title: COVID-Nets: Deep CNN Architectures for Detecting COVID-19 Using Chest CT Scans

abstract: This paper introduces two novel deep convolutional neural network (CNN) architectures for automated detection of COVID-19. The first model, CovidResNet, is inspired by the deep residual network (ResNet) architecture. The second model, CovidDenseNet, exploits the power of densely connected convolutional networks (DenseNet). The proposed networks are designed to provide fast and accurate diagnosis of COVID-19 using computed tomography (CT) images for the multi-class and binary classification tasks. The architectures are utilized in a first experimental study on the SARS-CoV-2 CT-scan dataset, which contains 4173 CT images for 210 subjects structured in a subject-wise manner for three different classes. First, we train and test the networks to differentiate COVID-19, non-COVID-19 viral infections, and healthy. Second, we train and test the networks on binary classification with three different scenarios: COVID-19 vs. healthy, COVID-19 vs. other non-COVID-19 viral pneumonia, and non-COVID-19 viral pneumonia vs. healthy. Our proposed models achieve up to 93.96% accuracy, 99.13% precision, 94% sensitivity, 97.73% specificity, and a 95.80% F1-score for binary classification, and up to 83.89% accuracy, 80.36% precision, 82% sensitivity, 92% specificity, and a 81% F1-score for the three-class classification tasks. The experimental results reveal the validity and effectiveness of the proposed networks in automated COVID-19 detection. The proposed models also outperform the baseline ResNet and DenseNet architectures while being more efficient.

category: radiology and imaging


title: Developing and comparing machine learning models to detect sleep apnoea using single-lead electrocardiogram (ECG) monitoring

abstract:
BackgroundSleep apnoea has a high disease burden but remains underdiagnosed, in part due to the expensive and resource intensive nature of polysomnography, its definitive investigation. Emerging literature suggests that it may be possible to detect sleep apnoea using single-lead ECG signals, such as those obtained from smartwatches. In this study, we use two forms of recurrent neural networks (RNNs) to detect sleep apnoea events from single-lead ECG signals.

MethodsWe use single-lead ECG data from the PhysioNet Apnea-ECG database, which contains data from 70 patients. We train a bidirectional gated recurrent unit (GRU) model and a bidirectional long short-term memory (LSTM) model on labelled ECG signals from 35 patients and test the models on the remaining 35 patients in the dataset.

ResultsBoth models achieved 97.1% accuracy, sensitivity and specificity to detect whether the ECG recordings belonged to a patient diagnosed with sleep apnoea. This corresponds to 34/35 patients in the dataset. At detecting individual apnoea events, the GRU and LSTM models achieved 90.4% and 91.7% accuracies respectively.

DiscussionThe models achieved high levels of accuracy, specificity and sensitivity. Bidirectional RNNs are strengthened by the ability of the models to be informed by both past and future states when analysing sequential data, such as ECGs. The models also require minimal human intervention as they automatically extract features from the data. If single-lead ECGs prove a suitable tool for sleep apnoea detection, this may enhance the diagnosis of sleep apnoea and potentially allow widespread screening for the condition.

ConclusionsWe note that using models such as bidirectional RNNs has the potential to augment model performance. However, more research and validation is required in order to test whether these may be applicable to other datasets and in clinical practice.

category: respiratory medicine


title: Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

abstract:
The pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative brain network aberrations and levels of serum neurofilament light chain (sNfL) as a neuroaxonal injury biomarker.

Multiple sclerosis patients (n = 328, mean age 42.9 years, 71 % female) were prospectively enrolled at four European multiple sclerosis centres, and reassessed after two years (n = 280). Post-processing of 3 Tesla (3T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patients white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient and centre as a random factor, sNfL, age, sex, timepoint for visit, diagnosis, and treatment as fixed factors were run.

Robust LMM revealed significant associations between higher levels of GD and increased sNfL (t = 2.30, {beta} = 0.03, p = 0.02), age (t = 5.01, {beta} = 0.32, p < 5.5 x 10-7), and diagnosis progressive multiple sclerosis (PMS); t = 1.97, {beta} = 1.06, p = 0.05), but not for sex (t = 0.78, p = 0.43), treatments (effective; t = 0.85, p = 0.39, highly-effective; t = 0.86, p = 0.39) or sNfL change between base line and two-year follow up (t = -1.65, p = 0.10). Voxel-wise analyses revealed distributed associations in cerebellar and brainstem regions.

In our prospective multi-site multiple sclerosis cohort, rLMMs demonstrated that the extent of global brain disconnectivity is sensitive to a systemic biomarker of axonal damage, sNfL, in patients with multiple sclerosis. These findings provide a neuropathological correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and clinical relevance in patients with brain disorders.

category: neurology


title: The correlation between fetal frontal lobe development parameters and gestational week: A preliminary study

abstract:
ObjectiveTo establish a reference range of developmental parameters related to the frontal lobe of normal fetuses in different gestational weeks, which can provide a basis for the evaluation of normal development of the frontal lobe and the diagnosis of suspected fetal microcephaly.

MethodsA prospective cross-sectional study was performed on 751 normal fetuses between 21 and 36 weeks, and the anterior-posterior diameter and transverse diameter of the frontal lobe were measured in transcerebellar plane. Linear regression analysis was performed by grouping different gestational weeks.

ResultsFetal anterior-posterior diameter and transverse diameter of the frontal lobe were positively correlated with gestational week with correlation coefficients 0.871 and 0.971 respectively. There was a linear relationship between gestational weeks and frontal lobe parameters, and the equations were simplified to obtain the simple correlation formula: fetal frontal lobe anterior-posterior diameter(mm)=14.5+0.7x(gestational week-21), frontal lobe transverse diameter (mm)=41+2.5x(gestational week-21).

ConclusionThe reference ranges of the frontal lobe anterior-posterior diameter and the frontal lobe transverse diameter of normal fetuses between 21 to 36 weeks in transcerebellar plane were established, which can provide valuable information for the evaluation of normal development of the frontal lobe and the diagnosis of suspicious fetal microcephaly.

Whats already known about this topic?We currently lack a golden standard to diagnosis microcephaly and fetal frontal lobe dysplasia is a clue for prenatal diagnosis of microcephaly.

What does this study add?This study presents a novel evaluation of the fetal frontal lobe to better assess brain development in the transcerebellar plane.

The fetal frontal lobe developmental diameters will be useful to aid diagnosis of suspicious microcephaly and other cortical developmental disorders.

category: obstetrics and gynecology


title: A study of the clearness rate of fetal Sylvian fissure shown on different sections by prenatal ultrasound

abstract:
ObjectiveTo compare the clearness rate of fetal Sylvian fissure revealed by prenatal ultrasonography on trans-cerebellar section and trans-thalamic section, and to provide scientific basis for selecting the best section of prenatal ultrasound to evaluate the developmental parameters related to fetal Sylvian fissure.

MethodsThis was a retrospective study. We analyzed all the fetal images on trans-cerebellar section and trans-thalamic section stored in the imaging system who were undergoing grade III prenatal ultrasound examination in our hospital from January 2017 to December 2018. The gestational age was divided into three groups which were 21 to 24 weeks, 25 to 28 weeks and 29 to 32 weeks respectively. The evaluation criteria for the clear appearance of the Sylvian fissure were complete morphology of the Sylvian fissure and clear apical and anteriorly edges of the Sylvian fissure. The results of showing Sylvian fissure clearly were divided into four groups: only on trans-cerebellar section shown clear, only on trans-thalamic section shown clear, both on trans-cerebellar section and trans-thalamic section shown clear, and both on trans-cerebellar section and trans-thalamic section not shown clear. The clearness rate of each group and the total clearness rate of each section were analyzed statistically.

ResultsThe clearness rates of showing Sylvian fissure only on trans-cerebellar section were 62.3% at 21 to 24 weeks, 70.1% at 25 to 28 weeks and 63.6% at 29 to 32 weeks. The clearness rates of showing Sylvian fissure only on trans-thalamic section were 11.1% at 21 [~] 24 weeks, 10.5% at 25 [~] 28 weeks and 9.1% at 29 [~] 32 weeks. The clearness rates of showing Sylvian fissure both on trans-cerebellar and trans-thalamic sections were 22.1% at 21 to 24 weeks, 15.0% at 25 to 28 weeks and 13.0% at 29 to 32 weeks. The unclearness rates of showing Sylvian fissure both on trans-cerebellar and trans-thalamic sections were 4.5%at 21 [~] 24 weeks, 4.4% at 25 [~] 28 weeks and 14.3% at 29 [~] 32 weeks. The clearness rate of showing Sylvian fissure on trans-cerebellar section was significantly higher than on trans-thalamic section (P < 0.05). The total clearness rate of showing Sylvian fissure on trans-cerebellar section and trans-thalamic section were 83.1% and 28.3% respectively.

