title: Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination

abstract:
ObjectivesTo determine whether spontaneous reporting rates of myocarditis and pericarditis differed in immunocompromised patients compared to the whole population overall, and in terms of demographics, vaccine dose, and time-to-onset.

DesignSystematic review of spontaneously reported data from the European Union/European Economic Area (EU/EEA), the United States (US) and the United Kingdom (UK).

Data SourcesEudraVigilance (EU/EEA), Vaccine Adverse Event Reporting System (VAERS; US) and the Medicines and Healthcare products Regulatory Agency (MRHA, UK) spontaneous reporting databases were searched from date of vaccine launch to 01 December 2021.

Eligibility criteriaPublicly available spontaneous reporting data for "Myocarditis" and "Pericarditis" from EU/EEA and US following COVID-19 mRNA vaccines. Reports with comorbidities or concurrent medication indicative of transplantation, HIV infection, or cancer ("immunocompromised" population) were compared with each overall database population.

Data extraction and synthesisTwo researchers extracted data. Spontaneously reported events of myocarditis and pericarditis were presented for immunocompromised populations for each data source, stratified by age, sex, dose, and time-to-onset (where available). Seriousness of each event was determined according to the ICH E2A definition. Proportional Reporting Ratio (PRR) was calculated.

ResultsThere were 178 reports of myocarditis and pericarditis amongst immunocompromised individuals overall. Seriousness was comparable between the immunocompromised and overall populations in both databases. No trends in age or sex were observed amongst immunocompromised individuals. Most reports followed a second vaccine dose and occurred within 14 days. The frequency of reporting was similar to the wider population (PRR=1.36 [95% CI= 0.89-1.82] for VAERS population).

ConclusionsMyocarditis and pericarditis following COVID-19 vaccination are very rare, and benefits of COVID-19 vaccination continue to outweigh any perceived risks. Reporting rates of myocarditis and pericarditis were similar in immunocompromised individuals, however defining characteristics differed compared to the whole population; therefore, continued monitoring of adverse events following vaccination remains vital to understand differences between population subgroups.

Strengths and Limitations of the StudyO_LIThis is the first study to bring together spontaneous reporting data from three regions (Europe, the United States, and the United Kingdom) comparing immunocompromised and immunocompetent populations adverse reactions following COVID-19 mRNA vaccination
C_LIO_LISpontaneously reported adverse drug reaction data is known to be subject to underreporting and missing information, including information on comorbidities and concomitant medications.
C_LIO_LIFurther biases that may have influenced results, include differences in vaccination strategies between the three regions examined, differences in data collected via spontaneous reporting systems, and the fact that serious events are more likely to be reported.
C_LIO_LIIt is not possible to estimate incidence rates using spontaneous reporting data due to a lack of precise denominator data, i.e. the number of people who received the vaccine in the corresponding period.
C_LI


title: Comparing the Performance of HIV Rapid Diagnostic Tests Used in Zambia: a Systematic Review of Clinical Data.

abstract:
ObjectiveTo investigate the performance of the HIV RDTs used in Zambia.

Method2,564 participants aged between 15 and 95 years from two sites in Lusaka province years were tested on OraQuick ADVANCE, Abbot Determine, and then confirmed on Uni-Gold Recombigen(R). The data from the participants were analyzed using SPSS version 25.0.

ResultsThe 3 RDTs when compared to the 4th generation Abbot Architect results had the following results: OraQuick ADVANCE(R), Alere Determine and Uni-Gold Ultra, at 95% CI had Sensitivities of: 91.8%, 93.3% and 92.5% respectively. The specificities of OraQuick ADVANCE(R) and Uni-Gold were the same (100.0%; 95% CI: 98.8 -100.0) but slightly different from Alere Determine (99.8%). Positive predictive values at 95% CI were 100% for OraQuick ADVANCE(R) and Uni-Gold and 98.4% for Alere Determine. Negative predictive values (at 95% CIs) were 99.1, 99.2 and 99.1 for OraQuick ADVANCE(R), Alere Determine, and Uni-Gold Ultra respectively. The results showed that these RDTs could only detect 12 out of every 13 HIV positive results.

ConclusionThird generation RDTs are not effective in detecting acute positive cases. Fourth generation Rapid Tests are required to capture the positive cases being missed out.

category: pathology


title: Associations between intimate partner violence and mental health in German men and women: a cross-sectional analysis of the German Health Interview and Examination Survey for Adults (DEGS1)

abstract: This work explores the cross-sectional associations between Intimate Partner Violence (IPV) and anxiety, depressive symptoms, stress symptoms, and health-related quality of life (HRQoL), in a representative sample of German adult men (n=2,789) and women (n=3,149), and considers their involvement as victims or perpetrators of physical and psychological IPV. In this sample, physical IPV victimization was associated with anxiety and stress among men. Psychological IPV victimization was associated with depression among men, and with stress among both sexes. Physical IPV perpetration was significantly associated only with womens depressive and stress symptoms. Psychological IPV perpetration was associated with stress for both men and women. The mental component of HRQoL was significantly lower for men and women involved in any type of IPV. These results support the need to consider the mental health consequences of IPV involvement for both men and women.

category: public and global health


title: Safety of the single-dose Ad26.CoV2.S vaccine among healthcare workers in the phase 3b Sisonke study in South Africa

abstract:
BackgroundThe Sisonke open-label phase 3b implementation study aimed to assess the safety and effectiveness of the Janssen Ad26.CoV2.S vaccine among health care workers (HCWs) in South Africa. Here, we present the safety data.

MethodsWe monitored adverse events (AEs) at vaccination sites, through self-reporting triggered by text messages after vaccination, health care provider reports and by active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from day of first vaccination (17 February 2021) until 28 days after the final vaccination (15 June 2021). COVID-19 breakthrough infections, hospitalisations and deaths were ascertained via linkage of the electronic vaccination register with existing national databases.

FindingsOf 477,234 participants, 10,279 (2.2%) reported AEs, of which 139 (1.4%) were serious. Women reported more AEs than men (2.3% vs. 1.6%). AE reports decreased with increasing age (3.2% for 18-30, 2.1% for 31-45, 1.8% for 46-55 and 1.5% in >55-year-olds). Participants with previous COVID-19 infection reported slightly more AEs (2.6% vs. 2.1%). The commonest reactogenicity events were headache and body aches, followed by injection site pain and fever, and most occurred within 48 hours of vaccination. Two cases of Thrombosis with Thrombocytopenia Syndrome and four cases of Guillain-Barre Syndrome were reported post-vaccination. Serious AEs and AEs of special interest including vascular and nervous system events, immune system disorders and deaths occurred at lower than the expected population rates.

InterpretationThe single-dose Ad26.CoV2.S vaccine had an acceptable safety profile supporting the continued use of this vaccine in our setting.

FundingFunding was provided by the National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation - Grant number 21-V0001, and the Bill & Melinda Gates Foundation - grant number INV-030342.


title: PREVALENCE AND PREDICTORS OF STRESS AMONG COVID 19 HEALTH WORKERS IN KABWE DISTRICT: A CROSS SECTIONAL STUDY

abstract:
OBJECTIVEThis study aimed at determining the magnitude of stress among COVID-19 health workers in Kabwe district.

METHODSThe study was a cross-sectional study which recruited 138 health care workers managing COVID-19 cases in Kabwe. Data were collected through structured questionnaires and in-depth interviews. Quantitative data was analyzed using SPSS version 16 while qualitative data was analyzed using Nvivo8.

RESULTSThe study obtained 100% responses from the respondents and the prevalence of stress among the respondents was 73%. The nurses were more perceived to experience stress compared to the pharmacy personnel (28% vs. 3%). Similarly, women displayed a higher likelihood of experiencing stress compared to men. Lack of support, increased workload and fear were among the factors leading to stress.

CONCLUSIONThe study went out to determine stress among healthcare workers in Kabwe district. It was established that nurses were more vulnerable than groups. And women were found to be more stressed than men. It is therefore recommended that effective and meaningful interventions be put in place to mitigate the impact of long-term psychological distress and physical well-being in healthcare workers during the COVID-19 pandemic and future outbreaks.

ARTICLE SUMMARYO_ST_ABSStrengths and limitations of the studyC_ST_ABSO_LIA cross-sectional study method was employed; it does not assist in determining the cause and effect, in addition, the timing of the snapshot may not guarantee representation of the situation overtime. Therefore, there may be need to evaluate the effects of the COVID-19 pandemic on health workers mental requirements using a longitudinal study design.
C_LIO_LIThere might have been bias from respondents as the outcomes were self-reported. However, irrespective of the aforementioned limitations, this is a novel study in Kabwe describing stress among health workers in the district during the COVID-19 pandemic.
C_LIO_LIThe study grants access to initial evidence on stress among health workers managing the COVID-19 pandemic in Kabwe district, with the expectation of drawing the attention to legislators, health facility supervisors and those involved in the response to COVID-19 or impending epidemics.
C_LI

category: emergency medicine


title: Accumulation of meningeal lymphocytes, but not myeloid cells, correlates with subpial cortical demyelination and white matter lesion activity in progressive MS patients

abstract: Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type of injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional activity relates to meningeal inflammation and subpial cortical injury is of interest. Using post-mortem formalin-fixed paraffin-embedded tissue blocks (range, 5-72 blocks; median, 30 blocks) for each of 27 progressive MS patients, we assessed the relationship between meningeal inflammation, the extent of subpial cortical demyelination, and the state of subcortical WM lesional activity. Meningeal accumulations of T cells and B cells, but not myeloid cells, were spatially adjacent to subpial cortical lesions and greater immune-cell accumulation was associated with higher subpial lesion numbers. Patients with a higher extent of meningeal inflammation harboured a greater proportion of active and mixed (active-inactive) WM lesions, and an overall lower proportion of inactive and remyelinated WM lesions. Our findings support the involvement of meningeal lymphocytes in subpial cortical injury, and also point to a potential link between inflammatory subpial cortical demyelination and pathological mechanisms occurring in the subcortical white matter.


