title: Using Survey Data to Estimate the Impact of the Omicron Variant on Vaccine Efficacy against COVID-19 Infection

abstract: Data collected in the Global COVID-19 Trends and Impact Surveys (UMD Global CTIS), and data on variants sequencing from GISAID, are used to evaluate the impact of the Omicron variant (in South Africa and other countries) on the prevalence of COVID-19 among unvaccinated and vaccinated population, in general and discriminating by the number of doses. In South Africa, we observe that the prevalence of COVID-19 in December (with strong presence of Omicron) among the unvaccinated population is comparable to the prevalence during the previous wave (in August-September), in which Delta was the variant with the largest presence. However, among vaccinated, the prevalence of COVID-19 in December is much higher than in the previous wave. In fact, a significant reduction of the vaccine efficacy is observed from August-September to December. For instance, the efficacy drops from 0.81 to 0.30 for those vaccinated with 2 doses, and from 0.51 to 0.09 for those vaccinated with one dose. The study is then extended to other countries in which Omicron has been detected, comparing the situation in October (before Omicron) with that of December. While the reduction measured is smaller than in South Africa, we still found, for instance, an average drop in vaccine efficacy from 0.53 to 0.45 among those vaccinated with two doses. Moreover, we found a significant negative (Pearson) correlation of around -0.6 between the measured prevalence of Omicron and the vaccine efficacy.


title: Multiomic investigations of Body Mass Index reveal heterogeneous trajectories in response to a lifestyle intervention

abstract: Multiomic profiling is useful in characterizing heterogeneity of both health and disease states. Obesity exerts profound metabolic perturbation in individuals and is a risk factor for multiple chronic diseases. Here, we report a global atlas of cross-sectional and longitudinal changes associated with Body Mass Index (BMI) across 1,100+ blood analytes, as well as their correspondence to host genome and fecal microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program. Machine learning-based models predicting BMI from blood multiomics captured heterogeneous states of both metabolic and gut microbiome health better than classically measured BMI, suggesting that multiomic data can provide deeper insight into host physiology. Moreover, longitudinal analyses identified variable trajectories of BMI in response to a lifestyle intervention, depending on the analyzed omics platform; metabolomics-based BMI decreased to a greater extent than actual BMI, while proteomics-based BMI exhibited greater resistance. Our analysis further elucidated blood analyte-analyte associations which were significantly modified by obesity and partially reversed in the metabolically obese population through the program. Altogether, our findings provide an atlas of the gradual blood perturbations accompanying obesity and serve as a valuable resource for robustly characterizing metabolic health and identifying actionable targets for obesity.

category: public and global health


title: Overdiagnosis and treatment of COPD in nonagenarians

abstract:
BackgroundThe prevalence of COPD is increasing with age. However, the effects of age-dependent decline in lung function on diagnosis and treatment of COPD in nonagenarians are uncertain.

ObjectivesTo determine performance of spirometry, prescription of COPD medications, and COPD-related acute care visits and hospitalizations in patients 90 years and older with physician-diagnosed COPD.

MethodsHealth records of 166 consecutive patients 90 years and older with physician-diagnosed COPD at a university-affiliated medical center in Chicago were reviewed. Pertinent demographic, clinical, and physiological data were extracted.

ResultsPatients were predominantly ex-smoker (96%), African American (52%) males (96%). Sixty patients (36%) had no spirometry testing on record. Of the remaining 106 patients, 11 (10%) had baseline FEV1/FVC[≥]0.70, 24 (23%) had post-bronchodilator FEV1/FVC [≥]0.70, 28 (26%) had FEV1/FVC <0.70 and [≥]LLN, and 43 (41%) had FEV1/FVC <0.70 and <LLN. Thus, only 71 of 166 patients 90 years and older (43%) fulfilled the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations. Nonetheless, COPD medications, predominantly short-acting {beta}2 agonists and long-acting muscarinic antagonists, were prescribed to 95 of the 166 patients (57%). No significant differences in prevalence of co-morbidities and prescribed COPD medications, including systemic corticosteroids and anti-infectives prescribed during unscheduled healthcare visits and hospitalizations, were found between the four groups.

ConclusionsThese data suggest that a large proportion of nonagenarians at our medical center are overdiagnosed with and treated for COPD. A larger, multi-center, prospective study is warranted to support or refute these retrospective observations.

category: respiratory medicine


title: Effects of amyloid and APOE4 on medial temporal lobe subregions in cognitively unimpaired elderly

abstract:
Medial temporal lobe (MTL) sub-structures are differentially affected in early Alzheimers disease (AD), with a specific involvement of the entorhinal cortex (ERC), the perirhinal cortex (PRC) and CA1. However, the impact of amyloid (A{beta}) pathology and APOE {varepsilon}4 on MTL subregional atrophy remains relatively unknown. Our aim was to uncover these effects to further our understanding of the mechanisms underlying MTL atrophy in a population at-risk for AD.

We used baseline data from 130 unimpaired older adults (mean age: 68.9 {+/-} 3.8 years) from the Age-Well randomized controlled trial for whom high-resolution structural MRI (T2-weighted; 0.4x0.4x2.5mm3), amyloid-PET (Florbetapir) and APOE genotype were available. Participants were dichotomized into amyloid positive (A{beta}+, n=27) and negative (A{beta}-, n=103), and APOE {varepsilon}4 carrier ({varepsilon}4+, n=35) and non-carriers ({varepsilon}4-, n=95). Hippocampal subfield (CA1, CA2, CA3, dentate gyrus [DG], subiculum [SUB]) and extra-hippocampal region (ERC, Brodmann area [BA] 35 and 36, and parahippocampal cortex [PHC]) volumes were estimated using ASHS and normalized by total intracranial volume. For each subregion, group comparisons were performed (A{beta}+ vs A{beta}- and {varepsilon}4+ vs {varepsilon}4-) using ANCOVAs, including age, sex and education as covariates. Interactions with age (i.e., A{beta} status * age and APOE {varepsilon}4 status * age) were also investigated for each subregion.

No significant differences were observed between A{beta}+ and A{beta}-, nor between {varepsilon}4+ and {varepsilon}4-. However, a significant A{beta} status * age interaction were observed for CA1 (p<0.05), where volumes were negatively associated with age in the A{beta}+ group only. In addition, significant APOE {varepsilon}4 status * age interactions were found for CA1, SUB, ERC, DG and the whole hippocampus (p<0.05), where volumes were negatively associated with age in the {varepsilon}4+ group only.

Overall, our analyses showed that both A{beta} and APOE {varepsilon}4 status interact with age on CA1, which is known to be specifically atrophied in early AD. In addition, APOE {varepsilon}4 status mediated the effects of age on other subregions (SUB, ERC, DG), suggesting a more important contribution of APOE {varepsilon}4 than amyloid to MTL atrophy in cognitively unimpaired population. These results are particularly important to develop MRI-based biomarkers to detect early AD and further our understanding of the mechanisms underlying MTL atrophy.

category: neurology


title: Risk Factors for Delirium in Elderly Patients After Lumbar Spinal Fusion

abstract:
Background ContextPostoperative delirium is a clinically significant acute disorder of consciousness especially prevalent in older adult patients, of which more than 100,000 per year undergo spinal fusion surgery. There are no proven preventative therapies, and delirium is associated with increased postoperative complications, functional decline, morbidity, and mortality.

PurposeTo identify perioperative risk factors for postoperative delirium (POD) after lumbar spinal fusion procedures in patients aged 65 or older.

Study DesignRetrospective Review

Patient Sample702 patients who underwent lumbar spinal fusion surgery from 11/13/2017 to 1/30/2021.

Outcome MeasuresThe primary outcome was the presence of postoperative delirium assessed by the Delirium Observation Screening Scale (DOSS) and Confusion Assessment Method for the ICU (CAM-ICU).

MethodsDemographic, surgical, and perioperative data were obtained from the electronic medical records. The primary outcome was presence of postoperative delirium. Univariate and multivariate analyses were performed. A binomial logistic regression model was designed using a custom written MATLAB script.

ResultsOf the 702 patients included in the study, 173 (24.6%) developed POD. Our analysis revealed that older age (p < 0.001), lower preoperative hemoglobin (p < 0.001), and higher ASA grade (p < 0.001), were significant preoperative risk factors for developing POD. The only significant intraoperative risk factor was a higher number of spinal levels that were instrumented (p < 0.001). Higher pain scores on postoperative day 1 (p < 0.001), and lower postoperative hemoglobin (p < 0.001) were associated with increased POD; as were ICU admission (p < 0.001) and increased length of ICU stay (p < 0.001). Patients who developed POD had a longer hospital stay (p < 0.001) with lower rates of discharge to home as opposed to an inpatient facility (p < 0.001).

ConclusionsRisk factors for older adults undergoing lumbar spinal fusion surgery include advanced age, lower preoperative and postoperative hemoglobin, higher ASA grade, greater extent of surgery, and higher postoperative pain scores. Patients with delirium had a higher incidence of postoperative ICU admission, increased length of stay, decreased likelihood of discharge to home and increased mortality, all consistent with prior studies. Further studies will determine whether adequate management of anemia and pain lead to a reduction in the incidence of postoperative delirium in these patients.

category: orthopedics


title: Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: Linear and nonlinear Mendelian randomization analyses in up to 356,069 European women

abstract:
BackgroundObservational studies have reported maternal short/long sleep duration to be associated with adverse pregnancy and perinatal outcomes. However, it remains unclear whether there are nonlinear causal effects. Our aim was to use multivariable regression (MVreg) and Mendelian randomization (MR) to examine nonlinear effects of sleep duration on stillbirth, miscarriage, gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, preterm birth, low/high offspring birthweight (LBW/HBW).

MethodsWe used data from European women in UK Biobank (UKB, N=208,140), FinnGen (N=[~]123,579), Avon Longitudinal Study of Parents and Children (N=6826), Born in Bradford (N=2940) and Norwegian Mother, Father and Child Cohort Study (MoBa, N=14,584). We used 78 previously identified genetic variants as instruments for sleep duration, and investigated its effectsusing two-sample MR and one-sample nonlinear MR (in UKB only). We compared MR findings with MVreg in MoBa (N=76,669), where maternal sleep duration was measured at 30 weeks.

