title: Individuals with Metabolic Syndrome show altered fecal lipidomic profiles with no signs of intestinal inflammation or increased intestinal permeability: a pilot study

abstract: Metabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low HDL cholesterol, hyperglycemia, hypertension or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS with the goal to evaluate for any signs of underlying gut inflammation, increased intestinal permeability, and alterations in host-microbiota metabolism as assessed by fecal metabolites. No signs of intestinal inflammation or increased intestinal permeability were observed in MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. An although our MetS cohort showed no signs of intestinal inflammation they presented with increased levels of serum TNF that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels, and decreasing HDL cholesterol levels. Taken together, our main results show MetS subjects show major alterations in fecal lipid profiles suggesting alterations in intestinal host-microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD.


title: Rapid genome surveillance of SARS-CoV-2 and study of risk factors using shipping container laboratories and portable DNA sequencing technology

abstract: In this paper we report on genome sequencing of 154 SARS-CoV-2 samples between June and July 2021 (Summer outbreak) in the Bailiwick of Jersey, a UK channel island. We have analysed extensive data collected on 598,155 RT-qPCR tests that identified 8,950 positive cases as part of public health surveillance from September 2020 to August 2021. Our study implemented an amplicon-based sequencing approach using the Oxford Nanopore Technology (ONT) portable device. This revealed the emergence of twelve AY sublineages and were clustered into the Delta sub-clades 21I and 21J. This was integrated alongside an existing RT-qPCR diagnostic laboratory to provide a sample-to-sequence turnaround time of approximately 30 hours with significant scope for optimisation. Owing to the geographic remoteness of the island from large scale sequencing infrastructure, this presents an opportunity to provide policy makers with near real-time sequencing findings. Our analysis suggests that age and sex remained a substantial risk factor for mortality. We observe viral loads are higher in advanced ages and unvaccinated individuals. The median age of SARS-CoV-2 positive individuals was higher during winter than the summer outbreak, and the contact tracing program showed that younger individuals stayed positive for longer.

category: epidemiology


title: Predictors of longitudinal cognitive ageing from age 70 to 82 including APOE e4 status, early-life and lifestyle factors

abstract: Discovering why some peoples cognitive abilities decline more than others is a key challenge for cognitive ageing research. The most effective strategy may be to address multiple risk factors from across the life-course simultaneously in relation to robust longitudinal cognitive data. We conducted a 12-year follow-up of 1091 (at age 70) men and women from the longitudinal Lothian Birth Cohort 1936 study. Comprehensive repeated cognitive measures of visuospatial ability, processing speed, memory, verbal ability, and a general cognitive factor, were collected over five assessments (age 70, 73, 76, 79, and 82 years) and analysed using multivariate latent growth curve modelling. Fifteen life-course variables were used to predict variation in cognitive ability levels at age 70 and cognitive slopes from age 70 to 82. Only APOE e4 carrier status was found to be reliably informative of general- and domain-specific cognitive decline, despite there being many life-course correlates of cognitive level at age 70. APOE e4 carriers had significantly steeper slopes across all three fluid cognitive domains compared with non-carriers, especially for memory ({beta} = -0.234, P< 0.001) and general cognitive function ({beta} = -0.246, P<0.001), denoting a widening gap in cognitive functioning with increasing age. Our findings suggest that when many other candidate predictors of cognitive ageing slope are entered en masse, their unique contributions account for relatively small proportions of variance, beyond variation in APOE e4 status. We conclude that APOE e4 status is important for identifying those at greater risk for accelerated cognitive ageing, even among ostensibly healthy individuals.


title: Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome

abstract: The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies of have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations that have been associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with thalamocortical function that has widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data was collected from participants affected by FXS (n=65) and matched controls (n=70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) a redistribution of lower-frequency boundaries indicating a "slower" dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS, and thus a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in mouse model research.

category: pediatrics


title: Atypical functional connectivity of the left fusiform gyrus in infants at familial risk for developmental dyslexia

abstract:
ImportanceDevelopmental dyslexia (dyslexia) is a genetic-based learning disorder affecting 7-10% of the general population and has detrimental impacts on mental health and vocational potential. Individuals with dyslexia show altered functional organization of the language and reading neural networks; however, it remains unknown how early these neural network alterations emerge in association with familial(genetic) vulnerability to dyslexia.

ObjectiveTo determine whether the early development of large-scale neural functional connectivity is altered as a function of familial risk for dyslexia.

DesignThis cohort study included 98 infants with (FHD+) and without (FHD-) a familial history of dyslexia recruited at Boston Childrens Hospital (BCH) between May 2011 and February 2019.

SettingParticipants underwent structural and resting-state functional magnetic resonance imaging in the Department of Pediatric Radiology at BCH.

ParticipantsFHD+ infants were defined as having at least one first-degree relative with dyslexia or reading difficulties and infants without familial risk for dyslexia (i.e., FHD-) were controls.

Main outcomes and measuresWhole-brain functional connectivity patterns associated with 20 pre-defined cerebral regions important for long-term language and reading development were computed for each infant. Multivariate pattern analyses were applied to identify specific functional connectivity patterns that differentiated between FHD+ and FHD-infants.

ResultsThe final sample consisted of 35 FHD+ (8.9 {+/-} 2.4 months, 15 females) and 63 FHD- (8.3 {+/-} 2.3 months, 36 females) infants. Multivariate pattern analyses identified distinctive functional connectivity patterns between the FHD+ and FHD-infants in the left fusiform gyrus (LFFG: accuracy = 0.55, pcorrected < 0.001, effect size: Cohens d = 0.76, 99% CI of the classification performance (classification accuracy-chance level) = [0.046, 0.062]). Moreover, the top five connections with greatest contribution to the classification performance connected LFFG with the frontal and temporoparietal regions of the language network.

Conclusion and relevanceThe current study demonstrates that familial vulnerability to dyslexia is associated with an early onset of atypical functional connectivity of regions important for subsequent word form recognition during reading acquisition. Longitudinal studies linking the atypical functional network and school-age reading x(dis)abilities will be essential for further elucidating the ontogenetic mechanisms underlying the development of dyslexia.

Key PointsO_ST_ABSQuestionC_ST_ABSAre functional topologies of language and reading-related regions in infancy associated with familial vulnerability to developmental dyslexia?

FindingsIn a cohort study examining the resting-state functional connectivity of 98 infants during natural sleep, distinctive functional connectivity patterns of the left fusiform gyrus were observed between infants with and without a familial risk for dyslexia. These differences were evident despite comparable behavioral and socio-economic/environmental characteristics between the two groups.

MeaningFamilial vulnerability of dyslexia is associated with early alterations in the infant functional connectivity of key regions important for subsequent word recognition, suggesting an atypical neural scaffold for reading acquisition.


title: NeuroEPO and cognitive function in Parkinsons disease in a randomized placebo-controlled and post-trial studies

abstract:
BackgroundCognitive impairment is a feature of Parkinsons Disease (PD) from the early stages, but currently, no treatment for cognitive deficits in PD is available. Erythropoietin (EPO) has been studied for its potential neuroprotective properties in neurologic disorders with a beneficial action on cognition.

ObjectiveTo evaluate if NeuroEPO, a new formulation of EPO with low content of sialic acid, improves the cognitive function in PD patients.

MethodsA double-blind, randomized, placebo-controlled physician lead trial was conducted. The sample was composed of 26 PD patients (HY stages I-II), where 15 received intranasal NeuroEPO for 5 weeks, and another age and gender-matched 11 patients were randomly assigned to the Placebo. All the samples received 9 months of intensive NeuroEPO treatment during a post-trial. The cognitive functions were assessed using a comprehensive neuropsychological battery before, one week, and 6 months after the first intervention and one week after a 9months post-trial. The effects of NeuroEPO were evaluated using a multivariate linear mixed-effects model using a latent variable for cognition instead of the raw neuropsychological scores.

ResultsA significant and direct effect of the Dose of NeuroEPO (p=0.00003) was found on cognitive performance with a strong positive influence of educational level (p=0.0032) and negative impact of age (p=0.0063).

ConclusionsThese preliminary results showed a positive effect of NeuroEPO on cognition in PD patients with better benefit for younger and higher educated patients.

category: neurology


title: NeuroEPO improves cognition in Parkinson's disease. Preliminary report.


title: Post-malnutrition growth and its associations with child survival and non-communicable disease risk: A secondary analysis of the Malawi ChroSAM cohort

abstract:
BackgroundRapid catch-up growth after prenatal undernutrition is associated with increased risk of non-communicable diseases (NCDs) in high-income countries. Severe malnutrition treatment programmes in low- and middle-income countries promote rapid post-malnutrition growth (PMGr) as desirable. Our aim was to explore patterns of PMGr during and in the year following treatment, and describe associations with survival and NCD risk seven years post-treatment.

MethodsSecondary data analysis from a cohort of children treated for severe malnutrition in Malawi in 2006/7. Six definitions of PMGr were derived based on a variety of timepoints, weight, weight-for-age z-score (WAZ) and height-for-age z-score (HAZ). Three categorisation methods included: no categorisation, quintiles, and latent class analysis (LCA). Associations with mortality risk, and with eight NCD indicators were analysed visually using scatter plots and boxplots, and statistically using simple and multivariable linear regression.

