the cavernous sinus was correlated with LF.

category: oncology


title: Single-cell RNA sequencing demonstrates the intratumoral heterogeneity of papillary thyroid carcinoma

abstract: Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Although PTC usually has a favorable prognosis, some aggressive PTC subtypes and lymph node (LN) metastasis contribute to high rates of recurrence and poor clinical outcomes. We analyzed single-cell RNA sequencing (scRNA-seq) data from 15 samples, including primary tumors of PTC, metastatic LNs, and paracancerous tissues. After quality filtering, 28,205 cells were detected. Of these, 13,390 cells originated from 7 tumor tissues, 2,869 cells from 2 metastatic LNs, and 11,945 cells from 6 paracancerous tissues. The increase in the proportion of CD4+ Tregs may be a key factor responsible for the immunosuppressive property of PTC. A novel cell type was identified, named Protective EGR1+CD4+ T cell, which might be antagonistic to the CD4+ Tregs and inhibit the formation of the immunosuppressive microenvironment and tumor immune evasion. Inhibitory checkpoints TIGIT and CD96 were found to be better targets than PD-1 for immune therapy in PTC patients with LN metastasis. For PTC patients without LN metastasis, however, PD-1, TIGIT, and CD96 could be suitable targets of immunotherapy. These findings would contribute to the further understanding of molecular mechanisms resulting in occurrence and development of PTC, and provide a theoretical rationale for targeted therapy and immunotherapy.


title: Single-cell RNA sequencing reveals a novel cell type and immunotherapeutic targets in papillary thyroid cancer


title: Self-reported Memory Problems Eight Months after Non-Hospitalized COVID-19 in a Large Cohort

abstract:
BackgroundNeurological manifestations of COVID-19 range from ageusia and anosmia, experienced by most patients, to altered consciousness and rare and severe encephalopathy. A direct affection of the central nervous system (CNS) in the disease has been supported by animal models and MRI findings in patients with mild and severe symptoms. Here we report eight-month data on memory problems for non-hospitalized COVID-19 patients compared to SARS-CoV-2 negative patients and untested volunteers.

ObjectiveTo explore the association between non-hospitalized COVID-19 eight months previously and self-reported memory problems.

MethodsWe followed a cohort of 13156 participants that was invited after (1) being tested for SARS-CoV-2 with a combined oropharyngeal- and nasopharyngeal swab or (2) randomly selected from the Norwegian population (untested). Participants completed online baseline- and follow-up questionnaires detailing underlying medical conditions, demographics, symptoms, and items from the RAND-36 questionnaire on health-related quality of life and known confounders for memory problems.

ResultsAfter repeated invitations, the participation rate was 40% (N=794) of SARS-CoV-2 positive, 26% (N=7993) of negative, and 22% (N=4369) of untested randomly selected invitees. All participants completed the baseline questionnaire as a part of inclusion.

The follow-up period was 248 days (SD=18) from baseline, and the follow-up questionnaire was completed by 75% of SARS-CoV-2 positive participants, 65% of negative participants, and 73% of untested randomly selected participants.

At follow-up, 49 (11.5%) of the SARS-CoV-2 positive participants reported memory problems in contrast to 173 (4.1%) of the SARS-CoV-2 negative participants and 65 (2.4%) of the untested randomly selected participants.

In a multivariate model, SARS-CoV-2 positivity remained strongly associated with reporting memory problems at eight months follow-up compared to the SARS-CoV-2 negative group (odds ratio (OR) 4.0, 95% confidence interval (CI) 2.8-5.2) and the untested group (OR 4.9, 95% CI 3.4-7.2).

Compared to the other groups, SARS-CoV-2 positive participants also reported more concentration problems and a significant worsening of health compared to one year ago at follow-up. Feeling depressed, less energy, or pain were reported relatively equally by the different groups.

