title: Fatigue symptoms associated with COVID-19 in convalescent or recovered COVID-19 patients; a systematic review and meta-analysis

abstract:
BackgroundThe prevalence and prognosis of post-acute stage SARS-CoV-2 infection fatigue symptoms remain largely unknown.

AimsWe performed a systematic review to evaluate the prevalence of fatigue in post-recovery from SARS-CoV-2 infection.

MethodMedline, Embase, PsycINFO, CINAHL, Web of Science, Scopus, trial registries, Cochrane Central Register of Controlled Trials and Google Scholar were searched for studies on fatigue in samples that recovered from PCR diagnosed COVID-19. English, French and Spanish studies were included. Meta-analyses were conducted separately for each recruitment setting.

ResultsWe identified 41 studies with 9362 patients that recovered from COVID-19. Post-COVID-19 patients self-report of fatigue was higher compared to healthy controls (RR = 3.688, 95%CI [2.502, 5.436], p < 0.001). Over 50% of patients discharged from inpatient care reported symptoms of fatigue during the first (ER = 0.517, 95%CI [0.278, 0.749]) and second month following recovery (ER = 0.527, 95%CI [0.337, 0.709]). 10% of the community patients reported fatigue in the first-month post-recovery. Patient setting moderated the association between COVID-19 recovery and fatigue symptoms (R2 = 0.11, p < 0.001). Female patients recovering from COVID-19 had a greater self-report of fatigue (OR = 1.782, 95%CI [1.531, 2.870]). Patients recruited through social media had fatigue above 90% across multiple time points. Fatigue was highest in studies from Europe.

ConclusionFatigue is a symptom associated with functional challenges which could have economic and social impacts. Developing long-term planning for fatigue management amongst patients beyond the acute stages of SARS-CoV-2 infection is essential to optimizing patient care and public health outcomes. Further studies should examine the impact of sociodemographic, pandemic-related restrictions and pre-existing conditions on fatigue.


title: Depression during the COVID-19 pandemic amongst residents of homeless shelters in France.

abstract:
BackgroundAccumulating evidence suggests that the COVID-19 pandemic has negatively affected global mental health and well-being. However, the impact amongst homeless persons has not been fully evaluated. The ECHO study reports factors associated with depression amongst the homeless population living in shelters in France during the Spring of 2020.

MethodsInterview data were collected from 527 participants living in temporary and/or emergency accommodation following Frances first lockdown (02/05/20 - 07/06/20), in the metropolitan regions of Paris (74%), Lyon (19%) and Strasbourg (7%). Interviews were conducted in French, English, or with interpreters (33% of participants, [~]20 languages). Presence of depression was ascertained using the Patient Health Questionnaire (PHQ-9).

ResultsAmongst ECHO study participants, 30% had symptoms of moderate to severe depression (PHQ-9[≥] 10). Multivariate analysis revealed depression to be associated with being female (aOR: 2.15; CI: 1.26-3.69), being single (aOR: 1.60; CI: 1.01-2.52), having a chronic illness (aOR: 2.32; CI: 1.43:-3.78), facing food insecurity (aOR: 2.12; CI: 1.40-3.22) and participants region of origin. Persons born in African and Eastern Mediterranean regions showed levels of depression comparable to those of French participants (30-33%) but higher than migrants from European countries (14%). Reduced rates of depression were observed amongst participants aged 30-49 (aOR: 0.60; CI: 0.38-0.95) and over 50 (aOR: 0.28; CI: 0.13-0.64), compared to 18-29-year-olds.

ConclusionsOur results indicate high levels of depression among homeless persons during the COVID-19 pandemic. The value of these findings extends beyond the health crisis, as predicted future instability and economic repercussions could particularly impact the mental health of this vulnerable group.

category: public and global health


title: Reopen or redistribute? Modeling years of life lost due to Covid-19, socioeconomic status, and non-pharmaceutical interventions

abstract: Research in the current pandemic has put a sharp focus on the health burden of Covid-19, thereby largely neglecting the cost to life from the socioeconomic consequences of its containment. The paper develops a model for assessing their proportionality. It compares the years of life lost (YLL) due to Covid-19 and the socioeconomic consequences of its containment. The model reconciles the normative life table approach with de facto socioeconomic realities by correcting YLL estimates for socioeconomic differences in life expectancy. It thereby aims to improve on the attribution of YLL due to immediate and fundamental sources of inequalities in life expectancy. The application of the approach to the pandemic suggests that the socioeconomic consequences of containment measures potentially come with a much higher life tag than the disease itself and therefore need urgent attention, especially in poorer and more unequal societies. Avoiding 3 million additional cases of extreme poverty may come with a similar life tag as protecting 1 million people from dying from Covid-19.


title: Comparison of structural MRI brain measures between 1.5T and 3T: data from the Lothian Birth Cohort 1936

abstract: Multi-scanner MRI studies are reliant on understanding the apparent differences in imaging measures between different scanners. We provide a comprehensive analysis of T1-weighted and diffusion MRI (dMRI) structural brain measures between a 1.5T GE Signa Horizon HDx and a 3T Siemens Magnetom Prisma using 91 community-dwelling older participants (aged 82 years). Although we found considerable differences in absolute measurements (global tissue volumes were measured as [~]6--11% higher and fractional anisotropy was 33% higher at 3T than at 1.5T), between-scanner consistency was good to excellent for global volumetric and dMRI measures (intraclass correlation coefficient [ICC] range: 0.612--0.993) and fair to good for 68 cortical regions (FreeSurfer) and cortical surface measures (mean ICC: 0.504--0.763). Between-scanner consistency was fair for dMRI measures of 12 major white matter tracts (mean ICC: 0.475--0.564), and the general factors of these tracts provided excellent consistency (ICC [≥] 0.769). Whole-brain structural networks provided good to excellent consistency for global metrics (ICC [≥] 0.612). Although consistency was poor for individual network connections (mean ICCs: 0.275 - 0.280), this was driven by a large difference in network sparsity (0.599 versus 0.334), and consistency was improved when comparing only the connections present in every participant (mean ICCs: 0.533--0.647). Regression-based k-fold cross-validation showed that, particularly for global volumes, between-scanner differences could be largely eliminated (R2 range 0.615--0.991). We conclude that low granularity measures of brain structure can be reliably matched between the scanners tested, but caution is warranted when combining high granularity information from different scanners.

category: radiology and imaging


title: Knowledge and Impact of COVID-19 on Middle-Aged and Older People living with HIV in Lima, Peru

abstract: COVID-19 has had an unprecedented worldwide impact, and Peru has had one of the highest COVID-19 case rates despite implementation of an early strict nationwide quarantine. Repercussions on Perus healthcare system may impact vulnerable populations, particularly people with HIV (PWH). We explored the knowledge of COVID-19 and the socioeconomic and health impact of the pandemic among middle-aged and older PWH. A cross-sectional telephone survey was administered to 156 PWH age [≥]40 years receiving care in one of two large HIV clinics in Lima, Peru. The majority of PWH (age 52{+/-}7.7 years, 41% female, 65% completed secondary school or less) were knowledgeable regarding COVID-19 symptoms and prevention methods. Nearly half of those employed prior to the pandemic reported job loss. Female sex (unadjusted prevalence ratio [PR] 1.85 [95%CI 1.27-2.69]), low educational level (PR 1.62 [1.06-2.48]) and informal work (PR 1.58 [1.06-2.36]) were risk factors for unemployment but not in adjusted models. Increased anxiety was reported in 64% and stress in 77%. COVID-19 has had a substantial socioeconomic and mental health impact on PWH living in Lima, Peru, particularly those with lower educational levels and informal workers. Efforts are needed to ensure continued medical care and socioeconomic support of PWH in Peru.

category: hiv aids


title: Risk factors associated with severe outcomes of COVID-19: An updated rapid review to inform national guidance on vaccine prioritization in Canada

abstract:
BackgroundTo inform vaccine prioritization guidance in Canada, we systematically reviewed evidence on the magnitude of association between risk factors and severe outcomes of COVID-19. The urgent nature of this review necessitated an adapted methodology, which may serve as an exemplar for reviews undertaken under strict timelines.

MethodsWe updated our existing review by searching online databases and websites for cohort studies providing multivariate adjusted associations. After piloting, one author screened studies and extracted data. Two authors estimated the magnitude of association between exposures and outcomes as little-to-no (odds, risk, or hazard ratio <2.0, or >0.50 for reduction), large (2.0-3.9, or 0.50-0.26 for reduction), or very large ([≥]4.0, or [≤]0.25 for reduction), and rated the evidence certainty using GRADE.

ResultsOf 11,734 unique records we included 134 reports. There is probably (moderate certainty) at least a large increase in mortality from COVID-19 among people aged 60-69 vs. <60 years (11 studies, n=517,217), with [≥]2 vs. no comorbidities (4 studies, n=189,608), and for people with (vs. without): Down syndrome (1 study, n>8 million), type 1 and 2 diabetes (1 study, n>8 million), end-stage kidney disease (1 study, n>8 million), motor neuron disease, multiple sclerosis, myasthenia gravis, or Huntingtons disease (as a grouping; 1 study, n>8 million). The magnitude of association with mortality is probably very large for Down syndrome and may (low certainty) be very large for age 60-69 years, and diabetes. There is probably little-to-no increase in severe outcomes with several cardiovascular and respiratory conditions, and for adult males vs. females.

ConclusionThere is strong evidence to support at least a large increase in mortality from COVID-19 among older adults aged 60 to 69 years versus <60 years; people having two or more versus no comorbidities; and for people affected by several pre-existing conditions. The methodology employed in this review may provide an important exemplar for future syntheses undertaken under urgent timelines.