FindingsFaster weight gain was associated with lower risk of death (g/day during treatment aOR 0.99, 95%CI 0.99 to 1.00, p=0.04; after treatment g/kg/month aOR 0.91, 95% CI 0.87 to 0.94, p<0.001). In survivors, it was associated with greater hand grip strength in some instances (g/day during treatment 0.02, 95%CI 0.00 to 0.03, p=0.007) and larger HAZ 7-years post-discharge (adjusted {Delta} WAZ per day during treatment 6.62, 95%CI 1.31 to 11.9, p=0.02), both indicators of better health. However, faster weight gain in treatment was also associated with increased waist:hip ratio (adjusted g/day during treatment 0.02, 95%CI 0.01 to 0.03, p=0.003), a key indicator of later life NCD risk. The clearest patterns of association were seen when defining PMGr based on weight gain in g/day during treatment, and using the LCA method to describe growth patterns. Weight deficit at admission was a major confounder.

ConclusionWe found a complex pattern of benefits and risks associated with faster PMGr with a possible trade-off between short- and long-term benefits/risks. Peripheral versus visceral weight distribution in particular requires further exploration. Both initial weight deficit and rate of weight gain have important implications for future health. Because conclusions from observational studies can go only so far, future randomised intervention trials are needed.

category: nutrition


title: Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

abstract:
BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease with variable severity throughout the ongoing illness. Patients experience relapses where symptoms increase in severity, leaving them with a marked reduction in quality of life. Previous work has investigated molecular differences between ME/CFS patients and healthy controls, but the dynamic changes specific to each individual patient are unknown. Precision medicine can determine how each patient responds individually during variations in their long-term illness. We apply precision medicine here to map genomic changes in two selected ME/CFS patients through a relapse recovery cycle.

ResultsDNA was isolated from Peripheral Blood Mononuclear Cells (PBMCs) from two patients and a healthy age/gender matched control in a longitudinal study to capture a patient relapse. Reduced representation DNA methylation sequencing profiles were obtained from each time point spanning the relapse recovery cycle. Both patients throughout the time course showed a significantly larger methylome variability (10-20 fold) compared with the control. During the relapse changes in the methylome profiles of the two patients were detected in regulatory-active regions of the genome that were associated respectively with 157 and 127 downstream genes, indicating disturbed metabolic, immune and inflammatory functions occurring during the relapse.

ConclusionsSevere health relapses in ME/CFS patients result in functionally important changes in their DNA methylomes that, while differing among patients, lead to similar compromised physiology. DNA methylation that is a signature of disease variability in ongoing ME/CFS may have practical applications for strategies to decrease relapse frequency.

category: genetic and genomic medicine


title: Cross-neutralizing activity against Omicron could be obtained in SARS-CoV-2 convalescent patients who received two doses of mRNA vaccination

abstract: The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n=23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Surprisingly and interestingly, after the second vaccination, the subjects neutralizing antibody titers including that against Omicron all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the subjects disease severity. Our findings thus demonstrate that at least two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.

category: infectious diseases


title: Booster protection against Omicron infection in a highly vaccinated cohort

abstract:
BackgroundEvaluation of COVID-19 vaccine booster effectiveness is essential as new variants of SARS-CoV-2 emerge. Data support the effectiveness of boosters in preventing severe disease and hospitalization; however, the real-world impact on reducing incident SARS-CoV-2 infections across specific variants is not yet clear.

ObjectivesAssess the impact of COVID-19 boosters on protection against SARS-CoV-2 infection in a real-world setting from a highly vaccinated (99%) population curated from a linked database with test results, vaccination history, patient demographics, and genomic sequencing information from the National Basketball Association (NBA).

MethodsIn this population, 1,613 fully vaccinated staff and players (median age 34.5 years, 88% male) who tested at least once between 1 December 2021 and 5 January 2022, were analyzed. Individuals were tested at the time of reporting any symptom, regardless of severity, after known exposure per self-report or contact tracing and/or during enhanced surveillance. Boosted individuals (n=1260) were compared to fully vaccinated and booster eligible individuals (n=162), defined as 2 months post-JNJ-78436735 or 5-months post-second dose of mRNA vaccine. Individuals not yet eligible for a booster and those who recovered from COVID-19 between 1 November and 30 November, 2021 (n=25) were examined in secondary analyses but excluded from the primary comparison. Individuals who were not fully vaccinated (n=27) or who received a booster within 14 days during or prior to the observation period (n=916) were excluded.

ResultsIn this closely monitored population, fully vaccinated booster-eligible individuals were 2.6 times more likely (RR = 2.6, 95% CI: 2.2 to 3.0, p<0.0001) to have a confirmed COVID-19 infection than boosted individuals. Secondary analysis including non-boosted individuals with recent vaccination or recent SARS-CoV-2 infection found that non-boosted individuals were at greater risk of infection compared with boosted individuals (RR = 2.1, 95% CI: 1.8 to 2.4, p<0.001). Results were similar when stratified by primary vaccination type with overlapping confidence intervals. No hospitalizations or deaths were observed in this cohort. Genetic sequencing confirmed 93% of infections to be Omicron (among n=330 sequenced).

ConclusionsThese results highlight the protective benefit of boosters against incident SARS-CoV-19 infection, not only for severe symptoms and death. Assessment of booster effectiveness remains vital for COVID-19 vaccines as new variants of SARS-CoV-2 emerge, as there is still uncertainty around performance in real-world settings. These data are needed to convince the general public that boosters remain effective at preventing in the spread of COVID-19.


title: Influence of Lamina Vastoadductoria Dissection on the Outcomes of Femoral Artery Extensive Lesion Stenting: A Pilot Randomised Investigation

abstract:
ObjectiveAim of the study was to improve the immediate and long-term results of stenting of the superficial femoral artery in extended lesions with the changing of the biomechanics of SFA and of the first portion of the popliteal artery.

MethodsPilot randomized prospective single-center study were included 70 patients. Patients were randomized into two groups in 1x1 format for 35 people using the envelope method. Self-expanding bare metal stents were used in all cases. At the first group standard revascularization procedures with SFA stenting were performed; in the second group, the superficial femoral artery stenting was supplemented with fasciotomy in the Hunters canal with the superficial femoral artery intersection. The total observation period was 2 years. During the observation period an assessment of the clinical symptoms of the lower extremities, measurement of the ankle-brachial index and ultrasound duplex scanning of the operated segment were performed.

ResultsAll procedures in both groups were successfully performed. Primary patency through 24 months was 28.5% (10 of 35) in group 1 and 60% (21 of 35) in group 2 (p=0,015).

ConclusionsChanging the biomechanical properties of the distal of the superficial femoral artery segment and of the first portion of the popliteal artery is safe and contributes to the primary patency improvement during the stenting of extended of the superficial femoral artery lesions compared to standard SFA stenting. Dissection of the lamina vastoadductoria with transection of the collateral branches of the knee joint network reduces frequent and severe damages of stents after the stenting of the superficial femoral artery extended lesion.

According to the frequency of complications in the early and mid-term postoperative period, limb salvage, mortality and the secondary patency rates, the new method is comparable with standard of the superficial femoral artery stenting.

category: cardiovascular medicine


title: Why Risk Factors Minimally Change the ROC Curve AUC

abstract:
Novel risk factors that improve statistical measures of fit on addition to established clinical prediction models often minimally change measures of discrimination (ROC curve AUC or c-index). As a result, measures of discrimination have been suggested to be insensitive in the evaluation of such models.

To understand this phenomenon, it is necessary to focus on the population risk distributions produced by models with and without the risk factor. This is because these risk distribution fully determines the risk distributions of cases/patients and controls/nonpatients, which in turn fully determine the ROC curve and its AUC. Broader population risk distributions result in larger ROC curve AUCs.

A fully independent risk factor with a relative risk of 2 added to the standard cardiovascular risk model produces risk distributions of those with or without the risk that are clearly different (which is evaluated by statistical measures of fit), while minimally broadening the population risk distributions (which is evaluated by measures of discrimination). The reason for this is that although addition of the risk factor replaces every risk stratum with higher and lower risk strata, this depopulated risk stratum is largely repopulated by similar splitting in neighboring risk strata. The interweaving of the the up and down migration paths to and from every point on the risk distribution results in a largely compensatory shuffling of risk assignments with minimal changes in the ROC curve AUC.


title: Waning Effectiveness of the Third Dose of the BNT162b2 mRNA COVID-19 Vaccine

abstract: The duration of protection of the third (booster) dose of the BioNTech/Pfizer BNT162b2 mRNA Coronavirus Disease 2019 vaccine has yet to be sufficiently researched, while global discussions around the necessity and effectiveness of a fourth dose are already underway. By conducting a retrospective study implementing a test-negative case-control design, analyzing 546,924 PCR tests performed throughout January 2022 by 389,265 persons who received three doses of the vaccine, we found that the effectiveness in each month since vaccination decreased significantly. Compared to those vaccinated early, on August 2021, relative protection against infection waned from 53.4% a month after vaccination to 16.5% three months after vaccination. These results suggest that there is a significant waning of vaccine effectiveness against the Omicron variant of the third dose of the BNT162b2 vaccine within a few months after administration and should prompt policy discussion as to additional booster doses and vaccine development.

category: public and global health


title: Loneliness and diurnal cortisol levels during COVID-19 lockdown: the roles of living situation, relationship status and relationship quality

abstract: Loneliness and social isolation have become increasing concerns during COVID-19 lockdown through neuroendocrine stress-reactions, physical and mental health problems. We investigated living situation, relationship status and quality as potential moderators for trait and state loneliness and salivary cortisol levels (hormonal stress-responses) in healthy adults during the first lockdown in Germany. N=1242 participants (mean age = 36.32, 78% female) filled out an online questionnaire on demographics, trait loneliness and relationship quality. Next, N=247 (mean age = 32.6, 70% female) completed ecological momentary assessment (EMA), collecting twelve saliva samples on two days and simultaneously reporting their momentary loneliness levels. Divorced/widowed showed highest trait loneliness, followed by singles and partnerships. The latter displayed lower momentary loneliness and cortisol levels compared to singles. Relationship satisfaction significantly reduced loneliness levels in participants with a partner and those who were living apart from their partner reported loneliness levels similar to singles living alone. Living alone was associated with lower loneliness levels. Hierarchical linear models revealed a significant cross-level interaction between relationship status and momentary loneliness in predicting cortisol. The results imply that widowhood, being single, living alone and low relationship quality represent risk factors for loneliness and having a partner buffers neuroendocrine stress responses during lockdown.


title: The effect of job strain and worksite social support on reported side effects of COVID-19 vaccine: a prospective study of employees in Japan

abstract:
ObjectivesThis prospective study aimed to examine the association of job demands, job control, and the lack of supervisor and coworker support with side effects after receiving COVID-19 vaccination in a sample of employees in Japan.