SummaryWe find that 11.5% of COVID-19 patients experience memory problems eight months after the disease. SARS-CoV-2 is a new virus, and the long-term consequences of infections are therefore unknown. Our results show that a relatively high proportion of non-hospitalized COVID-19 patients report memory problems eight months after the disease.


title: Bamlanivimab does not neutralize two SARS-CoV-2 variants carrying E484K in vitro

abstract:
The IgG1 monoclonal antibody (mAb) bamlanivimab (LY-CoV555) prevents viral attachment and entry into human cells by blocking attachment to the ACE2 receptor. However, whether bamlanivimab is equally effective against SARS-CoV-2 emerging variants of concern (VOC) is not fully known. Hence, the aim of this study was to determine whether bamlanivimab is equally effective against SARS-CoV-2 emerging VOC. The ability of bamlanivimab to neutralize five SARS-CoV-2 variants including B.1.1.7 (mutations include N501Y and del69/70), B.1.351 (mutations include E484K and N501Y) and P.2 (mutations include E484K in the absence of a N501Y mutation) was analyzed in infectious cell culture using CaCo2 cells. Additionally, we analyzed vaccine-elicited sera after immunization with BNT162b2, and convalescent sera for its ability to neutralize SARS-CoV-2 variants.

We found that the variant B.1.1.7, as well as two isolates from early 2020 (FFM1 and FFM7) could be efficiently neutralized by bamlanivimab (titer 1/1280, respectively), however, no neutralization effect could be detected against either B.1.135 or P.2, both harboring the E484K substitution. Vaccine-elicited sera showed slightly decreased neutralizing activity against B1.1.7, B.1.135 and P.2

Our in vitro findings indicate that, in contrast to vaccine-elicited sera, bamlanivimab may not provide efficacy against SARS-CoV-2 variants harboring the E484K substitution. Confirmation of the SARS-CoV-2 variant, including screening for E484K, may be needed before initiating mAb treatment with bamlanivimab to ensure both efficacious and efficient use of the antibody product. Hence, variant-specific mAb agents may be required to treat emerging VOC.


title: COVID-19 symptom frequency comparison: non-hospitalised positively and negatively tested persons with flu-like symptoms in Austria

abstract:
BackgroundMost clinical studies report the symptoms experienced by those infected with Coronavirus disease 2019 (COVID-19) via patients already hospitalised. Here we analyse the symptoms experienced by the general population in Vienna.

MethodsThe Vienna Social Fund (FSW, Vienna, Austria), the Public Health Services of the City of Vienna (MA15) and the private company Symptoma collaborated to implement Viennas official online COVID-19 symptom checker. Users answered 12 yes/no questions about symptoms to assess their risk for COVID-19. They could also specify their age and sex, and whether they had contact with someone who tested positive for COVID-19. Depending on the assessed risk of COVID-19 positivity, a SARS-CoV-2 nucleic acid amplification test (NAAT) was performed. In this publication, we analysed which factors (symptoms, sex or age) are associated with COVID-19 positivity. We also trained a classifier to correctly predict COVID-19 positivity from the collected data.

ResultsBetween the 2nd of November 2020 and the 18th of November 2021, 9133 people experiencing COVID-19-like symptoms were assessed as high risk by the chatbot and were subsequently tested by a NAAT. Symptoms significantly associated with a positive COVID-19 test were malaise, fatigue, headache, cough, fever, dysgeusia and hyposmia. Our classifier could successfully predict COVID-19 positivity with an Area Under the Curve (AUC) of 0.74.

ConclusionThis study provides reliable COVID-19 symptom statistics based on the general population verified by NAATs.


title: Symptoms associated with a COVID-19 infection in the general population of Vienna


title: Longitudinal analysis of SARS-CoV-2 seroprevalence using multiple serology platforms