Systematic review registrationPROSPERO #CRD42021230185.

category: infectious diseases


title: Risk factors associated with severe outcomes of COVID-19: A systematic rapid review to inform national guidance on vaccine prioritization in Canada


title: Geospatial characterizing of Under-Five Mortality in Alexandria, Egypt

abstract: This study aimed to identify geo-spatial pattern of under-five mortality (U5M) in Alexandria and its key determinants. We analyzed the geospatial distribution of 3064 deaths registered at 24 health offices reported from January 2018 to June 2019. The localities of Alexandria city were clustered into high and low incidence areas. Neonates represented 58.7% of U5M, while post-neonates and children were 31.1%, 10.2% respectively. Male deaths were significantly higher (P=0.036). The main leading causes of U5M were prematurity (28.32%), pneumonia (11.01%), cardiac arrest (10.57%), congenital malformation (9.95%), and childhood cardiovascular diseases (9.20%). Spatial distribution of U5M (including the most common three causes) tend to be clustered in western parts of Alexandria (El Hawaria, Bahig, Hamlis and Ketaa Maryiut). Another 9 clusters are at risk of being hotspots. Illiteracy, divorce, and poor locality characteristics (household size, population density, and access to water supply and sanitation), were statistically significant predictors of U5M.

category: epidemiology


title: Analyzing the multidimensionality of biological aging with the tools of deep learning across diverse image-based and physiological indicators yields robust age predictors

abstract: It is hypothesized that there are inter-individual differences in biological aging; however, differences in aging among (heart images vs. electrophysiology) and across (e.g., brain vs heart) physiological dimensions have not been systematically evaluated and compared. We analyzed 676,787 samples from 502,211 UK Biobank participants aged 37-82 years with deep learning approaches to build a total of 331 chronological age predictors on different data modalities such as videos (e.g. heart magnetic resonance imaging [MRI]), images (e.g. brain, liver and pancreas MRIs), time-series (e.g. electrocardiograms [ECGs], wrist accelerometer data) and scalar data (e.g. blood biomarkers) to characterize the multiple dimensions of aging. We combined these age predictors into 11 main aging dimensions, 31 subdimensions and 84 sub-subdimensions ensemble models based on specific organ systems. Heart dimension features predict chronological age with a testing root mean squared error (RMSE) and standard error of 2.83{+/-}0.04 years and musculoskeletal dimension features predict age with a RMSE of 2.65{+/-}0.04 years. We defined "accelerated" agers as participants whose predicted age was greater than their chronological age and computed the correlation between these different definitions of accelerated aging. We found that most aging dimensions are modestly correlated (average correlation=.139{+/-}.090) but that dimensions that are biologically related tend to be more positively correlated. For example, we found that heart anatomical (from MRI) accelerated aging and heart electrical (from ECG) accelerated aging are correlated (average Pearson of .249{+/-}.005). Overall, most dimensions of aging are complex traits with both genetic and non-genetic correlates. We identified 9,697 SNPs in 3,318 genes associated with accelerated aging and found an average GWAS-based heritability for accelerated aging of 26.1{+/-}7.42% (e.g. heart aging: 35.2{+/-}1.6%). We used GWAS summary statistics to estimate genetic correlation between aging dimensions and we found that most aging dimensions are genetically not correlated (average correlation=.104{+/-}.149). However, on the other hand, specific dimensions were genetically correlated, such as heart anatomical and electrical accelerated aging (Pearson rho .508{+/-}.089 correlated [r_g]). Finally, we identified biomarkers, clinical phenotypes, diseases, family history, environmental variables and socioeconomic variables associated with accelerated aging in each aging dimension and computed the correlation between the different aging dimensions in terms of these associations. We found that environmental and socioeconomic variables are similarly associated with accelerated aging across aging dimensions (average correlations of respectively .639{+/-}.180 and .607{+/-}.309). Dimensions are weakly correlated with each other, highlighting the multidimensionality of the aging process. Our results can be interactively explored on the following website: https://www.multidimensionality-of-aging.net/

category: health informatics


title: 6-Month Follow Up of 8679 Hospitalized COVID-19 Patients in Germany: A Nationwide Cohort Study

abstract:
BackgroundData on long-term outcomes of hospitalized COVID-19 patients are scarce.

ObjectiveTo provide a detailed account of hospitalized COVID-19 patients until 180 days after their initial hospitalization.

DesignNationwide cohort study using claims data from the German Local Health Care Funds, the health insurer of one-third of the German population.

SettingGermany.

PatientsAdult patients hospitalized in Germany between Feb 1 and April 30, 2020 with PCR-confirmed COVID-19 and a related principal diagnosis.

MeasurementsPatient characteristics and ventilation status, in-hospital, 30-, 90- and 180- day mortality measured from admission, and 180-day readmission measured from discharge. Multivariable logistic regression model of independent risk factors for 180-day mortality.

ResultsOf 8679 patients (median age, 72 years), 2161 (24.9%) died during the index hospitalization. 30-day mortality was 23.9% (2073/8679), 90-day mortality 27.9% (2425/8679), and 180-day mortality 29.6% (2566/8679). The latter was 52.3% (1472/2817) for patients aged [≥] 80 years, and 53.0% for patients who had been ventilated invasively (853/1608). Risk factors for 180-day mortality included coagulopathy, BMI [≥] 40, and age. Female sex was a protective factor. Of 6235 patients discharged alive, 1668 patients were readmitted a total of 2551 times within 180 days, resulting in an overall readmission rate of 26.8%.

LimitationsWe could not stratify patients by ICU treatment as it is not coded separately. Furthermore, we cannot exclude residual confounding in our analysis of risk factors nor determine causality between risk factors and long-term mortality given the observational nature of this study.

ConclusionThis nationwide cohort study of hospitalized COVID-19 patients in Germany found considerable long-term mortality and readmission rates, especially among patients with coagulopathy. Close follow-up after hospital discharge may improve long-term outcome.

category: intensive care and critical care medicine


title: Early diagnosis of coeliac disease in the Preventive Youth Health Care Centres in the Netherlands: study protocol of a case-finding study (GLUTENSCREEN).

abstract:
IntroductionCoeliac disease (CD) occurs in 1% of the population, develops early in life and is severely underdiagnosed. Undiagnosed and untreated disease is associated with short- and long-term complications. Treatment with a gluten-free diet results in health improvement. The current health care approach is unable to solve the underdiagnosis of CD and timely diagnosis and treatment is only achieved by active case finding. Aim of this study is to perform a novel case-finding project to detect CD in 12 months-4 years old symptomatic children who visit the YHCCs in a well-described region in the Netherlands to show that it is feasible, cost-effective and well accepted by the population.

Methods/analysisProspective intervention cohort study. Parents of all children aged 12 months-4 years attending the Youth Health Care Centres (YHCCs) for a regular visit are asked if their child has one or more CD-related symptoms from a standardized list. If so, they will be invited to participate in the case-finding study. After informed consent, a point of care test (POC) to assess CD-specific antibodies against tissue-transglutaminase (TG2A) from a droplet of blood, is performed onsite at the YHCCs. If the POC test is positive, CD is highly suspected and the child will be referred to hospital for definitive diagnosis according to the ESPGHAN guideline.

Main outcomes: 1. incidence rate of new CD diagnoses in the study region Kennemerland in comparison to the rest of the Netherlands.

2. Feasibility and cost-effectiveness of active case-finding for CD in the YHCCs. All costs of active case finding, diagnostics and treatment of CD and the potential short and long term consequences of the disease will be calculated for the setting with and without case finding.

3. Ethical acceptability: by questionnaires on parental and health care professionals satisfaction. A statistical analysis plan (SAP) has been written and will be published on the GLUTENSCREEN website.

Ethics and disseminationThe Medical Ethics Committee Leiden approved this study. If we prove that active case finding in the YHCC is feasible, efficient, cost-effective and well accepted by the population, implementation is recommended.

Trial registration numberNL63291.058.17

What is already known on this topic?O_LIDespite recommendation on  who should be tested for CD in guidelines, the diagnosis of CD remains severely underdiagnosed.
C_LIO_LIUntreated CD has a considerable health burden for society.
C_LIO_LIStudies have shown that an active case-finding strategy in adults is an effective means to improve the frequency of CD diagnosis.
C_LI

What this study hopes to add?O_LIEffectiveness and feasibility of active-case finding as secondary prevention strategy in the diagnosis of childhood CD in the primary care setting in the Netherlands
C_LIO_LIThis study will provide important information about the cost-effectiveness and acceptability of the general Dutch population concerning active case-finding
C_LI

category: pediatrics


title: Is large-scale rapid CoV-2 testing a substitute for lockdowns? The case of Tuebingen

abstract:
BACKGROUNDVarious forms of contact restrictions have been adopted in response to the Covid-19 pandemic. Around February 2021, rapid testing appeared as a new policy instrument. Some claim it may serve as a substitute for contact restrictions.

OBJECTIVES/METHODSWe evaluate the effects of a unique policy experiment: In March and April 2021, the city of Tubingen set up a testing scheme while relaxing contact restrictions. We compare case rates in Tubingen county to an appropriately identified control unit.

CONCLUSIONSThe experiment led to an increase in the reported case rate. This increase is robust across alternative statistical specifications. An epidemiological model that corrects for  more cases due to more testing and  reduced testing and reporting during the Easter holiday also confirms the finding.


title: Is large-scale rapid CoV-2 testing a substitute for lockdowns?


title: Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study

abstract:
BackgroundThe long-term sequelae of coronavirus disease 2019 (Covid-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with Covid-19 and associated risk factors.

MethodsThis is a prospective cohort study of children ([≤]18 years old) admitted with confirmed Covid-19 to Z.A. Bashlyaeva Childrens Municipal Clinical Hospital in Moscow, Russia. Children admitted to the hospital during the first wave of the pandemic, between April 2, 2020 and August 26, 2020, were included. Telephone interview using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Covid-19 Health and Wellbeing paediatric follow up survey. Persistent symptoms (>5 months) were further categorised by system(s) involved.