MethodsThe data were retrieved from an online panel of full-time employees (E- COCO- J). The analysis included participants who were employed and were not vaccinated at baseline (June 2021) but received vaccination at a four-month follow-up (October 2021). An 11-item scale measured the side effects of COVID-19 vaccines. Four types of psychosocial working conditions (i.e., job demands, job control, and supervisor and coworker support) were measured using the Brief Job Stress Questionnaire (BJSQ). Multiple linear regression analyses were conducted to examine the relationship between the psychosocial working conditions and side effects of COVID-19 vaccines, adjusting for gender, age, educational attainment, marital status, occupation, chronic disease, dose of vaccination, anxiety from potential side effects of vaccines, fear and worry about COVID-19, and psychological distress at baseline.

ResultsOverall, 747 employees were included in the analysis. The average number of side effects was 3.78 (SD=2.19): Arm pain (81.1%), fatigues (64.1%), muscle pains (63.3%), and fever (37.5 degrees Celsius +) (53.5%) were reported more frequently. Coworker support score was significantly and negatively associated with the numbers of side effects (standardized {beta}=-0.122, p=0.017). Women, young age, second time vaccination, and high psychological distress were significantly associated with several side effects.

ConclusionsEmployees with low coworker support may be more likely to have side effects after COVID-19 vaccinations. The findings of this study could inform employees with low coworker support that increasing workplace support may reduce the side effects.

Highlights The effect of poor psychosocial working conditions on side effects after COVID-19 vaccinations was unknown.
 Poor coworker support at baseline was significantly associated with increased side effects after COVID-19 vaccinations.
 Informing workers with low coworker support about the findings may help them prepare for the side effect and motivate them to improve coworker support to reduce side effects.

category: occupational and environmental health


title: Impact of body mass index on 5-year survival rates in patients undergoing allogeneic hematopoietic stem cell transplantation

abstract:
BackgroundThe association between cancer survival and body mass index (BMI) has been elucidated. However, the impact of patients baseline characteristics on allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes remains unclear.

ObjectivesTo examine the baseline clinical factors associated with 5-year survival rates in patients undergoing allo-HSCT.

Study designThis was a retrospective exploratory observational study. Patients (n=113, average age: 55 years; 52 women) who underwent allo-HSCT at the Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, between January 2008 and March 2015 were included in this study.

ResultsThe 5-year survival rate (65%) was associated with the baseline geriatric nutritional risk index (GNRI; odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.03-1.36, P <0.01) and the BMI (OR=1.06, 95% CI: 1.02-1.12, P <0.01). The cut-off values for BMI and GNRI were 20.5 kg/m2 and 101 points, respectively (area under the curve, 0.65017 and 0.67637, respectively). The 5-year survival rate was poorer for patients with sarcopenia (41.5%) than for those without sarcopenia prior to allo-HSCT (p=0.05).

ConclusionsBMI and GNRI values before allo-HCST pre-treatment were independent predictors of the 5-year survival rates. Patients undergoing allo-HSCT may require nutritional interventions during pre-treatment to reduce the risk of sarcopenia, which affects their survival rates.


title: A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study.

abstract:
The Circadia Study (Circadia) is a novel "direct to participant" research study investigating the genetics of circadian rhythm disorders. The long-term goals of this study are to better understand the genetics of circadian rhythm disorders, investigate the efficacy and accessibility of an at-home, self-directed DLMO collection, to improve health outcomes in the future for patients with circadian rhythm disorders, and to address the specific needs of the circadian rhythm disorder patient population.

In this manuscript, we briefly outline the standard methods of both circadian biology research protocols and circadian rhythm disorder diagnostic procedures. We describe some of the inherent limitations of current circadian research and diagnostic methods, which motivated our development of and informed the design of the Circadia Study. We discuss the main goals of the Circadia Study, and we outline key features of our study design that build upon current study methods and address limitations. Finally, we describe specific aspects of the Circadia Study, including our study population, data collection methods, and standard operating procedures so that others may replicate aspects of the study design.

The Circadia Study is approved for human subject research by the Mass General Brigham Institutional Review Board, Protocol # 2020P002779.


title: Self-management of depression and anxiety amongst frail older adults in the United Kingdom: a qualitative study

abstract:
ObjectivesDepression and anxiety are common in frail older people and are associated with high levels of morbidity and mortality, yet they typically face greater barriers to accessing mental health treatments than younger people and express preferences for self-managing their symptoms. This study aims to explore frail older adults experiences of self-managing symptoms of depression and/or anxiety.

DesignQualitative semi-structured interviews, exploring experiences of depression and/or anxiety, ways participants self-managed these and the contexts within which this took place. Interviews were audio-recorded and transcribed verbatim.

Participants28 frail older adults in the United Kingdom, purposively sampled for neighbourhood, frailty and symptoms of anxiety/depression.

AnalysisThematic analysis to inductively derive themes from the data.

ResultsOur findings suggest that frail older adults find maintaining routines, engaging in meaningful and creative activities and socialising important to self-manage depression and anxiety. These could all be adapted to the level of frailty experienced. Stoicism, acceptance, faith or addressing the perceived cause were helpful in some situations and for some personalities. Distraction and avoidance were helpful for more severe symptoms or where the causes of symptoms could not be resolved. Self-management strategies were less well-established for anxiety symptoms, especially when linked to newer health fears and worries about the future.

ConclusionsDeveloping services and sources of information that support and facilitate key therapeutic components of self-management, which align with older adults preferred coping styles and take into account levels of frailty, may be a way of supporting frail older people waiting for mental health treatments or those who prefer not to access these. Greater awareness of anxiety and how it can be self-managed in frail older people is needed.

category: geriatric medicine


title: Late-Ensemble of Convolutional Neural Networks with Test Time Augmentation for Chest XR COVID-19 Detection

abstract: COVID-19, a severe acute respiratory syndrome aggressively spread among global populations in just a few months. Since then, it has had four dominant variants (Alpha, Beta, Gamma and Delta) that are far more contagious than original. Accurate and timely diagnosis of COVID-19 is critical for analysis of damage to lungs, treatment, as well as quarantine management [7]. CT, MRI or X-rays image analysis using deep learning provide an efficient and accurate diagnosis of COVID-19 that could help to counter its outbreak. With the aim to provide efficient multi-class COVID-19 detection, recently, COVID-19 Detection challenge using X-ray is organized [12]. In this paper, the late-fusion of features is extracted from pre-trained various convolutional neural networks and fine-tuned these models using the challenge dataset. The DensNet201 with Adam optimizer and EffecientNet-B3 are fine-tuned on the challenge dataset and ensembles the features to get the final prediction. Besides, we also considered the test time augmentation technique after the late-ensembling approach to further improve the performance of our proposed solution. Evaluation on Chest XR COVID-19 showed that our model achieved overall accuracy is 95.67%. We made the code is publicly available1. The proposed approach was ranked 6th in Chest XR COVID-19 detection Challenge [1].

category: health informatics


title: Changes in the quality of cancer care as assessed through performance indicators during the first wave of the COVID-19 pandemic in 2020: a Scoping Review

abstract:
ObjectivesSummarize performance indicators used in the literature to evaluate the impact of the COVID-19 pandemic on cancer care (January-June 2020), and to assess changes in the quality of care as assessed via selected indicators.

MethodsScoping review. Indicators and their reported trends were collated following the cancer care pathway.

ResultsDatabase searches retrieved 6277 articles, 838 articles met the inclusion criteria, and 135 articles were included after full-text screening, from which 917 indicators were retrieved. Indicators assessing the diagnostic process showed a decreasing trend: from 33 indicators reporting on screening, 30 (91%) signalled a decrease during the pandemic (n=30 indicators, 91%). A reduction was also observed in the number of diagnostic procedures (n=64, 58%) and in the diagnoses (n=130, 89%). The proportion of diagnoses in the emergency setting and waiting times showed an increasing trend (n=8, 89% and n=14, 56%, respectively). Nine indicators (64%) showed stability in cancer stages distribution. A decreasing trend in the proportion of earliest stage cancers was reported by 63% of indicators (n=9), and 70% (n=43) of indicators showed an increasing trend in the proportion of advanced-stage cancers. Indicators reflecting the treatment process signalled a reduction in the number of procedures: 79% (n=82) of indicators concerning surgeries, 72% (n=41) of indicators assessing trends in radiotherapy, and 93% (n=40) of indicators related to systemic therapies. Modifications in cancer treatment were frequently reported: 64% (n=195) of indicators revealed changes in treatment. Ten indicators (83%) signalled a decreasing number of hospital admissions.