ConclusionIn this study, it was suggested that prenatal ultrasound selection of trans-cerebellar section is better than trans-thalamic section in evaluating the developmental parameters related to the Sylvian fissure.


title: A new Far-UVC based method for germ free hospitals and travel: Initus-V

abstract: Direct contact and airborne spread are main mechanisms of transmission for SARS-CoV-2, and virus can stay viable for at least 3 hours in aerosols. Initus-V system uses a Far-ultraviolet C (UVC) system, UVC resistant textile and googles to provide virus, bacteria and spore free environments in hospitals, crowded public places and travel environments. Initus-V system may help in prevention of epidemic diseases such as Coronavirus disease-19 (Covid-19), influenza, treatment of airborne viral diseases and spread of hospital-borne resistant infections.

category: occupational and environmental health


title: A novel artificial lung organoid for simulating a patient derived adenocarcinoma of lung for personalized oncology.

abstract:
Optimizing patient care based on precision oncology will inevitably become the standard of care. If we accept the principle that every persons cancer is different then the most effective therapies will have to be designed for the individual patient and for their tumors genetic profile. Access to tumor mutational profiling is now widely available but continues to be limited by cost and actionable information. For example, novel combinations of approved drugs are rarely considered. These considerations lead us to hypothesize that artificially induced Lung Adenocarcinoma (LUAD) derived lung organoids could provide a novel, alternate approach for LUAD disease modeling and large-scale targeted drug screening.

In this project, we used data from a commercially available tumor mutation profile to generate and then validate the artificially induced LUAD-derived lung organoid simulations (aiLUNG-LUAD) to model LUAD and identify several drug combinations that effectively reverse the tumors genotypic and phenotypic features when compared with placebo. These results complement previous LUAD-derived lung organoids research and provide a novel and widely applicable cancer drug-screening approach for precision/individualized oncology.

category: oncology


title: Use of Ketamine Infusions for Treatment of Complex Regional Pain Syndrome: A Systematic Review

abstract:
BackgroundThis systematic review aims to review clinical studies on the use of ketamine infusion for patients with treatment-resistant Complex Regional Pain Syndrome (CRPS).

MethodsThe following systematic review was registered on PROSPERO (CRD42021228470). Studies for the systematic review were identified through 3 databases; PubMed, CINAHL, and Cochrane Review. Inclusion criteria for studies consisted of randomized clinical trials or cohort studies that conducted trials on the use of ketamine infusion for pain relief in patients with Complex Regional Pain Syndrome (CRPS). Exclusion criteria for studies included any studies that were systematic review, meta-analyses, case reports, literature reviews, or animal studies. In the included studies, the primary outcome of interest was post drug administration pain score.

ResultsIn this systematic review, 14 studies met the inclusion criteria and were reviewed. In these studies, the dosage of ketamine infusion used ranged from 0.15 mg/kg to 7mg/kg with primary indication being treatment of Complex Regional Pain Syndrome (CRPS). In 13 of the studies, ketamine infusion resulted in a decrease in pain scores and relief of symptoms.

ConclusionsPatients who received Ketamine infusion for treatment-resistant CRPS self-reported adequate pain relief with treatment. This suggests that ketamine infusion may be a useful form of treatment for patients with no significant pain relief with other conservative measures. Future large-scale studies, including randomized double-blind placebo-controlled trials on the use of ketamine infusion for CRPS must be conducted in a large-scale population to further assess the effectiveness of ketamine infusion in these populations.

category: pain medicine


title: Informing patterns of health and social care utilisation in Irish older people according to the Clinical Frailty Scale

abstract:
There is increasing policy interest in the consideration of frailty measures (rather than chronological age alone) to inform a more equitable allocation of health and social care resources in the community. The Clinical Frailty Scale (CFS) has attracted interest for its simplicity and consideration of multiple relevant geriatric dimensions. However, a criticism of the CFS has been the possible subjectivity in the scoring, bringing the possible danger of lack of scoring consistency across agencies. For that reason, the authors of the CFS published a classification tree method to assist with routine scoring of the CFS.

The aim of the present study was to apply the CFS classification tree to data from adults aged 65 and over from The Irish Longitudinal Study on Ageing (TILDA) and correlate derived CFS categories with patterns of health and social care utilisation in Irish older people assessed in Wave 5 of the study (year 2018). In addition, we explored how CFS categories and states changed over 8 years in TILDA between Wave 1 (2010) and Wave 5.

Results showed the following prevalence of CFS categories in Wave 5: 6%  very fit (CFS1), 36%  fit (CFS2), 31%  managing well (CFS3), 16%  vulnerable (CFS4), 6%  mildly frail (CFS5), 4%  moderately frail (CFS6) and 1%  severely frail (CFS7). No participants were  very severely frail or  terminally ill. In wave 5, increasing CFS categories had an association with increasing utilisation of hospital and community health services, and increasing hours of formal and informal social care provision. The transitions analyses from Wave 1 to 5 suggested a dynamic picture of CFS transitions, with 2-year probability of transitioning from  fit (CFS1-3) to  vulnerable (CFS4), and  fit to  frail (CFS5+) at 34% and 6%, respectively.  Vulnerable and  frail had a 22% and 17% probability of reversal to  fit and  vulnerable, respectively.

Our results suggest that the CFS classification tree was able to stratify the TILDA population aged 65 and over into subgroups with increasing health and social care needs. The CFS classification tree could be used to aid the allocation of health and social care resources in older people in Ireland, but given the frequency of CFS transitions in the population, it is recommended that CFS status in individuals is reviewed at least every 2 years.

category: geriatric medicine


title: A Generalizable Data Assembly Algorithm for Infectious Disease Outbreaks

abstract:
Background & ObjectiveDuring infectious disease outbreaks, health agencies often share text-based information about cases and deaths. This information is usually text-based and rarely machine-readable, thus creating challenges for outbreak researchers. Here, we introduce a generalizable data assembly algorithm that automatically curates text-based, outbreak-related information and demonstrate its performance across three outbreaks.

MethodsAfter developing an algorithm with regular expressions, we automatically curated data from health agencies via three information sources: formal reports, email newsletters, and Twitter. A validation data set was also curated manually for each outbreak.

FindingsWhen compared against the validation data sets, the overall cumulative missingness and misidentification of the algorithmically curated data were [≤]2% and [≤]1%, respectively, for all three outbreaks.

ConclusionsWithin the context of outbreak research, our work successfully addresses the need for generalizable tools that can transform text-based information into machine-readable data across varied information sources and infectious diseases.

category: health informatics


title: The Impact of Face Masks on Performance and Physiological Outcomes during Exercise: A Systematic Review and Meta-analysis

abstract:
Face masks are promoted for preventing spread of viruses; however, wearing a mask during exercise might increase CO2 rebreathing, decrease arterial oxygenation, and decrease exercise performance. A systematic review and meta-analysis was conducted on the impact of wearing a mask during exercise. Data sources included SPORTDiscus, PubMed, and Medline. Eligibility criteria included all study designs comparing surgical, N95, or cloth masks to a no mask condition during any type of exercise where exercise performance and/or physiological parameters were evaluated. Healthy and clinical participants were included. Mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals were calculated and pooled effects assessed. Twenty-two studies involving 1,573 participants (620 females, 953 males) were included. Surgical, or N95 masks did not impact exercise performance (SMD -0.05 [-0.16,0.07] and -0.16 [-0.54,0.22], respectively) but increased ratings of perceived exertion (RPE) (SMD 0.33 [0.09,0.58] and 0.61 [0.23,0.99]) and dyspnea (SMD 0.6 [0.3,0.9] for all masks). End-tidal CO2 (MD 3.3 [1.0, 5.6] and 3.7 [3.0,4.4] mmHg), and heart rate (MD 2 [0,4] beats/min with N95 masks) slightly increased. Face masks can be worn during exercise with no influences on performance and minimal impacts on physiological variables.

PROSPERO RegistrationCRD42020224988

Novelty PointsFace masks can be worn during exercise with no impacts on performance and minimal impacts on physiological variables.

category: health policy


title: EVIDENCE FOR BIOLOGICAL AGE ACCELERATION AND TELOMERE2 SHORTENING IN COVID-19 SURVIVORS

abstract:
Introduction & Backgroundthe SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokines release, and immunodepression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called post-COVID19 syndrome (PPCS) is a common finding. In patients who survived the SARS-CoV-2 infection, overt PPCS presents one or more symptoms such as fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. The pathophysiology of PPCS is currently poorly understood, and whether epigenetic mechanisms are involved in this process is unexplored.

Methods & ResultsIn this study, a cohort of 117 COVID19 survivors (post-COVID19) and 144 non-infected volunteers (COVID19-free) were analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. Besides, telomere length (TL) and ACE2 and DPP4 receptor expression were determined. The results show a consistent biological age increase in the post-covid population (58,44 {+/-} 14,66 ChronoAge Vs. 67,18 {+/-} 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 {+/-} 7,29 years (+5.25 years above range of normality) compared to 3,68 {+/-} 8,17 years for the COVID19-free population (P<0,0001). A significant telomere shortening parallels this finding in the post-COVID19 cohort compared to COVID19-free subjects (post-COVID19 TL: 3,03 {+/-} 2,39 Kb vs. COVID19-free: 10,67 {+/-} 11,69 Kb; P<0,0001). Additionally, ACE2 expression was decreased in post-COVID19 patients compare to COVID19-free, while DPP-4 did not change.