FindingsOverall, 518 of 853 (61%) of eligible children were available for the follow-up assessment and included in the study. Median age was 10.4 years (IQR, 3-15.2) and 270 (52.1%) were girls; median follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: age "6-11 years" (odds ratio 2.74 (95% confidence interval 1.37 to 5.75) and "12-18 years" (2.68, 1.41 to 5.4), and a history of allergic diseases (1.67, 1.04 to 2.67).

InterpretationA quarter of children experienced persistent symptoms months after hospitalization with acute covid-19 infection, with almost one in ten experiencing multi-system involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up. Our findings highlight the need for replication and further investigation of potential mechanisms as well as clinical support to improve long term outcomes in children.

FundingNone.

O_TEXTBOXResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSEvidence suggests that Covid-19 may result in short- and long-term consequences to health. Studies in children and adolescents are limited and available evidence is scarce. We searched Embase for publications from inception to April, 25, 2021, using the following phrases or combinations of phrases "post-covid condition" or "post-covid syndrome" or "covid sequalae" or "post-acute covid" or "long covid" or "long hauler" with "pediatric*" or "paediatric*" or "child*" or "infant*" or "newborn*" or "toddler*" or "neonate*" or "neonatal" or "adolescent*" or "teen*". We found small case series and small cohort studies looking at Covid-19 consequences in children. No large cohort studies of previously hospitalised children, assessing symptom duration, categorisation or attempting multivariable analyses to identify independent risk factors for long Covid development were identified.

Added value of this studyTo our knowledge, this is the largest cohort study with the longest follow-up since hospital discharge of previously hospitalised children. We found that even months after discharge from the hospital, approximately a quarter of children experience persistent symptoms with one in ten having multi-system involvement. Older age and allergic diseases are associated with Covid-19 consequences. Parents of some children report emotional and behavioural changes in their children after Covid-19.

Implications of all the available evidenceOur findings highlight the need for continued global research of Covid-19 consequences in the paediatric population. Older children admitted to the hospital should be carefully monitored upon discharge. Large, controlled studies aiming to identify risk groups and potential intervention strategies are required to fill knowledge gaps.

C_TEXTBOX


title: Durability of three types of dual active ingredient long-lasting insecticidal net compared to a pyrethroid-only LLIN in Tanzania: protocol for a prospective cohort study nested in a cluster randomized controlled trial

abstract:
IntroductionProgress achieved by long-lasting insecticidal nets (LLINs) against malaria is threatened by the widespread selection of pyrethroid resistance among vector populations. LLINs with non-pyrethroid insecticides are urgently needed. This study aims to assess the durability of three novel dual active ingredient LLINs and to parameterise a mathematical model to predict epidemiological outcomes of these products for malaria vector control.

MethodsA WHO Phase 3 active ingredients and textile durability study will be carried out within a cluster randomised controlled trial in Misungwi district in 40 clusters. The following treatments will be evaluated; 1/ Interceptor G2(R) combining chlorfenapyr and a pyrethroid alpha-cypermethrin, 2/ Royal Guard(R) treated with pyriproxyfen and alpha-cypermethrin and 3/ Olyset Plus which incorporates a synergist piperonyl butoxide and the pyrethroid permethrin, and 4/ a reference standard pyrethroid-only LLIN (Interceptor(R)). 750 nets will be followed in 5 clusters per intervention arm at 6, 12, 24 and 36 months post distribution for survivorship and hole index assessment. A second cohort of 1950 nets per each type will be identified in 10 clusters, of which 30 LLINs will be withdrawn for bio-efficacy and chemical analysis every 6 months up to 36 months and another 30 collected for an experimental hut trial study every year. Bio-efficacy will be assessed using cone bioassays and tunnel tests against susceptible and resistant laboratory strains of Anopheles gambiae sensu stricto. Efficacy of field collected nets will be compared in six experimental huts. The main outcomes will be Anopheles mortality up to 72 hours post exposure, blood feeding and egg maturation using ovary dissection to assess impact on fecundity.

Ethics and disseminationEthical approval was received from the Tanzanian ethics review committee as well as from each institution. Study findings will be disseminated via reports and presentations to national and international stakeholders, conferences, and peer-reviewed publications.

Trial registration numberNCT03554616

Article summaryO_ST_ABSStrengths of this studyC_ST_ABSO_LIThis is the first study assessing the durability of these novel dual-A.I. LLINs over three years alongside a cluster randomised controlled trial (cRCT).
C_LIO_LIThe study will support the development of bio-efficacy and physical durability criteria of performance for the partner A.I. in relation to the cRCT efficacy outcomes and refine preferred product characteristics developed by the WHO.
C_LIO_LIAn experimental hut trial done in the vicinity of the cRCT, with similar vector population characteristics and using nets sampled from the main trial will allow us to understand the impact of field conditions, wear-and-tear and insecticidal deterioration on the efficacy of the dual-A.I. LLINs on entomological outcomes and relate these to the cRCT epidemiological and entomological outcomes.
C_LIO_LIAll other products falling under these novel dual-A.I. LLINs classes will be assessed according to those criteria alongside non-inferiority studies in experimental huts and modelling of these data.
C_LI

Limitations of this studyPotential limitations include 1/ the net loss of follow up used to calculate sample size, which was taken from another study site and might differ in Misungwi, and 2/ the experimental hut site is situated in the northern section of the cRCT study area and may not represent vector species composition of the southern section of the cRCT.


title: Osteophyte size and location on hip DXA scans are associated with hip pain: findings from a cross sectional study in UK Biobank

abstract:
ObjectiveIt remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method.

MethodsHip DXAs were obtained from UK Biobank. An automated method was developed to obtain minimum joint space width (mJSW) from points placed around the femoral head and acetabulum. Osteophyte areas at the lateral acetabulum, superior and inferior femoral head were derived manually. Semi-quantitative measures of osteophytes and joint space narrowing (JSN) were combined to provide a measure of rHOA. Logistic regression was used to examine the relationships between these variables and hip pain, obtained via questionnaires.

Results6,807 hip DXAs were examined. rHOA was present in 353 [5.2%] individuals and was associated with hip pain [OR 2.07 (95% CI 1.54-2.80)] and hospital diagnosed OA [5.73 (2.89-11.36)]. Total osteophyte area and mJSW were associated with hip pain [1.29 (1.21-1.36), 0.84 (0.77-0.92) respectively] in unadjusted models. After mutually adjusting and adding demographic covariates, total osteophyte area continued to have strong evidence of association with hip pain [1.31 (1.23-1.39)] but mJSW did not [0.95 (0.87-1.04)]. Acetabular, superior and inferior femoral osteophyte areas were all independently associated with hip pain [1.19 (1.13-1.26), 1.22 (1.15-1.29), 1.21 (1.14-1.28) respectively].

ConclusionThe relationship between DXA-derived rHOA and prevalent hip pain is explained by osteophyte area rather than mJSW. Osteophytes at different locations showed important, potentially independent, associations with hip pain, possibly reflecting the contribution of distinct biomechanical pathways.

category: rheumatology


title: Patterns of SARS-CoV-2 Aerosol Spread in Typical Classrooms

abstract: Although current industry guidelines to control the spread of SARS-CoV-2 (COVID-19) have adopted a six-foot ([~]1.8m) spacing between individuals indoors, recent evidence suggests that longer range spread is also responsible for infections in public spaces. The vehicle for long-range spread is smaller droplets or particles, termed bio-aerosols, or aerosols for short, which have a large surface area to volume ratio such that aerodynamic drag is much larger than gravity forces. The aerosols remain suspended in air for extended time periods and they essentially move with air currents. Prediction of the danger to occupants in a closed room when exposed to an infected individual requires knowledge of the period of exposure and the concentration level of aerosols in the breathing zone of an occupant. To obtain an estimate of the concentration level, a common assumption is well-mixed conditions within an interior space. This is obtained from a mass balance between the level of aerosol produced by an infected individual along with the airflow rate into and out of the entire space. In this work, we use computational fluid dynamics, verified by experimental results, to explore the aerosol concentration distribution in a typical classroom for several common conditions and compare these results to the well-mixed assumption. We use a tracer gas to simulate the flow and dispersion of the aerosol-air mixture. The two ventilation systems examined, ceiling diffusers and open windows, yield average concentrations at occupant breathing level 50% greater than the well mixed case, and some scenarios yield concentrations that are 150% greater than the well mixed concentration at specific breathing-level locations. Of particular concern are two conditions: horizontal air flow from an open window in line with a row of seating and, second, an infected individual seated near a sealed cold window. For the former, conditions are improved if a baffle is placed inside the open window to direct the air toward the floor, creating a condition similar to displacement ventilation. In the latter, the cold air flowing down along the cold window recirculates aerosols back into the breathing zone. Adding window covers or a portable heater below the window surface will moderate this condition.

category: occupational and environmental health


title: Penetrance of breast cancer genes from the eMERGE III Network

abstract: We studied the penetrance and clinical outcomes of seven breast cancer susceptibility genes (BRCA1, BRCA2, TP53, CHEK2, ATM, PALB2 and PTEN) in almost 25,000 participants unselected for personal or family history of breast cancer. We identified 420 participants with pathogenic or likely pathogenic variants, and 147 were women who did not previously know their genetic results. Out of these 147 women, 32 women were diagnosed with breast cancer at an average age of 52.8 years. Estimated penetrance by age 60 years ranged from 18-44%, depending on the gene. Within the first twelve months after genetic results disclosure, 42% of women had taken actions related to their genetic results and two new breast cancer cases were identified. Our study provides population-based penetrance estimates for the understudied genes, CHEK2, ATM, and PALB2, and highlights the importance of using unselected populations for penetrance studies. It also demonstrates the potential clinical impact of genetic testing to improve healthcare through early diagnosis and preventative screening.

category: oncology


title: Detection of SARS-CoV-2 variants by Abbott molecular, antigen, and serological tests

abstract:
BackgroundViral diversity presents an ongoing challenge for diagnostic tests, which need to accurately detect all circulating variants. The Abbott Global Surveillance program monitors severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and their impact on diagnostic test performance.