ResultsIn UKB, MR provided evidence of nonlinear effects of sleep duration on stillbirth, perinatal depression and LBW, but not for other outcomes. Shorter and longer duration increased stillbirth and LBW; shorter duration increased perinatal depression. For example, there was a lower risk of LBW with increasing duration (odds ratio 0.79 per one-hour/day (95% confidence interval (CI): 0.68, 0.93) in the shortest duration group and a higher risk (odds ratio 1.38 (95% CI: 1.06, 1.81) in the longest duration group, suggesting shorter and longer duration increased the risk. These were supported by the lack of evidence of a linear effect of sleep duration with any outcome using two-sample MR. In MVreg, risks of all outcomes (except for stillbirth showing opposite directions) were higher in the women reporting <5- and [≥]10-hours/day sleep compared with the reference category of 8-9-hours/day, despite some wide CIs including the null. Nonlinear models fitted the data better than linear models for most outcomes(likelihood ratio P-value=0.02 to 3.2x10-52), except for stillbirth and gestational diabetes.

ConclusionsOur results supported possible nonlinear sleep duration effects on perinatal depression and LBW. Statistical support for nonlinear models across outcomes suggests potential nonlinear effects on other outcomes that larger studies could detect.

category: epidemiology


title: Quantifying post-vaccination protective anti-SARS-CoV-2 IgG antibodies in blood and saliva with a fully automated, high throughput digital immunoassay

abstract:
BackgroundAntibodies induced by COVID-19 vaccination have been shown to wane over time. Current tests for assessing virus-neutralizing antibodies are complex and time-intensive. There is a need for a simple diagnostic test that measures levels of protective antibodies to help monitor immunity status.

MethodUsing a commercially available FDA-authorized semi-quantitative SARS-CoV-2 IgG test, we monitored the duration of the immune response in dried blood microsamples (DBS) and saliva to vaccination by 3 different vaccines across prospective cohorts of 8 COVID-19 naive and 29 COVID-19 recovered individuals over a six-month period. We correlated the results to a binding blockade assay validated to a live virus neutralization assay to validate the test for measurement of protective antibodies.

ResultsThe immune response characteristics between the two mRNA vaccines were similar over the 6-month period in both the COVID-19 naive and recovered cohorts. IgG titers in DBS were generally 3-4 orders of magnitude higher than in saliva, and longitudinal profiles were highly correlated between the two matrices (Rm = 0.80). Median IgG concentrations post-vaccination declined to <10% neutralization capacity with all vaccines by six months.

ConclusionsThe potential of a simple, fully automated high throughput anti-SARS-CoV-2 IgG test to quantitatively measure protective antibodies in samples collected remotely or at the point of care was demonstrated. The IgG immune response and protective immunity was shown to decline significantly by six months.

Plain Language SummaryIn response to infection the immune system produces proteins called antibodies that recognize and bind to foreign invaders. Vaccines train the immune system to recognize and produce antibodies against specific invaders, such as SAR-CoV-2. Measurement of antibody levels in blood help monitor a persons response to vaccination and have been shown to correlate with protection against disease, which wanes over time following vaccination. It is desirable to have an easy test that predicts protection against infection and measuring antibody levels may provide a solution, however different tests report results differently hindering the establishment of a cutoff for protected vs. not. We quantified antibody levels in saliva and dried blood microsamples (DBS) following vaccination using an automated semi-quantitative IgG test. By reporting concentration of antibodies, and if anchored to an international standard, this test could help establish a cutoff of protection that would be transferable across the multiple different test types. Furthermore, by measuring in saliva and DBS we demonstrate an easy path to at-home or point-of-care sample collection, which could allow wide-scale monitoring of immune protection against SARS-CoV-2.

category: infectious diseases


title: Prior health-related behaviours in children (2014-2020) and association with a positive SARS-CoV-2 test during adolescence (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK

abstract:
ObjectivesExamine if pre-COVID-19 pandemic (prior March 2020) health-related behaviours during primary school are associated with i) being tested for SARS-CoV-2 and ii) testing positive between 1 March 2020 to 31 August 2021.

DesignRetrospective cohort study using an online cohort survey (January 2018 to February 2020) linked to routine PCR SARS-CoV-2 test results.

SettingChildren attending primary schools in Wales (2018-2020), UK who were part of the HAPPEN school network.

ParticipantsComplete linked records of eligible participants were obtained for n=7,062 individuals. 39.1% (n=2,764) were tested (age 10.6{+/-}0.9, 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6{+/-}1.0, 54.5% girls).

Main outcome measuresLogistic regression of health-related behaviours and demographics were used to determine Odds Ratios (OR) of factors associated with i) being tested for SARS-CoV-2 and ii) testing positive for SARS-CoV-2.

ResultsConsuming sugary snacks (1-2 days/week OR=1.24, 95% CI 1.04 - 1.49; 5-6 days/week 1.31, 1.07 - 1.61; reference 0 days) can swim 25m (1.21, 1.06 - 1.39) and age (1.25, 1.16 - 1.35) were associated with an increased likelihood of being tested for SARS-CoV-2. Eating breakfast (1.52, 1.01 - 2.27), weekly physical activity [≥] 60 mins (1-2 days 1.69, 1.04 - 2.74; 3-4 days 1.76, 1.10 - 2.82, reference 0 days), out of school club participation (1.06, 1.02 - 1.10), can ride a bike (1.39, 1.00 - 1.93), age (1.16, 1.05 - 1.28) and girls (1.21, 1.00 - 1.46) were associated with an increased likelihood of testing positive for SARS-CoV-2. Living in least deprived quintiles 4 (0.64, 0.46 - 0.90) and 5 (0.64, 0.46 - 0.89) compared to the most deprived quintile was associated with a decreased likelihood.

ConclusionsAssociations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include co-participation with others, and exposure to SARS-CoV-2. A risk versus benefit approach must be considered given the importance of health-related behaviours for development.

STRENGTHS AND LIMITATIONSO_LIInvestigation of the association of pre-pandemic child health-related behaviour measures with subsequent SARS-CoV-2 testing and infection.
C_LIO_LIReporting of multiple child health behaviours linked at an individual-level to routine records of SARS-CoV-2 testing data through the SAIL Databank.
C_LIO_LIChild-reported health behaviours were measured before the COVID-19 pandemic (1 January 2018 to 28 February 2020) which may not reflect behaviours during COVID-19.
C_LIO_LIHealth behaviours captured through the national-scale HAPPEN survey represent children attending schools that engaged with the HAPPEN Wales primary school network and may not be representative of the whole population of Wales.
C_LIO_LIThe period of study for PCR-testing for and testing positive for SARS-CoV-2 includes a time frame with varying prevalence rates, approaches to testing children (targeted and mass testing) and restrictions which were not measured in this study.
C_LI


title: Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK


title: Remdesivir for the Treatment of COVID-19: An Updated Systematic Review and Meta-Analysis

abstract:
BackgroundThe benefits of remdesivir in the treatment of hospitalized patients with Covid-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use.

MethodsWe performed a systematic review of randomized controlled trials (RCTs) of remdesivir for the treatment of hospitalized patients with COVID-19. The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio (RR) scale and, to better contextualize the probabilistic benefits, we also performed a bayesian random effects meta-analysis on the risk difference scale.

ResultsWe identified 8 randomized trials, totaling 9157 participants. The RR for mortality comparing remdesivir versus control was 0.71 (95% confidence interval [CI] 0.42-1.22; I2=0.0%) in the patients who did not require supplemental oxygen; 0.83 (95%CI 0.73-0.95; I2=0.0%) for nonventilated patients requiring oxygen; and 1.19 (95%CI 0.98-1.44 I2=0.0%) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 74.7%, 96.9% and 8.9%, respectively. The probability that remdesivir reduced mortality by more than 1% was 88.1% for nonventilated patients requiring oxygen.

ConclusionBased on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy.


title: Comparison between mid-nasal swabs and buccal swabs for SARS-CoV-2 detection in mild COVID-19 patients

abstract:
BackgroundThe use of rapid antigen diagnostics tests (Ag-RDT) has gained widespread acceptance as an alternative method for diagnosis of COVID-19 outside of health care settings. Various authors have reported that saliva is a reliable specimen, alternative to nasopharyngeal and mid-nasal swabs, to detect SARS-CoV-2 infections by RT-PCR. We assessed the performance of buccal swabs containing saliva for SARS-CoV-2 detection by Ag-RDT, using mid-nasal specimens as a reference in the northern area of Barcelona (Catalonia, Spain)

MethodsIn the context of routine clinical diagnosis of mild COVID-19 patients, we enrolled 300 adults in a study to directly compare mid-nasal swabs and saliva specimens for SARS-CoV-2 detection by Ag-RDT.. When mid-nasal and buccal Ag-RDTs showed discordant results, a third mid-nasal swab was collected and analysed by RT-PCR.

ResultsPaired samples were successfully obtained in 300 suspected cases of SARS-CoV-2 infection. Of the 300 paired samples, Ag-RDT with the mid-nasal swab detected 139 (46.3%) positive COVID-19 cases. In comparison, buccal swabs showed a sensitivity and specificity of 31.7% (44/139) and 98.8% (159/161), respectively. 65 discordant results with positive mid-nasal swabs and negative buccal swabs were tested by RT-qPCR. All samples tested by Rt-PCR resulted positive, with a mean cycle threshold (Ct) of 28.3 (SD 7.3).