ConclusionIn light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID19 condition, particularly in the younger (<60 years). Although the consequences of such modifications on the long-term clinical outcome remain unclear, they might indicate a direction to investigate the pathophysiological basis of the post-COVID19 syndrome.

category: infectious diseases


title: EVIDENCE FOR BIOLOGICAL AGE ACCELERATION AND TELOMERE SHORTENING IN COVID-19 SURVIVORS


title: Mathematical modeling suggests pre-existing immunity to SARS-CoV-2

abstract: Mathematical models have largely failed to predict the unfolding of the COVID-19 pandemic. We revisit several variants of the SEIR-model and investigate various adjustments to the model in order to achieve output consistent with measured data in Manaus, India and Stockholm. In particular, Stockholm is interesting due to the almost constant NPIs, which substantially simplifies the mathematical modeling. Analyzing mobility data for Stockholm, we argue that neither behavioral changes, age and activity stratification nor NPIs alone are sufficient to explain the observed pandemic progression. We find that the most plausible hypothesis is that a large portion of the population, between 40 to 60 percent, have some protection against infection with the original variant of SARS-CoV-2.


title: Indicators for Risk of Airborne Transmission in Shared Indoor Environments and their application to COVID-19 Outbreaks

abstract:
Some infectious diseases, including COVID-19, can be transmitted via aerosols that are emitted by an infectious person and inhaled by susceptible individuals. Most airborne transmission occurs at close proximity and is effectively reduced by physical distancing, but as time indoors increases, infections occur in those sharing room air despite maintaining distancing. There have been calls for quantified models to estimate the absolute and relative contribution of these different factors to infection risk. We propose two indicators of infection risk for this situation, i.e., relative risk parameter (Hr) and risk parameter (H). They combine the key factors that control airborne disease transmission indoors: virus-containing aerosol generation rate, breathing flow rate, masking and its quality, ventilation and particulate air cleaning rates, number of occupants, and duration of exposure. COVID-19 outbreaks show a clear trend in relation to these factors that is consistent with airborne infection The observed trends of outbreak size (attack rate) vs. H (Hr) allow us to recommend values of these parameters to minimize COVID-19 indoor infection risk. Transmission in typical pre-pandemic indoor spaces is highly sensitive to mitigation efforts. Previous outbreaks of measles, flu, and tuberculosis were assessed along with recently reported COVID-19 outbreaks. Measles outbreaks occur at much lower risk parameter values than COVID-19, while tuberculosis outbreaks are observed at much higher risk parameter values. Since both diseases are accepted as airborne, the fact that COVID-19 is less contagious than measles does not rule out airborne transmission. It is important that future outbreak reports include information on the nature and type of masking, ventilation and particulate-air cleaning rates, number of occupants, and duration of exposure, to allow us to understand the circumstances conducive to airborne transmission of different diseases.

SynopsisWe propose two infection risk indicators for indoor spaces and apply them to COVID-19 outbreaks analysis and mitigation.


title: Practical Indicators for Risk of Airborne Transmission in Shared Indoor Environments and their application to COVID-19 Outbreaks


title: Practical Indicators for Risk of Airborne Transmission in Shared Indoor Environments and their Application to COVID-19 Outbreaks


title: One-Step Rapid Quantification of Serum Neutralizing Antibody after COVID-19 Vaccination by a High-Throughput Nanoplasmonic Sensor Platform

abstract: The COVID-19 vaccination efficacy depends on serum production level of the neutralizing IgG antibody (NA) specific to the receptor binding domain of SARS-Cov-2 spike protein. Therefore, a high-throughput rapid assay to measure the total SARS-CoV-2 NA level is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, vaccine development, and assessment. Here, we developed a nanoplasmonic immunosorbent assay (NanoPISA) platform for one-step rapid quantification of SARS-CoV-2 NAs in clinical serum samples for high-throughput evaluation of COVID-19 vaccine effectiveness. The NanoPISA platform enhanced by the use of nanoporous hollow gold nanoparticle coupling was able to detect SARS-CoV-2 NAs with a limit of detection of 0.1 ng/mL within 15 min. The one-step NanoPISA for SARS-CoV-2 NA detection in clinical specimens yielded good results, comparable to those obtained in the gold standard seroneutralization test and the surrogate virus neutralizing ELISA. Collectively, our findings indicate that the one-step NanoPISA may offer a rapid and high-throughput NA quantification platform for evaluating the effectiveness of COVID-19 vaccines.


title: A randomised clinical trial of azithromycin versus standard care in ambulatory COVID-19 - the ATOMIC2 trial

abstract:
BackgroundThe antibacterial, anti-inflammatory and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-moderate disease are lacking. We assessed whether azithromycin is effective in reducing hospitalisation in patients with mild-moderate COVID-19.

MethodsThis open-label, randomised superiority clinical trial at 19 centres in the United Kingdom enrolled adults, [≥]18 years, presenting to hospitals with clinically-diagnosed highly-probable or confirmed COVID-19 infection, with <14 days symptoms, considered suitable for initial ambulatory management. Patients were randomised (1:1) to azithromycin (500 mg daily orally for 14 days) or to standard care without macrolides. The primary outcome was the difference in proportion of participants with death or hospital admission from any cause over the 28 days from randomisation, assessed according to intention-to-treat (ITT). Trial registration: ClinicalTrials.gov, NCT04381962, Study closed.

Findings298 participants were enrolled from 3rd June 2020 to 29th January 2021. The primary outcome was assessed in 292 participants. The primary endpoint was not significantly different between the azithromycin and control groups (Adjusted OR 0{middle dot}91 [95% CI 0{middle dot}43-1{middle dot}92], p=0{middle dot}80). Rates of respiratory failure, progression to pneumonia, all-cause mortality, and adverse events, including serious cardiovascular events, were not significantly different between groups.

InterpretationIn patients with mild-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospitalisation or death. Our findings do not support the use of azithromycin in patients with mild-moderate COVID-19.

FundingNIHR Oxford BRC, University of Oxford and Pfizer Inc.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched MEDLINE and the Cochrane Central register of Controlled Trials (CENTRAL) with the terms ("azithromycin") AND ("COVID" OR "COVID-19") AND ("clinical trials"), until March 25, 2021, with no language restrictions. We identified 42 studies, among which there were four completed randomised trials of azithromycin (with or without hydroxychloroquine) in hospitalised patients with severe disease, and three completed randomised trials of azithromycin in mild COVID-19 in primary care. The four trials in hospitalised patients randomised 8,988 participants to azithromycin or standard care or hydroxychloroquine and found no evidence of a difference in mortality, duration of hospital stay or peak disease severity. Of the three trials in primary care, these randomised participants with early disease to 3 or 5 days of therapy, of which only one assessed azithromycin as standalone therapy. This large, adaptive platform trial in the UK randomised 540 participants in primary care to 3 days treatment with azithromycin versus 875 to standard care alone and found no meaningful difference in time to first reported recovery, or of rates of hospitalisation (3% versus 3%) and there were no deaths. We did not identify any randomised trials in patients with COVID-19 managed in ambulatory care.

Added value of this studyThe ATOMIC2 trial was uniquely-designed to assess azithromycin as a standalone therapy in those with mild-moderately COVID-19 presenting to emergency care, but assessed as appropriate for initial ambulatory management without hospital admission. ATOMIC2 also uniquely assessed high-dose, long-duration treatment to investigate the efficacy of putative anti-inflammatory effects. We found that azithromycin 500 mg daily for 14 days did not reduce the proportion of participants who died or required hospital admission from any cause over the 28 days from randomisation.

Implications of all the available evidenceOur findings, taken together with existing data, suggest there is no evidence that azithromycin reduces hospitalisation, respiratory failure or death compared with standard care, either in early disease in the community, or those hospitalised with severe disease, or in those with moderate disease managed on an ambulatory pathway.


title: A Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men

abstract:
BackgroundSeveral risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established.

MethodsA PRSCAD including the weighted effects of >1.14 million SNPs associated with CAD was calculated in UK Biobank (n=408,422), using LDPred. Cox regressions were performed, stratified by age quartiles and sex, for incident MI and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRSCAD to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI0.02) and continuous NRI (NRI>0).

ResultsFrom 7,746 incident MI cases and 393,725 controls, hazard ratio (HR) for MI reached 1.53 (95% CI [1.49-1.56], p=2.69e-296) per standard deviation (SD) increase of PRSCAD. PRSCAD was significantly associated with MI in both sexes, with a stronger association in men (interaction p=0.002), particularly in those aged between 40-51 years (HR=2.00, 95% CI [1.86-2.16], p=1.93e-72). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI0.02=0.199, 95% CI [0.157-0.248] and NRI>0=0.602, 95% CI [0.525-0.683]). From 23,982 deaths, HR for mortality was 1.08 (95% CI [1.06-1.09], p=5.46e-30) per SD increase of PRSCAD, with a stronger association in men (interaction p=1.60e-6).