ConclusionHealth systems struggled to ensure continuity of cancer care. As this pandemic keeps evolving, the trends reported over the first 6 months of 2020 provide an argument to monitor these changes closely. This information needs to be transparent, standardised, and timely, allowing to monitor quality and outcomes of care during crises and inform policy responses.

category: health systems and quality improvement


title: Duration of Protection Against SARS-CoV-2 Reinfection and Associated Risk of Reinfection Assessed with Real-World Data

abstract:
ImportanceBetter understanding of the protective duration of prior SARS-CoV-2 infection against reinfection is needed.

ObjectivePrimary: To assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection. Secondary: Evaluate the crude SARS-CoV-2 reinfection rate and associated characteristics.

Design and SettingRetrospective observational study of HealthVerity data among 144,678,382 individuals, during the pandemic era through April 2021.

ParticipantsIndividuals studied had SARS-CoV-2 molecular diagnostic or antibody index test results from February 29 through December 9, 2020, with [≥]365 days of pre-index continuous closed medical enrollment, claims, or electronic health record activity.

Main Outcome(s) and Measure(s)Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result.

ResultsAmong 22,786,982 individuals with index SARS-CoV-2 laboratory test data (2,023,341 index positive), the crude rate of reinfection during follow-up was significantly lower (9.89/1,000-person years) than that of primary infection (78.39/1,000 person years). Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals (hazard ratio, 0.13; 95% CI, 0.13, 0.13). The cumulative incidence of reinfection among index-positive individuals and infection among index-negative individuals was 0.85% (95% CI: 0.82%, 0.88%) and 6.2% (95% CI: 6.1%, 6.3%), respectively, over follow-up of 375 days. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk.

Conclusions and RelevanceThis large US population-based study demonstrates that SARS-CoV-2 reinfection is uncommon among individuals with laboratory evidence of a previous infection. Protection from SARS-CoV-2 reinfection is stable up to one year. Reinfection risk was primarily associated with age 85+ years, comorbid immunologic conditions and living in congregate care settings; healthcare workers demonstrated a decreased reinfection risk. These findings suggest that infection induced immunity is durable for variants circulating prior to Delta.

Key PointsO_ST_ABSQuestionC_ST_ABSHow long does prior SARS-CoV-2 infection provide protection against SARS-CoV-2 reinfection?

FindingAmong >22 million individuals tested February 2020 through April 2021, the relative risk of reinfection among those with prior infection was 87% lower than the risk of infection among individuals without prior infection. This protection was durable for up to a year. Factors associated with increased likelihood of reinfection included older age (85+ years), comorbid immunologic conditions, and living in congregate care settings; healthcare workers had lower risk.

MeaningPrior SARS-CoV-2 infection provides a durable, high relative degree of protection against reinfection.


title: IFNβ-1b treatment leads to changes in the B cell subset and cytokine secretion profile in patients with relapsing-remitting multiple sclerosis

abstract: In order to explore the effect of IFN{beta}-1b treatment on B cell phenotype and function in RRMS patients, blood was drawn from RRMS patients before treatment and again 2 and 6 months after every other day injections of IFN{beta}-1b. Cryopreserved peripheral blood mononuclear cells (PBMCs) were thawed and stained with panels of antibodies against B cell surface antigens and the intracellular cytokines, IL-10 and IL-6. At baseline, PBMCs from RRMS patients have increased frequencies of B1 cells and a decreased frequencies of memory B cells when compared with PBMCs from age- and gender-matched healthy controls. CpG-stimulated PBMCs from patients treated with IFN{beta}-1b show an increase in IL-10 production and a decrease in IL-6 production by naive, memory and B1 cells compared with healthy controls. In addition, this treatment alters the composition of circulating B cell subsets, leading to an increase after six months in circulating naive B cells and a decrease in both memory and B1 cells, both cell types of which are potentially pathogenic in RRMS. Patients were divided into two groups based on disease activity, no/low or moderate/high. A significantly higher frequency of B1 cells and higher expression of CD27 on these cells was seen at baseline in the moderate/high disease activity group to IFN{beta}-1b compared with patients in the no/low disease activity group. Although the number of subjects in this study was limited, these findings suggest that alterations in the B cell compartment may be a mechanism by which IFN{beta}-1b reduces disease activity.

category: allergy and immunology


title: Reassessment of persistent symptoms, self-reported COVID-19 infection and SARS-CoV-2 serology in the SAPRIS-SERO cohort: identifying possible sub-syndromes of Long Covid.

abstract:
BackgroundLong Covid remains a relatively new phenomenon with emerging understanding. Estimated UK prevalence of Long Covid with three or more symptoms lasting for 12 weeks or more was 2.2% at the end of 2021. The population-based French SAPRIS-SERO cohort has novel information about the pattern of symptoms of Long Covid that has been obscured by controversy around the original paper.

MethodsSecondary analysis was used to describe and re-interpret the frequencies of persistent symptoms by IgG seropositivity and self-reported Long Covid in the published report of the SAPRIS-SERO survey. Participants in the cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, the Euroimmun enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Surveyed online between December 2020 and January 2021, participants self-reported previous COVID-19 infection and physical symptoms during the previous four weeks that were new since March 2020, and had persisted for at least eight weeks.

ResultsThere was similarity of prevalence over the majority of symptoms in those self-reporting COVID-19 infection, regardless of blood test result. Persistent symptoms significantly associated with self-reported COVID-19 infection and common in both groups include respiratory tract symptoms and a group of symptoms that might be related to chronic fatigue, malaise or postural issues. Seropositivity for IgG antibodies did not predict symptoms independently of self-reported Long Covid, except for anosmia.

ConclusionsThere may be three common sub-syndromes of Long Covid, one with persistent anosmia, another with other respiratory tract symptoms and a third, currently under researched, with symptoms relatable to chronic fatigue. Antibody tests are insufficient for case detection while Long Covid remains poorly understood.

Key MessagesO_LIIgG seropositivity is insufficient to identify potential cases of Long Covid
C_LIO_LIPersistent anosmia is very strongly associated with IgG seropositivity and may define a subsyndrome of Long Covid
C_LIO_LIOther potential subsyndromes are those with persistent respiratory symptoms and those with persistent symptoms relatable to fatigue, malaise or postural issues
C_LIO_LIThe Long Covid research effort should be rebalanced towards understanding the fatigue/tiredness subsyndrome.
C_LI


title: Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study

abstract:
Background and AimsThe incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients.

MethodsWe identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients.

ResultsWe isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively.

Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days.

ConclusionsIn this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.

category: gastroenterology


title: Impact of Omicron variant on the response to SARS-CoV-2 mRNA vaccination in multiple myeloma and monoclonal gammopathies

abstract:
Multiple myeloma (MM) patients may have a reduced response to vaccination due to immunodeficiency. The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of spike variants, including the emerging Omicron one, are still unclear and have been investigated in this study in a cohort of MM patients and those with pre-malignant monoclonal gammopathies.

Firstly, we have shown that MM patients with relapsed-refractory disease (MMR) had a reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 mRNA full vaccination. Interestingly, all the analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and in smoldering MM too. Moreover, lower spike-specific IL-2-producing CD4+ T cells and reduced cytotoxic spike-specific IFN-{gamma} and TNF--producing-CD8+ T cells were found in MM patients as compared to MGUS.

Finally, we found that booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. On the other hand, in MMR patients, Omicron retain a negative impact on neutralizing ability, suggesting these patients need to be considered still at risk of Omicron SARS-CoV-2 infection with a clinically relevant disease.

category: hematology


title: Longitudinal analysis of UK Biobank participants suggests age and APOE-dependent alterations of energy metabolism in development of dementia

abstract: Experimental models shows that bioenergetic homeostasis changes with increasing age based on apolipoprotein E (APOE) gene. However, such link with dementia remains unclear in population. We used H1-NMR metabolome in blood from 118,021 random-selected participants in UK Biobank (n=118,021 individuals), and identified 56 metabolites associated with the risk of dementia. In the participants without developing dementia during follow-up, 82% (46/56) metabolites are also associated with reaction time, and dementia shares metabolite signatures with total brain volume. We found that incident Alzheimers disease (AD) is associated with energy metabolism-related metabolites, i.e, {beta}-hydroxybutyrate, acetone, and valine, whose concentrations in blood are influenced by age and APOE genotype. Valine shows a declined trajectories after a plateau at age around 60 years which is in parallel with body mass index. Moreover, we found associations of AD with valine and {beta}-hydroxybutyrate in brain tissue are different as their associations in the periphery, which implies the key role of transports in regulating the energy metabolism of AD. Our study provides strong evidence in population level that the onset of AD in APOE4 carriers is regulated by the impaired energy balance in the brain.


title: Assessment of private variants in PRKN, PARK7 and PINK1 in Parkinson's disease

abstract: Recessive mutations in PRKN, PARK7 and PINK1 are established causes of early-onset Parkinsons disease (EOPD). Previous studies have interrogated the role of heterozygous variants in these genes but mainly focused on rare (minor allele frequency [MAF] <1%) damaging variants or established mutations. Here, we assessed heterozygous private PRKN, PARK7 and PINK1 variants in PD risk in four large-scale PD case-control datasets by performing gene-wise burden analyses using sequencing data totaling 5,829 PD cases and 7,221 controls, and summary allele counts from 9,501 PD cases and 48,207 controls. Results showed no significant burden in all three genes after meta-analyses. Burden in EOPD (age at onset <50 years) and late-onset PD ([≥]50 years) remained nonsignificant. In summary, we found no evidence to support the association of the excess burden of heterozygous private variants in PRKN, PARK7, and PINK1 with PD risk in the European population. Larger, more diverse cohorts are needed to accurately determine their role in PD.