title: The impact of gastric acid suppression on the developing intestinal microbiome of a child

abstract: Gastric acid suppressing medications have been associated with an increased risk of Clostridioides difficile (C. difficile) infection, hypothesized to be due to underlying intestinal microbiome changes. Our goal is to characterize these changes in children as their microbiome is undergoing critical development. Our study included 5 children (< 3 years old) who were started on clinically indicated gastric acid suppression and 15 healthy age-matched controls. Stool samples were collected before and after 2 months of treatment. We analyzed the microbiome using 16S rRNA sequencing. Quantitative-PCR was used to detect C. difficile toxins. Subjects and controls had similar alpha and beta diversity. We found no significant change in alpha or beta diversity of subjects after treatment. C. difficile toxins were not found and there was no increase in C. difficile carriage after treatment. A significant increase in Lactobacillus was found after treatment, which has been associated with C. difficile in adults.

category: pediatrics


title: Field evaluation of Rapid SARS-Cov2 Antigen screening test on self-collected deep throat saliva samples in Malaysia

abstract:
Low cost Rapid Antigen Tests are widely used in Malaysia and the government has also mandated worksite screening as a condition for reopening. Numerous RAT kits have been approved by the Malaysian Medical Device Authority. However, it remains uncertain how these kits would perform in the field.

We enrolled workers between June and September 2021 from 23 worksites. They were trained and experienced in performing RAT selftest by virtue of their worksite participation in routine screening program. These workers also had reverse transcriptase polymerase chain reaction tests in the course of mass screening or contact tracing. We also enrolled patients with PCR confirmed Covid19 from a quarantine centre. These patients were instructed on selftesting and then immediately perform RAT under supervision. Two manufacturers donated RAT for this study.

A total of 340 participants were enrolled, 130 were from quarantine centre and 210 from worksites. The overall sensitivity of RAT compared to PCR was 70 percent. The specificity was 91 percent. Sensitivity decreased with increasing PCR cycle threshold values. Sensitivity is also lower among untrained subjects at each level of Ct. Logistic regression analysis confirmed false negative result is associated with Ct and participants prior training and experience.

This study shows that in the real world, RAT performance were markedly lower than that reported by the manufacturers. The test sensitivity is dependent on the operator training and experience, as well as on viral load as measured by Ct. User training and repeated testing for screening purpose is necessary to mitigate the low sensitivity of RAT.


title: Tree-informed Bayesian multi-source domain adaptation: cross-population probabilistic cause-of-death assignment using verbal autopsy

abstract: SO_SCPLOWUMMARYC_SCPLOWDetermining causes of deaths (COD) occurred outside of civil registration and vital statistics systems is challenging. A technique called verbal autopsy (VA) is widely adopted to gather information on deaths in practice. A VA consists of interviewing relatives of a deceased person about symptoms of the deceased in the period leading to the death, often resulting in multivariate binary responses. While statistical methods have been devised for estimating the cause-specific mortality fractions (CSMFs) for a study population, continued expansion of VA to new populations (or "domains") necessitates approaches that recognize between-domain differences while capitalizing on potential similarities. In this paper, we propose such a domain-adaptive method that integrates external between-domain similarity information encoded by a pre-specified rooted weighted tree. Given a cause, we use latent class models to characterize the conditional distributions of the responses that may vary by domain. We specify a logistic stick-breaking Gaussian diffusion process prior along the tree for class mixing weights with node-specific spike-and-slab priors to pool information between the domains in a data-driven way. Posterior inference is conducted via a scalable variational Bayes algorithm. Simulation studies show that the domain adaptation enabled by the proposed method improves CSMF estimation and individual COD assignment. We also illustrate and evaluate the method using a validation data set. The paper concludes with a discussion on limitations and future directions.


title: GB0139, an inhaled small molecule inhibitor of galectin-3, in COVID-19 pneumonitis: a randomised, controlled, open-label, phase 2a experimental medicine trial of the safety, pharmacokinetics, and potential therapeutic value

abstract:
RationaleHigh galectin-3 levels predict poor outcomes in patients with COVID-19. Galectin-3 activates monocytes and macrophages which are directly implicated in COVID-19 immunopathology and the cytokine storm. GB0139 is a potent thiodigalactoside galectin-3 inhibitor and may reduce the severe effects of the disease. We report safety and pharmacokinetics and pharmacodynamics of the inhaled galectin-3 inhibitor, GB0139, and assess clinical outcomes and key systemic inflammatory biomarkers in hospitalised patients with COVID-19 (ClinicalTrials.gov/EudraCT identifier: NCT04473053/2020-002230-32).

MethodsAdults with COVID-19 requiring oxygen, and with pneumonitis on x-ray, were randomised to receive standard of care (SOC; including dexamethasone; n=21) or SOC plus 10 mg GB0139 twice daily for 48 hours, then once daily for [≤]14 days (n=20).

ResultsPatients aged 27-87 years were enrolled from July 2020; the final patient completed the 90-day follow-up in April 2021. GB0139+SOC was well tolerated with no treatment-related serious adverse events reported. Incidences of adverse events were similar between treatment arms (40 with GB0139+SOC vs 35 with SOC). Plasma GB0139 was measurable in all patients after inhaled exposure, with moderate interpatient variability, and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc over days 2-7: p=0{middle dot}0099 vs SOC). Rate of decline in fraction of inspired oxygen (%) requirement was significantly greater in the GB0139+SOC arm with a posterior mean difference of -1{middle dot}51 (95% highest posterior density: -2{middle dot}90, -0{middle dot}189) versus SOC. Plasma levels of biomarkers associated with inflammation, coagulopathy, major organ function and fibrosis showed a downward trend versus SOC.

ConclusionsGB0139+SOC was well tolerated and achieved clinically relevant plasma concentrations and target engagement. This, and the reduction in markers associated with inflammatory, coagulation, fibrosis, and reduction in inspired oxygen (%) over SOC alone, indicates the therapeutic potential for inhaled GB0139 in hospitalised patients with COVID-19.

category: respiratory medicine


title: Hydroxychloroquine in the Pregnancies of Women with Lupus: A Meta-Analysis of Individual Participant Data

abstract:
ObjectiveMultiple guidelines recommend continuing hydroxychloroquine (HCQ) for systemic lupus erythematosus (lupus) during pregnancy based on observational data. The goal of this individual patient data meta-analysis was to combine multiple datasets to compare pregnancy outcomes in women with lupus on and off HCQ.

MethodsEligible studies included prospectively-collected pregnancies in women with lupus. After a manuscript search, 7 datasets were obtained. Pregnancy outcomes and lupus activity were compared for pregnancies with a visit in the first trimester in women who did or did not take HCQ throughout pregnancy. Birth defects were not systematically collected. This analysis was conducted in each dataset and results were aggregated to provide a pooled odds ratio.

ResultsSeven cohorts provided 938 pregnancies in 804 women. After selecting one pregnancy per patient with a 1st trimester visit, 668 pregnancies were included; 63% took HCQ throughout pregnancy. Compared to pregnancies without HCQ, those with HCQ had lower rates of highly active lupus, but did not have different rates of fetal loss, preterm birth, or preeclampsia. Among women with low lupus activity, HCQ reduced the risk for preterm delivery.

ConclusionThis large study of prospectively-collected lupus pregnancies demonstrates a decrease in SLE activity among woman who continue HCQ through pregnancy and no harm to pregnancy outcomes. Like all studies of HCQ in lupus pregnancy, this study is confounded by indication and non-adherence. As this study confirms the safety of HCQ and diminished SLE activity with use, it is consistent with current recommendations to continue HCQ throughout pregnancy.

category: rheumatology


title: Variability in physical inactivity responses of university students during COVID-19 pandemic: A monitoring of daily step counts using a smartphone application

abstract: This study investigated the changes in physical inactivity of university students during the COVID-19 pandemic, with reference to their academic calendar. We used the daily step counts recorded by a smartphone application (iPhone Health App) from April 2020 to January 2021 (287 days) for 603 students. The data for 287 days were divided into five periods based on their academic calendar. The median value of daily step counts across each period was calculated. A k-means clustering analysis was performed to classify the 603 participants into subgroups to demonstrate the variability in the physical inactivity responses. The median daily step counts, with a 7-days moving average, dramatically decreased from 5,000 to 2,000 steps/day in early April. It remained at a lower level (less than 2,000 steps/day) during the first semester, then increased to more than 5,000 steps/day at the start of summer vacation. The clustering analysis demonstrated the variability in physical inactivity responses. Independent of the academic calendar, many inactive students did not recover their original daily step counts after its dramatic decrement. Consequently, promoting physical activity is recommended for inactive university students over the course of the whole semester.

category: sports medicine


title: A tractometry investigation of white matter tract network structure and relationships with cognitive function in relapsing-remitting multiple sclerosis

abstract: Understanding the brain changes underlying cognitive dysfunction is a key priority in multiple sclerosis to improve monitoring and treatment of this debilitating symptom. Functional connectivity network changes are associated with cognitive dysfunction, but it is less well understood how changes in normal appearing white matter relate to cognitive symptoms. If white matter tracts share a similar network structure it would be expected that tracts within a network are similarly affected by MS pathology. In the present study, we used a tractometry approach to explore patterns of variance in diffusion metrics across white matter (WM) tracts. We investigated whether separate networks, based on normal variation or pathology, appear, and how this relates to neuropsychological test performance across cognitive domains. A sample of 102 relapsing-remitting MS patients and 27 healthy controls underwent MRI and neuropsychological testing. Tractography was performed on diffusion MRI data to extract 40 WM tracts and microstructural measures were extracted from each tract. Principal component analysis (PCA) was used to decompose metrics from all tracts to assess the presence of any co-variance structure among the tracts. Similarly, PCA was applied to cognitive test scores to identify the main cognitive domains. Finally, we assessed the ability of tract components to predict test performance across cognitive domains. We found that a single component which captured pathology across all tracts explained the most variance and that there was little evidence for separate, smaller network patterns of pathology. WM tract components were weak, but significant, predictors of cognitive function in MS. These findings highlight the need to investigate the relationship between the normal appearing white matter and cognitive impairment further and on a more granular level, to improve the understanding of the network structure of the brain in MS.

category: neurology


title: Validation of Genomic and Transcriptomic Models of Homologous Recombination Deficiency in a Real-World Pan-Cancer Cohort

abstract:
BackgroundWith the introduction of DNA-damaging therapies into standard of care cancer treatment, there is a growing need for predictive diagnostics assessing homologous recombination deficiency (HRD) status across tumor types. Following the strong clinical evidence for the utility of DNA-sequencing-based HRD testing in ovarian cancer, and growing evidence in breast cancer, we present analytical validation of the Tempus|HRD-DNA test. We further developed, validated, and explored the Tempus|HRD-RNA model, which uses gene expression data from 16,470 RNA-seq samples to predict HRD status from formalin-fixed paraffin-embedded (FFPE) tumor samples across numerous cancer types.