ConclusionOur PRSCAD predicts MI incidence and all-cause mortality, especially in men aged between 40-51 years. PRS could optimize the identification and management of individuals at risk for CAD.

category: cardiovascular medicine


title: Evaluation of Different Types of Face Masks to Limit the Spread of SARS CoV 2, A Modeling Study

abstract:
We updated a published mathematical model of SARS-CoV-2 transmission with laboratory-derived source and wearer protection efficacy estimates for a variety of face masks to estimate their impact on COVID-19 incidence and related mortality in the United States. When used at already-observed population rates of 80% for those [≥]65 years and 60% for those <65 years, face masks are associated with 69% (cloth) to 78% (medical procedure mask) reductions in cumulative COVID-19 infections and 82% (cloth) to 87% (medical procedure mask) reductions in related deaths over a 6-month timeline in the model, assuming a basic reproductive number of 2.5. If cloth or medical procedure masks source control and wearer protection efficacies are boosted about 30% each to 84% and 60% by cloth over medical procedure masking, fitters, or braces, the COVID-19 basic reproductive number of 2.5 could be reduced to an effective reproductive number [≤] 1.0, and from 6.0 to 2.3 for a variant of concern similar to delta (B.1.617.2).

Article Summary LineAdapting a published SARS-CoV-2 transmission model together with updated, laboratory-derived source control and wearer protection efficacy estimates for a variety of face coverings as well as N95 respirators, we demonstrate that community masking as currently practiced has likely reduced cases and deaths and that this benefit can be increased with wider adoption of better performing masks.

category: epidemiology


title: Predicting daily COVID-19 case rates from SARS-CoV-2 RNA concentrations across a diversity of wastewater catchments

abstract: We assessed the relationship between municipality COVID-19 case rates and SARS-CoV-2 concentrations in the primary sludge of corresponding wastewater treatment facilities. Over 1,000 daily primary sludge samples were collected from six wastewater treatment facilities with catchments serving 18 cities and towns in the State of Connecticut, USA. Samples were analyzed for SARS-CoV-2 RNA concentrations during a six-month time period that overlapped with fall 2020 and winter 2021 COVID-19 outbreaks in each municipality. We fit a single regression model to estimate reported case rates in the six municipalities from SARS-CoV-2 RNA concentrations collected daily from corresponding wastewater treatment facilities. Results demonstrate the ability of SARS-CoV-2 RNA concentrations in primary sludge to estimate COVID-19 reported case rates across treatment facilities and wastewater catchments, with coverage probabilities ranging from 0.94 to 0.96. Leave-one-out cross validation suggests that the model can be broadly applied to wastewater catchments that range in more than one order of magnitude in population served. Estimation of case rates from wastewater data can be useful in locations with limited testing availability or testing disparities, or delays in individual COVID-19 testing programs.


title: Approximate Reciprocal Relationship Between Two Cause-Specific Hazard Ratios in COVID-19 Data With Mutually Exclusive Events

abstract: COVID-19 survival data presents a special situation where not only the time-to-event period is short, but also the two events or outcome types, death and release from hospital, are mutually exclusive, leading to two cause-specific hazard ratios (csHRd and csHRr). The eventual mortality/release outcome can also be analyzed by logistic regression to obtain odds-ratio (OR). We have the following three empirical observations concerning csHRd, csHRr and OR: (1) The magnitude of OR is an upper limit of the csHRd: | log(OR) | [≥] | log(csHRd)|. This relationship between OR and HR might be understood from the definition of the two quantities; (2) csHRd and csHRr point in opposite directions: log(csHRd){middle dot} log(csHRr) < 0; This relation is a direct consequence of the nature of the two events; and (3) there is a tendency for a reciprocal relation between csHRd and csHRr: csHRd [~] 1/csHRr. Though an approximate reciprocal trend between the two hazard ratios is in indication that the same factor causing faster death also lead to slow recovery by a similar mechanism, and vice versa, a quantitative relation between csHRd and csHRr in this context is not obvious. These resutls may help future analyses of COVID-19 data, in particular if the deceased samples are lacking.


title: Geographic clusters of objectively measured physical activity and the characteristics of their built environment in a Swiss urban area

abstract:
IntroductionEvidence suggests that the built environment can influence the intensity of physical activity. However, despite the importance of the geographic context, most of the studies do not consider the spatial framework of this association. We aimed to assess individual spatial dependence of objectively measured moderate and vigorous physical activity (MVPA) and describe the characteristics of the built environment among spatial clusters of MVPA.

MethodsCross-sectional data from the second follow-up (2014-2017) of CoLaus|PsyCoLaus, a longitudinal population-based study of the Lausanne area (Switzerland), was used to objectively measure MVPA using accelerometers. Local Morans I was used to assess the spatial dependence of MVPA and detect geographic clusters of low and high MVPA. Additionally, the characteristics of the built environment observed in the clusters based on raw MVPA and MVPA adjusted for socioeconomic and demographic factors were described.

ResultsData from 1,889 participants (median age 63, 55% women) were used. The geographic distribution of MVPA and the characteristics of the built environment among clusters were similar for raw and adjusted MVPA. In the adjusted model, we found a low concentration of individuals within spatial clusters of high MVPA (median: 36.9 mins; 3% of the studied population) and low MVPA (median: 10.1 mins; 2% of the studied population). Yet, clear differences were found in both models between clusters regarding the built environment; high MVPA clusters were located in areas where specific compositions of the built environment favor physical activity.

ConclusionsOur results suggest the built environment may influence spatial patterns of MVPA independently of socioeconomic and demographic factors. Interventions in the built environment should be considered to promote physically active behaviors in urban areas.


title: Reliability of COVID-19 data: An evaluation and reflection

abstract:
ImportanceThe rapid proliferation of COVID-19 has left governments scrambling, and several data aggregators are now assisting in the reporting of county cases and deaths. The different variables affecting reporting (e.g., time delays in reporting) necessitates a well-documented reliability study examining the data methods and discussion of possible causes of differences between aggregators.

ObjectiveTo statistically evaluate the reliability of COVID-19 across aggregators.

Design, Setting, and ParticipantsCases and deaths were collected daily by volunteers via state and local health departments, as primary sources and newspaper reports, as secondary sources. In an effort to begin comparison for reliability statistical analysis, BroadStreet collected data from other COVID-19 aggregator sources, including USAFacts, Johns Hopkins University, New York Times, The COVID Tracking Project.

Main Outcomes and MeasuresCOVID-19 cases and death counts at the county and state levels.

ResultsLower levels of inter-rater agreement were observed across aggregators associated with the number of deaths, which manifested itself in state level Bayesian estimates of COVID-19 fatality rates.

Conclusions and RelevanceA national, publically available data set is needed for current and future disease outbreaks and improved reliability in reporting.


title: VGsim: scalable viral genealogy simulator for global pandemic

abstract: Accurate simulation of complex biological processes is an essential component of developing and validating new technologies and inference approaches. As an effort to help contain the COVID-19 pandemic, large numbers of SARS-CoV-2 genomes have been sequenced from most regions in the world. More than 5.5 million viral sequences are publicly available as of November 2021. Many studies estimate viral genealogies from these sequences, as these can provide valuable information about the spread of the pandemic across time and space. Additionally such data are a rich source of information about molecular evolutionary processes including natural selection, for example allowing the identification of new variants with transmissibility and immunity evasion advantages. To our knowledge, there is no framework that is both efficient and flexible enough to simulate the pandemic to approximate world-scale scenarios and generate viral genealogies of millions of samples. Here, we introduce a new fast simulator VGsim which addresses the problem of simulation genealogies under epidemiological models. The simulation process is split into two phases. During the forward run the algorithm generates a chain of population-level events reflecting the dynamics of the pandemic using an hierarchical version of the Gillespie algorithm. During the backward run a coalescent-like approach generates a tree genealogy of samples conditioning on the population-level events chain generated during the forward run. Our software can model complex population structure, epistasis and immunity escape. The code is freely available at https://github.com/Genomics-HSE/VGsim.


title: Effects of B.1.1.7 and B.1.351 on COVID-19 dynamics. A campus reopening study

abstract: The timing and sequence of safe campus reopening has remained the most controversial topic in higher education since the outbreak of the COVID-19 pandemic. By the end of March 2020, almost all colleges and universities in the United States had transitioned to an all online education and many institutions have not yet fully reopened to date. For a residential campus like Stanford University, the major challenge of reopening is to estimate the number of incoming infectious students at the first day of class. Here we learn the number of incoming infectious students using Bayesian inference and perform a series of retrospective and projective simulations to quantify the risk of campus reopening. We create a physics-based probabilistic model to infer the local reproduction dynamics for each state and adopt a network SEIR model to simulate the return of all undergraduates, broken down by their year of enrollment and state of origin. From these returning student populations, we predict the outbreak dynamics throughout the spring, summer, fall, and winter quarters using the inferred reproduction dynamics of Santa Clara County. We compare three different scenarios: the true outbreak dynamics under the wild-type SARS-CoV-2, and the hypothetical outbreak dynamics under the new COVID-19 variants B.1.1.7 and B.1.351 with 56% and 50% increased transmissibility. Our study reveals that even small changes in transmissibility can have an enormous impact on the overall case numbers. With no additional countermeasures, during the most affected quarter, the fall of 2020, there would have been 203 cases under base-line reproduction, compared to 4727 and 4256 cases for the B.1.1.7 and B.1.351 variants. Our results suggest that population mixing presents an increased risk for local outbreaks, especially with new and more infectious variants emerging across the globe. Tight outbreak control through mandatory quarantine and test-trace-isolate strategies will be critical in successfully managing these local outbreak dynamics.


title: Transdiagnostic neurocognitive deficits in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: A 1-year follow-up study

abstract:
BackgroundImpairments in neurocognition are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct comorbidity). This study sought to investigate the neurocognition and social functioning across T2DM, MDD, BD, and SZ using a transdiagnostic and longitudinal approach.