title: Distinct Genetic Loci and Variations in Blood Pressure and Pulse Rate in Europeans and Africans from the UK Biobank

abstract: Trans-ancestral variations exist for various anthropometric traits. These traits, including cardiovascular traits, are likely associated with different loci in individuals of different ancestry groups. We assessed the difference in systolic blood pressure, diastolic blood pressure, pulse rate and maximum heart rate among African and European ancestry individuals. Furthermore, we conducted a genome-wide association study of cardiovascular traits in 383,471 Europeans and 5,978 Africans represented in the UK Biobank. Here, we report 2 and 1,202 variants associated with cardiovascular traits in Africans and Europeans, respectively. We identify 2 novel variants in Africans, including rs9388010 located in the GJA1 gene previously associated with numerous cardiomyopathies. Remarkably, we find the associated variants are primarily unique to each ancestry group and map to largely different genes. Through integrative enrichment analyses we find that gene sets within each ancestral group are significantly enriched for pathways and phenotypes related to cardiovascular physiology and disease. Our discoveries provide a better understanding of variations in cardiovascular traits and the different associated variants in Africans and Europeans.


title: Exercise Training Outcomes in Patients with Chronic Heart Failure with Reduced Ejection Fraction Depend on Medications and Disease Conditions: Proposal of SEEM Score to Judge Exercise Suitability

abstract:
BackgroundExercise training is an accepted evidence-based adjunct treatment modality for patients with chronic heart failure. However, the influence of medications or conditions on exercise has not been fully explored.

MethodsThe patient records of the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study were obtained from the National Heart, Lung, and Blood Institute, and analyzed by medications used at baseline (renin-angiotensin system inhibitors [RASIs], beta-blockers [BBs], and combination of both) with multivariable Cox regression models focusing on the interactions with exercise effects, and a score to indicate exercise training suitability was proposed accordingly.

ResultsMedication type strongly influenced the exercise effect on all-cause death (AD) (P = 0.007) even though medication itself did not change prognosis significantly in HF-ACTION trial. In patients taking both BBs and RASIs at baseline, exercise reduced the AD risk (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.98), whereas in patients not taking BBs, exercise increased the risk (HR, 4.58; 95% CI, 2.90-6.86). The exercise on AD was also influenced by pulse pressure, hemoglobin level, electrocardiography conditions, body mass index, and history of stroke. Accordingly, we constructed the Score for Eligibility of Exercise on Mortality (SEEM). When exercise training was chosen based on SEEM score, both AD and AD and hospitalization (ADH) risks were expected to reduce significantly (HR, 0.54; 95% CI, 0.44-0.68; HR, 0.83; 95% CI, 0.75-0.93, respectively).

ConclusionsExercise training in patients with heart failure should be recommended carefully with consideration of patient background.

Clinical Trial RegistrationClinicaltrials.gov identifier: NCT00047437. Trial registration date: 4 October 2002.


title: Improving ascertainment of suicidal ideation and suicide attempt with natural language processing

abstract: Methods relying on diagnostic codes to identify suicidal ideation and suicide attempt in Electronic Health Records (EHRs) at scale are suboptimal because these phenotypes are heavily under-coded. We propose to improve the ascertainment of suicide phenotypes using natural language processing (NLP). We developed information retrieval methodologies to search over 200 million notes from the Vanderbilt EHR. Suicide query terms were extracted using word2vec. A weakly supervised approach was designed to label cases of suicidal outcomes. The NLP validation of the top 200 retrieved patients showed high performance for suicidal ideation (area under the receiver operator curve [AUROC]: 98.6, 95% confidence interval [CI]: 97.1-99.5) and suicide attempt (AUROC: 97.3, 95% CI: 95.2-98.7). Case extraction produced the best performance when combining NLP and diagnostic codes and when accounting for negated suicide expressions in notes. Overall, we demonstrated that scalable and accurate NLP methods can be developed to identify suicide phenotypes in EHRs to enhance prevention efforts, predictive models, and precision medicine.


title: Short-term improvement of mental health after a COVID-19 vaccination

abstract:
ImportanceThe role of COVID-19 vaccination on the mental health of the general population remains poorly understood.

ObjectiveTo assess the short-term change of depressive and anxiety symptoms in relation to COVID-19 vaccination among Swedish adults.

DesignA prospective cohort study with monthly data collections on self-reported depressive and anxiety symptoms from December 2020 to October 2021 and COVID-19 vaccination from July to October 2021.

SettingThe Omtanke2020 Study, Sweden.

Participants7,925 participants of the Omtanke2020 study with complete data on depressive and anxiety symptoms and vaccination status.

Intervention(s) or Exposure(s)Receiving the first or second dose of a COVID-19 vaccine.

Main outcomes(s) and Measure(s)Binary measures of depression (PHQ-9, cut-off [≥]10) and anxiety (GAD-7, cut-off [≥]10) one month before the first dose, one month after the first dose, and, if applicable, one month after the second dose. For individuals not vaccinated or chose to not report vaccination status (unvaccinated individuals), we selected three monthly measures of PHQ-9 and GAD-7 with 2-month intervals in-between based on data availability.

Results5,079 (64.1%) individuals received two doses of COVID-19 vaccine, 1,977 (24.9%) received one dose, 305 (3.9%) were not vaccinated, and 564 (7.1%) chose not to report vaccination status. There was a lower prevalence of depression and anxiety among vaccinated, compared with unvaccinated, individuals, especially after the second dose. Among individuals receiving two doses of vaccine, the prevalence of depression and anxiety was lower after both first (aRR=0.82, 95%CI 0.76-0.88 for depression; aRR=0.81, 95%CI 0.73-0.89 for anxiety) and second (aRR=0.79, 95%CI 0.73-0.85 for depression; aRR=0.73, 95%CI 0.66-0.81 for anxiety) dose, compared with before vaccination. Similar results were observed among individuals receiving only one dose (aRR=0.76, 95%CI 0.68-0.84 for depression; aRR=0.82, 95%CI 0.72-0.94 for anxiety, comparing after first dose to before vaccination). These results were independent of age, sex, recruitment type, body mass index, smoking, relationship status, history of psychiatric disorder, number of comorbidities, COVID-19 infection status, and seasonality.

Conclusions and RelevanceWe observed a positive short-term change in depressive and anxiety symptoms among adults receiving a COVID-19 vaccine in the current pandemic.

Key pointsO_ST_ABSQuestionC_ST_ABSIs COVID-19 vaccination associated with a short-term change in mental health?

FindingsThis longitudinal study included 7,925 Swedish adults with self-reported COVID-19 vaccination and symptoms of mental health responding from December 2020 to October 2021. The prevalence of depressive or anxiety symptoms was lower one month after vaccination compared to one month before vaccination. The effect size was greater among individuals receiving two doses of vaccine, compared with those receiving only one dose.

MeaningReceiving vaccination against COVID-19 is associated with short-term improvement in mental health.


title: Multicenter international assessment of a SARS-CoV-2 RT-LAMP test for point of care clinical application

abstract: Continued waves, new variants, and limited vaccine deployment mean that SARS-CoV-2 tests remain vital to constrain the COVID-19 pandemic. Affordable, point-of-care (PoC) tests allow rapid screening in non-medical settings. Reverse-transcription loop-mediated isothermal amplification (RT-LAMP) is an appealing approach. A crucial step is to optimize testing in low/medium resource settings. Here, we optimized RT-LAMP for SARS-CoV-2 and human {beta}-actin, and tested clinical samples in multiple countries. "TTTT" linker primers did not improve performance, and while guanidine hydrochloride, betaine and/or Igepal-CA-630 enhanced detection of synthetic RNA, only the latter two improved direct assays on nasopharygeal samples. With extracted clinical RNA, a 20 min RT-LAMP assay was essentially as sensitive as RT-PCR. With raw Canadian nasopharygeal samples, sensitivity was 100% (95% CI: 67.6% - 100%) for those with RT-qPCR Ct values [≤] 25, and 80% (95% CI: 58.4% - 91.9%) for those with 25 < Ct [≤] 27.2. Highly infectious, high titer cases were also detected in Colombian and Ecuadorian labs. We further demonstrate the utility of replacing thermocyclers with a portable PoC device (FluoroPLUM). These combined PoC molecular and hardware tools may help to limit community transmission of SARS-CoV-2.


title: Effect of physical activity calorie equivalent (PACE) labels on energy purchased in cafeterias: a stepped-wedge randomised controlled trial

abstract:
BackgroundA recent meta-analysis suggested that using physical activity calorie equivalent (PACE) labels results in people selecting and consuming less energy. Only one included study was conducted in a naturalistic setting, in four convenience stores. The current study aimed to estimate the effect of PACE labels on energy purchased in worksite cafeterias.

Methods and findingsA stepped-wedge randomised controlled trial to test the effect of PACE labels (which include kcal content and minutes of walking required to expend the energy content of the labelled food) on energy purchased. The setting was ten worksite cafeterias in England, which were randomised to the order in which they introduced PACE labels on selected food and drinks following a baseline period. The study ran for 12 weeks with over 250,000 transactions recorded on electronic tills. The primary outcome was total energy (kcal) purchased from intervention items per day. The secondary outcomes were: energy purchased from non-intervention items per day, total energy purchased per day, and revenue. Regression models showed no evidence of an overall effect on energy purchased from intervention items, -1.3% (95% CI -3.5% to 0.9%) during the intervention. Of the 10 cafeterias, there were null results in five, significant reductions in four, and a significant increase in one. There was also no evidence for an effect on energy purchased from non-intervention items, -0.0% (95% CI -1.8% to 1.8%), and no clear evidence for total items -1.6% (95% CI -3.3% to 0.0%). Revenue increased during the intervention, 1.1% (95% CI 0.4% to 1.9%). Study limitations include using energy purchased and not energy consumed, and access only to transaction-level sales, rather than individual-level data.