ObjectivesTo evaluate the capacity of Abbott molecular, antigen, and serologic assays to detect the SARS-CoV-2 B.1.1.7, B.1.351 and the P.1 variants.

Study designVirus variant culture stock dilutions (B.1.1.7, BEI NR-54011; B.1.351, BEI NR-54008 and 54009; P.1, BEI NR-54982) and clinical samples from patients with confirmed B.1.1.7 variant infection were run on the Abbott ID NOW COVID-19, m2000 RealTime SARS-CoV-2, Alinity m SARS-CoV-2, and Alinity m Resp-4-Plex molecular assays; the BinaxNOW COVID-19 Ag Card and Panbio COVID-19 Ag Rapid Test Device; and the ARCHITECT/Alinity i SARS-CoV-2 IgG and AdviseDx IgM assays, Panbio COVID-19 IgG assay, and ARCHITECT/Alinity i AdviseDx SARS-CoV-2 IgG II assay.

ResultsCultured virus stocks and B.1.1.7 clinical samples were detected with molecular, antigen, and serologic assays in the expected ranges, confirming in silico predictions. The ratio between genome equivalents (GE) and calculated median tissue culture infectious dose (TCID50) were 31-to 83-fold higher for B.1.1.7 cultures compared to B.1.351 and P.1 cultures, demonstrating that GE are more consistent units between cultures than TCID50.

ConclusionsAbbott molecular and antigen assays effectively detect B.1.1.7, B.1.351, and P.1 variant infections and Abbott serologic assays detect B.1.1.7 antibodies in patient sera. Future studies with SARS-CoV-2 virus cultures should use quantitative viral load values to compare detection of variants.

HighlightsO_LIAbbott SARS-CoV-2 molecular and antigen assays detect B.1.1.7, B.1.351, and P.1 variants
C_LIO_LIAbbott SARS-CoV-2 antibody assays detect B.1.1.7 antibodies in recovered patient sera
C_LIO_LIQuantitation of viral load in genome equivalents allows comparison of assay performance
C_LI


title: Impact of school-based malaria screening and treatment on P. falciparum infection and anemia prevalence in two transmission settings in Malawi

abstract:
BackgroundIn areas highly endemic for malaria, Plasmodium falciparum (Pf) infection prevalence peaks in school-age children, adversely affecting their health and education. School-based intermittent preventive treatment reduces this burden, however concerns about cost and widespread use of antimalarial drugs have limited enthusiasm for this approach. School-based screening-and-treatment is an attractive alternative. We conducted a school-based cohort study to evaluate the impact of screening-and-treatment on the prevalence of Pf infection and anemia in two different transmission settings.

MethodsWe screened 704 students in four Malawian primary schools for Pf infection using rapid diagnostic tests (RDTs). Those testing positive were treated with artemether-lumefantrine. Outcomes were Pf infections detected by microscopy or PCR and anemia after six weeks.

ResultsPrevalence of infection by RDT at screening was 37% (range among schools 9-64%). We detected a significant reduction after six weeks in infections by microscopy (adjusted relative reduction (aRR) 47.1%, p<0.0001) and PCR (aRR 23.1%, p<0.0001), but no reduction in anemia. In low, seasonal prevalence areas, sub-patent infections at screening led to persistent infection, but not disease, during follow-up. In high transmission settings, new infections frequently occurred within six weeks after treatment.

ConclusionsSchool-based screening-and-treatment reduced Pf infection but not anemia. This approach could be enhanced in low transmission settings by using more sensitive screening tests and in high transmission settings by repeating the intervention or using longer acting drugs.

SummaryMalaria screening-and-treatment reduced P. falciparum infections but not anemia. Because rapid diagnostic tests failed to detect low-density infections, screening tests with higher sensitivity may be needed in low transmission areas where low-density infections make-up a larger proportion of infections.


title: Contrasting epidemiology and population genetics of COVID-19 infections defined with 74 polymorphic loci in SARS-CoV-2 genomes sampled globally.

abstract: SARS-CoV-2, the coronavirus causing COVID-19, has infected and killed several millions of people worldwide. Since the first COVID-19 outbreak in December 2019, SARS-CoV-2 has evolved with a few genetic variants associated with higher infectivity. We aimed to identify polymorphic loci in SARS-CoV-2 that can be used to define and monitor the viral epidemiology and population genetics in different geographical regions. Between December 2019 and September 2020, we sampled 5,959 SARS-CoV-2 genomes. More than 80% of the genomes sampled in Africa, Asia, Europe, North America, Oceania and South America were reportedly isolated from clinical infections in older patients, [≥] 20 years. We used the first indexed genome (NC_045512.2) as a reference and constructed multilocus genotypes (MLGs) for each sampled genome based on amino acids detected at 74 polymorphic loci located in ORF1ab, ORF3a, ORF8, matrix (M), nucleocapsid (N) and spike (S) genes. Eight of the 74 loci were informative in estimating the risk of carrying infections with mutant alleles among different age groups, gender and geographical regions. Four mutant alleles - ORF1ab L4715, S G614, and N K203 and R204 reached 90% prevalence globally, coinciding with peaks in transmission but not COVID-19 severity, from March to August 2020. During this period, the MLG genetic diversity was moderate in Asia, Oceania and North America; in contrast to Africa, Europe and South America, where lower genetic diversity and absence of linkage disequilibrium indicated clonal SARS-CoV-2 transmission. Despite close relatedness to Asian MLGs, MLGs in the global population were genetically differentiated by geographic region, suggesting structure in SARS-CoV-2 populations. Our findings demonstrate the utility of the 74 loci as a genetic tool to study and monitor SARS-CoV-2 transmission dynamics and evolution, which can inform future control interventions.


title: Developing RT-LAMP Assays for Detection of SARS-CoV-2 in Saliva

abstract: The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has killed millions of people worldwide. The current crisis has created an unprecedented demand for rapid test of SARS-CoV-2 infection. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a fast and convenient method to amplify and identify the transcripts of a targeted pathogen. However, the sensitivity and specificity of RT-LAMP were generally regarded as inferior when compared with the gold standard RT-qPCR. To address this issue, we combined bioinformatic and experimental analyses to improve the assay performance for COVID-19 diagnosis. First, we developed an improved algorithm to design LAMP primers targeting the nucleocapsid (N), membrane (M), and spike (S) genes of SARS-CoV-2. Next, we rigorously validated these new assays for their efficacy and specificity. Further, we demonstrated that multiplexed RT-LAMP assays could directly detect as low as a few copies of SARS-CoV-2 RNA in saliva, without the need of RNA isolation. Importantly, further testing using saliva samples from COVID-19 patients indicated that the new RT-LAMP assays were in total agreement in sensitivity and specificity with standard RT-qPCR. In summary, our new LAMP primer design algorithm along with the validated assays provide a fast and reliable method for the diagnosis of COVID-19 cases.


title: Paradox of Predictors in Critically ill COVID-19 Patients: Outcome of a COVID-dedicated Intensive Care Unit

abstract:
BackgroundThe study aimed to analyze the demographic, comorbidities, biomarkers, pharmacotherapy, and ICU-stay with the mortality outcome of COVID-19 patients admitted in the intensive care unit of a tertiary care hospital in a low-middle income country, Bangladesh.

MethodsThe retrospective cohort study was done in Holy Family Red Crescent Medical College Hospital from May to September 2020. All 112 patients who were admitted to ICU as COVID-19 cases (confirmed by RT-PCR of the nasopharyngeal swab) were included in the study. Demographic data, laboratory reports of predictive biomarkers, treatment schedule, and duration of ICU-stay of 99 patients were available and obtained from hospital records (non-electronic) and treatment sheets, and compared between the survived and deceased patients.

ResultsOut of 99 patients admitted in ICU with COVID-19, 72 were male and 27 were female. The mean age was 61.08 years. Most of the ICU patients were in the 60 - 69 years of age group and the highest mortality rates (35.89%) were observed in this age range. Diabetes mellitus and hypertension were the predominant comorbidities in the deceased group of patients. A significant difference was observed in neutrophil count, creatinine and, NLR, d-NLR levels that raised in deceased patients. There was no significant difference as a survival outcome of antiviral drugs remdesivir or favipiravir, while the use of cephalosporin was found much higher in the survived group than the deceased group (46.66% vs 20.51%) in ICU.

ConclusionsSusceptibility to developing critical illness due to COVID-19 was found more in comorbid males aged more than 60 years. There were wide variations of the biomarkers in critical COVID-19 patients in a different population, which put the healthcare workers into far more challenge to minimize the mortality in ICU in Bangladesh and around the globe during the peak of the pandemic.


title: Dental-Facial Midline: An Esthetic Based Classification

abstract:
BackgroundThe facial midline and dental midline play an important role in facial esthetics, cosmetic dentistry, facial plastic surgery, and anthropologic studies.

ObjectivesThis study studied the dental-facial midline in Nepalese subjects and to classify the midline.

MethodsThe study was done in 150 Nepalese subjects, mostly consisting of University students (80 males and 70 females). After obtaining ethical approval, facial and dental midlines were analyzed using a scale.

ResultsIt showed 26 (18%) study subjects showed the coincidence of the facial midline with the maxillary and mandibular dental midlines. It showed that only 44 (30%) subjects showed the coincidence of facial midline with only maxillary dental midline, and 26 (17%) subjects showed the facial midline coincidence with only mandibular dental midline. The dental midline discrepancy was more prevalent in the maxillary arch and more prevalent on the right side. Midline discrepancy is seen more in males compared to females. The majority of the deviation showed 1 mm, followed by 2 mm, and 3 mm.