MethodsGenomic and transcriptomic profiling was performed using next-generation sequencing from Tempus|xT, Tempus|xO, Tempus|xE, Tempus|RS, and Tempus|RS.v2 assays on 48,843 samples. Samples were labeled based on their BRCA1, BRCA2 and selected Homologous Recombination Repair (HRR) pathway gene (CDK12, PALB2, RAD51B, RAD51C, RAD51D) mutational status to train and validate HRD-DNA, a genome-wide loss-of-heterozygosity biomarker, and HRD-RNA, a logistic regression model trained on gene expression, using several performance metrics and statistical tests.

ResultsIn a sample of 2,058 breast and 1,216 ovarian tumors, BRCA status was predicted by HRD-DNA with F1-scores of 0.98 and 0.96, respectively. Across an independent set of 1,363 samples across solid tumor types, the HRD-RNA model was predictive of BRCA status in prostate, pancreatic, and non-small cell lung cancer, with F1-scores of 0.88, 0.69, and 0.62, respectively.

ConclusionsWe predict HRD-positive patients across many cancer types and believe both HRD models may generalize to other mechanisms of HRD outside of BRCA loss. HRD-RNA complements DNA-based HRD detection methods, especially for indications with low prevalence of BRCA alterations.

category: oncology


title: Taiwan Biobank: a rich biomedical research database of the Taiwanese population

abstract: The Taiwan Biobank (TWB) is an ongoing prospective study of over 150,000 individuals aged 30-70 recruited from across Taiwan beginning in 2012. A comprehensive list of phenotypes was collected for each consented participant at recruitment and follow-up visits through structured interviews and physical measurements. Biomarkers and genetic data were also generated for all participants from blood and urine samples. We present here an overview of the genetic data quality, population structure, and familial relationship within TWB, which consists of predominantly Han Chinese-ancestry individuals, and highlight important attributes and genetic findings thus far from the biobank. A linkage to Taiwans National Health Insurance database of >25 years and other health-related registries is underway that will enrich the phenotypic spectrum of TWB and enable deep and longitudinal genetic investigations. TWB provides one of the largest biobank resources for biomedical and public health research in East Asia that will contribute to our understanding of the genetic basis of human health and disease in global populations through collaborative studies with other biobanks.

category: genetic and genomic medicine


title: Economic burden and catastrophic health expenditure associated with COVID-19 hospitalisations in Kerala, South India

abstract:
IntroductionCatastrophic health expenditure during COVID-19 hospitalization has altered the economic picture of households especially in low resource settings with high rates of COVID-19 infection. This study aimed to estimate the Out of Pocket (OOP) expenditure and the proportion of households that incurred catastrophic health expenditures due to COVID-19 hospitalisation in Kerala, South India.

Materials and MethodsA cross-sectional study was conducted among a representative sample of 155 COVID-19 hospitalised patients in Kottayam district over four months, using a pretested interview schedule. The direct medical and non-medical costs incurred by the study participant during hospitalisation and the total monthly household expenditure were obtained from the respective COVID-19 affected households. Catastrophic health expenditure was defined as direct medical expenditure exceeding 40% of effective household income.

ResultsFrom the study, median and mean Out of Pocket (OOP) expenditures were obtained as USD 93.57 and USD 502.60 respectively. The study revealed that 49.7% of households had Catastrophic health expenditure, with 32.9% having incurred Distress financing. Multivariate analysis revealed being Below poverty line, hospitalisation in private healthcare facility and presence of co-morbid conditions as significant determinants of Catastrophic health expenditure.

ConclusionHigh levels of Catastrophic health expenditure and distress financing revealed by the study unveils major unaddressed challenges in the road to Universal health coverage.

category: health economics


title: An Automated Heart Rate-based Algorithm for Sleep Stage Classification: Validation Using Conventional PSG and Innovative Wearable ECG Device

abstract:
Study ObjectivesValidate a HR-based deep-learning algorithm for sleep staging named Neurobit-HRV (Neurobit Inc., New York, USA).

MethodsThe algorithm can perform classification at 2-levels (Wake; Sleep), 3-levels (Wake; NREM; REM) or 4-levels (Wake; Light; Deep; REM) in 30-second epochs. The algorithm was validated using an open-source dataset of PSG recordings (Physionet CinC dataset, n=994 participants) and a proprietary dataset (Z3Pulse, n=52 participants), composed of HR recordings collected with a chest-worn, wireless sensor. A simultaneous PSG was collected using SOMNOtouch. We evaluated the performance of the models in both datasets using Accuracy (A), Cohens kappa (K), Sensitivity (SE), Specificity (SP).

ResultsCinC - The highest value of accuracy was achieved by the 2-levels model (0.8797), while the 3-levels model obtained the best value of K (0.6025). The 4-levels model obtained the lowest SE (0.3812) and the highest SP (0.9744) for the classification of Deep sleep segments. AHI and biological sex did not affect sleep scoring, while a significant decrease of performance by age was reported across the models. Z3Pulse - The highest value of accuracy was achieved by the 2-levels model (0.8812), whereas the 3-levels model obtained the best value of K (0.611). For classification of the sleep states, the lowest SE (0.6163) and the highest SP (0.9606) were obtained for the classification of Deep sleep segment.

ConclusionsResults demonstrate the feasibility of accurate HR-based sleep staging. The combination of the illustrated sleep staging algorithm with an inexpensive HR device, provides a cost-effective and non-invasive solution easily deployable in the home.

category: health informatics


title: Health impact assessment of salt reduction in bread in Portugal: a pilot study

abstract: Hypertension is a risk factor for cardiovascular diseases, which can be caused by excessive salt intake. In Portugal, one of the main foods to contribute to ingestion of salt is bread. Thus, a voluntary Protocol was signed between stakeholders with the aim to reduce salt content in bread by 2021. Herein, a retrospective HIA was carried out to assess the impact in blood pressure (BP) after this agreement. In order to find average values of salt intake and BP in Portuguese population, national surveys were used. Also, estimates of BP reduction and its size effects were calculated based upon meta-analysis data. It is expected that salt intake will be reduced mostly in individuals with low educational level, men, aged between 65-74 years old and residents in South region of Portugal. Results in hypertensive patients indicate that a higher effect on BP will occur in the same profile of individuals, except age (between 55 and 64 years old). However, the estimated effect is very low for all groups, suggesting that the Protocol will contribute to modest health gains. Complementary measures supported by HIA studies need to be adopted to actively promote salt intake reduction and effectively prevent hypertension.

category: health policy


title: VaxiMap: optimal delivery of vaccinations for housebound patients

abstract:
BackgroundThroughout the UKs Covid-19 vaccination campaign, responsibility for vaccinating housebound patients has rested with individual GP surgeries, posing them a difficult logistical challenge (the travelling salesman problem). In response to demand from GPs, and a lack of existing solutions tailored specifically to vaccination, VaxiMap was created. This tool provides optimal routes for vaccine delivery and has been free to all users since its inception in January 2021.

MethodsVaxiMap generates optimal routes subject to the constraint that the number of patients per route should be fixed. This ensures that a known quantity of vaccine can be set aside for each route and minimises wastage. The user need only upload an Excel spreadsheet of patient postcodes to be visited. A divide-and-conquer approach of iterative k-means clustering followed by within-cluster route optimisation is used to generate the routes.

FindingsWe find substantial savings in the time taken to plan vaccinations, as well as savings in the time taken to visit housebound patients. We estimate total savings to date of 4,700 hours of practitioner time, equivalent to 2.5 work-years, or approximately {pound}91k at typical practitioner salaries.

InterpretationThe adoption of VaxiMap yielded both time and cost savings for GP surgeries and accelerated the UKs Covid-19 vaccination campaign at a critical moment.