ConclusionOverall, the evidence was consistent with PACE labels not changing energy purchased in worksite cafeterias. There was considerable variation in effects between cafeterias, suggesting potentially important unmeasured moderators.

Trial registrationThe study was prospectively registered on ISRCTN (date: 30.03.21; ISRCTN31315776).


title: The comparison of Post-Operative Complications pre Covid era versus during Covid-Era based on Clavien-Dindo-classification: A Systematic Review and Meta-Analysis

abstract:
IntroductionCoronavirus Disease 2019 (COVID -19) pandemic challenged the healthcare system drastically, and it was concomitant with a remarkable decline in surgeries and modified routine care of patients worldwide. This systematic review and meta-analysis aimed to compare the surgical complications before COVID -19 (Pre-COVID) and after COVID -19 (post-COVID) appearance using the Clavien-Dindo classification (CDC).

Methodsbetween January 1, 2019, to November 3, 2021, we performed a comprehensive search in PubMed/Medline and Scopus for studies reporting the postoperative complications based on/transformable to CDC.

ResultFrom 909 screened articles, 34 studies were included for systematic review. Among included articles, 11 were eligible for meta-analysis. Nineteen thousand one hundred thirty-seven patients (pre-COVID: 3522, post-COVID: 15615) were included, mostly undergoing elective surgeries (86.32%). According to CDC classification, there were no significant change between pre-COVID and post-COVID for grade 1 (Odds ratio (OR) and 95% confidence interval (95-CI): 0.99, 0.60-1.63, p=0.96), grade 2 (OR and 95-CI: 0.65, 0.42-1.01, p = 0.055), grade 3 (OR and 95-CI: 0.86, 0.48-1.57, p=0.64), grade 4 (OR and 95-CI: 0.85, 0.46-1.57, p =0.60). However, the postoperative mortality was lower before the COVID -19 outbreak (OR and 95-CI: 0.51, 0.27-0.95, p= 0.035). The included studies for systematic review and meta-analysis had a low risk of bias and unsignificant publication bias.

ConclusionAlthough delivering routine surgery was challenging, the postoperative complications during the pandemic remained identical to the pre-pandemic era. The stricter patient selection tending to choose more critical states and more advanced clinical stages of the operated patients may explain some extent of higher mortality during the pandemic. Adopting preventive strategies helped deliver surgeries during the outbreak of COVID -19 while limiting the capacity of operations and admissions.

category: surgery


title: A Clinically Translatable Immune-based Classification of HPV-associated Head and Neck Cancer with Implications for Biomarker-Driven Treatment Deintensification and Immunotherapy

abstract:
PurposeHuman papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the fastest rising cancer in North America. There is significant interest in treatment de-escalation for these patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to predict the survival of patients with newly diagnosed HPV+ HNSCC.

MethodsWe created a prognostic score (UWO3) that was successfully validated in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Transcriptomic data from two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes.

ResultsA three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival at 5 years to the immune desert (HR= 9.0, 95% CI 3.2-25.5, P=3.6x10-5) and mixed (HR=6.4, 95%CI 2.2-18.7, P=0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation.

ConclusionsThe UWO3 immune score could enable biomarker-driven clinical decision-making for patients with HPV+ HNSCC based on robust outcome prediction across six independent cohorts. The superior survival of immune rich patients supports de-intensification strategies, while the inferior outcomes of the immune desert patients suggest the potential for intensification and/or immunotherapy. Prospective de-escalation and intensification clinical trials are currently being planned.

category: oncology


title: Tracing the trajectories of SARS-CoV-2 variants of concern between December 2020 and September 2021 in the Canary Islands (Spain)

abstract: Several variants of concern (VOCs) explain most of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic waves in Europe. We aimed to dissect the spread of the SARS-CoV-2 VOCs in the Canary Islands (Spain) between December 2020 and September 2021 at a micro-geographical level. We sequenced the viral genome of 8,224 respiratory samples collected in the archipelago. We observed that Alpha (B.1.1.7) and Delta (B.1.617.2 and sub-lineages) were ubiquitously present in the islands, while Beta (B.1.351) and Gamma (P.1/P.1.1) had a heterogeneous distribution and were responsible for fewer and more controlled outbreaks. This work represents the largest effort for viral genomic surveillance in the Canary Islands so far, helping the public health bodies in decision-making throughout the pandemic.


title: SARS-CoV-2 Exposures of Healthcare Workers from Primary Care, Long-Term Care Facilities and Hospitals: A Nationwide Matched Case-Control Study

abstract:
ObjectivesHealthcare workers (HCWs) are at higher risk of contracting coronavirus disease-19 (COVID-19) than the general population. This study assessed the roles of various exposures and personal protective equipment (PPE) use on that risk for HCWs working in primary care, long-term-care facilities (LTCFs) or hospitals.

MethodsWe conducted a matched case-control (1:1) study (10 April-9 July 2021). Cases (HCWs with confirmed COVID-19) and controls (HCWs without any COVID-19-positive test or symptoms) recruited by email were invited to complete an online questionnaire on their exposures and PPE use. Questions covered the 10 days preceding symptom onset for cases (or testing if asymptomatic) or inclusion for controls.

ResultsA total of 4152 matched cases and controls were included. The multivariable conditional logistic regression analysis retained exposure to an infected person outside work (adjusted odds ratio, 19.9 [95% confidence intervaI, 12.4-31.9]), an infected colleague (2.26 [1.53-3.33]) or COVID-19 patients (2.37 [1.66-3.40]), as independent predictors of COVID-19 in HCWs, while partial or complete immunization was protective. Eye protection (0.57 [0.37-0.87]) and wearing a gown (0.58 [0.34-0.97]) during COVID-19 patient care were protective, while wearing an apron slightly increased the risk of infection (1.47 [1.00-2.18]). N95-respirator protection was comparable to that of surgical masks. Results were consistent across healthcare-facility categories.

ConclusionsHCWs were more likely to get COVID-19 in their personal sphere than during occupational activities. Our results suggest that eye protection for HCWs during patient care should be actively promoted.


title: Factors associated with the decay of anti-SARS-CoV-2 neutralizing antibodies among recipients of an adenoviral vector-based AZD1222 and a whole-virion inactivated (BBV152) vaccine in Chennai, India: a cross-sectional cohort study

abstract:
BackgroundThe magnitude of protection conferred after recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous.

MethodsWe investigated the factors associated with antibody decay in 519 individuals who received treatment for COVID-19-related illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine in Chennai, India from March 2021. Blood samples collected during regular follow-up post-infection/vaccination andwere examined for anti-SARS-CoV-2 IgG by a commercial automated chemiluminescent immunoassay (CLIA).

ResultsAge and underlying comorbidities were the two variables that were independently associated with the development of breakthrough infection. Individuals who were >60 years of age with underlying comorbid conditions had a [~]15 times and [~]10 times greater risk for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the neutralizing antibody levels by a coefficient of -6 units.

ConclusionsOur findings advocate that the elderly with underlying comorbidities require a second booster dose with AZD1222 and BBV152.


title: Genomics of Post-Vaccination SARS-CoV-2 Infections During the Delta Dominated Second Wave of COVID-19 Pandemic, from Mumbai Metropolitan Region (MMR), India

abstract: Vaccination against SARS-CoV-2 was launched in India in January 2021. Though vaccination reduced hospitalization and mortality due to COVID-19, vaccine breakthrough infections have become common. The present study was initiated in May 2021 to understand the proportion of predominant variants in post-vaccination infections during the Delta dominated second wave of COVID-19 in the Mumbai Metropolitan Region (MMR) in India and to understand any mutations selected in the post-vaccination infections or showing association with any patient demographics. We collected samples (n=166) from severe/moderate/mild COVID-19 patients who were either vaccinated (COVISHIELD/COVAXIN - partial/fully vaccinated) or unvaccinated, from a city hospital and from home isolation patients in MMR. A total of 150 viral genomes were sequenced by Oxford Nanopore sequencing (using MinION) and the data of 136 viral genomes were analyzed for clade/lineage and for identifying mutations in all the genomes. The sequences belonged to three clades (21A, 21I and 21J) and their lineage was identified as either Delta (B.1.617.2) or Delta+ (B.1.617.2 + K417N) or sub-lineages of Delta variant (AY.120/AY.38/AY.99). A total of 620 mutations were identified of which 10 mutations showed an increase in trend with time (May-Oct 2021). Associations of 6 mutations (2 in spike, 3 in orf1a and 1 in nucleocapsid) were shown with milder forms of the disease and one mutation (in orf1a) with partial vaccination status. The results indicate a trend towards reduction in disease severity as the wave progressed.


title: Effectiveness of the BNT162b2 vaccine among children 5-11 and 12-17 years in New York after the Emergence of the Omicron Variant

abstract:
ImportanceThere is limited evidence on the effectiveness of the BNT162b2 vaccine for children, particularly those 5-11 years and after the Omicron variants emergence.

ObjectiveTo estimate BNT162b2 vaccine effectiveness against COVID cases and hospitalizations among children 5-11 years and 12-17 years during December, 2021 and January, 2022.

DesignAnalyses of cohorts constructed from linked statewide immunization, laboratory testing, and hospitalization databases.

Setting/ParticipantsNew York State children 5-17 years.