abstract: Serological tests are important tools helping to determine previous infection with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) and to monitor immune responses. The current tests are based on spike (S), the receptor binding domain (RBD), or the nucleoprotein (NP) as substrate. Here, we used samples from a high seroprevalence cohort of health care workers (HCWs) to perform a longitudinal analysis of the antibody responses using three distinct serological assays. 501 serum samples were tested using: a) a research-grade RBD and spike based tandem enzyme-linked immunosorbent assay (MS-RBD ELISA, MS-spike ELISA), b) a commercial RBD and spike based tandem ELISA (Kantaro-RBD, -spike), and c) a commercial NP-based chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). Seroprevalence ranged around 28% during the early stage of the pandemic (a: 28.4% positives; b: 28.1%; c: 27.3%). Good correlation was observed between the MS and Kantaro RBD ELISAs and between the MS and Kantaro spike ELISAs. By contrast, modest correlations were observed between the Abbott Architect and both RBD and spike-based assays. A proportion of HCWs (n=178) were sampled again 3-5 months after the first time point. Although antibody levels declined in most of the positive individuals, the overall seroprevalence measured by RBD-spike based assays remained unchanged. However the seroprevalence of NP-reactive antibodies significantly declined. Lastly, we tested six samples of individuals who received two doses of SARS-CoV-2 mRNA vaccine and found that seroconversion was detected by the RBD-spike assays but - of course as expected - not the NP based assay. In summary, our results consolidate the strength of different serological assays to assess the magnitude and duration of antibodies to SARS-CoV-2.


title: Control of COVID-19 transmission on an urban university campus during a second wave of the pandemic

abstract:
ImportanceThe COVID-19 pandemic had a wide-ranging impact on educational institutions across the United States. Given potential financial challenges and adverse psychosocial effects of campus closure, as done in the spring of 2020 in response to the first wave, many institutions of higher education developed strategies to allow campuses to reopen and operate in the fall despite the ongoing threat of COVID-19. Many however opted to have limited campus re-opening in order to minimize potential risk of spread of SARS-CoV-2.

ObjectiveTo analyze how Boston University (BU) fully reopened its campus in the fall of 2020 and controlled COVID-19 transmission despite worsening transmission in the city of Boston.

DesignMulti-faceted intervention case study.

SettingLarge urban university campus.

InterventionsThe BU response included a high-throughput SARS-CoV-2 PCR testing facility with capacity to delivery results in less than 24 hours; routine asymptomatic screening for COVID-19; daily health attestations; compliance monitoring and feedback; robust contact tracing, quarantine and isolation in on campus facilities; face mask use; enhanced hand hygiene; social distancing recommendations; de-densification of classrooms and public places; and enhancement of all building air systems.

Main Outcomes and MeasuresBetween August and December 2020, BU conducted >500,000 COVID-19 tests and identified 719 individuals with COVID-19: 627 (87.2%) students, 11 (1.5%) faculty, and 212 (25.5%) staff. Overall, about 1.8% of the BU community tested positive. Infections among faculty and staff were mostly acquired off campus, while undergraduate infections were more likely acquired in non-classroom campus settings. Of 837 close contacts traced, 86 (10.3%) tested positive for COVID-19. BU contact tracers identified a source of transmission for 51.5% of cases with 55.7% identifying a source outside of BU. Among infected faculty and staff with a known source of infection, the majority reported a transmission source outside of BU (100% for faculty and 79.8% for staff).

Conclusions and RelevanceBU was successful in containing COVID-19 transmission on campus while minimizing off campus acquisition of COVID-19 from the greater Boston area. A coordinated strategy of testing, contact tracing, isolation and quarantine, with robust management and oversight, can control COVID-19 transmission, even in an urban university setting.


title: The Public Health Impact of Delaying a Second Dose of the BNT162b2 or mRNA-1273 COVID-19 Vaccine

abstract:
ObjectivesTo estimate population health outcomes under delayedsecond dose versus standard schedule SARS-CoV-2 mRNA vaccination.

DesignAgent-based modeling on a simulated population of 100,000 based on a real-world US county. The simulation runs were replicated 10 times. To test the robustness of these findings, simulations were performed under different estimates for single-dose efficacy and vaccine administration rates, and under the possibility that a vaccine prevents only symptoms but not asymptomatic spread.

Settingpopulation level simulation.

Participants100,000 agents are included in the simulation, with a representative distribution of demographics and occupations. Networks of contacts are established to simulate potentially infectious interactions though occupation, household, and random interactions

Interventionswe simulate standard Covid-19 vaccination, versus delayed-second-dose vaccination prioritizing first dose. Sensitivity analyses include first-dose vaccine efficacy of 70%, 80% and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread; and an alternative vaccination strategy that implements delayed-second-dose only for those under 65 years of age.