ConclusionsThe coincidence of the facial midline with both the maxillary and mandibular dental midlines is uncommon. Midline discrepancy is seen more in males compared to females. The majority of the subjects show a mild discrepancy of 1 mm. The midline discrepancy was more seen on the right side and in the maxillary arch.

category: dentistry and oral medicine


title: Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens among children: A cluster-randomized, placebo-controlled trial in Niger

abstract:
BackgroundThe Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality. Additional endpoints in the trial have attempted to elucidate the mechanisms for mortality reduction. In this pre-specified secondary analysis, we assessed the effect of azithromycin compared with placebo on IgG- based measures of infectious disease exposure with a multiplex bead assay that included antigens to malaria parasites (Plasmodium falciparum, P. vivax, P. malariae, P. ovale), bacterial pathogens (Campylobacter spp., enterotoxigenic Escherichia coli, Vibrio cholerae, Salmonella enterica, Streptococcus pyogenes) and protozoans (Cryptosporidium parvum, Giardia duodenales).

Methods and FindingsThirty communities in rural Niger were randomized 1:1 to biannual distributions of azithromycin or placebo among children ages 1-59 months. The analysis included 5,642 blood specimens collected from 3,814 children ages 1-59 months, measured at 6, 12, 24, and 36 months of follow-up in a repeated cross-sectional design. Campylobacter spp. seroprevalence averaged over all study visits was lower in azithromycin communities compared to placebo (91% vs 94%, difference = -3%, 95% CI: -5%, -1%; P=0.03), which corresponded to a 29% lower seroconversion rate (1.30 versus 1.84 seroconversions per year, hazard ratio = 0.71, 95% CI: 0.56, 0.89; P=0.004). Antibody-based measures of infection with P. falciparum and group A streptococcus were consistently lower in azithromycin communities, but were not statistically different from placebo, and there were no other differences across pathogens. Strengths of the study included masking of participants, investigators, and analysts, high treatment coverage, large sample size, and objective outcomes. Principal limitations included the timing of blood collection with respect to treatment (approximately 6 months later, which could have missed transient effects in the weeks immediately following treatment), and the durability of IgG response following clearance of infection. Both limitations would lead the trial to under-estimate effects on antibody-based measures of infection.

ConclusionsThe reduction in Campylobacter spp. despite these limitations suggests an effect on carriage, findings which align with an independent metagenomic analysis of rectal swabs collected in the same villages and with previously reported reductions in dysentery-associated mortality. Given significant sequelae of Campylobacter infection among preschool aged children, our results support at least one possible mechanism through which biannual mass distribution of azithromycin likely reduced mortality in this study population.


title: Sufficient strategies for travel quarantine and testing

abstract:
BackgroundNumerous countries imposed strict travel restrictions, contributing to the large socioeconomic burden during the COVID-19 pandemic. The long quarantines that apply to contacts of cases may be excessive for travel policy.

MethodsWe developed an approach to evaluate imminent countrywide COVID-19 infections after 0-14-day quarantine and testing. We identified the minimum travel quarantine duration such that the infection rate within the destination country did not increase compared to a travel ban, defining this minimum quarantine as "sufficient."

FindingsWe present a generalised analytical framework and a specific case study of the epidemic situation on November 21, 2021, for application to 26 European countries. For most origin-destination country pairs, a three-day or shorter quarantine with RT-PCR or antigen testing on exit suffices. Adaptation to the European Union traffic-light risk stratification provided a simplified policy tool. Our analytical approach provides guidance for travel policy during all phases of pandemic diseases.

InterpretationFor nearly half of origin-destination country pairs analysed, travel can be permitted in the absence of quarantine and testing. For the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. The estimated travel quarantine durations are substantially shorter than those specified for traced contacts.

FundingEasyJet (JPT and APG), the Elihu endowment (JPT), the Burnett and Stender families endowment (APG), the Notsew Orm Sands Foundation (JPT and APG), the National Institutes of Health (MCF), Canadian Institutes of Health Research (SMM) and Natural Sciences and Engineering Research Council of Canada EIDM-MfPH (SMM).

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSEvidence from early in the pandemic indicates that border closures at the epicentre slowed global dissemination of COVID-19. As community transmission became established in many nations, studies have suggested that the benefit of strict border closures in mitigating the transmission of disease from travellers diminished. Research for community settings has shown that testing later during quarantine, rather than upon entry into quarantine, can substantially shorten the duration of quarantine needed to reduce post-quarantine transmission. In particular for international air travellers, a 14-day quarantine can effectively be shortened to five or seven days. The number of infectious COVID-19 cases that escape from these quarantines depends on the prevalence of disease in the country the traveller originated as well as the travel volume into the country.

Added value of this studyWe developed a framework to identify quarantine and testing strategies that enable travel from specific origins without increasing their infection rates per capita within destinations. No prior study has evaluated the appropriate duration of quarantine necessary to prevent any rise in infection rates per capita in the destination countries as a result of travel. By accounting for prevalence, daily incidence, vaccine coverage, immunity, age demographics, and travel flow between countries, we quantified the contribution of travel towards within-country the imminent infections in the destination country under different quarantine and testing strategies. For travel between 26 European countries, our results for the pandemic situation observed on November 21, 2021 demonstrate that there are often less burdensome quarantine and testing strategies that can serve as effective alternatives to strict border closure. Specifically, these estimated sufficient quarantine durations are especially dependent on COVID-19 prevalence and immunity within the two countries. We also found that asymmetry in the travel flow, just not the volume of travel flow, can also influence the estimated sufficient quarantine durations. Using data on variants of concern, including Omicron, we found that the adequacy of a border control strategy to limit variant spread depends strongly on the geographical distribution of the variant. While our results pertain to European countries, we also provide an interactive spreadsheet that can be used to determine appropriate quarantine durations between any two countries. Moreover, our framework can also be applied at any spatial or population scale within which movement restrictions could feasibly be implemented.

Implications of all available evidenceTravel quarantine and testing strategies can effectively mitigate importation and onward transmission within a country. Identifying sufficient strategies can allow countries to permit travel to and from other countries, without risking a short-term increase in infection rates. As long as the community transmission is occurring, the long-term epidemic trend within the destination country is more apt to be determined by other disease control measures, e.g., contact tracing, vaccination, and non-pharmaceutical interventions. Together, travel quarantine and other related control measures can mitigate the risk of transmission between countries, limiting the threat of variants of concern.


title: Quarantine and testing strategies for safe pandemic travel


title: Quarantine and testing strategies to ameliorate transmission due to travel during the COVID-19 pandemic


title: Quarantine and testing strategies to ameliorate transmission due to travel during the COVID-19 pandemic: a modelling study


title: MORTALITY OF CARE HOME RESIDENTS AND COMMUNITY-DWELLING CONTROLS DURING THE COVID-19 PANDEMIC IN 2020: MATCHED COHORT STUDY

abstract:
ObjectiveTo estimate mortality of care home (CH) residents, and matched community-dwelling controls, during the Covid-19 pandemic from primary care electronic health records.

DesignMatched cohort study

SettingGeneral practices contributing to the Clinical Practice Research Datalink Aurum Database in England.

ParticipantsThere were 83,627 CH residents contributing data in 2020, with 26,923 deaths; 80,730 (97%) were matched on age, gender and general practice with 300,445 community-dwelling adults.

Main outcome measuresAll-cause mortality. Adjusted rate ratios (RR) by negative binomial regression were adjusted for age, gender, number of long-term conditions (LTCs), frailty category, region, calendar month or week, and clustering by general practice.

ResultsDuring April 2020, the mortality rate of CH residents was 27.2 deaths per 1,000 patients per week, compared with 2.31 per 1,000 for controls, RR 11.1 (95% confidence interval 10.1 to 12.2). Compared with CH residents, LTCs and frailty were differentially associated with greater mortality in community-dwelling controls. During April 2020, mortality rates per 1,000 patients per week for persons with 9+ LTCs were: CH, 37.9; controls 17.7; RR 2.14 (1.18 to 3.89). In severe frailty, mortality rates were: CH, 29.6; controls 5.1; RR 6.17 (5.74 to 6.62).

ConclusionsIndividual-patient data from primary care electronic health records may be used to estimate mortality in care home residents. Mortality is substantially higher than for community-dwelling comparators and showed a disproportionate increase in the first wave of the Covid-19 pandemic. Multiple morbidity and frailty were associated with greater absolute risks but lower relative risks because community-dwelling frail or multi-morbid patients also experienced high mortality.


title: Mortality of care home residents and community-dwelling controls during the covid-19 pandemic in 2020: matched cohort study


title: Platelet Activation by Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Patient Serum is Blocked by COX, P2Y12 and Kinase Inhibitors

abstract:
BackgroundThe novel coronavirus SARS-CoV-2 has caused a global pandemic. Vaccines are an important part of the response. Although rare, unusual thrombotic events and thrombocytopenia in recipients 4-16 days after vaccination with the AstraZeneca AZD1222 have been reported. This syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) clinically resembles heparin induced thrombocytopenia (HIT), which is caused by platelet activating antibodies against platelet factor 4 (PF4). Here, we investigate the effect of serum from patients with VITT on platelet activation, and assess the ability of clinically available therapeutics to prevent platelet activation.

MethodsAggregation responses of healthy donor washed platelets were assessed in response to serum from patients with VITT pre- and post-intravenous immunoglobulin (IVIg) treatment and in the presence of anti-Fc{gamma}RIIA blocking IV.3 F(ab), anti-platelet drugs and kinase inhibitors.

FindingsFour patients (21 - 48 years old) presented with thrombosis (three patients: cerebral venous sinus thrombosis, one patient: ischemic stroke) and thrombocytopenia 10-14 days after AZD1222 vaccination. All patients tested positive for anti-PF4 antibody despite no prior heparin exposure. Serum from patients with VITT, but not healthy donor controls, induced platelet aggregation, which was abrogated following IVIg treatment. Aggregation to patient sera was blocked by IV.3 F(ab) which targets Fc{gamma}RIIA, and inhibitors of Src, Syk and Btk kinases downstream of the receptor. Anti-platelet therapies indomethacin and ticagrelor also blocked aggregation.