FundingFinancial support for VaxiMap was provided by Magdalen College, Oxford, Oxford University Innovation, and JHubMed, part of UK Strategic Command. These parties were not involved in the preparation of this manuscript.

category: health systems and quality improvement


title: Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations

abstract: SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection. The novel variant of concern (VoC) Omicron (B.1.1.529) has the largest number of amino acid alterations in its Spike protein to date. Thus, it may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (93-100%) towards SARS-CoV-2 wild-type, but some reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination or vector-based AZD1222 or Ad26.CoV2.S performed less well with peak responder rates of 33%, 50% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argues for urgent booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based immunization scheme.

category: allergy and immunology


title: A nationwide deep learning pipeline to predict stroke and COVID-19 death in atrial fibrillation

abstract: Deep learning (DL) and machine learning (ML) models trained on long-term patient trajectories held as medical codes in electronic health records (EHR) have the potential to improve disease prediction. Anticoagulant prescribing decisions in atrial fibrillation (AF) offer a use case where the benchmark stroke risk prediction tool (CHA2DS2-VASc) could be meaningfully improved by including more information from a patients medical history. In this study, we design and build the first DL and ML pipeline that uses the routinely updated, linked EHR data for 56 million people in England accessed via NHS Digital to predict first ischaemic stroke in people with AF, and as a secondary outcome, COVID-19 death. Our pipeline improves first stroke prediction in AF by 17% compared to CHA2DS2-VASc (0.61 (0.57-0.65) vs 0.52 (0.52-0.52) area under the receiver operating characteristics curves, 95% confidence interval) and provides a generalisable, opensource framework that other researchers and developers can build on.

category: cardiovascular medicine


title: Cardiovascular Complications of Modern Multiple Myeloma Therapy: Analysis of FDA Adverse Event Reporting System

abstract:
PurposeMultiple myeloma accounts for over 15% of hematological malignancies. In attempt to tackle this malady, the FDA approved four drugs in 2015 which has propagated further development of new anti-multiple myeloma since. However, the health safety of these new agents is still ill-defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs.

MethodsWe searched the cardiac adverse events of the newly approved FDA drugs since 2015 using the U.S. Food and Drug Administration Adverse Events Reporting System database (FAERS). We calculated the reporting odds ratio (ROR) with 95% confidence for four drugs that have the highest incidence of cardiovascular adverse events.

ResultsAmong the medications that have approved for MM Between 2015-2020, four novel drugs showed the highest incidence of cardiotoxicity. ROR (95% CI) for atrial fibrillation due to elotuzumab, Ixazomib, daratumumab, and panobinostat compared to other FAERS drugs was 5.8 (4.4-7.7), 1.93 (1.5-2.3), 4.8 (4.2-5.6), and 5.7 (4.1-8.1), respectively. The ROR (95% CI) for cardiac failure was 8.2 (6.4-10.5), 4.7 (4.1-5.4), 5.8 (4.9-6.7), and 5.6 (3.8-8.1) and ROR (95% CI) for coronary disease was 2.7 (1.9-3.9), 2.7 (2.3-3.2), 2,3 (1.9-2.8), and 4.6 (3.2-6.6) due to elotuzumab, Ixazomib, daratumumab, and panobinostat versus all other drugs in FAERS.

ConclusionsThe newly approved multiple myeloma therapy (elotuzumab, Ixazomib, daratumumab, panobinostat) are significantly associated with cardiotoxicity. These results highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.


title: Statistical Forecasting : Third Wave of COVID-19-With an Application to India

abstract: The pandemic due to the SARS-CoV-2 virus impacted the entire world in different waves. An important question that arise after witnessing the first and second waves of COVID-19 is - Will the third wave also arrive and if yes, then when. Various types of methodologies are being used to explore the arrival of third wave. A statistical methodology based on the fitting of mixture of Gaussian distributions is explored in this paper and the aim is to forecast the third wave using the data on the first two waves of pandemic. Utilizing the data of different countries that are already facing the third wave, modelling of their daily cases data and predicting the impact and timeline for the third wave in India is attempted in this paper. The Gaussian mixture model based on algorithm for clustering is used to estimate the parameters.

category: epidemiology


title: Immunity acquired by a minority active fraction of the population could explain COVID-19 spread in Greater Buenos Aires (June-November 2020)

abstract: The COVID-19 pandemic had an uneven development in different countries. In Argentina, the pandemic began in march 2020 and, during the first 3 months, the vast majority of cases were concentrated in a densely populated region that includes the city of Buenos Aires (country capital) and the Greater Buenos Aires area that surrounds it. This work focuses on the spread of COVID-19 between June and November 2020 in Greater Buenos Aires. Within this period of time there was no vaccine, basically only the early wild strain of SARS-CoV-2 was present, and the official restriction and distancing measures in this region remained more or less constant. Under these particular conditions, the incidences show a sharp rise from June 2020 and begin to decrease towards the end of August until the end of November 2020. In this work we study, through mathematical modelling and available epidemiological information, the spread of COVID-19 in this region and period of time. We show that a coherent explanation of the evolution of incidences can be obtained assuming that only a minority fraction of the population got involved in the spread process, so that the incidences decreased as this group of people was becoming immune. The observed evolution of the incidences could then be a consequence at the population level of lasting immunity conferred by SARS-CoV-2.


title: Spatiotemporal patterns and progression of the Delta variant of COVID-19 and their health intervention linkages in Southeast Asia

abstract: The global pandemic of COVID-19 presented an unprecedented challenge to all countries in the world, among which Southeast Asia (SEA) countries managed to maintain and mitigate the first wave of COVID-19 in 2020. However, these countries were caught in the crisis after the Delta variant was introduced to SEA, though many countries had immediately implemented non-pharmaceutical intervention (NPI) measures along with vaccination in order to contain the disease spread. To investigate the potential linkages between epidemic dynamics and public health interventions, we adopted a prospective space-time scan method to conduct spatiotemporal analysis at the district level in the seven selected countries in SEA from June 2021 to October 2021. Results reveal the spatial and temporal propagation and progression of COVID-19 risks relative to public health measures implemented by different countries. Our research benefits continuous improvements of public health strategies in preventing and containing this pandemic.


title: Analytical sensitivity of seven SARS-CoV-2 antigen-detecting rapid tests for Omicron variant

abstract:
BackgroundThe emergence of each novel SARS-CoV-2 variants of concern (VOCs) requires investigation of its potential impact on the performance of diagnostic tests in use, including Antigen-detecting rapid diagnostic tests (Ag-RDT). Although anecdotal reports have been circulating that the newly emerged Omicron variant is in principle detectable by Ag-RDTs, few data on sensitivity are available.

MethodsWe have performed 1) analytical sensitivity testing with cultured virus in eight Ag-RDTs and 2) retrospective testing in duplicates with clinical samples from vaccinated individuals with Omicron (n=18) or Delta (n=17) breakthrough infection on seven Ag-RDTs.

FindingsOverall, we have found large heterogenicity between Ag-RDTs for detecting Omicron. When using cultured virus, we observed a trend towards lower sensitivity for Omicron detection compared to earlier circulating SARS-CoV-2 and the other VOCs. When comparing performance for Delta and Omicron in a comparable set of clinical samples in seven Ag-RDTs, 124/252 (49.2%) of all test performed showed a positive result for Omicron compared to 156/238 (65.6%) for Delta samples. Sensitivity for both Omicron and Delta between Ag-RDTs was highly variable. Four out of seven Ag-RDTs showed significantly lower sensitivity (p<0.001) to detect Omicron when compared to Delta while three had comparable sensitivity to Delta.

InterpretationSensitivity for detecting Omicron is highly variable between Ag-RDTs, necessitating a careful consideration when using these tests to guide infection prevention measures. While analytical and retrospective testing may be a proxy and timely solution to generate performance data, it is not a replacement for clinical evaluations which are urgently needed. Biological and technical reasons for detection failure by some Ag-RDTs need to be further investigated.

FundingThis work was supported by the Swiss National Science Foundation (grant numbers 196383, 196644 and 198412), the Fondation Ancrage Bienfaisance du Groupe Pictet, the Fondation Privee des Hopiteaux Universitaires de Geneve and FIND, the global alliance for diagnostics.

category: infectious diseases


title: Sensitivity of SARS-CoV-2 antigen-detecting rapid tests for Omicron variant


title: An in silico analysis of early SARS-CoV-2 variant B.1.1.529 (Omicron) genomic sequences and their epidemiological correlates

abstract:
BackgroundA newly emerged SARS-CoV-2 variant B.1.1.529 has worried the health policy makers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) has designated it as a global variant of concern (VOC) and has named as  Omicron. A surge in new COVID-19 cases have been reported from certain geographical locations, primarily in South Africa (SA) following the emergence of Omicron.

Materials and methodsWe performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID (until 2021-12-10) to predict the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. The mutations present at the receptor binding domain (RBD) of the variants were assessed using an open analysis pipeline which integrates a yeast-display platform with deep mutational scanning. Further, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-10th Dec, 2021) with the current epidemiological data (new COVID-19 cases and deaths) from SA to understand whether the Omicron has an epidemiological advantage over existing variants.

ResultsCompared to the current list of global VOCs/VOIs (as per WHO) Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with Alpha variant for the complete sequence as well as for RBM. The mutations were found primarily condensed in spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to - 0.97) in the sequences reported from SA post-emergence of the new variant, later showing a decrease. There has been a steep rise in the new COVID-19 cases in parallel with increase in the proportion of Omicron since the first case (74-100%), on the contrary, the incidences of new deaths have not been increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58).

ConclusionsOmicron may have greater immune escape ability than the existing VOCs/VOIs. However, there are no clear indications coming out from the predictive mutational analysis that the Omicron may have higher virulence/lethality than other variants, including Delta. The higher ability for immune escape may be a likely reason for the recent surge in Omicron cases in SA.

HighlightsO_LIHigher immune escape ability than the existing VOCs/VOIs
C_LIO_LINo clear indications of increased affinity for ACE2 binding
C_LIO_LIDriving a new COVID-19 wave in South Africa
C_LIO_LIOutcompeting Delta variant
C_LIO_LICurrently, no clear evidence for increased virulence/lethality
C_LI


title: Deep learning based models to study the effect of glaucoma genes on angle dysgenesis in-vivo

abstract:
ObjectiveTo predict the presence of Angle Dysgenesis on Anterior Segment Optical Coherence Tomography (ADoA) using deep learning and to correlate ADoA with mutations in known glaucoma genes.