Main outcome measurescumulative Covid-19 mortality over 180 days, cumulative infections and hospitalizations.

ResultsOver all simulation replications, the median cumulative mortality per 100,000 for standard versus delayed second dose was 226 vs 179; 233 vs 207; and 235 vs 236; for 90%, 80% and 70% first-dose efficacy, respectively. The delayed-second-dose strategy was optimal for vaccine efficacies at or above 80%, and vaccination rates at or below 0.3% population per day, both under sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100,000. The delayed-second-dose for those under 65 performed consistently well under all vaccination rates tested.

ConclusionsA delayed-second-dose vaccination strategy, at least for those under 65, could result in reduced cumulative mortality under certain conditions.


title: Virtual handover of patients in the pediatric intensive care unit during COVID-19 crisis

abstract:
ObjectivesA key measure to mitigate coronavirus disease 2019 (COVID-19) has been social distancing. Incorporating video-conferencing applications in the patient handover process between healthcare workers can enhance social distancing while maintaining handover elements. This study describes pediatric intensive care unit (PICU) physicians experience of using an online video-conferencing application for handover during the COVID-19 pandemic. Design: qualitative content analysis

SettingPICU at a university hospital in Riyadh, Saudi Arabia Subjects: PICU Physicians

InterventionsDue to the pandemic, the hospitals PICU used Zoom(R) as a remote conferencing application, instead of a face-to-face handover. Following institutional review board approval, data were collected over two weeks (July 1, 2020 to July 14, 2020). Measurements: Demographic data and narrative descriptions of the perceived efficacy of remote handover were collected using open-ended questions through a created online link. The analysis process included open coding, creating categories, and abstraction.

Main ResultsAll 37 PICU physicians who participated in the handover completed the survey. The participants comprised six attendings, nine specialists, and 22 residents. They had variable previous teleconferencing experiences. Most physicians (78.4%) were comfortable conducting a remote endorsement. Most found that Situation-Background- Assessment-Recommendation handover elements were properly achieved through this remote handover process. The perceived advantages of online handover included fewer interruptions, time efficiency, and facilitation of social distancing. The perceived disadvantages were the paucity of nonverbal communication and teaching during virtual meetings.

ConclusionsVideo-conferencing applications used for online handovers could supplement traditional face-to-face intensive care unit patient endorsement during outbreaks of infectious diseases. The use of video streaming and more emphasis on teaching should be encouraged to optimize the users experience.

category: intensive care and critical care medicine


title: Obesity may hamper SARS-CoV-2 vaccine immunogenicity

abstract:
BackgroundThe first goal of the study was to analyse the antibody titre 7 days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and BMI.

MethodsParticipants were assigned to receive the priming dose at baseline and booster dose at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine.

Findings248 HWCs were analysed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response.

The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7); was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. The antibody titre was found to be higher in young and female participants. A strong correlation of BMI classes with antibody titres was noticed: humoral response was more efficient in the group with under- and normal-weight vs the group with pre- and obesity participants (p<0.0001 at T1).

InterpretationThese findings imply that females, lean and young people have an increased capacity to mount humoral immune responses compared to males, overweight and the older population. Although further studies are needed, this data may have important implications for the development of vaccination strategies for COVID-19, particularly in obese people.

FundingNone

category: allergy and immunology


title: Longitudinal protection following natural SARS-CoV-2 infection and early vaccine responses: insights from a cohort of community based dental health care professionals

abstract:
BackgroundThe threshold of protection for anti-SARS-CoV-2 spike glycoprotein antibodies and their longevity are not known. Interpretation of serological results in with respect to international reference material can inform this essential question.

Methods1,507 West Midlands dental care professionals were recruited into this study in June 2020. Baseline seroprevalence of antibodies directed against the SARS-CoV-2 spike glycoprotein was determined and the cohort was followed longitudinally for 6 months until January/February 2021 through the second wave of the COVID-19 pandemic in the United Kingdom, and commencement of vaccination.