InterpretationIn conclusion, serum from patients with VITT activates platelets via the Fc{gamma}RIIA, which can be blocked in vitro by anti-platelet therapies suggesting possible new therapeutic interventions for this rare syndrome.

FundingThis work was supported by an Accelerator Grant (AA/18/2/34218) from the British Heart Foundation (BHF).

Key pointsO_LISerum from patients with VITT activates platelets via the Fc{gamma}RIIA.
C_LIO_LIPlatelet activation by serum from patients with VITT can be blocked by COX, P2Y12, Src, Syk and Btk inhibition.
C_LI

category: cardiovascular medicine


title: Effective vaccine allocation strategies, balancing economy with infection control against COVID-19 in Japan

abstract: Due to COVID-19, many countries including Japan have implemented a suspension of economic activities for infection control. It has contributed to reduce the transmission of COVID-19 but caused severe economic losses. Today, several promising vaccines have been developed and are already being distributed in some countries. Therefore, we evaluated various vaccine and intensive countermeasure strategies with constraint of economic loss using SEIR model to obtain knowledge of how to balance economy with infection control in Japan. Our main result is that the vaccination strategy that prioritizes younger generation outperformed the other strategies in terms of deaths. On the other hand, when we focused on strategies that prioritize older generation, as Japan has decided to do, the optimal vaccination strategy was determined by the basic reproduction number and acceptable economic loss. The strategy vaccinating the young next to the old age group was the best when acceptable economic loss was high, or the basic reproduction number was low. Alternatively, the strategy vaccinating the middle next to the old age group was superior to the others with a moderate acceptable economic loss and the high basic reproduction number setting.


title: Increasing Sample Diversity in Psychiatric Genetics - Introducing a new Cohort of Patients with Schizophrenia and Controls from Vietnam - Results from a Pilot Study

abstract:
ObjectivesGenome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry.

MethodsIn a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical Universitys associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: i) European, ii) East-Asian and iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis.

ResultsSCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability=4.9%, p=6.83*10-8), East-Asian (R2 liability=4.5%, p=2.73*10-7) and European (R2 liability=3.8%, p = 1.79*10-6) discovery samples.

DiscussionOur results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.

category: genetic and genomic medicine


title: Re-emergence of COVID-19 in Beijing was triggered by frozen virus: evidence from molecular clock

abstract: The COVID-19 outbreak in Xinfadi (XFD) Wholesale market in Beijing, China in June, 2020 caused 368 reported cases within 39 days. Genetic evidences indicated that imported SARS-CoV-2 (belong to the lineage B1.1.29) initiated this outbreak. However, the transmission route of the virus is still unknown. We obtained from public database three SARS-CoV-2 genomes isolated in XFD (XFD genomes) and adopted the leaf-dating method to calculate their expected collection dates using temporal calibrating information from other 241 genomes collected in mainland of China. All three XFD genomes were calculated to have earlier collection dates than the recorded (Bayes factor >1), and hence exhibited a lack of genetic divergence. We additionally combined the XFD genomes with other 225 genomes subsampled from those of the lineage B1.1.29, among which five sequences were also included for control analysis. Two of three XFD genomes were calculated to have earlier collection dates than the recorded (Bayes factor >1), while no control genomes provided such evidence. According to present understanding of SARS-CoV-2, a lack of genetic divergence is most likely due to being frozen. Considering the fact that the XFD outbreak started from a booth of frozen food, we judged that the XFD outbreak was caused by contaminated frozen food. Our results provided molecular evidence for the source of COVID-19 outbreak in Beijing XFD, which highlights new targets for SARS-CoV-2 surveillance for the public health.


title: Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells

abstract: Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 COVID-19 patients longitudinally up to eight months and find durable broad-based immune responses. SARS-CoV-2 spike binding and neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. SARS-CoV-2 infection also boosts antibody titers to SARS-CoV-1 and common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist, which bodes well for a rapid antibody response upon virus re-exposure or vaccination. Virus-specific CD4+ and CD8+ T cells are polyfunctional and maintained with an estimated half-life of 200 days. Interestingly, CD4+ T cell responses equally target several SARS-CoV-2 proteins, whereas the CD8+ T cell responses preferentially target the nucleoprotein, highlighting the potential importance of including the nucleoprotein in future vaccines. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.

category: allergy and immunology


title: ASSESSING VACCINATION STRATEGIES FOR THE COVID-19 EPIDEMIC IN MINAS GERAIS (BRAZIL)

abstract: AO_SCPLOWBSTRACTC_SCPLOWIn this work we analyze the effectiveness of vaccination strategies for the COVID-19 epidemic in the Brazilian state of Minas Gerais. Firstly we study the effectiveness of general vaccination in the decreasing of the number of infected individuals using a traditional non structured SEIR model. Secondly we consider an age-structured SEIR model with 3 age groups (youngster, adult and elderly) and we analyze the current strategy in the Brazilian state of Minas Gerais, of focusing the vaccination on the elderly group. We conclude by showing this strategy to be mistaken and that a vaccination focusing on the age group of the adults would be much more efficient in decreasing the total number of infected individuals.


title: Have news reports on suicide and attempted suicide during the COVID-19 pandemic adhered to guidance on safer reporting? A UK-wide content analysis study

abstract: Associations between sensational news coverage of suicide and subsequent increases in suicidal behaviour in the general population have been well documented. Amidst growing concern over the impact of the COVID-19 pandemic on suicide rates, it is especially important that news coverage of suicidal behaviour adheres to recommended standards for the responsible reporting of suicide. Using a set of dimensions based on international media guidelines, we analysed the quality and content of all UK news reports of possible COVID-19 related suicides and suicide attempts in the first four months of the pandemic (N=285 reports of 78 individual incidents published in print and online newspapers between 16th March and 12th July 2020). The majority of news reports made an explicit link between suicidal behaviour and the COVID-19 pandemic in the headline (187/285, 65.5%), and portrayed this association as strong and direct (n=196/272, 72.1%), mostly based on statements by family, friends or acquaintances of the deceased (171/285, 60%). The impact of the pandemic on suicidal behaviour was most often attributed to feelings of isolation (78/285, 27.4%), poor mental health (42, 14.7%) and sense of entrapment (41, 14.4%) as a result of government-imposed restrictions. Although rarely of poor overall quality, reporting was biased towards young people, frontline staff and relatively unusual suicides (including those involving a celebrity, murder-suicide and violent methods) Also, to varying degrees, reports failed to meet recommended standards; for example, 41.1% (117/285) did not signpost readers to sources of support, a quarter (69, 24.2%) included examples of sensational language and a third provided over-simplistic explanations for the suicidal behavior (93, 32.6%). While news reporting has improved compared to earlier coverage of suicide in the UK, it is essential that careful attention is paid to the quality and content of reports, especially as longer-term consequences of the COVID-19 pandemic develop.


title: Perceived public health threat a key factor for willingness to get the COVID-19 vaccine in Australia

abstract:
BackgroundVaccination rollout against COVID-19 has begun across multiple countries worldwide. Although the vaccine is free, rollout might still be compromised by hesitancy or concerns about COVID-19 vaccines.

MethodsWe conducted two online surveys of Australian adults in April (during national lockdown; convenience cross-sectional sample) and November (virtually no cases of COVID-19; nationally representative sample) 2020, prior to vaccine rollout. We asked about intentions to have a potential COVID-19 vaccine (If a COVID-19 vaccine becomes available, I will get it) and free-text responses (November only).

ResultsAfter adjustment for differences in sample demographics, the estimated proportion agreeing to a COVID-19 vaccine if it became available in April (n=1146) was 76.2%. In November (n=2034) this was estimated at 71.4% of the sample; additional analyses identified that the variation was driven by differences in perceived public health threat between April and November. Across both surveys, female gender, being younger, having inadequate health literacy and lower education were associated with reluctance to be vaccinated against COVID-19. Lower perceived susceptibility to COVID-19, belief that data on the efficacy of vaccines is  largely made up, having lower confidence in government, and lower perception of COVID-19 as a public health threat, were also associated with reluctance to be vaccinated against COVID-19. The top three reasons for agreeing to vaccinate (November only) were to protect myself and others, moral responsibility, and having no reason not to get it. For those who were indifferent or disagreeing to vaccinate, safety concerns were the top reason, followed by indecision and lack of trust in the vaccine respectively.

CONCLUSIONSThese findings highlight some factors related to willingness to accept a COVID-19 vaccine prior to one being available in Australia. Now that the vaccine is being offered, this study identifies key issues that can inform public health messaging to address vaccine hesitancy.

HIGHLIGHTSO_LIPerceived public health threat is associated with intentions to vaccinate
C_LIO_LIThose believing the efficacy of vaccines is made up were less willing to get vaccinated
C_LIO_LITo protect myself and others was the top reason for getting the vaccine
C_LIO_LISafety concerns was the top reason against getting the vaccine
C_LI


title: Detection of local microvascular proliferation in IDH wild-type Glioblastoma using relative Cerebral Blood Volume.

abstract:
BackgroundThe microvascular proliferation (MVP) and the microvessel area (MVA) are known as diagnostic and prognostic biomarkers for glioblastoma; nevertheless, its measurement is costly, labor-intense, and invasive. MRI perfusion biomarkers such as such as relative cerebral blood volume (rCBV) may be a feasible alternative to predict MVP and estimate MVA.

PurposeThis study aims to evaluate the detection capacity of MRI markers such as rCBV to detect local microvascular proliferation in IDH wild-type glioblastoma. In addition, we aim to analyze the association between rCBV values and the microvessel area in different regions of the tumor.

Study typeRetrospective study.

Population and subjectsData from 71 tissue blocks belonging to 17 IDH wild-type glioblastoma patients were compiled from the Ivy GAP database.

Field Strength/Sequence1.5T or 3.0T. Pregadolinium and postgadolinium-based contrast agent-enhanced T1-weighted MRI, T2- and FLAIR T2-weighted, and dynamic susceptibility contrast (DSC) T2* perfusion.