DesignA cross-sectional observational study.

ParticipantsEight hundred, high definition anterior segment optical coherence tomography (ASOCT) B-scans were included, out of which 340 images (One scan per eye) were used to build the machine learning (ML) model and the rest were used for validation of ADoA. Out of 340 images, 170 scans included PCG (n=27), JOAG (n=86) and POAG (n=57) eyes and the rest were controls. The genetic validation dataset consisted of another 393 images of patients with known mutations compared with 320 images of healthy controls

MethodsADoA was defined as the absence of Schlemms canal(SC), the presence of extensive hyper-reflectivity over the region of trabecular meshwork or a hyper-reflective membrane (HM) over the region of the trabecular meshwork. Deep learning was used to classify a given ASOCT image as either having angle dysgenesis or not. ADoA was then specifically looked for, on ASOCT images of patients with mutations in the known genes for glaucoma (MYOC, CYP1B1, FOXC1 and LTBP2).

Main Outcome measuresUsing Deep learning to identify ADoA in patients with known gene mutations.

ResultsOur three optimized deep learning models showed an accuracy > 95%, specificity >97% and sensitivity >96% in detecting angle dysgenesis on ASOCT in the internal test dataset. The area under receiver operating characteristic (AUROC) curve, based on the external validation cohort were 0.91 (95% CI, 0.88 to 0.95), 0.80 (95% CI, 0.75 to 0.86) and 0.86 (95% CI, 0.80 to 0.91) for the three models. Amongst the patients with known gene mutations, ADoA was observed among all the patients with MYOC mutations, as it was also observed among those with CYP1B1, FOXC1 and with LTBP2 mutations compared to only 5% of those healthy controls (with no glaucoma mutations).

ConclusionsThree deep learning models were developed for a consensus-based outcome to objectively identify ADoA among glaucoma patients. All patients with MYOC mutations had ADoA as predicted by the models.

category: ophthalmology


title: Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

abstract:
PurposeAlthough haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized the clinical, molecular and functional spectra of ANKRD11 missense variants.

MethodsWe collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants by in silico analyses and cell-based experiments.

ResultsWe identified 29 individuals with (mostly de novo) ANKRD11 missense variants, who presented with syndromic neurodevelopmental disorders and were phenotypically similar to individuals with KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in Repression Domain 2. Cellularly, most variants caused reduced ANKRD11 stability. One variant resulted in decreased proteasome degradation and loss of ANKRD11 transcriptional activity.

ConclusionOur study indicates that pathogenic heterozygous missense variants in ANKRD11 cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges, as the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping.


title: Minimal observed impact of HLA genotype on hospitalization and severity of SARS-CoV-2 infection

abstract: HLA is a critical component of the viral antigen presentation pathway. We investigated the relationship between severity of SARS-CoV-2 disease and HLA type in 3,235 individuals with confirmed SARS-CoV-2 infection. We found only the DPB1 locus to be associated with the binary outcome of whether an individual developed any COVID-19 symptoms. The number of peptides predicted to bind to an HLA allele had no significant relationship with disease severity both when stratifying individuals by ancestry or age and in a pooled analysis. Age, BMI, asthma status, and autoimmune disorder status were predictive of severity across multiple age and individual ancestry stratificiations. Overall, at the population level, we found HLA type is significantly less predictive of COVID-19 disease severity than certain demographic factors and clinical comorbidities.


title: External validation of six clinical models for prediction of unknown chronic kidney disease in a German population

abstract:
BackgroundChronic kidney disease (CKD) is responsible for large personal health and societal burdens. Screening populations at higher risk for CKD is effective to initiate earlier treatment and decelerate disease progress. We externally validated clinical prediction models for unknown CKD that might be used in population screening.

MethodsWe validated six risk models for prediction of unknown CKD using only non-invasive parameters. Validation data came from 4,185 participants of the German Heinz-Nixdorf-Recall study (HNR), drawn in 2000 from a general population aged 45-75 years. We estimated discrimination and calibration using the full model information, and calculated the diagnostic properties applying the published scoring algorithms of the models using various thresholds for the sum of scores.

ResultsThe risk models used four to nine parameters. Age and hypertension were included in all models. Five out of six c-values ranged from 0.71 to 0.73, indicating fair discrimination. Positive predictive values ranged from 15% to 19%, negative predictive values were >93% using score thresholds that resulted in values for sensitivity and specificity above 60%.

ConclusionsMost of the selected CKD prediction models show fair discrimination in a German general population. The estimated diagnostic properties indicate that the models are suitable for identifying persons at higher risk for unknown CKD without invasive procedures.

category: nephrology


title: Infant malnutrition in low- and middle-income countries: assessment and prevalence of small and nutritionally at-risk infants aged under 6 months in 54 Demographic & Health Survey datasets

abstract:
BackgroundThere is increasing global focus on malnutrition in infants aged under 6 months (u6m) but evidence on how best to identify and manage at-risk individuals is sparse. Our objectives were to: explore data quality of commonly used anthropometric indicators; describe prevalence and disease burden of infant u6m malnutrition; compare wasting and underweight as measures of malnutrition by determining the strength and consistency of associations with biologically plausible risk factors.

MethodsWe performed a cross-sectional secondary analysis of Demographic and Health Survey (DHS) datasets, focussing on infants u6m. We calculated underweight (low weight-for-age), wasting (low weight-for-length), stunting (low length-for-age), and concurrent wasting and stunting. We explored data quality by recording extreme (flagged, as per standard criteria) or missing values. We calculated the population-weighted prevalence of each type of malnutrition and extrapolated the burden to all low- and middle-income countries (LMICs). We explored associations between infant, maternal and household risk factors with underweight and wasting using logistic regression models.

ResultsWe analysed 54 DHS surveys. Data quality in terms of refusals and missingness was similar for both weight and length. There were more extreme (flagged) values for length-based measures (6.1% flagged for weight-for-length, 4.8% for length-for-age) than for weight-for-age (1.0% flagged). Overall, 20.1% of infants (95% CI: 19.5, 20.7) were underweight, 21.3% (95% CI: 20.7, 22.3) were wasted, 17.6% (95% CI: 17.0, 18.2) were stunted, and 2.0% (95% CI: 1.8, 2.2) were concurrently wasted and stunted. This corresponds to an estimated burden in LMICs of 23.8m underweight infants, 24.5m wasted infants, 21.5m stunted infants and 2.2m concurrently wasted and stunted. Logistic regression models showed that numerous risk factors were associated with wasting and underweight. Effect sizes of risk factors tended to be stronger and more consistently associated with underweight compared to wasting.

ConclusionMalnutrition in infants u6m is a major problem in LMICs. This is true whether assessed by underweight, wasting or stunting. Our data build on other evidence suggesting that underweight may be a better anthropometric case definition than wasting: data quality is better when length is not involved; biologically plausible risk factors are better reflected by an infant being underweight. Future research, ideally from intervention trials, should further explore how best to identify malnourished (small and nutritionally at-risk) infants u6m. For now, treatment programmes should note that many factors might underlie problems in this age group: services should thus consider how to address maternal health and wider social circumstances as well as caring for infants themselves.

category: nutrition


title: Cleaning and disinfecting surfaces in hospitals and long-term care facilities for reducing hospital and facility-acquired bacterial and viral infections: A systematic review

abstract:
BackgroundMultiply drug-resistant organisms (MDROs) in hospitals and long-term care facilities (LTCFs) of particular concern include meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus, multidrug-resistant Acinetobacter species and extended spectrum beta-lactamase producing organisms. Respiratory viruses include influenza and SARS-CoV-2.

AimTo assess effectiveness of cleaning and disinfecting surfaces in hospitals and LTCFs.

MethodsCINAHL, Cochrane CENTRAL Register of Controlled Trials, EMBASE, Medline, and Scopus searched inception to 28 June 2021, no language restrictions, for randomized controlled trials, cleaning, disinfection, hospitals, LTCFs. Abstracts and titles were assessed and data abstracted independently by two authors.

FindingsOf fourteen c-RCTs in hospitals and LTCFs, interventions in ten were focused on reducing patient infections of four MDROs and/or healthcare-associated infections (HAIs). In four c-RCTs patient MDRO and/or HAI rates were significantly reduced with cleaning and disinfection strategies including bleach, quaternary ammonium detergents, ultraviolet irradiation, hydrogen peroxide vapour and copper-treated surfaces or fabrics. Of three c-RCTs focused on reducing MRSA rates, one had significant results and one on Clostridioides difficile had no significant results. Heterogeneity of populations, methods, outcomes and data reporting precluded meta-analysis. Overall risk of bias assessment was low but high for allocation concealment, and GRADE assessment was low risk. No study assessed biofilms.