ConclusionOur findings show that mid-nasal swabs have better performance than buccal swabs for detecting SARS-CoV-2 with Ag-RDT tests. Of note, the sensitivity of buccal samples was affected in samples with high viral loads (Ct<33), suggesting that buccal swabs might not be sensitive enough to detect individuals at risk of transmission. Taken together, the existing literature and the results provided in our analysis we advise against the use of buccal specimens for SARS-CoV-2 diagnostics with Ag-RDT.


title: Severe outcomes in residents of Long Term Care Facilities following infection with SARS-CoV-2 Omicron variant (VIVALDI study)

abstract:
BackgroundRecently there has been a rapid, global increase in SARS-CoV-2 infections associated with the Omicron variant (B.1.1.529). Although severity of Omicron cases may be reduced, the scale of infection suggests hospital admissions and deaths may be substantial. Definitive conclusions about disease severity require evidence from populations with the greatest risk of severe outcomes, such as residents of Long-Term Care Facilities (LTCFs).

MethodsWe used a cohort study to compare the risk of hospital admission or death in LTCF residents in England who had tested positive for SARS-CoV-2 in the period shortly before Omicron emerged (Delta dominant) and the Omicron-dominant period, adjusting for age, sex, vaccine type, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset.

ResultsRisk of hospital admission was markedly lower in 1241 residents infected in the Omicron-period (4.01% hospitalised, 95% CI: 2.87-5.59) compared to 398 residents infected in the pre-Omicron period (10.8% hospitalised, 95% CI: 8.13-14.29, adjusted Hazard Ratio 0.50, 95% CI: 0.29-0.87, p=0.014); findings were similar in residents with confirmed variant. No residents with previous infection were hospitalised in either period. Mortality was lower in the Omicron versus the pre-Omicron period, (p<0.0001).

ConclusionsRisk of severe outcomes in LTCF residents with the SARS-CoV-2 Omicron variant was substantially lower than that seen for previous variants. This suggests the current wave of Omicron infections is unlikely to lead to a major surge in severe disease in LTCF populations with high levels of vaccine coverage and/or natural immunity.

Trial Registration NumberISRCTN 14447421


title: B.1.617.2 SARS-CoV-2 (Delta) variant is associated with increased risk of hospitalization and death compared with B.1.1.7 SARS-CoV-2 (Alpha) variant

abstract:
IntroductionThe B.1.617.2 variant (Delta) was associated with increased transmissibility and lower vaccine effectiveness than the B.1.1.7 variant (Alpha). However, the effect of the B.1.617.2 variant on disease severity remains unclear. This study aims to assess whether infection with the B.1.617.2 variant was associated with a higher risk of serious illness, compared with other co-circulating variants, measured through hospitalization and death by COVID-19 in Portugal.

MethodsWe conducted a matched cohort study in adult individuals diagnosed with SARS-CoV-2/COVID-19 infection between March 29 and August 1, 2021. Cases were individuals with a positive PCR test notified to the surveillance system. SARS-CoV-2 variants were classified first by genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure.

Delta (B.1.617.2) and Alpha (B.1.1.7) cases were matched on the week of diagnosis at a 1 to k ratio (k being the maximum number of unexposed available in that week) to maximize the inclusion of unexposed, using the nearest-neighbor algorithm. The hazard risk and 95% confidence intervals of hospitalization and death among those infected with the Delta (B.1.617.2) variant vs. Alpha (B.1.1.7) was estimated using a Cox proportional hazards model, adjusting for confounding for sex, age, and vaccination status.

ResultsA total of 2,778 cases were included in the study. Of the total, 1 742 (68%) were identified as B.1.617.2 variant cases and 3 629 (32%) as B.1.1.7 variant. Within the B.1.1.7 variant cases 106 (2.9%) were hospitalized, and 110 (6.3%) within the B.1.617.2 variant cases. A total of 29 deaths were reported, 8 (0.2%) in patients infected with B.1.1.7 variant and 21 (1.2%) in patients with the B.1.617.2 variant. The confounding adjusted risk of hospitalization, in persons infected with the B.1.617.2 variant was 2.44 (95%CI 1.85; 3.20) times higher than the risk of hospitalization among B.1.1.7 variant cases, and the confounding-adjusted risk of death for B.1.617.2 variant cases was 5.20 (95%CI 2.20; 12.29) times higher than the risk of death in patients infected by B.1.1.7 variant.

ConclusionThe B.1.617.2 variant is associated with an increased risk of hospitalization and death compared with the B.1.1.7 variant.


title: Omicron (BA.1) SARS-CoV-2 variant is associated with reduced risk of hospitalization and length of stay compared with Delta (B.1.617.2)

abstract:
IntroductionEarly reports showed that Omicron (BA.1) SARS-CoV-2 could be less severe. However, the magnitude of risk reduction of hospitalization and mortality of Omicron (BA.1) infections compared with Delta (B.1.617.2) is not yet clear. This study compares the risk of severe disease among patients infected with the Omicron (BA.1) variant with patients infected with Delta (B.1.617.2) variant in Portugal.

MethodsWe conducted a cohort study in individuals diagnosed with SARS-CoV-2 infection between 1st and 29th December 2021. Cases were individuals with a positive PCR test notified to the national surveillance system. SARS-CoV-2 variants were classified first by whole genomic sequencing (WGS) and, if this information was unavailable, by detecting the S gene target failure. We considered a hospitalization for all the patients admitted within the 14 days after the SARS-CoV-2 infection; after that period, they were censored.

The comparison of the risk of hospitalization between Omicron (BA.1) and Delta (B.1.617.2) VOC was estimated using a Cox proportional hazards model. The mean length of stay was compared using linear regression, and the risk of death between Omicron and Delta patients was estimated with a penalized logistic regression. All models were adjusted for sex, age, previous infection, and vaccination status.

ResultsWe included 15 978 participants aged 16 or more years old, 9 397 infected by Delta (B.1.617.2) and 6 581 infected with Omicron (BA.1). Within the Delta (B.1.617.2) group, 148 (1.6%) were hospitalized, and 16 (0.2%) were with the Omicron (BA.1). A total of 26 deaths were reported, all in participants with Delta (B.1.617.2) infection. Adjusted HR for hospitalization for the Omicron (BA.1) variant compared with Delta (B.1.617.2) was 0.25 (95%CI 0.15 to 0.43). The length of stay in hospital for Omicron (BA.1) patients was significantly shorter than for Delta (confounding-adjusted difference -4.0 days (95%CI -7.2 to -0.8). The odds of death were 0.14 (95% CI 0.0011 to 1.12), representing a reduction in the risk of death of 86% when infected with Omicron (BA.1) compared with Delta (B.1.617.2).

ConclusionOmicron (BA.1) was associated with a 75% risk reduction of hospitalization compared with Delta (B.1.617.2) and reduced length of hospital stay.


title: Gaseous micro-embolism (GME) is associated with systemic inflammatory response syndrome (SIRS) after open heart surgery. A missing piece of a complex puzzle?

abstract:
BackgroundGaseous micro-embolism (GME) occurring during contemporary open heart surgery is poorly studied. Current understanding of the biological impact of cardiac surgery focuses on the surgical aggression itself together with contact activation of inflammatory cascades by the extracorporeal circulation (ECC), both promoting various degrees of a systemic inflammatory response syndrome (SIRS).

Methods and FindingsWe prospectively collected data on GME in the ECC circuit according to a quality control protocol during a 12-month period at our institution. Bubbles were measured means of a last generation multi-channel ultrasound measuring unit (BCC300, Gampt GmbH, Meerseburg, Germany) upstream of the arterial line filter. For analysis, bubbles were separated in three size categories: small (S) (10-40 {micro}m), medium (M) (41-200 {micro}m) and large (L) (201-2000 {micro}m). Small bubbles were considered as noise and excluded. A total of 58 out of 70 open heart procedures were included in the final evaluation performed on 58 patients (45 males, 13 females, mean age 66 {+/-} 9 years). Patient baseline data, type of procedure and perfusion data were retrieved. Preoperative treatment with beta-blockers, ACE-inhibitors, calcium-antagonists and statins was considered. Postoperative SIRS was identified according to modified SIRS and qSOFA criteria.

A variably high amount of GME was detected (mean count 847 {+/-} 2560), we focused on M-sized GME (mean count 820 {+/-} 2546, mean volume 233 {+/-} 730 nL). A total of 22 patients (38%) developed SIRS. To account for differences between patient groups (SIRS-/ SIRS+) propensity score (PS) matching was performed on the presence of M-bubbles at or above the 75th percentile (count and volume). The impact of such GME on the development of SIRS was statistically highly significant, as shown by the corresponding average treatment effects (ATE).

ConclusionsSignificant GME was associated with postoperative SIRS after cardiac surgery in our setting. This novel finding warrants further confirmation.

category: cardiovascular medicine


title: Waning of Vaccine-Conferred Protection against SARS-CoV-2 Infection: Matched Case-Control Test-Negative Design Study in Two High-Risk Populations

abstract: To distinguish waning of vaccine responses from differential variant protection, we performed a test-negative case-control analysis during a Delta variant-dominant period in Californias prisons. We found that infection odds increased each 28-day period post-vaccination, reaching 3.4-fold (residents) to 4.7-fold (staff) increased odds of infection after 180 days.


title: Inflammation in children with chronic kidney disease linked to gut dysbiosis and metabolite imbalance

abstract: Chronic kidney disease (CKD) is characterized by a sustained pro-inflammatory response. The underlying mechanisms are incompletely understood, but may be linked to gut dysbiosis. Dysbiosis has been described in adults with CKD; however, comorbidities limit CKD-specific conclusions. We analyzed the fecal microbiome, metabolites and immune phenotypes in children at three different CKD stages (G3-G4, G5 (hemodialysis), after kidney transplantation) and healthy controls. Serum TNF- and sCD14 were stage-dependently elevated, indicating inflammation and gut barrier dysfunction. We observed microbiome alterations in CKD, including a diminished production of short-chain fatty acids. Bacterial tryptophan metabolites were increased in CKD. CKD serum activated the aryl hydrocarbon receptor and stimulated TNF- production by monocytes, corresponding to a shift towards intermediate/non-classical monocytes. Unsupervised T cell analysis revealed pro-inflammatory shifts in MAIT and Treg cells. Thus, gut barrier dysfunction and microbial metabolites exacerbate inflammation and may therefore contribute to the increased cardiovascular burden in CKD.

category: pediatrics


title: Impact of COVID-19 symptoms on social aspects of life of female long haulers: A qualitative study

abstract:
IntroductionPersistent COVID-19 symptoms (long COVID) may bring numerous challenges to long haulers social lives. Women may have to endure more profound impacts given their social roles and existing structural inequality. This study aims to explore the impacts of long COVID on various aspects of social life among female long haulers.