MethodsA total of 165 subjects, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HC), were assessed twice at a 1-year interval using a comprehensive, integrated test battery on neuropsychological and social functioning.

ResultsCommon neurocognitive impairments in somatic and psychiatric disorders were identified, including deficits in short-term memory and cognitive reserve (p < 0.01; {eta}2p = 0.08-0.31). Social functioning impairments were observed in almost all the disorders (p < 0.0001; {eta}2p = 0.29-0.49). Transdiagnostic deficits remained stable across the 1-year follow-up (p < 0.001; {eta}2p = 0.13-0.43) and could accurately differentiate individuals with somatic and psychiatric disorders ({chi}2 = 48.0, p < 0.0001).

ConclusionsThis longitudinal study provides evidence of the overlap in neurocognition deficits across somatic and psychiatric diagnostic categories, such as T2DM, MDD, BD, and SZ, which have high comorbidity. This overlap may be a result of shared genetic and environmental etiological factors. The findings further lay forth promising avenues for research on transdiagnostic phenotypes of neurocognition in these disorders, in addition to their biological bases.

category: psychiatry and clinical psychology


title: The Barrier to Vaccination Is Not Vaccine Hesitancy: Patterns of COVID-19 Vaccine Acceptance over the Course of the Pandemic in 23 Countries

abstract:
BackgroundAt present, evidence is inconclusive regarding what factors influence vaccine intent, and whether there are widespread disparities across populations and time. The current study provides new insights regarding vaccine intent and potential differences across 23 countries and over time.

MethodsOur data come from a unique longitudinal survey that contains responses from Facebook users (N=1,425,172) from the 23 countries from four continents collected in 18 waves from July 2020 through March 2021.

ResultsWe find that vaccine intent varies significantly across countries and over time. Across countries, there are notable disparities in intent to vaccinate. Regarding time, intent has recently reached an all-time high. Our data demonstrates that intent to vaccinate has increased as countries have deployed vaccines on larger scales with undecidedness declining. However, there are some countries where vaccine intent is stagnant and in one country - Egypt - where it seems to have declined.

InterpretationsLarge numbers of citizens across the world are willing to get vaccinated. In the vast majority of countries in our sample, these were high enough to reach more conservative levels of herd immunity1 if combined with numbers of persons already infected. As such, the main barrier to vaccination is not vaccine hesitancy, but the shortage of vaccines. This sends a clear message to politicians who need to work on a quick and fair distribution of vaccine; and to scientists who need to focus their attention on understanding remaining pockets of vaccine skepticism or undecidedness and on factors that explain actual vaccine behavior, rather than intent.

category: public and global health


title: Cognitive training in Parkinson's disease induces local, not global, changes in white matter microstructure

abstract: Previous studies have shown that cognitive training can improve cognitive performance in various neurodegenerative diseases but relatively little is known about the effects of cognitive training on the brain. Here we investigated the effects of our cognitive training paradigm, COGTIPS, on regional white matter microstructure and topology of the structural network. We previously showed that COGTIPS has small, positive effects on processing speed. A subsample of 79 PD patients (N=40 cognitive training group, N=39 active control group) underwent multi-shell diffusion weighted imaging pre- and post-intervention. Our pre-registered analysis plan (osf.io/cht6g) entailed calculating white matter microstructural integrity in five tracts of interest, including the anterior thalamic radiation (ATR) and calculating the topology of the structural connectome. Training-induced changes were analyzed with linear mixed-models. Relative to the active control condition, cognitive training had no effect on network topology. Cognitive training did lead to a reduction in fractional anisotropy in the ATR (B[SE]: -0.32 [0.12], p=0.01). This reduction was associated with faster responses on the ToL task (r = 0.42, P = 0.007), but this just fell short of our statistical threshold (P<0.006). Post-hoc analyses showed that this was not due to changes in fiber density and cross-section, suggesting that that the observed effect in the ATR are due to training-induced alterations in neighboring fibers running through the same voxels, such as intra-striatal and thalamo-striatal fibers. These results indicate that eight weeks of cognitive training do not alter network topology, but can have subtle local effects on structural connectivity.


title: Information nudges for influenza vaccination: Evidence from a large-scale cluster-randomized controlled trial

abstract:
BackgroundVaccination is the most effective means to prevent the spread of infectious diseases. Despite the proven benefits of vaccination, complacency, constraints, and lacking confidence keep many people away from getting vaccinated. This study investigates how written reminders with varying information contents to address vaccine hesitancy affect influenza vaccination coverage in two large and representative samples of older adults.

MethodsWe implemented a large-scale cluster-randomized controlled trial in Finland. The study included the entire elderly population ([≥] 65 years of age) in two culturally and geographically distinct regions with a historically low (31{middle dot}8%, N = 7398) and high (57{middle dot}7%, N = 40727) influenza vaccination coverage. Participants were randomized before the influenza season 2018 - 2019 into three treatments: (i) no information letter, (ii) a standard information letter, reminding recipients about the individual benefits of vaccination, and (iii) a tailored information letter, reminding recipients about the additional social benefits of vaccination due to herd effect. The impact of varying information treatments on influenza vaccination coverage was measured using individual-level administrative health records.

FindingsOur results showed that a low-cost and scalable information intervention relying on individually mailed letters increased influenza vaccination coverage by 6{middle dot}4 percentage points (95% CI: 4{middle dot}1 to 8{middle dot}8). The effect was particularly large among individuals with no prior influenza vaccination (8{middle dot}8 pp, 95% CI: 6{middle dot}5 to 11{middle dot}1). Moreover, we observed a substantial positive effect (5{middle dot}3 pp, 95% CI: 2{middle dot}8 to 7{middle dot}8) among the most consistently non-vaccinated individuals who had not received any type of vaccine during the previous nine years. There were no cross-vaccine spillovers to other age-appropriate vaccines. Our results further suggest that there was no difference in influenza vaccination coverage between the standard letter and the tailored letter that informed individuals about the social benefits of vaccination (0{middle dot}2 pp, 95% CI: - 0{middle dot}1 to 1{middle dot}3).

InterpretationSending information letters is an effective and easily scalable low-cost intervention strategy to increase vaccine uptake in an elderly population. Communicating the social benefits of vaccination in addition to individual benefits does not enhance influenza vaccine uptake. The effectiveness of behavioral interventions aiming to improve vaccination coverage crucially depends on the prior vaccination history of the target population. These findings have meaningful implications for public health authorities who implement vaccine communication strategies to enhance vaccine uptake and aim to curb the spread of infectious diseases.

FundingThe authors received no external funding for this work. The costs of preparing (e.g. printing the letters and acquiring envelopes) and mailing the letters (postal fees) were paid by the Finnish Institute for Health and Welfare and the City of Espoo.

category: health economics


title: Curating and translating the evidence about SARS-CoV-2 and COVID-19 for frontline public health and clinical care: The Novel Coronavirus Research Compendium (NCRC)

abstract: The public health crisis created by the SARS-CoV-2 pandemic has spurred a deluge of scientific research aimed at informing public health and medical response to the COVID-19 pandemic. However, those working in frontline public health and clinical care had insufficient time to parse the rapidly evolving evidence and use it for decision making. Academics in public health and medicine were well-placed to translate the evidence for use by frontline clinicians and public health practitioners. The Novel Coronavirus Research Compendium (NCRC), a group of >50 faculty and trainees, began in March 2020 with the goal to quickly triage and review the large volume of preprints and peer-reviewed publications on SARS-CoV-2 and COVID-19, and to summarize the most important, novel evidence to inform pandemic response. From April 6, 2020 through January 1, 2021, 54,192 papers and preprints were screened by NCRC teams and 527 were selected for review and uploaded to the NCRC website for public consumption. The majority of papers reviewed were peer-reviewed publications (n=395, 75%), published in 102 journals; 25% (n=132) of papers reviewed were of preprints. The NCRC is a successful model of how academics can support practitioners by translating scientific knowledge into action and help to build capacity among students for this work. This approach could be used for health problems beyond COVID-19, but the effort is resource intensive and may not be sustainable over the long term.


title: Interleukin-6 receptor genetic variation and tocilizumab treatment response to COVID-19

abstract: Interleukin-6 receptor (IL6R) stimulates the inflammatory pathways as part of the acute-phase response to infection. Tocilizumab is a monoclonal antibody that inhibits both membrane-bound and soluble IL6R and is used to treat inflammatory conditions, including COVID-19. Despite the disproportionate incidence of COVID-19 among underserved, racial, and ethnic minority populations, the efficacy of tocilizumab in hospitalized COVID-19 patients from these populations is unclear. In this work, three genetic markers for the IL6R gene were analyzed across diverse ethnic backgrounds to identify population differences in response to tocilizumab treatment. Genetic structure analyses showed that African populations were significantly different from other described populations. In addition, mapped frequencies of these alleles showed that Sub-Saharan African populations were 3.4x more likely to show an impaired response to tocilizumab than East Asian populations, and 1.8x more likely than European ancestry populations. Existing IL6R genotype results may identify populations at increased therapeutic failure risk. As results from current clinical trials on the efficacy of tocilizumab treatment for extreme COVID-19 infections are conflicting, more studies are needed across diverse patient backgrounds to better understand the genetic factors necessary to predict treatment efficacy. This work demonstrates how pharmacogenomics studies can elucidate genetic variation on treatment efficacy on COVID-19.

category: genetic and genomic medicine


title: Implementation of Rapid and Frequent SARS-CoV2 Antigen Testing and Response in Congregate Homeless Shelters

abstract:
BackgroundPeople experiencing homelessness who live in congregate shelters are at high risk of SARS-CoV2 transmission and severe COVID-19. Current screening and response protocols using rRT-PCR in homeless shelters are expensive, require specialized staff and have delays in returning results and implementing responses.