ResultsBaseline seroprevalence was 16.3% in this cohort, compared to estimates in the general population of between 6-7%. Seropositivity was retained in over 70% of participants at 3 and 6-month follow up and conferred a 74% reduced risk of infection. During follow-up, no PCR-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. Post-vaccination, antibody responses were more rapid and of higher magnitude in individuals with who were seropositive at baseline.

ConclusionNatural infection leads to a serological response that remains detectable in over 70% of individuals 6 months after initial sampling and 9 months from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech vaccine is associated with an antibody response indicative of immunological memory.

FundingThe Association of Clinical Biochemistry and Laboratory Medicine and The Institute for Global Innovation (IGI) of the University of Birmingham.


title: Plasma Amino Acids Metabolomics Profile Important for Glucose Management in Jordanian people with Type 2 Diabetes

abstract:
BackgroundThe disturbances in plasma free amino acid metabolome in diabetes mellitus was studied before but not in Jordanian population. This study aimed to assess the association between type 2 diabetes (T2D) and amino acid metabolome in a representative group of people from Jordan.

MethodsBlood samples from 124 people with T2D and 67 age-, gender- and BMI-matched healthy controls were collected and assayed for glucose and HbA1c. Twenty one amino acids belonging to different categories (essential, non-essential, semi-essential, and metabolic indicators) were evaluated in both groups using amino acids analyser.

ResultsPlasma free amino acids concentrations of total amino acids, total essential amino acids, total non-essential amino acids, and total semi-essential amino acids were not different in T2D compared to healthy controls. However, plasma concentrations of four essential amino acids (Leucine, Lysine, Phenylalanine, Tryptophan) were increased in the presence of T2D (Leucine, p<0.01, Lysine, p<0.001, Phenylalanine, p<0.01, Tryptophan, p<0.05). Conversely, amongst the non-essential amino acids, Alanine and Serine were reduced in type 2 diabetes (Alanine, p<0.01, Serine, p<0.001), whereas, Aspartate and Glutamate were increased in T2D compared to healthy control plasma (Aspartate, p<0.001, Glutamate, p<0.01). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls (p<0.01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2Dcompared to healthy controls (p<0.01).

ConclusionSeveral amino acids from different categories are dysregulated in T2D, which could be used as a therapeutic target to improve T2D management and its complications.

category: endocrinology


title: A novel morphometric signature of brain alterations in type 2 diabetes: patterns of changed cortical gyrification

abstract:
Type 2 diabetes is a chronic disease that creates atrophic signatures in the brain, including decreases of total and regional volume of grey matter, white matter, and cortical thickness. However, there is a lack of studies assessing cortical gyrification in type 2 diabetes. Changes in this emerging feature has been associated mainly with genetic legacy, but environmental factors may also play a role. Here, we investigated alterations of the gyrification index and classical morphometric measures in type 2 diabetes, a disease with complex etiology with both underlying genetic and more preponderant environmental factors.

In this cross-sectional study we analyzed brain anatomical magnetic resonance images of 86 participants with type 2 diabetes and 40 healthy control participants, to investigate structural alterations in type 2 diabetes, including whole-brain volumetric measures, local alterations of grey matter volume, cortical thickness and the gyrification index.

We found concordant significant decrements in total and regional grey matter volume, and cortical thickness. Surprisingly, the cortical gyrification index was found to be mainly increased in cortical sensory areas in type 2 diabetes. Moreover, it correlated with features of metabolic control. Our findings challenge the classical neurodevelopmental association of gyrification mostly with genetic determinants. While we found mainly increased gyrification in more genetically constrained sensory areas in type 2 diabetes, our correlation results concurrently suggest an influence of metabolic control in alterations of gyrification in type 2 diabetes. Further studies should address causal influences of genetic and/or environmental factors in patterns of cortical gyrification in type 2 diabetes.


title: Epidemiological Philosophy of Pandemics

abstract:
ObjectivesCurrent estimates of the total number of cases of COVID-19 are largely based on previously-determined case fatality rates (CFRs). In this study, we aim to find an association between the Covid-19 number of cases / million inhabitants (M) and mortality rate (MR), and the association of Covid MR -19 and CFR. The background theory in this study is based on two factors: (1) There is no evidence that the CFR is fixed throughout time or place during an epidemic and (2) there is evidence that an increased viral load (density of infection) leads to more fatalities.