ConclusionsTen c-RCTs focused on reducing multiple MDROs and/or HAIs and four had significant reductions. Three c-RCTs reported only patient MRSA colonization rates (one significant reductions), and one focused on Clostridioides difficile (no significant differences). Standardised primary and secondary outcomes are required for future c-RCTs including detailed biofilm cleaning/disinfection interventions.


title: A magnetic bead immunoassay to detect human IgG reactive to SARS-CoV-2 Spike S1 RBD produced in Escherichia coli

abstract: Immunological assays to detect SARS-CoV-2 Spike receptor binding domain antigen seroconversion in humans are important tools to monitor the levels of protecting antibodies in the population in response to infection and/or immunization. Here we describe a simple, low cost and high throughput Ni2+ magnetic bead immunoassay to detect human IgG reactive to Spike S1 RBD Receptor Binding Domain produced in Escherichia coli. A 6xHis tagged Spike S1 RBD was expressed in E. coli and purified by affinity chromatography. The protein was mobilized on the surface of Ni2+ magnetic beads and used to investigate the presence of reactive IgG in the serum obtained from pre-pandemic and COVID-19 confirmed cases. The method was validated with a cohort of 290 samples and an area under the receiver operating characteristics curve of 0.94 was obtained. The method operated with>82% sensitivity at 98% specificity and was also able to track human IgG raised in response to vaccination with Comirnaty with 85% sensitivity. The IgG signal obtained with the described method was well correlated with the signal obtained when pre fusion Spike produced in HEK cell lines were used as antigen. This novel low-cost and high throughput immunoassay may act as an important tool to investigate protecting IgG antibodies against SARS-CoV-2 in the human population.


title: Persistent symptoms among children and adolescents with and without anti-SARS-CoV-2 antibodies: a population-based serological study in Geneva, Switzerland

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSIt is now established that a significant proportion of adults experience persistent symptoms after SARS-CoV-2 infection. However, evidence for children and adolescents is still inconclusive. In this population-based study, we examine the proportion of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection, as assessed by serological status, and compare this to a seronegative control group.

MethodsWe conducted a serosurvey in June-July 2021, recruiting 660 children and adolescents from 391 households selected randomly from the Geneva population. We tested participants for anti-SARS-CoV-2 antibodies targeting the nucleocapsid (N) protein to determine previous infection. A parent filled a questionnaire including questions on COVID-19-related symptoms lasting at least 2 weeks.

FindingsAmong children seropositive for anti-SARS-CoV-2 antibodies, the sex- and age-adjusted prevalence of symptoms lasting longer than two weeks was 18.3%, compared to 11.1% among seronegative children (prevalence difference ({Delta}aPrev)=7.2%, 95%CI:1.5-13.0). Main symptoms declared among seropositive children were fatigue (11.5%) and headache (11.1%). For 8.6% (aPrev, 95%CI: 4.7-12.5) of seropositives, these symptoms were declared to be highly limiting of daily activities. Adolescents aged 12-17 years had a higher adjusted prevalence of persistent symptoms (aPrev=29.1%, 95%CI:19.4-38.7) than younger children. Comparing seropositive and seronegative adolescents, the estimated prevalence of symptoms lasting over four weeks is 4.4% ({Delta}aPrev, 95%CI:-3.8-13.6).

InterpretationA significant proportion of children aged 12 to 17 years had symptoms lasting over two weeks after SARS-CoV-2 infection, with an estimated prevalence of symptoms lasting over 4 weeks of 4.4% in this age group. This represents a large number of adolescents in absolute terms, and should raise concern in the context of unknown long-term evolution of symptoms. Younger children appear to experience long-lasting symptoms less frequently, as no difference was observed between the seropositive and seronegative sample. Further studies with larger samples sizes are needed.

FundingSwiss Federal Office of Public Health, Geneva General Directorate of Health, HUG Private Foundation, SSPH+, Fondation des Grangettes.

category: public and global health


title: Parental preferences for a mandatory vaccination scheme in England; a discrete choice experiment

abstract:
BackgroundMandatory vaccination has been mooted to combat falling childhood vaccine uptake rates in England. This study investigated parental preferences for a mandatory vaccination scheme.

MethodsDiscrete choice experiment. Six attributes were investigated: vaccine (MMR, 6-in-1), child age group (2 years and older, 5 years and older), incentive ({pound}130 cash incentive for parent, {pound}130 voucher incentive for child, no incentive), penalty ({pound}450 fine, parent not able to claim Child Benefits for an unvaccinated child, unvaccinated child not able to attend school or day care), ability to opt out (medical exemption only, medical and religious belief exemption), and compensation scheme (not offered, offered). Mixed effects conditional logit regression models were used to investigate parental preferences and relative importance of attributes.

FindingsParticipants were 1,001 parents of children aged 5 years and under (53% female, mean age=33{middle dot}6 years, SD=7{middle dot}1, 84% white British). Parental preferences were mostly based on incentives (slight preference for cash pay-out for the parent versus a voucher for the child) and penalties (preference for schemes that did not allow unvaccinated children to attend school or day care and those that withheld financial benefits for parents of unvaccinated children). Parents also preferred schemes that: offered a compensation scheme, mandated the 6-in-1 vaccine, mandated vaccination in children aged 2 years and older, and that offered only medical exemptions.

InterpretationResults can inform policymakers decisions about how best to implement a mandatory childhood vaccination scheme in England.

FundingData collection was funded by a British Academy/Leverhulme Small Research Grants (SRG1920\101118).

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSUptake of childhood vaccines in high-income countries has decreased in recent years. Making vaccination mandatory has the potential to increase uptake. There is no standard approach to mandatory vaccination schemes. Research suggests that the cultural context will affect perceived acceptability of vaccine laws. Mandatory vaccination has been mooted in England as a way to increase vaccine uptake. However, there is no recent research investigating parental preferences for how a mandatory vaccine scheme could be implemented.

Added value of this studyWe used a discrete choice experiment to investigate English parents preferences for a mandatory vaccination scheme. Variables included were parameters that are likely to be considered by policymakers if a mandatory vaccination scheme were to be proposed.

Implications of all the available evidenceStudy results indicate that parents prefer mandatory vaccination schemes that offer financial incentives for vaccination. The penalty imposed for missing a vaccine dose, and the inclusion of a compensation scheme for severe adverse effects also influenced preferences. These results can be used to inform policy should a mandatory vaccination scheme be proposed in England.


title: A systematic review of observational methods used to quantify personal protective behaviours among members of the public during the COVID-19 pandemic, and the concordance between observational and self-report measures in infectious disease health protection

abstract:
ObjectivesTo assess the quantity and quality of studies using an observational measure of behaviour during the COVID-19 pandemic, and to narratively describe the association between self-report and observational data for behaviours relevant to controlling an infectious disease outbreak.

DesignSystematic review and narrative synthesis of observational studies.

Data sourcesWe searched Medline, Embase, PsychInfo, Publons, Scopus and the Public Health England behavioural science LitRep database from inception to 17th September 2021 for relevant studies.

Study selectionWe included studies which collected observational data of at least one of three health protective behaviours (hand hygiene, face covering use and maintaining physical distance from others ( social distancing)) during the COVID-19 pandemic. Studies where observational data were compared to self-report data in relation to any infectious disease were also included.

Data extraction and synthesisWe evaluated the quality of studies using the NIH quality assessment scale for observational studies, extracted data on sample size, setting and adherence to health protective behaviours, and synthesized results narratively.

ResultsOf 27,279 published papers on COVID-19 relevant health protective behaviours that included one or more terms relating to hand hygiene, face covering and social distancing, we identified 48 studies that included an objective observational measure. Of these, 35 assessed face covering use, 17 assessed hand hygiene behaviour and seven assessed physical distancing. The general quality of these studies was good. When expanding the search to all infectious diseases, we included 21 studies that compared observational versus self-report data. These almost exclusively studied hand hygiene. The difference in outcomes was striking, with self-report over-estimating observed adherence by up to a factor of five in some settings. In only four papers did self-report match observational data in any domains.

ConclusionsDespite their importance in controlling the pandemic, we found remarkably few studies assessing protective behaviours by observation, rather than self-report, though these studies tended to be of reasonably good quality. Observed adherence tends to be substantially lower than estimates obtained via self-report. Accurate assessment of levels of personal protective behaviour, and evaluation of interventions to increase this, would benefit from the use of observational methods.


title: Seroconversion rate after primary vaccination with two doses of BNT162b2 versus mRNA-1273 in solid organ transplant recipients: a systematic review and meta-analysis

abstract: In the general population, the seroconversion rate after primary vaccination with two doses of anti-SARS-CoV-2 mRNA vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here, we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients. A systematic literature research was performed in Pubmed, Web of Science, and the Cochrane library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated. Six studies that described the development of antibodies against receptor-binding domain (RBD) and/or S1 subunit of the spike protein were eligible for meta-analysis. Two of them also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 (45.2%; 95% confidence interval (CI) 32.5%-58.3%) than patients vaccinated with two doses of mRNA-1273 (60.4%; 95% CI 47.4%-72.7%. The relative seroconversion rate amounted 0.79 (95% CI 0.71-0.88). This systematic review and meta-analysis indicates that, in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared to BNT162b2.


title: Prevalence of HIV and Syphilis and their Co-infection among Men Having Sex with Men in Asia: A Systematic Review and Meta-analysis

abstract:
BackgroundStudies found that the group of men who have sex with men (MSM) is at a very high level of risk of HIV and sexually transmitted infections (STIs) in Asian regions due to multiple reasons. Although the prevalence of HIV among general people in Asia is considered low, the prevalence of HIV and Syphilis among MSM in this region was found very high and usually, it goes unnoticed. This study aimed to inspect the prevalence and trends of HIV, Syphilis, and their co-infection among MSM in Asia.

MethodsA systematic search was performed on January 5, 2021, in PubMed, MEDLINE, and Google Scholar databases. To evaluate the heterogeneity, Q-tests and were used. To explore the publication bias, Eggers test and funnel plot were used. The random-effect model and subgroup analysis were performed due to the significant heterogeneity.

ResultsA total of 2,872 articles were identified, and 66 articles of high quality were included in the final analysis. The overall prevalence of HIV among MSM and Syphilis was estimated considering 69 estimates from 66 studies whereas 19 estimates of co-infection were found in 17 studies. The pooled HIV prevalence was 8.48% (CI: 7.01-9.95) and the pooled Syphilis prevalence was 9.86% (CI: 8.30-11.41) with significant heterogeneity and publication bias. The pooled prevalence of HIV and Syphilis co-infection was 2.99% (CI: 1.70-4.27) with significant heterogeneity and no publication bias. The HIV, Syphilis, and HIV and Syphilis co-infection prevalence estimates exhibited an upward trend during 2002-2017.