MethodsWe conducted 15 semi-structured interviews with female long haulers in the United States purposely recruited from Facebook groups, Slack groups, and organization websites. The interviews were audio recorded after appropriate consent and transcribed verbatim. Inductive approach was applied in thematic analysis, which consists of six stages: becoming familiar with data, developing initial codes, extracting themes, refining themes, labeling themes, and reporting. The MAXQDA software was used in data analysis.

ResultsPersistent COVID-19 symptoms negatively affected female long haulers social lives in many aspects including physical function, financial security, social relationship, conflict of social roles, and social stigma. Physical limitations changed their body image. Social isolation and work-family conflicts caused huge stress. They experienced internalization of stigma and job insecurities. Shifting to new methods of communication, especially social media may buffer the negative effects of social isolation because of long COVID.

ConclusionExisting policies and intervention programs need to be adapted to address the challenges and barriers that long haulers face in returning to normal social life, especially for females. Tailored social life-related recommendations and social support are needed for female long haulers.


title: Impact of persistent COVID-19 symptoms on social life of female long haulers: A qualitative study


title: The Effects of Messaging on Expectations and Understanding of Long COVID: An Online Randomised Trial

abstract:
ObjectivesWe examined whether providing different types of information about Long COVID would affect expectations about the illness.

DesignA 2 (Illness description: Long COVID vs ongoing COVID-19 recovery) x 2 (Illness uncertainty: uncertainty emphasised vs uncertainty not emphasised) x 2 (Efficacy of support: enhanced support vs basic support) between-subjects randomised online experimental study.

SettingThe online platform Prolific, collected in October 2021.

ParticipantsA representative sample of 1110 members of the public in the UK.

InterventionsParticipants were presented with a scenario describing a positive COVID-19 test result and then presented with one of eight scenarios describing a Long COVID diagnosis.

Primary and Secondary Outcome MeasuresVarious outcome measures relating to illness expectations were captured including: symptom severity, symptom duration, quality of life, personal control, treatment control and illness coherence.

ResultsWe ran a series of 2 x 2 x 2 ANOVAs on the outcome variables. We found a main effect of illness description: individuals reported longer symptom duration and less illness coherence when the illness was described as Long COVID (compared to ongoing COVID-19 recovery). There was a main effect of illness uncertainty: when uncertainty was emphasised, participants reported longer expected symptom duration, less treatment control, and less illness coherence than when uncertainty was not emphasised. There was also a main effect of efficacy of support: participants reported higher personal control and higher treatment control when support was enhanced (compared to basic support). We also found an interaction between illness description and efficacy of support: when support was enhanced, participants reported less illness coherence for Long COVID (compared to ongoing COVID-19 recovery).

ConclusionsCommunications around Long COVID should not emphasise symptom uncertainty and should provide people with information on how they can facilitate their recovery and where they can access additional support. The findings also suggest that use of the term ongoing COVID-19 recovery, where possible, may reduce negative expectations associated with the illness.

Strengths and Limitations of this studyO_LIThis is one of the first experimental designed studies to assess the impact of different types of communication about Long COVID.
C_LIO_LIParticipants were a UK representative sample, although these findings are not necessarily applicable to all population groups (i.e., ethnic minorities).
C_LIO_LIThis study is one of the first applications of the IPQ-R in a hypothetical, online experiment, with high reliability.
C_LIO_LIThis was an online experiment, with hypothetical scenarios and participants with no experience of COVID-19 or Long COVID, therefore outcomes may be different in a real-world context.
C_LI


title: Proteomic deconvolution reveals distinct immune cell fractions in different body sites in SARS-Cov-2 positive individuals

abstract:
BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a significant public health challenge globally. SARS-CoV-2 is a novel virus, and what constitutes immunological responses in different human body sites in infected individuals is yet to be presented. We set to determine the various immune cell fractions in gargle solution, bronchoalveolar lavage fluid, nasopharyngeal, and urine samples post-SARS-CoV-2 infection in humans.

Materials and methodsWe downloaded proteomics data from (https://www.ebi.ac.uk/pride/) with the following identifiers: PXD019423, n=3 (gargle solution), PXD018970, n=15 (urine), PXD022085, n=5 (Bronchoalveolar lavage fluid), PXD022889, n=18 (nasopharyngeal). MaxQuant was used for the peptide spectral matching using humans, and SARS-CoV-2 was downloaded from the UniProt database (Access date 9th January 2022). The protein count matrix was extracted from the proteins group file and used as an input for the cibersort for the immune cells fraction determination.

ResultsThe body of individuals infected with the SARS-CoV-2 virus is characterized by different fractions of immune cells in Bronchoalveolar lavage fluid (BALF), nasopharyngeal, urine, and gargle solution. BALF has more abundant memory B cells, CD8, activated mast cells, and resting macrophages than urine, nasopharyngeal, and gargle solution. Our analysis also demonstrates that each body site comprises different immune cell fractions post-SARS-CoV-2 infection in humans.

ConclusionDifferent body sites are characterized by different immune cells fractions in SARS-CoV-2 infected individuals. The findings in this study can inform public health policies and health professionals on treatment strategies and drive SARS-CoV-2 diagnosis procedures.

category: health informatics


title: CAR Density Influences Antitumoral Efficacy of BCMA CAR T cells and Correlates with Clinical Outcome

abstract:
Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study we address the impact of CAR density on the functionality of BCMA-CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with upregulation of exhaustion markers, increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of Gene Regulatory Networks using scRNA-seq identified regulons associated to activation and exhaustion upregulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Finally, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with significant impact on clinical response.

TeaserHigh CAR molecule density affects CAR T cell activity and associates with impaired clinical response.

category: hematology


title: Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a cohort study

abstract:
BackgroundThe SARS-CoV-2 pandemic remains a worldwide challenge. The CRIT-Cov-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression. Following the interim analysis demanded by the German government, the full dataset was analysed to consolidate findings and propose clinical applications.

MethodsIn eight European countries, 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression, receiver operating curve analysis with comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalistion costs standardised across countries.

FindingsThe entry WHO scores were 1-3, 4-5 and 6 in 445 (44{middle dot}0%), 529 (52{middle dot}3%), and 38 (3{middle dot}8%) patients, of whom 119 died and 271 progressed. The standardised odds ratios associated with COV50 for death were 2{middle dot}44 (95% CI, 2{middle dot}05-2{middle dot}92) unadjusted and 1{middle dot}67 (1{middle dot}34-2{middle dot}07) if adjusted for sex, age, body mass index, comorbidities and baseline WHO score, and 1{middle dot}79 (1{middle dot}60-2{middle dot}01) and 1{middle dot}63 (1{middle dot}40-1{middle dot}90), respectively, for disease progression (p<0{middle dot}0001 for all). The predictive accuracy of optimised COV50 thresholds were 74{middle dot}4% (95% CI, 71{middle dot}6-77{middle dot}1) for mortality (threshold 0{middle dot}47) and 67{middle dot}4% (64{middle dot}1-70{middle dot}3) for disease progression (threshold 0{middle dot}04). On top of covariables and the baseline WHO score, these thresholds improved AUCs from 0{middle dot}835 to 0{middle dot}853 (p=0{middle dot}0331) and from 0{middle dot}697 to 0{middle dot}730 (p=0{middle dot}0008) for death and progression, respectively. Of 196 ambulatory patients, 194 (99{middle dot}0%) did not reach the 0{middle dot}04 threshold. Earlier intervention guided by high-risk COV50 levels should reduce hospital days with cost reductions expressed per 1000 patient-days ranging from M{euro} 1{middle dot}208 (95% percentile interval, 1{middle dot}035-1{middle dot}406) at low risk (COV50 <0{middle dot}04) to M{euro} 4{middle dot}503 (4{middle dot}107-4{middle dot}864) at high risk (COV50 [≥]0{middle dot}04 and age [≥]65 years).

InterpretationThe urinary proteomic COV50 marker is accurate in predicting adverse COVID-19 outcomes. Even in mild-to-moderate PCR-confirmed infections (WHO scores 1-5), the 0{middle dot}04 threshold justifies earlier drug treatment, thereby reducing hospitalisation days and costs.

FundingGerman Federal Ministry of Health acting upon a decree from the German Federal Parliament.


title: Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review

abstract:
BackgroundA correlate of protection (CoP) is an immunological marker associated with protection against infection. A CoP can be used to determine whether an individual is protected from infection, evaluate candidate vaccines, guide vaccination dosing intervals and policy, and understand population-level immunity against a pathogen. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined, leaving an evidence gap for informing public health policy and adapting it appropriately as new variants of concern emerge. The objective of this study was to systematically review and assess the evidence for a humoral SARS-CoV-2 CoP.

Methods and FindingsWe searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus from inception to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) from inception to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment. Twenty-five studies were included in our systematic review. Several studies reported re-infection or breakthrough cases that occurred in the presence of robust antibody levels. Studies that compared aggregate antibody concentrations from individuals who experienced re-infection or breakthrough compared to those who remained protected did not always find differences that were statistically significant. However, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, and a correlation between antibody levels and vaccine efficacy (VE). Estimates of the contribution of antibody levels to VE varied from 48.5% to 94.2%, suggesting that both humoral immunity and other immune components contribute to protection. Only two studies estimated a quantitative CoP. For Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. As of our search date, no studies reported an Omicron-specific CoP.

ConclusionsThe reviewed literature was limited by a wide variation in assay methodology and antibody targets. Few studies reported SARS-CoV-2 lineage. The studies included in our review suggest that if it exists, a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.


title: Mortality risks associated with empirical antibiotic activity in E. coli bacteraemia: an analysis of electronic health records

abstract:
BackgroundReported bacteraemia outcomes following inactive empirical antibiotics (as judged by in vitro testing) are conflicting, potentially reflecting heterogeneous effects of species, minimum inhibitory concentration (MIC) breakpoints defining resistance/susceptibility, and times to rescue therapy.