Study DesignWe chose 31 countries with testing coverage levels of > 400,0000 tests /M and populations greater than 1 million inhabitants.

MethodsWe used ANOVA regression analyses to test the associations.

ResultsThere was a very highly significant correlation between MR and the total number of cases/ million population inhabitants(M) (P-value 0.0000).

The CRF changed with a change in the MR. A very high positive influence of the COVID-19 MR on the CFR (P-value = 0.0002).

ConclusionsIncreased number of cases per million inhabitants is associated with increased MR. Increased MR is associated with increased CFR. This finding might explain variable mortality rates that happened during this pandemic and possibly previous pandemics. This evidence will give us an idea of the behavior of epidemics in general.


title: A meta-analysis of 20 years of data on people who inject drugs in metropolitan Chicago to inform computational modeling

abstract: Progress toward hepatitis C virus (HCV) elimination in the United States is not on track to meet targets, as injection drug use continues to drive increasing HCV incidence. Computational models are useful in understanding the complex interplay of individual, social, and structural level factors that might alter HCV incidence, prevalence, transmission, and disease progression. However, these models need to be informed with real socio-behavioral data. We conducted a meta-analysis of research studies spanning 20 years of research and interventions with people who inject drugs in metropolitan Chicago to produce parameters for a synthetic population for a computational model. We then fit an exponential random graph model (ERGM) using the network estimates from the meta-analysis in order to develop the dynamic component of a realistic agent-based model.


title: Scalable Epidemiological Workflows to Support COVID-19 Planning and Response

abstract: The COVID-19 global outbreak represents the most significant epidemic event since the 1918 influenza pandemic. Simulations have played a crucial role in supporting COVID-19 planning and response efforts. Developing scalable workflows to provide policymakers quick responses to important questions pertaining to logistics, resource allocation, epidemic forecasts and intervention analysis remains a challenging computational problem. In this work, we present scalable high performance computing-enabled workflows for COVID-19 pandemic planning and response. The scalability of our methodology allows us to run fine-grained simulations daily, and to generate county-level forecasts and other counter-factual analysis for each of the 50 states (and DC), 3140 counties across the USA. Our workflows use a hybrid cloud/cluster system utilizing a combination of local and remote cluster computing facilities, and using over 20,000 CPU cores running for 6-9 hours every day to meet this objective. Our state (Virginia), state hospital network, our university, the DOD and the CDC use our models to guide their COVID-19 planning and response efforts. We began executing these pipelines March 25, 2020, and have delivered and briefed weekly updates to these stakeholders for over 30 weeks without interruption.


title: Using next generation matrices to estimate the proportion of cases that are not detected in an outbreak

abstract: Contact tracing, where exposed individuals are followed up to break ongoing transmission chains, is a key pillar of outbreak response for infectious disease outbreaks. Unfortunately, these systems are not fully effective, and infections can still go undetected as people may not remember all their contacts or contacts may not be traced successfully. A large proportion of undetected infections suggests poor contact tracing and surveillance systems, which could be a potential area of improvement for a disease response. In this paper, we present a method for estimating the proportion of infections that are not detected during an outbreak. Our method uses next generation matrices that are parameterized by linked contact tracing data and case line-lists. We validate the method using simulated data from an individual-based model and then investigate two case studies: the proportion of undetected infections in the SARS-CoV-2 outbreak in New Zealand during 2020 and the Ebola epidemic in Guinea during 2014. We estimate that only 5.26% of SARS-CoV-2 infections were not detected in New Zealand during 2020 (95% credible interval: 0.243 - 16.0%) but depending on assumptions 39.0% or 37.7% of Ebola infections were not detected in Guinea (95% credible intervals: 1.69 - 87.0% or 1.7 - 80.9%).