ConclusionsHIV, Syphilis, and their co-infection are quite prevalent among MSM in the Asia-Pacific region. Integrated and intensified intervention strategies, HIV testing, and improved access to antiretroviral treatment as well as increased awareness are needed to reduce HIV, Syphilis, and their co-infection among the discussed vulnerable group.

category: hiv aids


title: Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

abstract: Vaccination against SARS-CoV-2 results in protection from acquisition of infection as well as improved clinical outcomes even if infection occurs, likely reflecting a combination of residual vaccine-elicited immunity and the recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and T cell immunity after vaccination of seropositive individuals, and after breakthrough infection in vaccinated individuals. Intensive and early longitudinal sampling reveals the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titres. In breakthrough infections, the delayed kinetics of humoral immune recall provides a mechanism for the lack of early control of viral replication but likely underpins accelerated viral clearance and the protective effects of vaccination against severe COVID-19.


title: Surveillance and correlation of SARS-CoV-2 viral RNA, antigen, virus isolation, and self-reported symptoms in a longitudinal study with daily sampling

abstract: The novel coronavirus pandemic incited unprecedented demand for assays that detect viral nucleic acids, viral proteins, and corresponding antibodies. The 320 molecular diagnostics in receipt of FDA emergency use authorization mainly focus on viral detection; however, no currently approved test can be used to infer infectiousness, i.e., the presence of replicable virus. As the number of tests conducted increased, persistent SARS-CoV-2 RNA positivity by RT-PCR in some individuals led to concerns over quarantine guidelines. To this end, we attempted to design an assay that reduces the frequency of positive test results from individuals who do not shed culturable virus. We describe multiplex quantitative RT-PCR (qRT-PCR) assays that detect genomic RNA (gRNA) and subgenomic RNA (sgRNA) species of SARS-CoV-2, including spike (S), nucleocapsid (N), membrane (M), envelope (E), and ORF8. The absolute copy number of each RNA target was determined in longitudinal specimens from a household transmission study. Calculated viral RNA levels over the 14-day follow up period were compared with antigen testing and self-reported symptoms to characterize the clinical and molecular dynamics of infection and infer predictive values of these qRT-PCR assays relative to culture isolation. When detection of sgS RNA was added to the CDC 2019-Novel Coronavirus Real-Time RT-PCR Diagnostic Panel, we found a qRT-PCR positive result was 98% predictive of a positive culture (negative predictive value was 94%). Our findings suggest sgRNA presence correlates with active infection, may help identify individuals shedding culturable virus, and that similar multiplex assays can be adapted to current and future variants.


title: Omicron outbreak at a private gathering in the Faroe Islands, infecting 21 of 33 triple-vaccinated healthcare workers

abstract: There are concerns that the SARS-CoV-2 Omicron variant evades immune responses due to unusually high numbers of mutations on the spike protein. Here we report a super-spreading event of Omicron infections amongst triple-vaccinated healthcare workers, infecting 21 of 33 attending a private gathering in the Faroe Islands.


title: SARS-CoV-2 Antigen Tests Predict Infectivity Based on Viral Culture: Comparison of Antigen, PCR Viral Load, and Viral Culture Testing on a Large Sample Cohort

abstract: The relationship of SARS-CoV-2 antigen testing results, viral load, and viral culture detection remains to be fully defined. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals, and thereby inform how and where to most appropriately deploy available diagnostic testing modalities. We therefore determined the relationship of antigen testing results from three lateral flow and one microfluidics assay to viral culture performed in parallel in 181 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. We found that antigen tests were predictive of viral culture positivity, with the LumiraDx method showing enhanced sensitivity (90%; 95% confidence interval (95% CI) 83-94%) compared with the BD Veritor (74%, 95% CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver-operator characteristic curves (ROCs) of 0.94-0.97 and 0.92, respectively. In particular, a viral load threshold of 100,000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Taken together, the detection of SARS-CoV-2 antigen identified highly infectious individuals, some of whom may harbor 10,000-fold more virus in their samples than those with any detectable infectious virus. As such, our data support use of antigen testing in defining infectivity status at the time of sampling.


title: Breakthrough Infections with SARS-CoV-2 in Vaccinated Students After a Festive Event - Identification of Risk Factors

abstract:
We report an outbreak with SARS-CoV-2 breakthrough infections related to a festive event in Northern Bavaria, Germany in October 2021, with 24 of 95 participants infected. Correlation analyses among 15 interrogated variables revealed that duration at the event and conversation with the supposed index person were significant risk factors.

Article Summary LineThe risk of infection with SARS-CoV-2 in a vaccinated cohort associated with a private festive event was significantly increased upon conversation with the putative index person and positively correlated to the duration of stay at the event.


title: Altered Intercellular Communication and Extracellular Matrix Signaling as a Potential Disease Mechanism in Human Hypertrophic Cardiomyopathy

abstract:
ObjectivesTo understand Hypertrophic Cardiomyopathy-associated alterations in gene expression and intercellular communication at the single cell level in left ventricular outflow tract lesions.

BackgroundHuman hypertrophic cardiomyopathy (HCM) is considered a disorder of the sarcomere (i.e., cardiomyocytes) but the paradoxical association of nonmyocyte phenotypes such as fibrosis, mitral valve anomalies and microvascular occlusion is unexplained.

MethodsTo understand the interplay between cardiomyocyte and nonmyocyte cell types in human HCM, single nuclei RNA-sequencing (snRNA-seq) was performed on myectomy specimens from HCM patients with left ventricular outflow tract obstruction and control samples from donor hearts free of cardiovascular disease.

ResultsClustering analysis identified a total of 34 distinct cell populations, which were classified into 10 different cell types based on marker gene expression. Differential gene expression analysis comparing HCM to Normal datasets revealed differences in sarcomere and extracellular matrix gene expression. Analysis of expressed ligand-receptor pairs across multiple cell types indicated profound disruption in HCM intercellular communication, particularly between cardiomyocytes and fibroblasts, fibroblasts and lymphocytes and involving integrin {beta}1 and its multiple extracellular matrix (ECM) cognate ligands.

ConclusionsThese findings provide evidence for intercellular interactions in HCM that link sarcomere dysfunction with altered cardiomyocyte secretion of ECM ligands, altered fibroblast ligand-receptor interactions with a variety of cell types and increased fibroblast to lymphocyte signaling, which can further alter the ECM composition, disrupt cellular function and promote nonmyocyte phenotypes.


title: Comparative effectiveness of ChAdOx1 versus BNT162b2 vaccines against SARS-CoV-2 infections in England and Wales: A cohort analysis using trial emulation in the Virus Watch community data

abstract:
IntroductionInfections of SARS-CoV-2 in vaccinated individuals have been increasing globally. Understanding the associations between vaccine type and a post-vaccination infection could help prevent further COVID-19 waves. In this paper, we use trial emulation to understand the impact of a phased introduction of the vaccine in the UK driven by vulnerability and exposure status. We estimate the comparative effectiveness of COVID-19 vaccines (ChAdOx1 versus BNT162b2) against post-vaccination infections of SARS-CoV-2 in a community setting in England and Wales.

MethodTrial emulation was conducted by pooling results from six cohorts whose recruitment was staggered between 1st January 2021 and 31st March 2021 and followed until 12th November 2021. Eligibility for each trial was based upon age (18+ at the time of vaccination), without prior signs of infection or an infection within the first 14 days of the first dose. Time from vaccination of ChAdOx1 or BNT162b2 until SARS-CoV-2 infection (positive polymerase chain reaction or lateral flow test after 14 of the vaccination) was modelled using Cox proportional hazards model for each cohort and adjusted for age at vaccination, gender, minority ethnic status, clinically vulnerable status and index of multiple deprivation quintile. For those without SARS-CoV-2 infection during the study period, follow-up was until loss-of-follow-up or end of study (12th November 2021). Pooled hazard ratios were generated using random-effects meta-analysis.

ResultsAcross six cohorts, there were a total of 21,283 participants who were eligible and vaccinated with either ChAdOx1 (n = 13,813) or BNT162b2 (n = 7,470) with a median follow-up time of 266 days (IQR: 235 - 282). By November 12th 2021, 750 (5.4%) adults who had ChAdOx1 as their vaccine experienced a SARS-CoV-2 infection, compared to 296 (4.0%) who had BNT162b2. We found that people who received ChAdOx1 vaccinations had 10.54 per 1000 people higher cumulative incidence for SARS-CoV-2 infection compared to BNT162b2 for infections during a maximum of 315 days of follow-up. When adjusted for age at vaccination, sex, minority ethnic status, index of multiple deprivation, and clinical vulnerability status, we found a pooled adjusted hazard ratio of 1.35 [HR: 1.35, 95%CI: 1.15 - 1.58], demonstrating a 35% increase in SARS-CoV-2 infections in people who received ChAdOx1 compared to BNT162b2.

DiscussionWe found evidence of greater effectiveness of receiving BNT162b2 compared to ChAdOx1 vaccines against SARS-CoV-2 infection in England and Wales during a time period when Delta became the most prevalent variant of concern. Our findings demonstrate the importance of booster (third) doses to maintain protection and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.


title: Increased Long-Term Mortality in Patients Admitted to the Intensive Care Unit with Health-Care Associated Pneumonia

abstract:
BackgroundPneumonia is a leading cause of death in the United States. Guidelines for its diagnosis and management are periodically updated, but long-term mortality in critically ill patients has not been well studied.

ObjectiveTo determine differences in one-year mortality between patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia or hospital-acquired pneumonia (HCAP/HAP).

MethodsA retrospective multivariate analysis of a prospective cohort study that included all patients admitted to a single-center medical intensive care unit (ICU) from October 1, 2007, through September 30, 2008, with a diagnosis of pneumonia.