Main outcomes/measuresNew laboratory-confirmed COVID-19 cases and hospitalizations. Comparisons were made using the incidence rate ratio (IRR), comparing outcomes by vaccination status, and estimated vaccine effectiveness (VE: 1-[1/IRR]).

ResultsFrom December 13, 2021 to January 30, 2022, among 852,384 fully-vaccinated children 12-17 years and 365,502 children 5-11 years, VE against cases declined from 66% (95% CI: 64%, 67%) to 51% (95% CI: 48%, 54%) for those 12-17 years and from 68% (95% CI: 63%, 72%) to 12% (95% CI: 6%, 16%) for those 5-11 years. During the January 24-30 week, VE for children 11 years was 11% (95%CI -3%, 23%) and for those age 12 was 67% (95% CI: 62%, 71%). VE against hospitalization declined changed from 85% (95% CI: 63%, 95%) to 73% (95% CI: 53%, 87%) for children 12-17 years, and from 100% (95% CI: -189%, 100%) to 48% (95% CI: -12%, 75%) for those 5-11 years. Among children newly fully-vaccinated December 13, 2021 to January 2, 2022, VE against cases within two weeks of full vaccination for children 12-17 years was 76% (95% CI: 71%, 81%) and by 28-34 days it was 56% (95% CI: 43%, 63%). For children 5-11, VE against cases declined from 65% (95% CI: 62%, 68%) to 12% (95% CI: 8%, 16%) by 28-34 days.

Conclusions and RelevanceIn the Omicron era, the effectiveness against cases of BNT162b2 declined rapidly for children, particularly those 5-11 years. However, vaccination of children 5-11 years was protective against severe disease and is recommended. These results highlight the potential need to study alternative vaccine dosing for children and the continued importance layered protections, including mask wearing, to prevent infection and transmission.

category: epidemiology


title: Drivers of adaptive evolution during chronic SARS-CoV-2 infections

abstract: In some immunocompromised patients with chronic SARS-CoV-2 infection, dramatic adaptive evolution occurs, with substitutions reminiscent of those in variants of concern (VOCs). Here, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of twenty-seven chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations, yet a subset of mutations associated with successful global transmission was absent from chronic infections. The emergence of these mutations might dictate when variants from chronic infections can dramatically spread onwards. Next, we tested the ability to predict antibody-evasion mutations from patient- and viral-specific features, and found that viral rebound is strongly associated with the emergence of antibody-evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody-evasion in particular niches in a patients body. We suggest that a trade-off exists between antibody-evasion and transmissibility that potentially constrains VOC emergence, and that monitoring chronic infections may be a means to predict future VOCs.


title: Clinical prediction of pathogenic variants in non-coding regions of the human genome.

abstract: Whole genome sequencing has become a wide-spread diagnostic tool for rare diseases patients. This broadens analyses to non-coding regions of the genome showing strong evidence of clinical significance for human Mendelian diseases. Notwithstanding its importance, current in-silico prediction tools are restricted to coding sequences which limits its applicability. Additionally, lack of power in discriminating variants of uncertain significance (VUS) limits its clinical utility. Here we present PANCO, a genome-wide pathogenicity prediction tool aiming at reclassification of VUS with a rigorous imputation workflow adapted for non-coding variants. PANCO integrates functional, evolutionary and population frequency information to capture emerging biological signals correctly reclassifying VUS. Importantly, PANCO shows remarkable power in an external validation set, on VUS (AUROC=0.99 and AUROC=0.89, respectively).


title: Impact of a sanitation intervention on quality of life and mental wellbeing in low-income urban neighbourhoods of Maputo, Mozambique

abstract:
ObjectivesToilet users often report valuing privacy and safety more highly than reduced disease, but effects of urban sanitation interventions on such outcomes have never been assessed quantitatively. In this study, we evaluate the impact of a shared sanitation intervention on quality of life (QoL) and mental wellbeing.

DesignWe interviewed individuals living in intervention and control clusters of a recent non-randomised controlled trial, and used generalised linear mixed regression models to make an observational comparison of outcomes.

Settinglow-income unsewered areas of Maputo City, Mozambique

ParticipantsWe interviewed 424 participants, 222 from the prior trials intervention group, and 202 from the control group.

InterventionsThe control group used low-quality pit latrines. The intervention group received high-quality shared toilets, contributing 10-15% of capital cost.

OutcomesOur primary outcome was the sanitation-related quality of life (SanQoL) index, which applies respondent-derived weights to combine toilet users perceptions of sanitation-related disgust, privacy, safety, health, and shame. Secondary outcomes were the WHO-5 mental wellbeing index and a sanitation visual analogue scale.

ResultsThe intervention group experienced a 1.6 standard deviation gain in SanQoL compared to the control group. This adjusted SanQoL gain was 0.34 (95% CI: 0.29-0.38) on a 0-1 scale with control mean 0.49. Effect sizes were largest for safety and privacy attributes. Intervention respondents also experienced a 0.2 standard deviation gain in mental wellbeing. The adjusted gain was 6.2 (95% CI: 0.3-12.2) on a 0-100 scale with control mean 54.4.

ConclusionsQuality of life outcomes highly valued by toilet users and can be improved by sanitation interventions. Such outcomes should be measured in future sanitation trials, to help identify interventions which most improve peoples lives. Since SanQoL weights are derived from respondent valuation, the measure can also be used in economic evaluation.

category: health economics


title: Study on the usefulness of Direct Saliva sample Collection (DiSC) by polyester swab

abstract: Saliva sample can be self-collected and used in testing of SARS-CoV-2 nucleic acid amplification tests (NAATs) test in Japan. However, this may have difficulty collecting a proper specimen when collecting for the first time. We compared 2 collection methods, conventional methods and Direct Saliva Sample Collection method (DiSC) from 44 asymptomatic or symptomatic individuals who were in quarantine in Toho university hospital. RT-PCR by DiSC method showed about 70 % positive percent agreement compared to RT-PCR by conventional methods. In addition, comparing RT-PCR and TMA by DiSC method, TMA showed about 90 % positive percent agreement compared to RT-PCR. DiSC method is easy to perform by every person, does not have complicated restrictions/instructions and can be used in RT-PCR and TMA. This method allows for ease of saliva collection in certain patient populations.


title: BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

abstract: The number of mutations in the omicron (B1.1.529) BA.1 variant of concern (VOC) led to an unprecedented evasion of vaccine induced immunity. However, despite the remarkable rise in global infections, severe disease and death did not increase proportionally, linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of a new sublineage, BA.2, that is more transmissible compared to BA.1, despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine induced responses that may be key to protection against infection and disease. Here we comprehensively profiled the BNT162b2 vaccine induced response to several VOCs including the omicron BA.1 and BA.2, after the primary vaccine series, 8 months following vaccination, and after a boost. While vaccine induced immune responses were compromised against both Omicron sublineages, vaccine induced antibody isotype titers, Fc{gamma}R3a- and Fc{gamma}R3b-receptor binding levels, and non-neutralizing opsonophagocytic functions were significantly attenuated to the omicron BA.2 Spike compared to the BA.1 lineage. Conversely, Fc{gamma}R2a and Fc{gamma}R2b binding was elevated to BA.2 potentially contributing to persistent protection against severity of disease. These data point to an attenuation of particular non-neutralizing antibody properties that may be key to protection against transmission, but the maintenance of others that may continue to confer protection against disease.


title: Comparison of Rapid Antigen Tests' Performance between Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) Variants of SARS-CoV-2: Secondary Analysis from a Serial Home Self-Testing Study

abstract:
BackgroundThere is a need to understand the performance of rapid antigen tests (Ag-RDT) for detection of the Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) SARS-CoV-2 variants.

MethodsParticipants without any symptoms were enrolled from October 18, 2021 to January 24, 2022 and performed Ag-RDT and RT-PCR tests every 48 hours for 15 days. This study represents a non-pre-specified analysis in which we sought to determine if sensitivity of Ag-RDT differed in participants with Delta compared to Omicron variant. Participants who were positive on RT-PCR on the first day of the testing period were excluded. Delta and Omicron variants were defined based on sequencing and date of first RT-PCR positive result (RT-PCR+). Comparison of Ag-RDT performance between the variants was based on sensitivity, defined as proportion of participants with Ag-RDT+ results in relation to their first RT-PCR+ result, for different duration of testing with rapid Ag-RDT. Subsample analysis was performed based on the result of participants second RT-PCR test within 48 hours of the first RT-PCR+ test.

ResultsFrom the 7,349 participants enrolled in the parent study, 5,506 met the eligibility criteria for this analysis. A total of 153 participants were RT-PCR+ (61 Delta, 92 Omicron); among this group, 36 (23.5%) tested Ag-RDT+ on the same day, and 84 (54.9%) tested Ag-RDT+ within 48 hours as first RT-PCR+. The differences in sensitivity between variants were not statistically significant (same-day: Delta 16.4% [95% CI: 8.2-28.1] vs Omicron 28.2% [95% CI: 19.4-38.6]; and 48-hours: Delta 45.9% [33.1-59.2] vs. Omicron 60.9% [50.1-70.9]). This trend continued among the 86 participants who had consecutive RT-PCR+ result (48-hour sensitivity: Delta 79.3% [60.3-92.1] vs. Omicron: 89.5% [78.5-96.0]). Conversely, the 38 participants who had an isolated RT-PCR+ remained consistently negative on Ag-RDT, regardless of the variant.