MethodsWe piloted a program to offer frequent, rapid antigen-based tests (BinaxNOW) to residents and staff of congregate-living shelters in San Francisco, California, from January 15th to February 19th, 2021. We used the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) framework to evaluate the implementation.

ResultsO_ST_ABSReachC_ST_ABSWe offered testing at ten of twelve eligible shelters. Shelter residents and staff had variable participation across shelters; approximately half of eligible individuals tested at least once; few tested consistently during the study.

Effectiveness2.2% of participants tested positive. We identified three outbreaks, but none exceeded 5 cases. All BinaxNOW-positive participants were isolated or left the shelters.

AdoptionWe offered testing to all eligible participants within weeks of the projects initiation.

ImplementationAdaptations made to increase reach and improve consistency were promptly implemented.

MaintenanceSan Francisco Department of Public Health expanded and maintained testing with minimal support after the end of the pilot.

ConclusionRapid and frequent antigen testing for SARS-CoV2 in homeless shelters is a viable alternative to rRT-PCR testing that can lead to immediate isolation of infectious individuals. Using the RE-AIM framework, we evaluated and adapted interventions to enable the expansion and maintenance of protocols.

category: health systems and quality improvement


title: Stimulation of vascular organoids with SARS-CoV-2 antigens increases endothelial permeability and regulates vasculopathy

abstract:
ObjectiveThrombotic complications and vasculopathy have been extensively associated with severe COVID-19 infection, however the mechanisms by which endotheliitis is induced remain poorly understood. Here we investigate vascular permeability in the context of SARS-CoV-2-mediated endotheliitis in patient samples and a vascular organoid model.

Methods and ResultsWe report the presence of the Spike glycoprotein in pericytes associated with pericyte activation and increased endothelial permeability in post-mortem COVID-19 lung autopsies. A pronounced decrease in the expression of the adhesion molecule VE-cadherin is observed in patients with thrombotic complications. Interestingly, fibrin-rich thrombi did not contain platelets, did not colocalize with tissue factor and have heterogenous levels of Von Willebrand factor, suggesting a biomarker-guided therapy might be required to target thrombosis in severe patients. Using a 3D vascular organoid model, we observe that ACE2 is primarily expressed in pericytes adjacent to vascular networks, consistent with patient data, indicating a preferential uptake of the S glycoprotein by these cells. Exposure of vascular organoids to SARS-CoV-2 or its antigens, recombinant trimeric Spike glycoprotein and Nucleocapsid protein, reduced endothelial cell and pericyte viability as well as CD144 expression with no additive effect upon endothelial activation via IL-1{beta}.

ConclusionsOur data suggest that pericyte uptake of SARS-CoV-2 or Spike glycoprotein contributes to vasculopathy by altering endothelial permeability increasing the risk of thrombotic complications.


title: High proportion of post-acute sequelae of SARS-CoV-2 infection in individuals 1-6 months after illness and association with disease severity in an outpatient telemedicine population

abstract:
BackgroundIndividuals with coronavirus disease 2019 (COVID-19) may have persistent symptoms following their acute illness. The prevalence and predictors of these symptoms, termed post-acute sequelae of SARS-CoV-2 (PASC), are not fully described.

MethodsParticipants discharged from an outpatient telemedicine program for COVID-19 were emailed a survey (1-6 months after discharge) about ongoing symptoms, acute illness severity, and quality of life. Standardized telemedicine notes from acute illness were used for covariates (comorbidities and provider-assessed symptom severity). Bivariate and multivariable analyses were performed to assess predictors of persistent symptoms.

ResultsTwo hundred and ninety patients completed the survey, of whom 115 (39.7%) reported persistent symptoms including fatigue (n= 59, 20.3%), dyspnea on exertion (n=41, 14.1%), and mental fog (n=39, 13.5%) among others. Proportion of persistent symptoms did not differ based on duration since illness (<90 days: n=32, 37.2% versus >90 days: n=80, 40.4%, p = 0.61). Predictors of persistent symptoms included provider-assessed moderate-severe illness (aOR 3.24, 95% CI 1.75, 6.02), female sex (aOR 1.99 95% 0.98, 4.04; >90 days out: aOR 2.24 95% CI 1.01, 4.95), and middle age (aOR 2.08 95% CI 1.07, 4.03). Common symptoms associated with reports of worse physical health included weakness, fatigue, myalgias, and mental fog.

ConclusionsSymptoms following acute COVID-19 are common and may be predicted by factors during the acute phase of illness. Fatigue and neuropsychiatric symptoms figured prominently. Select symptoms seem to be particularly associated with perceptions of physical health following COVID-19 and warrant specific attention on future studies of PASC.


title: A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL)

abstract:
ObjectivesChronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary tuberculosis (TB). CPA may also be misdiagnosed as bacteriologically-negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia; a country with a high incidence of TB.

MethodsIn this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (>3 months), characteristic radiological features and positive Aspergillus serology, and categorized as proven, probable and possible.

ResultsOf the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence of proven and probable CPA at baseline was 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (2 with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA.

ConclusionCPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.

Key messagesO_ST_ABSWhat is the key question?C_ST_ABSDo what extent is chronic pulmonary aspergillosis (CPA) both a) mistaken for TB and b) co-exists with TB during the course of 6 months therapy

What is the bottom line?Features consistent with CPA were present in 6% of patients when starting TB therapy and 8% at the end of therapy, with some resolving and some developing CPA de novo during TB therapy. At the end of B therapy symptoms, cavitations with Aspergillus-specific IgG detectable were the key features of CPA.

Why read on?Co-existence of TB and CPA is present in a substantial minority of patients starting and ending TB therapy, and needs addressing in terms of diagnosis, dual therapy and follow up.


title: SARS-CoV-2 subgenomic RNA kinetics in longitudinal clinical samples

abstract:
BackgroundGiven the persistence of viral RNA in clinically recovered COVID-19 patients, subgenomic RNAs (sgRNA) have been reported as potential molecular viability markers for SARS-CoV-2. However, few data are available on their longitudinal kinetics, compared with genomic RNA (gRNA), in clinical samples.

MethodsWe analyzed 536 samples from 205 patients with COVID-19 from placebo-controlled, outpatient trials of Peginterferon Lambda-1a (Lambda; n=177) and favipiravir (n=359). Nasal swabs were collected at three time points in the Lambda (Day 1, 4 and 6) and favipiravir (Day 1, 5, and 10) trials. N-gene gRNA and sgRNA were quantified by RT-qPCR. To investigate the decay kinetics in vitro, we measured gRNA and sgRNA in A549ACE2+ cells infected with SARS-CoV-2, following treatment with remdesivir or DMSO control.

ResultsAt six days in the Lambda trial and ten days in the favipiravir trial, sgRNA remained detectable in 51.6% (32/62) and 49.5% (51/106) of the samples, respectively. Cycle threshold (Ct) values for gRNA and sgRNA were highly linearly correlated (Pearsons r=0.87) and the rate of increase did not differ significantly in Lambda (1.36 cycles/day vs 1.36 cycles/day; p = 0.97) or favipiravir (1.03 cycles/day vs 0.94 cycles/day; p=0.26) trials. From samples collected 15-21 days after symptom onset, sgRNA was detectable in 48.1% (40/83) of participants. In SARS-CoV-2 infected A549ACE2+ cells treated with remdesivir, the rate of Ct increase did not differ between gRNA and sgRNA.

ConclusionsIn clinical samples and in vitro, sgRNA was highly correlated with gRNA and did not demonstrate different decay patterns to support its application as a viability marker.