title: Knowledge, Attitude, and Practices towards SARS-COV-2 Infection in the United Arab Emirates Population: a Cross-sectional Survey-based Study

abstract: In the current situation involving the novel coronavirus disease (COVID-19), the disease containment depends mainly on the populations preventive practices and self-isolation. In this study, we explored the adult populations approach towards COVID-19 in UAE between the 4th and 14th of April 2020. We used a community-based, cross-sectional study using a self-administered electronic questionnaire covering five different aspects: demographics, knowledge, practice, attitude, source and trust of information, and a patient health questionnaire (PHQ-2) for depression screening. A total of 1,867 people responded to the survey. Knowledge results were better in people with higher education levels, non-UAE nationals, those with a higher PHQ-2 score, or with a positive contact history with a SARS-COV-2 infected patient. The best practice scores were shown by participants with high knowledge scores and education levels. Depression risk was significantly higher in men, non-UAE nationals, in those with lower knowledge scores, and younger ages. The most followed practices were staying home, handwashing, avoiding social gatherings, limiting three people per vehicle, and avoiding public transportation. The least practiced measures were covering the face while sneezing or coughing and wearing masks. Although staying home was reported by 92.5% of participants, 22.6% mentioned that they were visited by more than 2 people and visited others in 18.4% during the last week. Social media was the source of information for 82.1% of the participants, and most trusted doctors and healthcare providers. A depression risk was present in 18.9% of the participants and the majority of respondents agreed that SARS-COV-2 infection will finally be successfully controlled. The obtained results on knowledge and practices, although satisfactory, could be insufficient to prevent this pandemic from being contained. We recommend the intensification of awareness programs and good practices. Mental health is an area worth further studies.


title: The neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

abstract:
ObjectivesThere is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.

MethodsWe searched MEDLINE, Embase, PsycInfo and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.

Results13,292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% [35.2--51.3], n=15,975, 63 studies), weakness (40.0% [27.9--53.5], n=221, 3 studies), fatigue (37.8% [31.6--44.4], n=21,101, 67 studies), dysgeusia (37.2% [30.0--45.3], n=13,686, 52 studies), myalgia (25.1% [19.8--31.3], n=66.268, 76 studies), depression (23.0 % [11.8--40.2], n=43,128, 10 studies), headache (20.7% [95% CI 16.1--26.1], n=64,613, 84 studies), anxiety (15.9% [5.6--37.7], n=42,566, 9 studies) and altered mental status (8.2% [4.4--14.8], n=49,326, 19 studies). Heterogeneity for most clinical manifestations was high.

ConclusionsNeurological and neuropsychiatric symptoms of COVID-19 in the pandemics early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

category: psychiatry and clinical psychology


title: Genetic Variations in Evolutionary Accelerated Regions Disrupt Cognition in Schizophrenia

abstract: Cognition is believed to be a product of human evolution, while schizophrenia is ascribed as the by-product with cognitive impairment as its genetically mediated endophenotype. Genomic loci associated with these traits are enriched with recent evolutionary markers such as Human accelerated regions (HARs). HARs are markedly different in humans since their divergence with chimpanzees and mostly regulate gene expression by binding to transcription factors and/or modulating chromatin interactions. We hypothesize that variants within HARs may alter such functions and thus contribute to disease pathogenesis. 49 systematically prioritized variants from 2737 genome-wide HARs were genotyped in a north-Indian schizophrenia cohort (331 cases, 235 controls). Six variants were significantly associated with cognitive impairment in schizophrenia, thirteen with general cognition in healthy individuals. These variants were mapped to 122 genes; predicted to alter 70 transcription factors binding sites and overlapped with promoters, enhancers and/or repressors. These genes and TFs are implicated in neurocognitive phenotypes, autism, schizophrenia and bipolar disorders; a few are targets of common or repurposable antipsychotics suggesting their draggability; and enriched for immune response and brain developmental pathways. Immune response has been more strongly targeted by natural selection during human evolution and has a prominent role in neurodevelopment. Thus, its disruption may have deleterious consequences for neuronal and cognitive functions. Importantly, among the 15 associated SNPs, 12 showed association in several independent GWASs of different neurocognitive functions. Further analysis of HARs may be valuable to understand their role in cognition biology and identify improved therapeutics for schizophrenia.