AssessmentWe analyzed preoperative MRIs to establish the association between the maximum and mean relative cerebral blood volume (rCBVmax and rCBVmean) with the presence/absence of microvascular proliferation and with the microvessel area for each tumor block.

Statistical testsSpearmans correlation and Mann-Whitney test.

ResultsSignificant positive correlations were found between rCBV and MVA in the analyzed tumor blocks (p<0.001). Additionally, significant differences in rCBV were found between blocks with MVP and blocks without MVP (p<0.0001).

Data conclusionThe rCBV is shown as significantly different in those tissue blocks with microvascular proliferation from those blocks without it, and it is significantly correlated with microvessels area. This method allows a local detection and definition of MVP and MVA in different regions of the glioblastoma since the first diagnostic stage and in a non-invasive way.


title: Men and sexual and reproductive healthcare in the Nordic countries: a scoping review

abstract:
ContextMen generally seek healthcare less often than women and, other than traditional gender norms, less is known about the explanation. The aim was to identify knowledge gaps and factors influencing men regarding sexual and reproductive healthcare (SRHC) in the Nordic countries.

MethodsWe searched PubMed and SveMed+ for peer-reviewed articles published between 2010 and 2020. The analyses identified factors influencing mens experiences of and access to SRHC.

ResultsThe majority of the 68 articles included focused on pregnancy, birth, infertility, and sexually transmitted infections including HIV. During pregnancy and childbirth, men were treated as accompanying partners rather than individuals with their own needs. The knowledge and attitudes of healthcare providers were crucial for their ability to provide SRHC and for the experiences of men. Organizational obstacles, such as women-centred SRHC and no assigned profession, hindered mens access to SRHC. Lastly, the literature rarely discussed the impact of health policies on mens access to SRHC.

ConclusionsThe identified knowledge gap indicates the necessity of the improved health and medical education of healthcare providers, as well as of health system interventions.

category: sexual and reproductive health


title: T-cell responses to acute cardiorespiratory or resistance exercise in cohorts of physically active or physically inactive older adults: A randomized complete crossover

abstract:
Aging is associated with many chronic diseases that are maintained and perpetuated by immune dysregulation and chronic systemic inflammation. T-cells often undergo age-related changes, including an accumulation of memory cells, which places individuals at increased risk for novel infections and may predispose them to increased inflammation. Regular exercise training has been suggested to offset age-related changes in T-cells, but the majority of literature is derived from cardiorespiratory exercise (CRE) studies. Much less is understood about the T-cell response to resistance exercise (RE). The purpose of this study was to examine the effects of acute CRE and acute RE on the T-cell response among a cohort of physically active older adults (PA) compared to a cohort of physically inactive older adults (PI).

METHODSTwenty-four healthy older adults (PA n=12; PI n=12; mean {+/-} SD; age (yrs) PA 62 {+/-} 5, PI 64 {+/-} 5; height (cm) PA 170.9 {+/-} 6.9, PI 162.9 {+/-} 8.0; weight (kg) PA 69.3 {+/-} 10.2, PI 68.2 {+/-} 12.8; BMI (kg/m2) PA 23.9 {+/-} 3.0, PI 25.6 {+/-} 3.5) completed one bout of CRE and one bout of RE in a randomized order, both at a moderate intensity, and separated by at least 7 days. Blood samples drawn pre-exercise, post-exercise, and 1h post-exercise (recovery) were analyzed for CD4+ and CD8+ T-cells and their differentiation status using surface markers CD45RA, CD62L, and CD57, as well as for Th17 cells (CD4+ CD161+ CD196+) using flow cytometry.

RESULTSPI had higher numbers of circulating CD57+ EMRA CD4+ T-cells (PA, mean {+/-} SE, 1 {+/-} 2 cells/uL; PI, 6 {+/-} 2 cells/uL; p=0.01; z=2.32) than PA at pre-exercise. Both CRE and RE elicited a significant mobilization of highly-differentiated (CD45RA+ CD62L-; CD57+ CD45RA+ CD62L-) CD8+ T-cells into the circulation post-exercise in both PA and PI groups. Furthermore, CRE resulted in a decrease in the number of circulating Th17 cells post-exercise, while RE increased Th17 cell mobilization compared to the CRE response.

CONCLUSIONTaken together, T-cells in PA and PI respond similarly to acute CRE and support previously reported data showing a significant mobilization of highly differentiated T-cells. The present study confirms that moderate intensity RE also elicits this response, but highlights potential differences between CRE and RE on the immune responses of T-cells, particularly in PI individuals.

Clinical trial registrationThis research study was registered at clinicaltrials.gov NCT03794050

category: sports medicine


title: Locus Coeruleus Integrity from 7T MRI Relates to Apathy and Cognition in Parkinson's Disease and Progressive Supranuclear Palsy

abstract:
ObjectiveThe loss of noradrenergic neurons in the locus coeruleus contributes to neuropsychiatric symptoms in both Parkinsons disease (PD) and progressive supranuclear palsy (PSP). This study aimed to characterise the spatial patterns of locus coeruleus pathological change in PD and PSP, and its relationship to cognitive and psychiatric symptoms.

MethodsTwenty-five patients meeting clinical criteria for idiopathic PD, fourteen probable PSP-Richardsons syndrome and twenty-four age-matched healthy controls (HC) were recruited. All participants underwent clinical assessments for cognition and apathy, and high-resolution (0.08 mm3) 7T-magnetisation-transfer imaging to measure LC integrity in vivo. To establish spatial patterns of locus coeruleus change, we obtained sub-region summaries of mean contrast ratios and significant locus coeruleus clusters using voxelwise analyses (family-wise-corrected p<0.05); we further correlated the locus coeruleus contrast with measures of apathy and cognition.

ResultsReduced contrast was observed in the caudal locus coeruleus for both PD and PSP relative to controls, with significant regional and voxelwise differences (HC>PD, right caudal locus coeruleus, 37 voxels; HC>PSP, bilateral caudal locus coeruleus, 206 voxels). PSP and PD patients showed similar levels of locus coeruleus degeneration relative to controls, but this was spatially more extensive in PSP. Across both groups, variability of locus coeruleus integrity was associated with cognitive performance (MoCA: 200 voxels; ACE-R: 70 voxels) and apathy (Apathy Scale: 99 voxels).

ConclusionsThe relationship between locus coeruleus structure and non-motor symptoms highlights a role for noradrenergic dysfunction across both PD and PSP, confirming the potential for noradrenergic therapeutic strategies to address transdiagnostic cognitive and behavioural features in neurodegenerative disease.

category: neurology


title: Episodic memory deficits are associated with impaired insight in traumatic encephalopathy syndrome: Initial findings of the SNAP-CTE study

abstract: Chronic traumatic encephalopathy (CTE) has been identified at post-mortem in Australian football codes players. Detailed and objective clinical and radiological characterization of patients at-risk of sporting and non-sporting repetitive concussive and subconcussive traumatic brain injury (RC/SCI) is important to our understanding of traumatic encephalopathy syndrome (TES) and CTE. This paper presents the initial findings of the symptomatology, neurocognitive, and pathophysiological changes in CTE (SNAP-CTE) study. A preliminary, retrospective, cohort study of 28 patients (25 males and 3 females) presenting with complaints of mood, behavioral, and cognitive decline, comprising TES, aged 24 to 78 years (M = 53, SD = 15.3) with at least 10 years of exposure to RC/SCI (mostly through contact sport) and cognitive decline were examined including: demographics; duration of play; age of first exposure to RC/SCI; and neuropsychology. Participants performed significantly worse in tests of auditory, visual, immediate, and delayed memory compared to a normative sample. Those with absent insight, compared to those with preserved insight, had a larger discrepancy between predicted and actual auditory memory scores, and had more severe mood disturbances. Insight, a hallmark sign of dementia, was either absent or impaired in a significant proportion (M = 36.4%, 95% CI =17.2% - 59.3%) of the sample aged under 65, compared with normative epidemiological data. This indicates that RC/SCI may be associated with risk of an early onset dementia syndrome representing probably TES/CTE. CTE is increasingly of concern to the Australian community, and further research in this area is necessary. This retrospective preliminary study will form the basis of large, prospective, longitudinal cohort studies, assessing the natural history of TES/CTE in Australian athletes.


title: Antibody response after COVID-19 mRNA vaccination in relation to age, sex, and side effects

abstract:
BackgroundThe mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses.

MethodsWe here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations.

FindingsOur findings show a robust immune response to the Spike proteins RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose.

InterpretationThe Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine.

FundingThe study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe first studies addressing the immune responses in older individuals after the single-dose administration of the SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms "SARS-CoV-2", "COVID-19", "vaccine response", "mRNA vaccine", up to April 15th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the role of age, sex and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within 1-2 weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Even less information is available on sex differences or correlations with mRNA vaccine side effects.

Added value of this studyIn this study, we assessed the antibody response up to 6 weeks after the second dose of Pfizer-BioNTech Comirnaty mRNA vaccine in 118 individuals. Our findings show a strong initial immune response after the first dose and an even higher Spike RBD antibody levels at 1 week after the second dose, but these significantly declined at 6 weeks after the second dose. We also found a weaker immune response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Furthermore, although overall female and male vaccinees responded similarly, we found that age-related waning of the vaccine-related antibodies was stronger amongst older males whereas in females the impact of age was lost at 6 weeks after the second dose.

Implications of all the available evidenceNew mRNA vaccines are now applied worldwide as they have shown high efficacy in clinical trials. Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody response to Spike RBD region but these high levels decline 1.5 months after the second dose in most of the vaccinated individuals. Nevertheless, even at 6 weeks after the second dose, they stay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. These findings also implicate that fewer adverse effects may indicate lower antibody response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.


title: Declined antibody responses to COVID-19 mRNA vaccine within first three months


title: Association of ABO blood group with COVID-19 severity, acute phase reactants and mortality

abstract:
Background and objectiveThe ABO blood group system has been associated with infectious and noninfectious disease, including dengue, hepatitis B virus (HBV), and severe respiratory syndrome coronavirus (SARS), etc. Coronavirus disease 2019 (COVID-19) is the ongoing pandemic with multitude of manifestations and association of ABO blood group in South-East Asian population needs to be explored.