MethodsWe investigated adult inpatients with Escherichia coli bacteraemia at Oxford University Hospitals, UK, from 04-February-2014 to 30-June-2021 receiving empirical amoxicillin-clavulanate with/without other antibiotics. We analysed 30-day all-cause mortality from index blood culture using Cox models by in vitro amoxicillin-clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (>8/2mg/L), categorical MIC, and a higher resistance breakpoint (>32/2mg/L), adjusting for other antibiotic activity and multiple confounders including comorbidities, vital signs, and blood tests.

Results1720 E. coli bacteraemias (1626 patients) were treated with empirical amoxicillin-clavulanate. 30-day mortality was 193/1400 (14%) [any active baseline therapy] and 52/320 (16%) [inactive baseline therapy] (p=0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive vs. active amoxicillin-clavulanate (adjusted HR, aHR=1.27 [95%CI 0.83-1.93;p=0.28]), nor of an association with other antibiotic activity (p>0.18). Considering categorical amoxicillin-clavulanate MIC, MICs>32/2 were associated with mortality (aHR=1.85 vs. MIC=2/2 [0.99-3.73;p=0.054]). Using the higher resistance breakpoint, MICs>32/2 were independently associated with higher mortality (aHR=1.82 [1.07-3.10;p=0.027]), as were MICs>32/2 with active baseline aminoglycoside (aHR=2.34 [1.40-3.89;p=0.001), but not MICs>32/2 with active baseline non-aminoglycoside antibiotic(s) (aHR=0.87 [0.40-1.89;p=0.72).

ConclusionsEUCAST-defined amoxicillin-clavulanate resistance was not associated with increased mortality, but a higher resistance breakpoint was. Additional active baseline non-aminoglycoside antibiotics prevented amoxicillin-clavulanate resistance-associated mortality, but active baseline aminoglycosides did not. Granular phenotyping and comparison with clinical outcomes may improve AMR breakpoints.

SummaryIn patients with E. coli bacteraemia, high-level resistance to baseline empirical amoxicillin-clavulanate (minimum inhibitory concentration >32/2 mg/L) was associated with increased 30-day mortality, which was not compensated for by single-dose aminoglycosides.


title: Effectiveness of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections during the Delta variant epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS)

abstract:
BackgroundAlthough high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines was reported in studies in several countries, data is limited from Asian countries, especially against the Delta (B.1.617.2) variant.

MethodsWe conducted a multicenter test-negative case-control study in patients aged [≥]16 visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from July 1 to September 30, 2021, when the Delta variant was dominant ([≥]90% of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16 to 64 was also assessed.

ResultsWe enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving two doses [≥]14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8-93.9) among patients aged 16 to 64 and 90.3% (95% CI, 73.6-96.4) among patients aged [≥]65. Among patients aged 16 to 64, vaccine effectiveness within one to three months after full vaccination was 91.8% (95% CI, 80.3-96.6), and was 86.4% (95% CI, 56.9-95.7) within four to six months.

ConclusionsmRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July 1 to September 30, 2021, when the Delta variant was dominant nationwide.


title: Modelling Quarantine Effects on SARS-CoV-2 Epidemiological Dynamics in Chilean Communes and their Relationship with the Social Priority Index

abstract: An epidemiological model [Susceptible, Un-quarantined infected, Quarantined infected, Confirmed infected (SUQC)] has previously been developed and applied to incorporate quarantine measures and calculate COVID-19 contagion dynamics and pandemic control in some Chinese regions. Here, we generalized this model to incorporate the disease recovery rate and applied our model to records of the total number of confirmed cases of people infected with the SARS-CoV-2 virus in some Chilean communes. In each commune, two consecutive stages were considered: a stage without quarantine and an immediately subsequent quarantine stage imposed by the Ministry of Health. To adjust the model, typical epidemiological parameters were determined, such as the confirmation rate and the quarantine rate. The latter allowed us to calculate the reproduction number. The mathematical model adequately reproduced the data, indicating a higher quarantine rate when quarantine was imposed by the health authority, with a corresponding decrease in the reproduction number of the virus down to values that prevent or decrease its exponential spread. In general, during this second stage, the communes with the lowest social priority indices had the highest quarantine rates, and therefore, the lowest effective viral reproduction numbers. This study provides useful evidence to address the health inequity of pandemics. The mathematical model applied here can be used in other regions or easily modified for other cases of infectious disease control by quarantine.


title: Identifying Bipolar patients from controls, using post- mortem cerebellum gene expression data and fully Automated Machine Learning

abstract:
ObjectiveComplex machine learning classification algorithms using transcriptome data from post-mortem cerebellar tissue of bipolar patients and unaffected controls, have been recently included in pipelines for patient - control classification and identification of characteristic biomarkers. Transcriptomic profile differences between patients and controls, can provide useful information about the role of the cerebellum in the pathogenesis of bipolar disorder and mood deregulation and in normal mood regulation and physiology. User-friendly, fully automated machine learning algorithms, using data extracted from established repositories, could achieve extremely high classification scores and disease-related predictive biomarker identification, in very short time frames and scaled down to small datasets, thus facilitating research on mood disorders.

MethodAn application of a fully automated machine learning platform, based on the most suitable algorithm selection and relevant set of hyper-parameter values, for classification between patients and controls and the production of models for biosignature selection, is presented. Transcriptome data used for the analysis were downloaded from the BioDataome preprocessed datasets database. The Dataome dataset, derived from the parent Gene Expression Omnibus GSE35974 (2013) and GSE35978 datasets, which have been originally produced from the cerebellar and parietal lobe tissue of deceased bipolar patients and unaffected controls, (from the Stanley Medical Research Institutes Neuropathology Consortium and Array collections), using Affymetrix Human Gene 1.0 ST Array. Patient and control groups were closely matched for age and sex.

ResultsBipolar patients have been identified from controls based on the cerebellar transcriptomic profile with AUC 0.929 and Average Precision 0.955. Patients and Controls have been classified in two separated groups with no close-to-the-boundary cases. Using 6 of the characteristic features discovered during the selection process, 99,6% classification accuracy was achieved. The three biomarkers contributing most to the predictive power of the model (92,7%), are also deregulated in temporal lobe epilepsy.

ConclusionThe cerebellar transcriptome of bipolar patients has a discrete profile and can be used for further exploration of the role of this area in health and disease.

93% AUC and 96% Precision were achieved during classification between unaffected controls and patients with Bipolar Disorder.

category: psychiatry and clinical psychology


title: Social isolation during the COVID-19 pandemic in Spain: a population study

abstract: Since March of 2020, billions of people worldwide have been asked to limit their social contacts in an effort to contain the spread of the SARS-CoV-2 virus. However, little research has been carried out to date on the impact of such social distancing measures on the social isolation levels of the population. In this paper, we study the impact of the pandemic on the social isolation of the Spanish population, by means of 32,359 answers to a citizen survey collected over a period of 7 months. We uncover (1) a significant increase in the prevalence of social isolation in the population, reaching almost 26%; (2) gender and age differences, with the largest prevalence of isolation among middle-aged individuals; (3) a strong relationship between economic impact and social isolation; and (4) differences in social isolation, depending on the number of COVID-19 protection measures and on the perception of coronavirus infection risk by our participants. Our research sheds quantitative light on the sociological impact of the pandemic, and enables us to identify key factors in the interplay between the deployment of non-pharmaceutical interventions to contain the spread of an infectious disease and a populations levels of social isolation.


title: PRICE COVID19 Data Report December 2021 Pakistan Registry of Intensive Care

abstract:
Pakistan Registry of Intensive Care (PRICE) is a platform that has enabled standardized COVID-19 clinical data collection based on ISARIC/WHO Clinical Characterization Protocol. The near real-time data platform includes epidemiology, severity of illness, microbiology, treatment and outcomes of patients admitted with suspected or laboratory confirmed COVID19 infection to 67 intensive care and high dependency units across the country. Data has been extracted and analysed at regular intervals to inform stakeholders and improve care practices. This is our 28th report including all patients with suspected or confirmed COVID-19 from 26th March 2020 to 26th December 2021.

Key findings from 8624 patients who met eligibility criteria, are as follows:

 Median age of 60 years (IQR 50-70).
 The most common symptoms were shortness of breath (n = 6428, 77.8%), fever (n = 6091, 73.8%), and Cough (n = 3354, 38.9%)
 The most common comorbidity was hypertension followed by diabetes.
 During the course of illness 2804 (32.6%) patients received non-invasive ventilation, whereas 2474 (28.8%) patients had mechanical ventilation as their highest organ support. In addition, 2246 (26.1%) patients needed haemodynamic support and 1249 (14.7%) patients required renal replacement therapy as their highest organ support.
 Median APACHE II score was 18
 Overall mortality at ICU discharge was 39.2%
 Increasing age and requirement for invasive mechanical ventilation were independent risk factors for mortality increased the risk of death

category: intensive care and critical care medicine


title: Cardiovascular Risk Models in Chronic Kidney Disease: A Systematic Review and External Validation of Models

abstract:
Background and ObjectivesRisk factors for cardiovascular disease in chronic kidney disease differ to the general population due to the increased role of inflammation, calcification and arteriosclerosis. Over 350 cardiovascular risk models ("models") exist in the general population but most have not undergone testing ("external validation") in other populations, such as cohorts with chronic kidney disease. We aimed to update a previous systematic review of models in chronic kidney disease and then perform external validation of these and general population models in a chronic kidney disease cohort.

Design, Setting, Participants and MeasurementsWe searched Medline up to 26th August 2020 for models in chronic kidney disease. We performed external validation of models using a primary care chronic kidney disease cohort of 17,248 individuals with 2,072 (12.0%) cardiovascular events, 5,108 (29.6%) deaths and a median follow-up of 5.0 years. Model discrimination and calibration was assessed and where appropriate models were re-calibrated. Multiple imputation was used to account for missing data.