title: Risk factors for increased COVID-19 case-fatality in the United States: A county-level analysis during the first wave

abstract: The ongoing COVID-19 pandemic is causing significant morbidity and mortality across the US. In this ecological study, we identified county-level variables associated with the COVID-19 case-fatality rate (CFR) using publicly available datasets and a negative binomial generalized linear model. Variables associated with decreased CFR included a greater number of hospitals per 10,000 people, banning religious gatherings, a higher percentage of people living in mobile homes, and a higher percentage of uninsured people. Variables associated with increased CFR included a higher percentage of the population over age 65, a higher percentage of Black or African Americans, a higher asthma prevalence, and a greater number of hospitals in a county. By identifying factors that are associated with COVID-19 CFR in US counties, we hope to help officials target public health interventions and healthcare resources to locations that are at increased risk of COVID-19 fatalities.


title: Parental attitudes towards mandatory vaccination; a systematic review

abstract: While mandatory vaccination schemes can increase vaccine uptake rates, they can also cause backlash among some parents. We conducted a systematic review investigating parental beliefs about vaccine mandates and factors associated with support for mandatory vaccination schemes. We searched Embase, Ovid MEDLINE, Global Health, APA PsycINFO and Web of Science from inception to 17th September 2020. Seventeen studies (five qualitative, twelve quantitative) were eligible for inclusion. We synthesised results of qualitative and quantitative studies separately. Studies were heterogeneous with regard to schemes investigated and factors investigated. Quantitative studies found little evidence for any factors being consistently associated with support for mandatory vaccination. Qualitative studies found that parents perceived mandatory vaccination schemes as an infringement of their rights and that they preferred universal, compared to targeted, schemes. To optimise engagement with existing child mandatory vaccination legislation, schemes should be designed with parental beliefs in mind.


title: A national mixed-mode seroprevalence random population-based cohort on SARS-CoV-2 epidemic in France: the socio-epidemiological EpiCov study

abstract:
Backgroundthe EpiCov study, initiated at the end of the first national lockdown in France, aimed to provide national and regional estimates of the seroprevalence of SARS-CoV-2 infection, and to analyze relations between living conditions and the dynamics of the epidemic. We present and discuss here the survey methodology, and describe the first-round fieldwork.

Method371,000 individuals aged 15 years or more were randomly selected from the national tax register, stratified by departments, including three overseas departments, and by poverty level with over-representation of people living below the poverty line. Health, socio-economics, migration history, and living conditions were collected through self-computed-assisted web interviews or via computer-assisted telephone interviews. The first-round survey was conducted in May. A random subsample was eligible to receive material for home blood self-sample on dried blood spot (DBS), in order to detect IgG antibodies against the spike protein (Euroimmun ELISA-S), and neutralizing antibodies for non-negative ELISA-S. For the second-round conducted in November, all respondents were eligible for the antibodies detection from home DBS sample, as well as the other household members aged 6 years or more for 20% of them.

Participation and adjustment for nonresponse134,391 respondents completed the first-round questionnaire from May 2 to June 1, 2020, including 16,970 (12.6%) respondents under the poverty line. Multimodal web/tel interviews was randomly assigned to 20% of the sample. The other were assigned to exclusive CAWI. Overall 17,441 respondents were eligible for home blood sample, among them 12,114 returned the DBS (interquartile date: May 25-June 5). The response probability was first estimated from logit models adjusted on a wide range of auxiliary demographic and socio-economic variables available from the sampling frame, and final weights calibrated to the margins of the population census permitted to correct for a large part of the non-response bias.

ConclusionThe Epicov study is one of the largest national random population-based seroprevalence cohort, with both an epidemiological and sociological approaches to evaluate the spread of the COVID-19 epidemic, and the impact on health and living conditions. One of the major interests of this study is the broad coverage of the socio-economic and territorial diversity of the population.