MethodsIt was a retrospective study of patients with real time polymerase chain reaction (RT-PCR) diagnosis of COVID-19 at Advanced Diagnostics and Liver Center between April 2020 to January 2021. Blood group A, B, O, and AB were identified in every participant, irrespective of their RH type and allotted groups 1, 2,3, and 4, respectively. Cox regression and logistic regression were used for inferential statistics.

ResultsThe cohort included 1067 patients: 521 (48.8%) of blood group O, 295 (27.6%) of blood group B, 202 (18.9%) of blood group A, and 49 (4.5%) of blood group AB. The majority of the patients were males 712 (66.7%) with an average body mass index (BMI) of 27.45 {+/-} 3.53. Patients with AB blood group stayed a median (IQR) of 14 (5, 27) days while A blood group cohort stayed 13 (6,27) days and overall 10.6% COVID-19-related mortality was observed at our center, with 13.9% in blood group A as the majority of COVID-19 deaths. Regarding severity of COVID-19 disease, there was a trend towards critical disease in blood group A and O (n=83, 41.1%; n=183, 35.1%; OR, 11.34 (95% CI, 46.79-53.22); p<0.001). Logistic regression demonstrates blood group O and AB as predictors for severe COVID-19 disease (O: OR: 0.438 (95% CI: 0.168-1.139) p=0.090; AB: OR: 0.415 (95% CI: 0.165-1.046) p=0.062) and cause-specific hazards ratio (HR) for survival function was 3.206 (p=0.361) among all blood groups.

ConclusionAlthough the prevalence of blood group O was higher in this cohort, hospital stay, severity of disease, and mortality were associated with blood group A. Further studies are needed for understanding the underlying mechanism behind the association of blood groups with COVID-19.


title: Blood transcriptomes of anti-SARS-CoV2 antibody positive healthy individuals with prior asymptomatic versus clinical infection

abstract: Despite tremendous efforts by the international research community to understand the pathophysiology of SARS-CoV-2 infection, the reasons behind the clinical variability, ranging from asymptomatic infection to lethal disease, are still unclear. Existing inter-individual variations of the immune responses, due to environmental exposures and genetic factors, may be critical to the development or not of symptomatic disease after infection with SARS-CoV-2, and transcriptomic differences marking such responses may be observed even later, after convalescence. Herein, we performed genome-wide transcriptional whole-blood profiling to test the hypothesis that immune response-related gene signatures may differ between healthy individuals with prior entirely asymptomatic versus clinical SARS-CoV-2 infection, all of which developed an equally robust antibody response. Among 12.789 protein-coding genes analyzed, there were only six and nine genes with significantly decreased or increased expression, respectively, in those with prior asymptomatic infection (n=17, mean age 34 years) relatively to those with clinical infection (n=15, mean age 37 years). All six genes with decreased expression (IFIT3, IFI44L, RSAD2, FOLR3, PI3, ALOX15), are involved in innate immune response while the first two are interferon-induced proteins. Among genes with increased expression six are involved in immune response (GZMH, CLEC1B, CLEC12A), viral mRNA translation (GCAT), energy metabolism (CACNA2D2) and oxidative stress response (ENC1). Notably, 8/15 differentially expressed genes are regulated by interferons. Our results suggest that an intrinsically weaker expression of some innate immunity-related genes may be associated with an asymptomatic disease course in SARS-CoV-2 infection. Whether a certain gene signature predicts, or not, those who will develop a more efficient immune response upon exposure to SARS-CoV-2, with implications for prioritization for vaccination, warrant further study.


title: Pharmacovigilance Analysis on Cerebrovascular Accidents and Coronavirus disease 2019 Vaccines

abstract:
IntroductionRecently, there have been reports of cerebrovascular accidents (CVA) occurring in individuals who have received the Coronavirus disease 2019 (COVID-19) vaccine.

ObjectiveThe objective of this analysis was to determine if a statistically significant signal exists in post-marketing safety reports between CVA and the three COVID-19 vaccines being administered in the United States of America (Pfizer, Moderna, Janssen).

MethodsA pharmacovigilance disproportionality analysis on adverse events reported with COVID-19 vaccines was conducted using data from Vaccine Adverse Event Reporting System.

ResultsA statistically significant signal was found between CVA events and each of the three COVID-19 vaccines (Pfizer/BioNTechs, Modernas and Janssens) in the VAERS database. Females and individuals of age 65 or older had higher number of case reports of CVA events with the COVID-19 vaccines. Females had also more COVID-19 adverse event reports in which a CVA was reported and resulted in the patient having permanent disability or death.

LimitationsRandomized controlled trials are needed to further analyze this signal.

ConclusionPatients should be made aware of the risk-benefit and symptoms to watch out for that may indicate the onset of a CVA and informed to seek medical care as soon as possible if they develop these symptoms.


title: Estimating the false positive rate of highly automated SARS-CoV-2 nucleic acid amplification testing

abstract: Molecular testing for infectious diseases is generally both very sensitive and specific. Well-designed PCR primers rarely cross-react with other analytes, and specificities seen during test validation are often 100%. However, analytical specificities measured during validation may not reflect real-world performance across the entire testing process. Here, we use the unique environment of SARS-CoV-2 screening among otherwise well individuals to examine the false positivity rate of high throughput so-called "sample-to-answer" nucleic acid amplification testing (NAAT) on three commercial assays: the Hologic Panther Fusion(R), Hologic Aptima(R) transcription mediated amplification (TMA), and Roche cobas(R) 6800. We used repetitive sampling of the same person as the gold standard to determine test specificity rather than retesting of the same sample. We examined 451 people repetitively sampled over 7 months via nasal swab, comprising 7,242 results. During the study period there were twelve positive tests (0.17%) from 9 people. Eight positive tests (0.11%, five individuals) were considered bona fide true positives based on repeat positives or outside testing and epidemiological data. One positive test had no follow-up testing or metadata and could not be adjudicated. Three positive tests (three individuals) did not repeat as positive on a subsequent collection, nor did the original positive specimen test positive on an orthogonal platform. We consider these three tests false positives and estimate the overall false positive rate of high-throughput automated, sample-to-answer NAAT testing to be approximately 0.041% (3/7242). These data help laboratorians, epidemiologists, and regulators understand specificity and positive predictive value associated with high-throughput NAAT testing.


title: When can we stop wearing masks? Agent-based modeling to identify when vaccine coverage makes nonpharmaceutical interventions for reducing SARS-CoV-2 infections redundant in indoor gatherings

abstract: As vaccination efforts to combat the COVID-19 pandemic are ramping up worldwide, there are rising concerns that individuals will begin to eschew nonpharmaceutical interventions for preventing SARS-CoV-2 transmission and attempt to return to pre-pandemic normalcy before vaccine coverage levels effectively mitigate transmission risk. In the U.S.A., some governing bodies have already weakened or repealed guidelines for nonpharmaceutical intervention use, despite a recent spike in national COVID-19 cases and majority population of unvaccinated individuals. Recent modeling suggests that repealing nonpharmaceutical intervention guidelines too early into vaccine rollouts will lead to localized increases in COVID-19 cases, but the magnitude of nonpharmaceutical intervention effects on individual-level SARS-CoV-2 infection risk in fully- and partially-vaccinated populations is unclear. We use a previously-published agent-based model to simulate SARS-CoV-2 transmission in indoor gatherings of varying durations, population densities, and vaccination coverage levels. By simulating nonpharmaceutical interventions in some gatherings but not others, we were able to quantify the difference in SARS-CoV-2 infection risk when nonpharmaceutical interventions were used, relative to scenarios with no nonpharmaceutical interventions. We found that nonpharmaceutical interventions will often reduce secondary attack rates, especially during brief interactions, and therefore there is no definitive vaccination coverage level that makes nonpharmaceutical interventions completely redundant. However, the reduction effect on absolute SARS-CoV-2 infection risk conferred by nonpharmaceutical interventions is likely proportional to COVID-19 prevalence. Therefore, if COVID-19 prevalence decreases in the future, nonpharmaceutical interventions will likely still confer protective effects but potential benefits may be small enough to remain within "effectively negligible" risk thresholds.


title: Machine Learning and Prediction of All-Cause Mortality among Chinese Older Adults

abstract:
Background and aimMortality risk stratification was vital for targeted intervention. This study aimed at building the prediction model of all-cause mortality among Chinese dwelling elderly with different methods including regression models and machine learning models and to compare the performance of machine learning models with regression model on predicting mortality. Additionally, this study also aimed at ranking the predictors of mortality within different models and comparing the predictive value of different groups of predictors using the model with best performance.

MethodWe used data from the 2008 and 2011 waves of Chinese Longitudinal Healthy Longevity Survey (CLHLS). The follow-up of CLHLS was conducted every 2-3 years till 2018. The analysis sample included 2,448 participants. We used totally 117 predictors to build the prediction model for survival including 61 questionnaire, 41 biomarker and 15 genetics predictors. Four models were built (XG-Boost, random survival forest [RSF], Cox regression with all variables and Cox-backward). We used C-index and integrated Brier score to evaluate the performance of those models.

ResultsThe XG-Boost model and RSF model shows slightly better predictive performance than Cox models and Cox-backward models based on the C-index and integrated Brier score in predicting surviving. Age, activity of daily living and Mini-Mental State Examination score were identified as the top 3 predictors in the XG-Boost and RSF models. Biomarker and questionnaire predictors have a similar predictive value, while genetic predictors have no addictive predictive value when combined with questionnaire or biomarker predictors.

ConclusionIn this work, it is shown that machine learning techniques can be a useful tool for both prediction and its performance sightly outperformed the regression model in predicting survival.

category: public and global health