ResultsSeven chronic kidney disease specific models were identified. These models and three general population models underwent external validation. All models had worse discrimination of events than in their original cohorts, particularly in the chronic kidney disease specific models. General population models were miscalibrated and overpredicted risk. The major contributor to this was the high competing risk of death from non-cardiovascular causes.

ConclusionsExisting chronic kidney disease cardiovascular risk models performed poorly in external validation. General population cardiovascular disease risk models should be interpreted with caution in individuals with chronic kidney disease as they may overestimate risk due to the competing risk of death. Further development of models to include simultaneous risk prediction for cardiovascular and non-cardiovascular disease risk is required.


title: Beyond vaccination: A Cross-Sectional Study of the importance of Behavioral and Native Factors on COVID-19 Infection and Severity.

abstract: The COVID-19 pandemic has a major impact on a global scale. Understanding the innate and lifestyle-related factors influencing the rate and severity of COVID-19 is important for making evidence-based recommendations. This cross-sectional study aimed at establishing a potential relationship between human characteristics and vulnerability/resistance to SARS-CoV-2. We hypothesize that the impact of virus is not the same due to cultural and ethnic differences. A cross-sectional study was performed using an online questionnaire. The methodology included a development of a multi-language survey, expert evaluation and data analysis. Data was collected using a 13-item pre-tested questionnaire based on a literature review. Data was statistically analyzed using the logistic regression. For a total of 1125 respondents, 332 (29.5%) were COVID-19 positive, among them 130 (11.5%) required home-based treatment, and 14 (1.2%) intensive care. The significant factors included age, physical activity and health status all found to have a significant influence on the infection (p < 0.05). The severity of infection was associated with preventive measures and tobacco (p < 0.05). This suggests the importance of behavioral factors compared to innate ones. Apparently, the individual behavior is mainly responsible for the spread of the virus. Adopting a healthy lifestyle and scrupulously observing preventive measures including vaccination would greatly limit the probability of infection and prevent the development of severe COVID-19.


title: Evaluation of the effects of vaccination regimes on the transmission dynamics of COVID-19 pandemic

abstract: The COVID-19 pandemic has yet to be eliminated globally despite the advancement of immunization programs. Evaluation of the effects of the vaccination regimes of COVID-19 is critical for understanding the potential capacity of countermeasures and informing subsequent prioritization strategies of responses. Research and observational data provide broad support regarding the importance of effective vaccines, in contrast, debates remain on the timing and priority of booster vaccination under the assumption of resource constraint. This study aims to evaluate the effect of vaccination regimes on the trajectory of the COVID-19 pandemic from the medium-term perspective. We employ a mathematical model to infer critical epidemiological characteristics associated with COVID-19, thereafter perform simulation on the transmission dynamics of the epidemic up to 3 years. The outcomes imply that in the absence of severe variants of the pathogen, administration of booster vaccination curtails the peak size of total cases and share of severe infections at later waves. Nevertheless, it can be better off by prioritizing the primary doses to unvaccinated individuals when vaccine shortage is challenged. The effects of priority categories are consistent across a broad range of profiles. Increasing the rollout capacity (i.e., administration rate) of doses can render the reproduction number lower than one and hence contain the transmission of pandemic ultimately controlling for other factors. The timing of rollout of primary doses is pivotal in reducing the magnitude of transmission saturation. It is of importance to prioritize the administration of primary vaccination series to vulnerable individuals efficiently and thereafter increment of administration capacity when the supply of vaccine increases over time to scale down the size of an epidemic.


title: Disorder-and cognitive demand-specific neurofunctional alterations during social emotional working memory in generalized anxiety disorder and major depressive disorder

abstract: Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers. This study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naive first-episode GAD (n=35) and MDD (n=37) patients compared to healthy controls (n=35) by employing a social-emotional n-back fMRI paradigm. No behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load. These findings suggest that the dmPFC engaged in integrating of affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPF communication with insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.


title: Risk of COVID-19 Reinfection and Vaccine Breakthrough Infection, Madera County, California, 2021

abstract:
The probability of either testing COVID-19 positive or dying for three cohorts in Madera County, California in 2021 was compared. These cohorts included 1. those unvaccinated, 2. those vaccinated and 3. persons with a previous COVID-19 infection. The three groups were made generally comparable by matching on age, gender, postal zip code of residence, and the date of either COVID-19 infection or of vaccination.

The hazard ratio (HR) for death (from all causes) after COVID-19 infection vs. vaccination was 11.7 (95% CI 5.91-23.1, p<0.05). The HR for testing positive for COVID-19 >14 days after initial COVID-19 infection or after completing primary COVID-19 vaccination was 1.98 (95% CI 1.53-2.58 p<0.001). As the majority of positive COVID-19 tests in the post COVID-19 cohort occurred within 90 days of the initial infection, and as these early positives may not represent a new infection, we also compared rates of testing COVID-19 positive [≥] 90 days after initial infection or vaccination. After removing these early positive COVID-19 tests that occurred between days 14-90, the HR ratio for testing COVID-19 positive is now lower for the post COVID-19 cohort compared with the vaccinated cohort. The risk for having a positive COVID-19 test occurring 90 days after an initial COVID-19 infection or after vaccination was 0.54 (95% CI 0.33-0.87, p<0.05) for the post COVID-19 group vs Vaccinated group.

Thus the risk for testing COVID-19 positive was higher in the first 90 days after COVID-19 infection compared to those vaccinated. However, from 90 to 300 days after COVID-19 infection, the post COVID-19 infection cohort had a lower risk of testing COVID-19 positive than those fully vaccinated.


title: Expert Surgeons and Deep Learning Models Can Predict the Outcome of Surgical Hemorrhage from One Minute of Video

abstract:
BackgroundMajor vascular injury resulting in uncontrolled bleeding is a catastrophic and often fatal complication of minimally invasive surgery. At the outset of these events, surgeons do not know how much blood will be lost or whether they will successfully control the hemorrhage (achieve hemostasis). We evaluate the ability of a deep learning neural network (DNN) to predict hemostasis control ability using the first minute of surgical video and compare model performance with human experts viewing the same video.

MethodsThe publicly available SOCAL dataset contains 147 videos of attending and resident surgeons managing hemorrhage in a validated, high-fidelity cadaveric simulator. Videos are labeled with outcome and blood loss (mL). The first minute of 20 videos was shown to four, blinded, fellowship trained skull-base neurosurgery instructors, and to SOCALNet (a DNN trained on SOCAL videos). SOCALNet architecture included a convolutional network (ResNet) identifying spatial features and a recurrent network identifying temporal features (LSTM). Experts independently assessed surgeon skill, predicted outcome and blood loss (mL). Outcome and blood loss predictions were compared with SOCALNet.

ResultsExpert inter-rater reliability was 0.95. Experts correctly predicted 14/20 trials (Sensitivity: 82%, Specificity: 55%, Positive Predictive Value (PPV): 69%, Negative Predictive Value (NPV): 71%). SOCALNet correctly predicted 17/20 trials (Sensitivity 100%, Specificity 66%, PPV 79%, NPV 100%) and correctly identified all successful attempts.

Expert predictions of the highest and lowest skill surgeons and expert predictions reported with maximum confidence were more accurate. Experts systematically underestimated blood loss (mean error -131 mL, RMSE 350 mL, R2 0.70) and fewer than half of expert predictions identified blood loss > 500mL (47.5%, 19/40). SOCALNet had superior performance (mean error -57 mL, RMSE 295mL, R2 0.74) and detected most episodes of blood loss > 500mL (80%, 8/10).

In validation experiments, SOCALNet evaluation of a critical on-screen surgical maneuver and high/low-skill composite videos were concordant with expert evaluation.

ConclusionUsing only the first minute of video, experts and SOCALNet can predict outcome and blood loss during surgical hemorrhage. Experts systematically underestimated blood loss, and SOCALNet had no false negatives. DNNs can provide accurate, meaningful assessments of surgical video. We call for the creation of datasets of surgical adverse events for quality improvement research.

category: surgery


title: Trends in underlying causes of death in solid organ transplant recipients between 2010 and 2020: Using the CLASS method for determining specific causes of death

abstract:
Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges.

This retrospective cohort study includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality.

Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N=57, 19%), graft rejection (N=55, 18%) and infections (N=52, 17%) being the most frequent causes of death.

We observed a lower risk of all-cause death with increasing transplant year (HR 0.91, 95% CI 0.86-0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74-0.95) and death from infections (HR 0.87 per year, 95% CI 0.77-0.98).

Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease.

All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, causes from a broad range of diseases have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future.

category: transplantation


title: Regional healthy brain activity, glioma occurrence and symptomatology

abstract:
It is unclear why exactly gliomas show preferential occurrence in certain brain areas. Increased spiking activity around gliomas leads to faster tumor growth in animal models, while higher non-invasively measured brain activity is related to shorter survival in patients. However, it is unknown how regional intrinsic brain activity, as measured in healthy controls, relates to glioma occurrence. We first investigated whether gliomas occur more frequently in regions with intrinsically higher brain activity. Secondly, we explored whether intrinsic cortical activity at individual patients tumor locations relates to tumor and patient characteristics.

Across three cross-sectional cohorts, 306 patients with different tumor subtypes were included. Tumor masks were created for each patient. Intrinsic regional brain activity was assessed through resting-state magnetoencephalography (MEG) acquired in healthy controls, which was then source-localized to 210 cortical brain regions according to the Brainnetome atlas. Brain activity was operationalized as (1) broadband power and (2) offset of the aperiodic component of the power spectrum, which both reflect neuronal spiking of the underlying neuronal population. We additionally assessed (3) the slope of the aperiodic component of the power spectrum, which is thought to reflect the neuronal excitation/inhibition (E/I) balance. First, correlation coefficients were calculated between group-level regional glioma occurrence, as obtained by concatenating tumor masks across patients, and group-averaged regional intrinsic brain activity. Second, intrinsic brain activity at specific tumor locations was calculated by overlaying patients individual tumor masks with regional intrinsic brain activity of the controls and was associated with tumor and patient characteristics.