SummaryWe observed prolonged detection of subgenomic RNA in nasal swabs and equivalent decay rates to genomic RNA in both longitudinal nasal swabs and in remdesivir-treated A549ACE2+ cells infected with SARS-CoV-2. Taken together, these findings suggest that subgenomic RNA from SARS-CoV-2 is comparably stable to genomic RNA and that its detection is therefore not a more reliable indicator of replicating virus.


title: It's complicated: characterizing the time-varying relationship between cell phone mobility and COVID-19 spread in the US

abstract: Restricting in-person interactions is an important technique for limiting the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Although early research found strong associations between cell phone mobility and infection spread during the initial outbreaks in the United States, it is unclear whether this relationship persists across locations and time. We propose an interpretable statistical model to identify spatiotemporal variation in the association between mobility and infection rates. Using one year of US county-level data, we found that sharp drops in mobility often coincided with declining infection rates in the most populous counties in spring 2020. However, the association varied considerably in other locations and across time. Our findings are sensitive to model flexibility, as more restrictive models average over local effects and mask much of the spatiotemporal variation. We conclude that mobility does not appear to be a reliable leading indicator of infection rates, which may have important policy implications.


title: Chronic kidney disease in Low- and Middle- Income Countries: Protocol for a systematic review of diagnostic and prognostic models

abstract:
BackgroundChronic Kidney Disease (CKD) is a highly prevalent condition with a large disease burden globally. In low- and middle-income countries (LMIC) the CKD screening challenges the health system. This systematic and comprehensive search of all CKD diagnostic and prognostic models in LMIC will inform screening strategies in LMIC following a risk-based approach.

ObjectiveTo summarize all multivariate diagnostic and prognostic models for CKD in adults in LMIC.

MethodsSystematic review. Without date or language restrictions we will search Embase, Medline, Global Health (these three through Ovid), SCOPUS and Web of Science. We seek multivariable diagnostic or prognostic models which included a random sample of the general population. We will screen titles and abstracts; we will then study the selected reports. Both phases will be done by two reviewers independently. Data extraction will be performed by two researchers independently using a pre-specified Excel form (CHARMS model). We will evaluate the risk of bias with the PROBAST tool.

ConclusionThis systematic review will provide the most comprehensive list and critical appraisal of diagnostic and prognostic models for CKD available for the general population in LMIC. This evidence could inform policies and interventions to improve CKD screening in LMIC following a risk-based approach, maximizing limited resources and reaching populations with limited access to CKD screening tests. This systematic review will also reveal methodological limitations and research needs to improve CKD diagnostic and prognostic models in LMIC.


title: Performance Decay of Molecular Assays Near the Limit of Detection: Probabilistic Modeling using Real-World COVID-19 Data

abstract: The gold standard for diagnosis of COVID-19 is detection of SARS-CoV-2 RNA by RT-PCR. However, the effect of systematic changes in specimen viral burden on the overall assay performance is not quantitatively described. We observed decreased viral burdens in our testing population as the pandemic progressed, with median sample Ct values increasing from 22.7 to 32.8 from weeks 14 and 20, respectively. We developed a method using computer simulations to quantify the implications of variable SARS-CoV-2 viral burden on observed assay performance. We found that overall decreasing viral burden can have profound effects on assay detection rates. When real-world Ct values were used as source data in a bootstrap resampling simulation, the sensitivity of the same hypothetical assay decreased from 97.59 (95% CI 97.3-97.9) in week 12, to 74.42 (95% CI 73.9-75) in week 20. Furthermore, simulated assays with a 3-fold or 10-fold reduced sensitivity would both appear to be >95% sensitive early in the pandemic, but sensitivity would fall to 85.55 (95% CI 84.9-86.2) and 74.38 (95% CI 73.6-75.1) later in the pandemic, respectively. Our modeling approach can be used to better quantitate the impact that specimen viral burden may have on the clinical application of tests and specimens.

category: pathology


title: Virtual mindfulness interventions to promote well-being in young adults: A mixed-methods systematic review

abstract:
BackgroundWith the onset of the COVID-19 pandemic, students have experienced drastic changes in their academic and social lives with ensuing consequences towards their physical and mental well-being. The purpose of this systematic review is to identify virtual mindfulness-based interventions for the well-being of young adults aged 15 to 40 years in developed countries and examine the efficacy of these techniques/exercises.

MethodsThis mixed-methods systematic review follows the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines with a registered PROSPERO protocol. With a convergent integrated synthesis approach, IEEE Xplore, PsychInfo, Web of Science and OVID were searched with a predetermined criteria and search strategy employing booleans and filters for peer-reviewed and grey literature. Data screening and extraction were independently performed by two authors, with a third author settling disagreements after reconciliation. Study quality of selected articles was assessed with two independent authors using the Mixed Methods Appraisal Tool (MMAT). Studies were analyzed qualitatively (precluding meta and statistical analysis) due to the heterogeneous study results from diverse study designs in present literature.

ResultsCommon mindfulness-based interventions used in the appraised studies included practicing basic mindfulness, Mindfulness-Based Stress Reduction (MBSR) programs, Mindfulness-Based Cognitive Therapy programs (MBCT) and the Learning 2 BREATHE (L2B) program.

ConclusionStudies implementing mindfulness interventions demonstrated an overall improvement in well-being. Modified versions of these interventions can be implemented in a virtual context, so young adults can improve their well-being through an accessible format.


title: COVID-19 vaccine acceptance in older Syrian refugees: preliminary findings from an ongoing study

abstract: This study assesses COVID-19 vaccine intentions among a sample of Syrian refugees ([≥]50 years) beneficiaries of a humanitarian organization in Lebanon, and explores factors associated with vaccine refusal. The findings are part of an ongoing rotating 4-wave panel study. The sample was limited to participants from the first panel who completed a phone interview between January-February, 2021. Out 1,037 beneficiaries, almost a third (29%) reported no intention to vaccinate. Reasons for refusal were: newness of the vaccine (35%); preference to maintain precaution measures (21%); belief that COVID-19 vaccine is not essential (21%); and other reasons (23%). COVID-19 vaccine refusal was significantly associated with perceptions regarding vaccine safety (OR: 5.97; 95%CI: 4.03-8.84) and effectiveness (OR: 6.80; 95%CI:4.44-10.42) but did not differ by age, presence of chronic conditions, self-reported adherence to COVID-19 measures, and perceptions of susceptibility to and severity of COVID-19. Addressing vaccine hesitancy among Syrian refugees in Lebanon necessitates disseminating accurate, accessible, and culturally appropriate information about vaccine safety and effectiveness.


title: The SARS-CoV2 pandemic explained via asymptomatic infection and susceptibility heterogeneity. Buenos Aires First Wave

abstract:
BackgroundThe rapid global spread of SARS-COV-2 forced governments to implement drastic interventions. The existence of a large but undetermined number of mild or non-symptomatic but infectious cases seems to be involved in the rapid spread, creating a high level of uncertainty due to the difficulty to measure them, and difficulty for epidemiologic modelling.

MethodsWe developed a compartmental model with deterministic equations, that accounts for clinical status, mobility, r heterogenous susceptibility and non-pharmaceutical interventions. The model was calibrated using data from different regions and we used it to predict the dynamic in Buenos Aires Metropolitan Area (AMBA).

ResultsThe model adjusted well to different geographical regions. In AMBA the model predicted 21400 deaths at 300 days, with 27% of the population in the region immunized after the first wave, partly due to the high incidence of asymptomatic cases. The mobility restriction is approximately linear, with any restriction bringing a positive effect. The other interventions have a combined effect of 27% reduction in infection rates.

ConclusionOur research underlines the role of asymptomatic cases in the epidemics dynamic and introduces the concept of susceptibility heterogeneity as a potential explanation for otherwise unexplained outbreak dynamics. The model also shows the big role of non-pharmaceutical interventions both in slowing down the epidemic dynamics and in reducing the eventual number of deaths. The model results are closely compatible with observed data.


title: Miami-Dade: A Case Study of Domestic Violence Arrests During the COVID-19 Pandemic

abstract: The global health crisis that started early in 2020 has triggered a surge of interest in the effect (if any) of COVID-19 on patterns of domestic violence.1 The first systematic review and meta-analysis examining domestic violence during the pandemic revealed quite a lot of diversity in the approaches used to measure potential effects. Drawing on the time series forecasting literature, this brief report contributes to the growing body of evidence around the issue of domestic violence during the pandemic. Arrest data from Miami-Dade County (US) are leveraged along with a robust approach towards model identification, which is used to generate a suitably accurate forecast against which the observed pandemic period domestic violence data can be compared. The pattern uncovered for Miami-Dade County was similar what was found in other U.S. cities that during the pandemic experienced spikes (+95 CI) in the level of domestic violence arrests that were greater than expected. Interestingly these spikes appeared shortly after dips (-95 CI) in observed arrests fell below the expected level.


title: How the COVID-19 pandemic is shaping research in Africa: inequalities in scholarly output and collaborations and new opportunities for scientific leadership

abstract:
BackgroundScientometrics enables scholars to assess and visualize emerging research trends and hot-spots in the scientific literature from a quantitative standpoint. In the last decades, Africa has nearly doubled its absolute count of scholarly output, even though its share in global knowledge production has dramatically decreased. This limited contribution of African scholars to the global research output is in part impacted by the availability of adequate infrastructures and research collaborative networks. The still ongoing COVID-19 pandemic has profoundly impacted the way scholarly research is conducted, published and disseminated. However, the COVID-19 related research focus, the scientific productivity and the research collaborative network of African researchers during the ongoing COVID-19 pandemic remain to be elucidated yet.