ResultsThere were 181 patients admitted to the medical ICU with a diagnosis of pneumonia, 58.0% with HCAP/HAP and 42.0% with CAP. Those with HCAP/HAP had an older age distribution and higher proportions of cardiovascular (79.1% vs. 63.2%, P=0.02) and neurological (36.2% vs. 18.4%, P=0.01) comorbidities. The HCAP/HAP patients demonstrated an increased risk of death within one a year in the unadjusted analysis (HR 1.6, 95% CI 1.1-2.2, P=0.01) that did not remain significant in the multivariate analysis (HR 1.3, 95% CI 0.80-2.10. P=0.29) when adjusting for simplified acute physiology score (SAPS) II score, age category, source of admission and a history of diabetes mellitus, neurological disease or malignancy.

ConclusionCompared to patients admitted to a medical ICU with CAP, those with HCAP/HAP had a higher one-year mortality that is accounted for by the increased co-morbidities associated with a HCAP/HAP diagnosis.

Summary of Key PointsO_LIThe American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) developed and periodically update guidelines for the diagnosis and management of community-acquired and nosocomial pneumonia based on the patient-care setting in which pneumonia evolved. ATS/IDSA provides guidelines for empiric antibiotic choices based on the category of pneumonia that is diagnosed.
C_LIO_LIPneumonia is a significant cause of mortality in the United States and when combined with influenza ranks as the eighth leading cause of death nationwide yet little is known about the mortality of critically ill patients with pneumonia that require admission to a medical intensive care unit (ICU).
C_LIO_LIOur findings suggest that older age, higher severity of illness at ICU admission, and chronic comorbid illnesses are the main contributors to long-term mortality from pneumonia requiring ICU admission.
C_LIO_LIIn this cohort, we found an independent association between increased mortality and admission from the general hospital ward rather than directly from the emergency department.
C_LIO_LIOur study did not demonstrate that initial guideline-based antibiotic therapy was associated with a reduction in short-term mortality; however, it did demonstrate a high prevalence of resistant pathogens in HCAP/HAP patients, which reflects ATS/IDSA guideline expectations.
C_LI

category: respiratory medicine


title: Neutralization of SARS-CoV-2 Omicron pseudovirus by BNT162b2 vaccine-elicited human sera

abstract: A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage, B.1.1.529, was recently detected in Botswana and South Africa and is now circulating globally. Just two days after it was first reported to the World Health Organization (WHO), this strain was classified as a variant of concern (VOC) and named Omicron. Omicron has an unusually large number of mutations, including up to 39 amino acid modifications in the spike (S) protein, raising concerns that its recognition by neutralizing antibodies from convalescent and vaccinated individuals may be severely compromised. In this study, we tested pseudoviruses carrying the SARS-CoV-2 spike glycoproteins of either the Wuhan reference strain, the Beta, the Delta or the Omicron variants of concern with sera of 51 participants that received two doses or a third dose ([≥]6 months after dose 2) of the mRNA-based COVID-19 vaccine BNT162b2. Immune sera from individuals who received two doses of BNT162b2 had more than 22-fold reduced neutralizing titers against the Omicron as compared to the Wuhan pseudovirus. One month after a third dose of BNT162b2, the neutralization titer against Omicron was increased 23-fold compared to two doses and antibody titers were similar to those observed against the Wuhan pseudovirus after two doses of BNT162b2. These data suggest that a third dose of BNT162b2 may protect against Omicron-mediated COVID-19, but further analyses of longer-term antibody persistence and real-world effectiveness data are needed.


title: Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breastfeeding

abstract: Although there have been many studies on antibody responses to SARS-CoV-2 in breastmilk, very few have looked at the fate of these in the baby. We carried out a study in 22 mother/baby pairs (mothers who breastfed and who were SARS-CoV-2 vaccinated before or after delivery) looking at mother blood, mother milk, baby blood, baby nose, and baby stool. Breastfed infants only acquired systemic anti-SARS-CoV-2 IgG antibodies if their mothers were vaccinated antepartum. None of the infants had SARS-CoV-2-specific IgA in the blood, but surprisingly, half of the infants in the Antepartum group had high titer SARS-CoV-2-specific IgA in the nose that exceeded titers found in breastmilk. Vaccination antepartum followed by breastfeeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants.


title: SARS-CoV-2 detection in multi-sample pools in a real pandemic scenario: a screening strategy of choice for active surveillance

abstract:
BackgroundThe current COVID-19 pandemic has overloaded the diagnostic capacity of laboratories by the gold standard method rRT-PCR. This disease has a high spread rate and almost a quarter of infected individuals never develop symptoms. In this scenario, active surveillance is crucial to stop the virus propagation.

MethodsBetween July 2020 and April 2021, 11580 oropharyngeal swab samples collected in closed and semi-closed institutions were processed for SARS-CoV-2 detection in pools, implementing this strategy for the first time in Cordoba, Argentina. Five-sample pools were constituted before nucleic acid extraction and amplification by rRT-PCR. Comparative analysis of cycle threshold (Ct) values from positive pools and individual samples along with a cost-benefit report of the whole performance of the results was performed.

ResultsFrom 2314 5-sample pools tested, 158 were classified as positive (6.8%), 2024 as negative (87.5%), and 132 were categorized as indeterminate (5.7%). The Ct value shift due to sample dilution showed an increase in Ct of 2.6{+/-}1.53 cycles for N gene and 2.6{+/-}1.78 for ORF1ab gene. Overall, 290 pools were disassembled and 1450 swabs were analyzed individually. This strategy allowed correctly identifying 99.8% of the samples as positive (7.6%) or negative (92.2%), avoiding the execution of 7,806 rRT-PCR reactions which represents a cost saving of 67.5%.

ConclusionThis study demonstrates the feasibility of pooling samples to increase the number of tests performed, helping to maximize molecular diagnostic resources and reducing the work overload of specialized personnel during active surveillance of the COVID-19 pandemic.


title: TROPONIN IS INDEPENDENTLY ASSOCIATED WITH DEATH IN PATIENTS WITH COVID: A RETROSPECTIVE STUDY

abstract:
ObjectiveWe performed a single-centre retrospective observational study investigating the association between troponin positivity in patients hospitalised with COVID-19 and increased mortality in the short term.

MethodsAll adults admitted with swab-proven RT-PCR COVID-19 to Homerton University Hospital (HUH) from 04.02.20 to 30.04.20 were eligible for inclusion.

We retrospectively analysed demographic and biochemical data collected from the physical and electronic patient records according to the primary outcome of death at 28 days during hospital admission.

Troponin positivity was defined above the upper limit of normal according to our local laboratory assay (>15.5ng/l for females, >34 ng/l for males). Univariate and multivariate logistical regression analyses were performed to evaluate the link between troponin positivity and death.

ResultsMean length of stay for all 402 hospitalised COVID-19 patients at HUH was 9.1 days (SD 12.0). Mean age was 65.3 years for men compared to 63.8 years for women. A chi-squared test showed that survival of COVID-19 patients was significantly higher in those with a negative troponin (p = 3.23 x10-10) compared to those with a positive troponin. In the multivariate logistical regression, lung disease, age, troponin positivity and CPAP were all significantly associated with death, with an AUC of 0.8872, sensitivity of 0.9004 and specificity of 0.6292 for the model. Within this model, troponin positivity was independently associated with short term mortality (OR 3.23, 95% CI 1.53-7.16, p=0.00278).

ConclusionsWe demonstrated an independent association between troponin positivity and increased short-term mortality in COVID-19 in a London district general hospital.

Key QuestionsO_ST_ABSWhat is already known about this subject?C_ST_ABSAn elevated Troponin is associated with increased mortality. Troponin is known to be elevated in some patients who test positive for COVID-19 infection.

What does this study add?This study shows an association between an elevated troponin in hospitalised COVID-19 patients and increased short-term mortality.

How might this impact on clinical practice?Troponin is a readily available, easy to measure biomarker which can be used to predict the severity of COVID-19 illness and could aid prognostication in hospital.


title: Covid Vaccines for Children with Developmental Disabilities: Parent Survey of Willingness and Concerns

abstract:
ObjectiveWhile 1-in-6 US children has a developmental disability (DD), and such children are disproportionately affected by COVID-19, little is known about their vaccination status. We surveyed US parents of children with DDs to ascertain willingness and concerns regarding COVID-19 vaccines.

MethodsAn online survey was distributed to national, statewide, and regional DD networks from June-September 2021. (Vaccines were authorized for adolescents in May 2021.) We report associations between vaccine willingness and concerns and: race/ethnicity, child age, in-person schooling, routine/flu vaccinations, and DD diagnoses. Willingness was categorized as Got /Will Get ASAP (high), Wait and See/Only if Required, or Definitely Not.

Results393 parents (51.2% white) responded. Willingness differed by age (p<.001). High willingness was reported for 75.3%, 48.9%, and 38.1% of children aged 12-17, 6-11 and 0-5 years-old, respectively. Willingness differed by Autism diagnosis (p<.001) and routine and flu vaccination status (p<.01). Predominant concerns included side effects (89%) and children with disabilities not being in trials (79%). Less common concerns were: COVID not serious enough in children to warrant vaccine (22%) and misinformation (e.g., microchips, 5G, DNA changes) (24%). Concerns about vaccine safety differed by age (p<.05) and were highest for young children. In age-stratified adjusted models, Autism was positively associated with high willingness for 6-11year-olds (OR= 2.66, 95% CI= 1.12-6.35).

ConclusionParents of children with DD are more willing for them to receive COVID-19 vaccines, compared to the general population. While few factors predicted willingness to vaccinate, addressing safety and developmental concerns regarding young children is warranted.

category: pediatrics