As hypothesized, more malignant glioma preferentially occurred in brain regions characterized by higher intrinsic brain activity in controls as reflected by higher offset. Secondly, intrinsic brain activity at patients individual tumor locations differed according to glioma subtype and performance status: the most malignant IDH-wildtype glioblastoma patients had the lowest E/I balance at their individual tumor locations, while lower E/I balance weakly related to poorer Karnofsky performance status, independent of glioma subtype.

In conclusion, malignant gliomas more frequently occur in cortical brain regions with intrinsically higher activity levels, suggesting that more active regions are more vulnerable to glioma development. Moreover, indices of healthy, intrinsic E/I balance at patients individual tumor locations may capture both tumor biology and patients performance status. These findings contribute to our understanding of the complex and bidirectional relationship between normal brain functioning and glioma growth, which is at the core of the relatively new field of  cancer neuroscience.


title: ESTIMATING THE EFFECT OF VACCINATION ON THE CASE-FATALITY RATE FOR COVID-19

abstract:
ObjectiveTo evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections.

DesignMultivariate modeling of data from electronic medical records

Setting130 medical centers of the United States Department of Veterans Affairs

Participants339,772 patients with COVID-19 confirmed by nucleic acid amplification testing as of September 30, 2021

MethodsThe primary outcome was death within 60 days of the diagnosis. Patients were considered vaccinated if they had completed a full series >= 14 days prior to diagnosis. Cases presenting in July - September of 2021 were considered to have the delta variant. Logistic regression was used to derive adjusted odds ratios (OR) for vaccination and infection with delta versus earlier variants. Models were adjusted for demographic traits, standard comorbidity indices, selected clinical terms, and 3 novel parameters representing all prior diagnoses, all prior vital signs/ baseline laboratory tests, and current outpatient treatment. Patients with a delta infection were divided into 8 cohorts based upon the time from vaccination to diagnosis (in 4-week blocks). A common model was used to estimate the odds of death associated with vaccination for each cohort relative that of all unvaccinated patients.

Results9.1% of subjects had been fully vaccinated, and 21.5% were presumed to have the delta variant. 18,120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for delta infection was 1.87 +/- 0.05 which corresponds to a relative risk of 1.78. The overall adjusted OR for prior vaccination was 0.280 +/- 0.011 corresponding to a relative risk of 0.291. The study of vaccine cohorts with a delta infection showed that the raw CFR rose steadily after 10-14 weeks. However, the OR for vaccination remained stable for 10-34 weeks.

ConclusionsOur study confirms that delta is substantially more lethal than earlier variants and that vaccination is an effective means of preventing COVID death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks.


title: MAGNITUDE AND DURABILITY OF THE EFFECT OF VACCINATION ON THE CASE FATALITY RATE FOR COVID-19


title: SUSTAINED BENEFICIAL EFFECTS OF VACCINATION ON THE CASE FATALITY RATE FOR COVID-19 INFECTIONS


title: Shorter serial intervals in SARS-CoV-2 cases with Omicron variant compared to Delta variant in the Netherlands, 13 - 19 December 2021

abstract: The SARS-CoV-2 Omicron variant has a growth advantage over the Delta variant, due to higher transmissibility, immune evasion, or a shorter serial interval. Using S-gene target failure (SGTF) as indication for Omicron BA.1, we identify 908 SGTF and 1621 non-SGTF serial intervals in the same period. Within households, we find that the mean serial interval for SGTF cases is 0.2-0.6 days shorter than for non-SGTF cases. This suggests that the growth advantage of Omicron is partly due to a shorter serial interval.


title: Shorter serial intervals in SARS-CoV-2 cases with Omicron BA.1 variant compared to Delta variant in the Netherlands, 13 - 26 December 2021


title: COVID-19 and its clinical severity are associated with alterations of plasma sphingolipids and enzyme activities of sphingomyelinase and ceramidase

abstract:
In the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19), a better understanding of the underlying mechanisms is essential to reduce morbidity and mortality and treat post-COVID-19 disease. Here, we analyzed alterations of sphingolipids and their metabolizing enzymes in 125 men and 74 women tested positive for SARS-CoV-2 and hospitalized with mild, moderate or severe symptoms or after convalescence.

The activities of acid and neutral sphingomyelinases (ASM, NSM), which hydrolyze sphingomyelin to ceramide, were significantly increased in COVID-19 patients, while the activity of neutral ceramidase (NC), which hydrolyzes ceramide to sphingosine, was reduced. These alterations could each contribute to elevated ceramide levels in patients. Accordingly, liquid chromatography tandem-mass spectrometry (LC-MS/MS) yielded increased levels of ceramides 16:0 and 18:0 with highest levels in severely affected patients and similar effects for dihydroceramides 16:0 and 18:0, whereas levels of (dihydro-)ceramides 24:0 were reduced. Furthermore, sphingomyelin 20:0; 22:0 and 24:0 as substrates of ASM and NSM as well as their dihydrosphingomyelin counterparts were reduced in patients as well as sphingosine-1-phosphate further downstream of NC activity. Effects of NSM, NC, ceramides and sphingomyelins remained significant after Bonferroni correction. SARS-CoV-2 antibody levels in convalescent patients were associated with age but none of the sphingolipid parameters. Based on our data, COVID-19 is associated with a dysregulation of sphingolipid homeostasis in a severity-dependent manner, particularly focused around a reduction of sphingomyelins and an accumulation of ceramides by increased enzyme activities leading to ceramide elevation (ASM, NSM) combined with a decreased activity of enzymes (NC) reducing ceramide levels. The potential of a combined sphingolipid/enzyme pattern as a diagnostic and prognostic marker and therapeutic target deserves further exploration.


title: Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 S antibodies

abstract:
BackgroundChile was severely affected by COVID19 outbreaks but was also one of the first countries to start a nationwide program to vaccinate against the disease. Furthermore, Chile became one of the fastest countries to inoculate a high percentage of the target population and implemented homologous and heterologous booster schemes in late 2021 to prevent potential immunological waning. The aim of this study is to compare the immunogenicity and time course of the humoral response elicited by the CoronaVac vaccine in combination with homologous versus heterologous boosters.

Methods and FindingsWe compared the immunogenicity of two doses of CoronaVac and BNT162b2 vaccines and studied the effect of different booster regimes in the Chilean population. Our results demonstrate that a two-dose vaccination scheme with CoronaVac induces lower levels of anti-SARS-CoV-2 S antibodies than BNT162b2 in a broad age range. Furthermore, antibody production declines with time in individuals vaccinated with CoronaVac and less noticeably, with BNT162b2. Remarkably, analysis of booster schemes revealed that individuals vaccinated with two doses of CoronaVac generate immunological memory against the SARS-CoV-2 ancestral strain, which can be re-activated with homologous or heterologous (BNT162b2 and ChAdOx1) boosters. Nevertheless, the magnitude of the antibody response with the heterologous booster regime was considerably higher and persistent (over 100 days) than the responses induced by the homologous scheme.

ConclusionsTwo doses of CoronaVac induces antibody titers against the SARS-CoV-2 ancestral strain which are lower in magnitude than those induced by the BNT162b2 vaccine. However, the response induced by CoronaVac can be greatly potentiated with a heterologous booster scheme with BNT162b2 or ChAdOx1 vaccines. Furthermore, the heterologous booster regimes induce a durable antibody response which does not show signs of decay 3 months after the booster dose.


title: A Cross-Country Analysis of the Effectiveness of COVID-19 Vaccines in Reducing Mortality Rates within the EU

abstract: We use a linear mixed model in order to estimate the effect of the number of people vaccinated against COVID-19 on the overall death toll on a monthly basis. We limit our analysis for the duration of the year 2021 and within 25 countries which are current or former (UK) members of the EU since these countries follow similar approaches to testing and reporting different COVID-19 related statistics. We explored the effect in question by comparing the total number of people vaccinated up to the end of each month and the total number of deaths occurring during the next month while controlling for several measures including number of new COVID-19 cases, diabetes prevalence, cardio vascular death rates and time trends among others. Our results indicated that one percentage point monthly increase in the total number of vaccinated people was associated, on average, with a decrease of two deaths per general population of 1 million for the next month with the effect being highly significant. An Individual Growth Curves Analysis further corroborates these findings and suggests that vaccination rates may possibly exert additional indirect effects unaccounted for by our main model.


title: Vaccine hesitancy and access to psoriasis care in the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.

abstract:
BackgroundCOVID-19 vaccination is efficacious at protecting against severe COVID-19 outcomes in the general population. However, vaccine hesitancy (unwillingness for vaccination despite available vaccination services) threatens public health. Individuals taking immunosuppression for psoriasis have been prioritised for COVID-19 vaccination, however there is a paucity of information on vaccine hesitancy in this population, including contributing factors. While global healthcare has been severely disrupted in the pandemic, the impact on access to psoriasis care and whether this may negatively influence vaccine uptake, is underexplored.

ObjectivesTo explore organisational and individual factors associated with COVID-19 vaccine hesitancy in individuals with psoriasis.

MethodsIndividuals with psoriasis, identified through global patient organisations and social media, completed a cross-sectional self-reported online survey. The primary outcome was COVID-19 vaccine hesitancy. Logistic regression was used to examine the association between predictor variables (organisational and individual factors) and outcome.

ResultsSelf-reported data from 802 individuals with psoriasis across 89 countries were available (65.6% female, median age 51 years [IQR 37-61], 43.7% taking systemic immunosuppression). Eight percent (n=63) reported vaccine hesitancy. Those reporting vaccine hesitancy were younger, more likely to be of non-white ethnicity, non-UK resident, have a lower BMI, not taking systemic immunosuppression and with shorter disease duration compared to those not reporting vaccine hesitancy. The commonest reasons for vaccine hesitancy were concerns regarding vaccine side-effects, that the vaccine is too new or that psoriasis may worsen post-vaccination. Forty percent (n=322) reported that their psoriasis care had been disrupted by the pandemic. These individuals were younger, of non-white ethnicity, with shorter duration and more severe psoriasis. Disruption to psoriasis care was associated with vaccine hesitancy (unadjusted OR 2.97 (95%CI 1.23-7.13), p=0.015), although not statistically significant in the adjusted model.