ConclusionsThe performance of Ag-RDT is not inferior among individuals infected with the SARS-CoV-2 Omicron variant as compared to the Delta variant. The improvement in sensitivity of Ag-RDT noted with serial testing is consistent between Delta and Omicron variant. Performance of Ag-RDT varies based on duration of RT-PCR+ results and more studies are needed to understand the clinical and public health significance of individuals who are RT-PCR+ for less than 48 hours.


title: Genomic surveillance of SARS-CoV-2 in a university community: insights into tracking variants, transmission, and spread of Gamma (P.1) variant

abstract: Using a combination of data from routine surveillance, genomic sequencing, and phylogeographic analysis we tracked the spread and introduction events of SARS-CoV-2 variants focusing on a large university community. Here, we sequenced and analyzed 677 high-quality SARS-CoV-2 genomes from positive RNA samples collected from Purdue University students, faculty, and staff who tested positive for the virus between January 2021 and May 2021, comprising an average of 32% of weekly cases across the time frame. Our analysis of circulating SARS-CoV-2 variants over time revealed periods when Variant of Concern (VOC) Alpha (B.1.1.7) and Iota (B.1.526) reached rapid dominance and documented that VOC Gamma (P.1) was increasing in frequency as campus surveillance was ending. Phylodynamic analysis of Gamma genomes from campus alongside a subsampling of >20,000 previously published P.1 genomes revealed ten independent introductions of this variant into the Purdue community, predominantly from elsewhere in the United States, with introductions from within the state of Indiana and from Illinois, and possibly Washington and New York, suggesting a degree of domestic spread. We conclude that a robust and sustained active and passive surveillance program coupled with genomic sequencing during a pandemic offers important insights into the dynamics of pathogen arrival and spread in a campus community and can help guide mitigation measures.


title: Common and distinct cortico-striatal volumetric changes in cocaine and heroin use disorder

abstract: Drugs of abuse impact cortico-striatal dopaminergic targets and their morphology across substance types in common and unique ways. While the dorsal striatum drives addiction severity across drug classes, opiates impact ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAcc) neuroplasticity in preclinical models, and psychostimulants alter inhibitory control, rooted in cortical regions such as the inferior frontal gyrus (IFG). We hypothesized parallel gray matter volume (GMV) changes in individuals with cocaine or heroin use disorder (CUD/HUD): decreased GMV of vmPFC/NAcc in HUD and IFG in CUD, and putamen GMV to be associated with addiction severity. We quantified GMV in age/sex/IQ-matched individuals with CUD (n=20; 5 women), HUD (n=20; 6 women), and healthy controls (HC; n=20; 5 women), further replicated in an extended sample (combined n=96). Overall, addicted individuals had smaller vmPFC volumes than HC (p<0.05-corrected), driven by HUD (p<0.05-corrected; similar NAcc reduction). Right IFG reductions were specifically evident in CUD vs. HUD (p<0.05-corrected). Posterior putamen volume increased as a function of craving in CUD vs. HUD (p<0.05-corrected). These results indicate compression of dopamine-innervated regions (in the vmPFC and NAcc) across cocaine- or heroin-addicted individuals, more severely in the latter. For the first time we demonstrate IFG compression specifically in CUD. This group also showed a unique association between craving and increased putamen volume, together indicating a signature of enhanced cue-sensitivity and habit formation. Results suggest common and substance-specific morphometry volumetric changes in human psychostimulant or opiate addiction, with implications for fine-tuning biomarker and treatment identification by primary drug of abuse.

category: addiction medicine


title: Post-acute symptoms, new onset diagnoses and health problems 6 to 12 months after SARS-CoV-2 infection: a nationwide questionnaire study in the adult Danish population

abstract:
BackgroundA considerable number of individuals infected with SARS-CoV-2 continue to experience symptoms after the acute phase. More information on duration and prevalence of these symptoms in non-hospitalized populations is needed.

MethodsWe conducted a nationwide cross-sectional study including 152 880 individuals aged 15-years or older, consisting of RT-PCR confirmed SARS-CoV-2 cases between September 2020-April 2021 (N=61 002) and a corresponding test-negative control group (N=91 878). Data were collected 6, 9 or 12 months after the test using web-based questionnaires. The questionnaire covered acute and post-acute symptoms, selected diagnoses, sick leave and general health, together with demographics and life style at baseline. Risk differences (RDs) between test-positives and -negatives were reported, adjusted for age, sex, single comorbidities, Charlson comorbidity score, obesity and healthcare-occupation.

FindingsSix to twelve months after the test date, the risks of 18 out of 21 physical symptoms were elevated among test-positives and one third (29.6%) of the test-positives experienced at least one physical post-acute symptom. The largest risk differences were observed for dysosmia (RD = 10.92%, 95%CI 10.68-11.21%), dysgeusia (RD=8.68%, 95%CI 8.43-8.93%), fatigue/exhaustion (RD=8.43%, 95%CI 8.14-8.74%), dyspnea (RD=4.87%, 95%CI 4.65-5.09%) and reduced strength in arms/legs (RD=4.68%, 95%CI 4.45-4.89%). More than half (53.1%) of test-positives reported at least one of the following conditions: concentration difficulties (RD=28.34%, 95%CI 27.34-28.78%), memory issues (RD=27.25%, 95%CI 26.80-27.71%), sleep problems (RD=17.27%, 95%CI 16.81-17.73%), mental (RD=32.58%, 95%CI 32.11-33.09%) or physical exhaustion (RD=40.45%, 95%CI 33.99-40.97%), compared to 11.5% of test-negatives. New diagnoses of anxiety (RD=1.15%, 95%CI 0.95-1.34%) or depression (RD=1.00%, 95%CI 0.81-1.19%) were also more common among test-positives.

InterpretationAt the population-level, where the majority of test-positives (96.0%) were not hospitalized during acute infection, a considerable proportion experience post-acute symptoms and sequelae 6-12 months after infection.

FundingNone

Research in contextO_ST_ABSEvidence before the studyC_ST_ABSTo identify existing studies on the epidemiology and clinical nature of post-acute COVID-19 symptoms, we searched PubMed for articles published until January 4, 2022 using the search string (((SARS-CoV-2[Title/Abstract]) OR (COVID-19[Title/Abstract]) OR (coronavirus[Title/Abstract])) AND ((post-acute[Title/Abstract]) OR ("post acute"[Title/Abstract]) OR ("long haul*"[Title/Abstract]) OR ("long-term symptoms"[Title/Abstract]) OR ("long-term disease"[Title/Abstract]) OR ("long-term illness"[Title/Abstract]) OR ("persistent symptoms"[Title/Abstract]) OR ("persistent disease"[Title/Abstract]) OR ("persistent illness"[Title/Abstract]) OR ("prolonged symptoms"[Title/Abstract]) OR ("prolonged disease"[Title/Abstract]) OR ("prolonged illness"[Title/Abstract]))) OR (long-covid[Title/Abstract]) OR ("Post-COVID-19 syndrome"[Title/Abstract]) OR ("Post-COVID-19 condition"[Title/Abstract]) OR ("Post-COVID-19 symptoms"[Title/Abstract]). This resulted in 870 articles. When screening these, we focused on articles covering symptoms comprehensively or a broader area, e.g. mental health problems, rather than in-depth studies of symptoms within a single area, case stories or studies focusing on clinical management.

A very wide range of post-acute symptoms originating from many different organ systems have been reported. This includes pulmonary, cardiovascular, hematologic, gastrointestinal, renal, endocrine, dermatologic, neurological and cognitive symptoms, as well as more general health problems, in particular fatigue.

Based on two systematic reviews covering the period December 2019-March 2021, the majority of studies of persistent COVID-19 symptoms had until then been conducted among hospitalized patients and thus were not representative of the general population, where the majority will only have suffered mild or moderate disease. Since then some larger register-based studies as well as some smaller questionnaire- or interview-based studies have been conducted among non-hospitalized patients. Both types of studies offer advantages and disadvantages in relation to obtaining the full overview of long-term effects. Register-based studies are best suited for capturing more severe conditions confirmed by a trained physician and defined by diagnostic classification schemes, whereas questionnaires including self-reported symptoms are able to capture symptoms and health outcomes that do not easily confirm to disease diagnoses, but which are nevertheless critical to our understanding of the burden of post-acute symptoms.

The number of sstudies of post-acute conditions among non-hospitalized patients with a follow-up time of more than 6 months is still limited. Some of the major remaining knowledge gaps regarding post-acute symptoms are: 1) What is the prevalence and variety of post-acute symptoms in the general population of infected persons, where the majority will only have suffered mild or moderate disease, 2) For how long do post-acute symptoms persist, and 3) Which subgroups of individuals, if any, are at higher risk of post-acute symptoms.

Added value of this studyThe present nationwide questionnaire-study is based on a large, mainly adult study population (N=152 880), where all individuals in Denmark, who tested positive during the study period, were invited to participate along with comparable test-negative controls.

Marked levels of post-acute symptoms and conditions were reported with changes in sense of smell and taste being the most frequently reported single physical symptoms. As many as half (53.1%) of the participants report having experienced general health problems in the form of either mental or physical exhaustion, sleep problems or cognitive problems, compared to 11.5% of control persons 6 to 12 months after the test. Our results suggest that a considerable proportion of the general population, who did not experience severe disease, are still affected 6 to 12 months after infection and that post-acute symptoms are more often experienced by females and middle-aged individuals.

Implications of all available evidenceDiverse post-acute symptoms following infection with SARS-CoV-2 occur frequently. Even up to 12 months after the onset of infection, a considerable proportion of individuals, who did not experience severe disease, continue to experience symptoms. Post-acute symptoms are generally more often reported by females than males, whereas the influence of age remains unclear.