ConclusionA minority of individuals with psoriasis from our study reported COVID-19 vaccine hesitancy. Similar to general population trends, vaccine hesitancy in our psoriasis sample is most common in younger age and ethnic minority groups. Our data highlight patient concerns regarding COVID-19 vaccination, which are important to address during patient-clinician interactions to help optimise vaccine uptake and mitigate risks from the ongoing pandemic in individuals with psoriasis.

Key pointsO_ST_ABSWhats already known about this topic?C_ST_ABSO_LIThe COVID-19 vaccine is highly efficacious at protecting against severe COVID-19 outcomes in the general population. Vaccine hesitancy (unwillingness to receive vaccination despite available vaccination services) poses a major threat to global public health and is more common in women, younger age and ethnic minority groups in the general population.
C_LIO_LIIndividuals with psoriasis taking systemic immunosuppression were considered at high risk of severe COVID-19 outcomes and prioritised for vaccination, however there is a paucity of information on vaccine hesitancy in this group, including contributing factors.
C_LIO_LIWhile global healthcare has been severely disrupted by the COVID-19 pandemic, access to psoriasis care and its potential impact on vaccine hesitancy is underexplored.
C_LI

What does this study add?O_LIA substantial proportion (40%) of individuals with psoriasis reported disrupted access to psoriasis care during the COVID-19 pandemic. Disrupted care was most commonly reported in younger age and ethnic minority groups.
C_LIO_LICOVID-19 vaccine hesitancy was reported by a minority (8%) of individuals with psoriasis. Those reporting vaccine hesitancy were younger and more likely to be of non-white ethnicity, in keeping with trends in the general population.
C_LIO_LIThe commonest reasons for vaccine hesitancy were concerns regarding vaccine side effects, that the vaccine is too new or that psoriasis may worsen post-vaccination. These concerns are important to address during patient-clinician interactions to help mitigate risks from the ongoing pandemic in individuals with psoriasis.
C_LI


title: Impact of accelerating booster vaccination amidst Omicron surge in the United States

abstract:
COVID-19 infections driven by the Omicron variant are sweeping across the United States. Although early evidence suggests that the Omicron variant may cause less severe disease than previous variants, the explosive spread of infections threatens to drive hospitalizations and deaths to unprecedented high levels, swamping already overburdened hospitals. Booster vaccination appears to be effective at preventing severe illness and hospitalization. However, the pace of booster vaccination in the US has been slow despite the available infrastructure to administer doses at a much higher rate.

We used an age-stratified, multi-variant agent-based model to project the reduction in COVID-related deaths and hospitalizations that could be achieved by accelerating the current daily pace of booster vaccination in the US. We found that doubling the rate of booster vaccination would prevent over 400,000 hospitalizations and 48,000 deaths. Tripling the booster vaccination rate would avert over 600,000 hospitalizations and save 70,000 lives during the first four months of 2022.


title: Potential for emergence of foodborne and waterborne trematodiases in California

abstract: We document that three human-pathogenic zoonotic trematodes are introduced and widespread throughout southern California in their first intermediate host snail (Melanoides tuberculata). We highlight the need to consider these introductions from a public health perspective in California and elsewhere in the United States the snail has invaded.


title: Risk factors for developing symptomatic COVID-19 in older residents of nursing homes: A hypothesis-generating observational study

abstract:
BackgroundCOVID-19 pandemic has had a major impact on society, including on residents of nursing homes (NH), who have a higher risk of complications and mortality due their physical and intellectual disabilities.

AimTo identify which risk factors associated with developing COVID-19 infection with symptoms in institutionalized older people.

MethodsA 1-year longitudinal multicenter study was conducted in 5 NH during the period December 2019 to March 2021. The inclusion criteria used were residents aged 65 years or over, living in the NH permanently, with a diagnostic test for COVID-19 confirmed by reverse transcription polymerase chain reaction and/or serological test. The main variable was symptomatic COVID-19, with at least one of the following symptoms (fever, respiratory difficulties, cough, diarrhea, sudden urinary incontinence and disorientation or delirium). Three assessments were performed: baseline, six and twelve months follow-up. Descriptive and bivariate analysis (calculating relative risk-RR) were performed, considering a 95% confidence level and a statistically significant p <0.05.

ResultsOf the total sample of 78 individuals who tested positive for COVID-19, mean age 84.6 years (SD={+/-}7.8), 62 (79.5%) were female; 40 (51.3%) participants presented with COVID-19 symptoms. Living in a private NH (RR=3.6, 95% CI [1.2-11.0], p=0.023) and having suffered a stroke (RR=4.1, 95% CI [1.1-14.7], p=0.033) were positively associated with developing COVID-19 infection with symptoms.

ConclusionsHaving suffered a stroke and living permanently in a private health care facility were positively associated with symptomatic COVID-19 in this sample of institutionalized older people.

category: geriatric medicine


title: Factors associated with adherence to HIV testing guidelines among HIV negative female sex workers in Kampala Uganda.

abstract:
BackgroundFrequent HIV testing at intervals of every three to six months is recommended among HIV negative female sex workers as the first entry point to HIV prevention and treatment. In this study, we examined the extent to which HIV negative female sex workers adhere to the testing guidelines by measuring the frequency of testing in the last 12 months and identified associated factors among female sex workers in Kampala Uganda.

MethodsWe conducted a cross-sectional study using structured questionnaires. Using equal probability selection method, 12 hotspots were selected, and 200 participants interviewed based on proportional allocation in each hotspot. We used descriptive statistics to describe female sex workers characteristics, and multivariable logistic regression model to determine the factors associated with their adherence to the HIV testing guidelines. Adherence to the HIV testing guidelines was defined as having tested three or more times in the last 12 months. Factors with p-value [≤]0.05 significance level were considered statistically significant.

ResultsFrom the 200 study participants, 43% were aged 25-30 years, joined sex work between the ages of 18 to 24 years, 49% had attained primary and 41% secondary school respectively. 88% reported HIV testing status, of which 56% had tested three or more times in the 12 months preceding the survey. Attaining secondary education, was independently associated with adherence to the HIV testing guidelines (OR 1.86, 95% CI: 1.01 - 3.44, p=0.047). Those that had tested for STIs in the last three months (OR= 2.13, 95% CI: 0.95 - 4.74, p=0.065) and accessed HIV testing in a drop-in centre (OR= 5.90, 95% CI: 0.71 - 49.1, p=0.101) had higher odds of adhering to the HIV testing guidelines

ConclusionThis study found suboptimal adherence to the HIV testing guidelines among HIV negative female sex workers. Interventions such as HIV self-testing that improve access to, and frequency of HIV testing need to be taken to scale. There is need for rigorous behaviour change program evaluation to continually refine understanding of the message mix, to ensure simplified and easy to comprehend awareness messages are designed for female sex workers with no formal education.

category: hiv aids


title: Whole genome sequence analysis of Salmonella Typhi provides evidence of phylogenetic linkage between cases of typhoid fever in Santiago, Chile in the 1980s and 2010-2016

abstract:
Typhoid fever epidemiology was investigated rigorously in Santiago, Chile during the 1980s, when Salmonella enterica serovar Typhi (S. Typhi) caused seasonal, hyperendemic disease. Targeted interventions reduced the annual typhoid incidence rates from 128-220 cases/105 population occurring between 1977-1984 to <8 cases/105 from 1992 onwards. As such, Santiago represents a contemporary example of the epidemiologic transition of an industrialized city from amplified hyperendemic typhoid fever to a period when typhoid is no longer endemic. We used whole genome sequencing (WGS) and phylogenetic analysis to compare the genotypes of S. Typhi cultured from acute cases of typhoid fever occurring in Santiago during the hyperendemic period of the 1980s (n=74) versus the nonendemic 2010s (n=80) when typhoid fever was rare. The genotype distribution between "historical" (1980s) isolates and "modern" (2011-2016) isolates was similar, with genotypes 3.5 and 2 comprising the majority of isolations, and 73/80 (91.3%) of modern isolates matching a genotype detected in the 1980s. Additionally, phylogenomically  ancient genotypes 1.1 and 1.2.1, uncommon in the global collections, were also detected in both eras, with a notable rise amongst the modern isolates. Thus, genotypes of S. Typhi causing acute illness in the modern nonendemic era match the genotypes circulating during the hyperendemic 1980s. The persistence of historical genotypes may be explained by chronic typhoid carriers originally infected during or before the 1980s.

Author summaryStudies of Salmonella Typhi (the cause of typhoid fever) rarely include isolates collected both before and after the interruption of hyperendemic transmission because this typically occurred decades before modern bacteria preservation methods. After interruption, it was assumed that sporadic cases and infrequent outbreaks were due to either chronic biliary carriers or importations, but this was difficult to characterize with low resolution bacterial typing methods. In Santiago, Chile, typhoid fever persisted at hyperendemic levels through the 1980s until organized control efforts in the 1980s and changes to wastewater policy in 1991 caused annual typhoid incidence to plummet.

In this study, we used whole genome sequencing (WGS) to investigate whether recent sporadic cases occurring in Santiago in the 2010s were genomically similar to S. Typhi circulating in the 1980s, or dissimilar, possibly representing importations of S. Typhi from outside of Chile. We found concordance amongst S. Typhi genotypes between the 1980s and 2010s, and differences from genotypes circulating in Southeast Asia and Africa where typhoid remains hyperendemic. Our findings suggest that a proportion of modern, rare typhoid cases in Santiago are autochthonous, and that chronic carriers or another unknown reservoir likely contribute. Broadly, our findings corroborate the epidemiologic importance of long-term reservoirs of typhoid fever decades after typhoid elimination.