MethodsThis study aimed to clarify the COVID-19 research patterns among African researchers and estimate the strength of collaborations and partnerships between African researchers and scholars from the rest of the world during the COVID-19 pandemic, collecting data from electronic scholarly databases such as Web of Sciences (WoS), PubMed/MEDLINE and African Journals OnLine (AJOL), the largest and prominent platform of African-published scholarly journals.

ResultsIn the present bibliometric study, we found that COVID-19 related collaboration patterns varied among African regions, being shaped and driven by historical, social, cultural, linguistic, and even religious determinants. For instance, most of the scholarly partnerships occurred with formerly colonial countries (like European or North-American countries). In other cases, scholarly ties of North African countries were above all with the Kingdom of Saudi Arabia. In terms of amount of publications, South Africa and Egypt were among the most productive countries.

DiscussionBibliometrics and, in particular, scientometrics can help scholars identify research areas of particular interest, as well as emerging topics, such as the COVID-19 pandemic. With a specific focus on the still ongoing viral outbreak, they can assist decision- and policy-makers in allocating funding and economic-financial, logistic, organizational, and human resources, based on the specific gaps and needs of a given country or research area.

ConclusionsIn conclusion, the ongoing COVID-19 pandemic has exerting a subtle, complex impact on research and publishing patterns in African countries. On the one hand, it has distorted and even amplified existing inequalities and disparities in terms of amount of scholarly output, share of global knowledge, and patterns of collaborations. On the other hand, COVID-19 provided new opportunities for research collaborations.


title: Analysis of fragment ends in plasma DNA from patients with cancer

abstract:
Fragmentation patterns observed in plasma DNA reflect chromatin accessibility in contributing cells. Since DNA shed from cancer cells and blood cells may differ in fragmentation patterns, we investigated whether analysis of genomic positioning and nucleotide sequence at fragment ends can reveal the presence of tumor DNA in blood and aid cancer diagnostics. We analyzed whole genome sequencing data from >2700 plasma DNA samples including healthy individuals and patients with 11 different cancer types. We observed higher fractions of fragments with aberrantly positioned ends in patients with cancer, driven by contribution of tumor DNA into plasma. Genomewide analysis of fragment ends using machine learning showed overall area under the receiver operative characteristic curve of 0.96 for detection of cancer. Our findings remained robust with as few as 1 million fragments analyzed per sample, suggesting that analysis of fragment ends can become a cost-effective and accessible approach for cancer detection and monitoring.

One-sentence summaryAnalyzing the positioning and nucleotide sequence at fragment ends in plasma DNA may enable cancer diagnostics.


title: A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets

abstract: Current methods to evaluate gene-by-environment (GxE) interactions on biobank-scale datasets are limited. MonsterLM enables multiple linear regression on genome-wide datasets, does not rely on parameters specification and provides unbiased estimates of variance explained by GxE interaction effects. We applied MonsterLM to the UK Biobank for eight blood biomarkers (N=325,991), identifying significant genome-wide interaction variance with waist-to-hip ratio for five biomarkers, with variance explained by interactions ranging from 0.11 to 0.58. 48% to 94% of GxE interaction variance can be attributed to variants without significant marginal association with the phenotype of interest. Conversely, for most traits, >40% of interaction variance was explained by less than 5% of genetic variants. We observed significant improvements in polygenic score prediction with incorporation of GxE interactions in four biomarkers. Our results imply an important contribution of GxE interaction effects, driven largely by a restricted set of variants distinct from loci with strong marginal effects.


title: Clinical validation of RCSMS: a rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva

abstract: Early detection of SARS-CoV-2 using molecular techniques is paramount to the fight against COVID-19. Due to its high sensitivity and specificity, RT-qPCR is the "gold standard" method for this purpose. However, its technical requirements, processing time and elevated costs hamper its use towards massive and timely molecular testing for COVID-19 in rural and socioeconomically deprived areas of Latin America. The advent and rapid evolution of CRISPR-Cas technology has boosted the development of new pathogen detection methodologies. Recently, DETECTR -a combination of isothermal RT-LAMP amplification and Cas12a-mediated enzymatic detection-has been successfully validated in the Netherlands and the USA as a rapid and low-cost alternative to RT-qPCR for the detection of SARS-CoV-2 from nasopharyngeal swabs. Here, we evaluated the performance of RCSMS, a locally adapted variant of DETECTR, to ascertain the presence of SARS-CoV-2 in saliva samples from 276 patients in two hospitals in Lima, Peru (current status over a total of 350 samples). We show that a low-cost thermochemical treatment with TCEP/EDTA is sufficient to inactivate viral particles and cellular nucleases in saliva, eliminating the need to extract viral RNA with commercial kits, as well as the cumbersome nasopharyngeal swab procedure and the requirement of biosafety level 2 laboratories for molecular analyses. Our clinical validation shows that RCSMS detects up to 5 viral copies per reaction in 40 min, with sensitivity and specificity of 93.8% and 99.0% in the field, respectively, relative to RT-qPCR. Since CRISPR-Cas biosensors can be easily reprogrammed by using different guide RNA molecules, RCSMS has the potential to be quickly adapted for the detection of new SARS-CoV-2 variants. Notably, estimation of its negative and positive predictive values suggests that RCSMS can be confidently deployed in both high and low prevalence settings. Furthermore, our field study validates the use of lateral flow strips to easily visualize the presence of SARS-CoV-2, which paves the way to deploy RCSMS as a "point of care" test in environments with limited access to state-of-the-art diagnostic laboratories. In sum, RCSMS is a fast, efficient and inexpensive alternative to RT-qPCR for expanding COVID-19 testing capacity in low- and middle-income countries.


title: The dark side of SARS-CoV-2 rapid antigen testing: screening asymptomatic patients.

abstract: Most of the reports describing SARS-CoV-2 rapid antigen tests (RATs) performances derive from COVID-19 symptomatic subjects in outpatient settings during periods of highest incidence of infections and high rates of hospital admissions. Here we investigated the role of RATs in an Emergency Department, as a screening tool before admission for COVID-19 asymptomatic patients. Each patient was screened with two simultaneous nasopharyngeal swabs: one immediately analyzed at the bedside using RAT and the other sent to the laboratory for RT-PCR analysis. A total of 116 patients were screened at hospital admission in a 250-bed community hospital in Morges (EHC), Switzerland. With a disease prevalence of 6% based on RT-PCR results, RAT detected only two out of seven RT-PCR positive patients (sensitivity 28.6%) and delivered two false positive results (specificity 98.2%), thus resulting not fiable enough to be used as a screening method in this clinical scenario.


title: Rapid and simultaneous identification of three mutations by the NovaplexTM SARS-CoV-2 Variants I Assay kit

abstract:
BackgroundThe emergence of SARS-CoV-2 variants has caused an unexpected rebound globally. The World Health Organization has listed three variants (B.1.1.7, B.1.351, and P.1) as variants of concern. To understand the epidemiology and thereby plan appropriate safety measures, differential identification of the variants is indeed critical.

ObjectivesAlthough whole-genome sequencing is the gold standard for variant identification, it is time-consuming and relatively expensive. Therefore, a rapid, easy, and cost-effective platform targeting multiple regions of the genome is required. Here, we assessed the usefulness of the Novaplex SARS-CoV-2 Variants I Assay kit in identifying mutations in the variants.

Study designWe retrospectively examined 30 stored nasal swabs from COVID-19-positive patients tested between November 2020 and March 2021. RNA extracted from these swabs was subjected to the commercial kit and real-time reverse transcription-PCR was performed. To determine the genome sequences of SARS-CoV-2 in the collected samples and deduce the consensus sequences among the identified variants, genome sequencing libraries were prepared and mapped to the reference genome.

ResultsFour of the tested samples were determined as variants. Of them, two harbored both H69/V70 deletion and N501Y substitution, whereas two harbored E484K substitution alone.

ConclusionsThe variant with E484K substitution alone ("R.1") has been now categorized as a variant of interest in Japan. Additionally, the kit-based assay was found to be feasible, convenient, and user-friendly in identifying the abovementioned mutations with a turnaround time of only 2 hours.


title: Outcome Disparities by Insurance Plan and Educational Attainment in Patients with Atrial Fibrillation

abstract:
ObjectivesDespite efforts to cut poverty, improve public health, and raise educational attainment, countries still suffer from disparities. Since 2002, Thailand has successfully implemented the Universal Health Coverage Scheme (UCS) to eradicate health care access inequity. Here, we explored the interlink between insurance plan, educational attainment, and adverse clinical outcomes in the national registry of patients with atrial fibrillation (AF) in Thailand.

DesignA nationwide prospective multicenter cohort of non-valvular 3402 AF.

Primary OutcomesPatients were followed for 36 months for primary outcomes of all-cause mortality, ischemic stroke, and major bleeding. Survival analysis was performed using restricted mean survival time (RMST) and adjusted with multiple covariates.

ResultsData from 3026 AF patients (mean age 67, 59% male) were analyzed. The mean CHA2DS2VASc and HASBLED scores were 3.0 (SD 1.7) and 1.5 (SD 1.0) respectively. Most of the patients attained the elementary level of education (N=1739, 57.4%). The major health insurance plans were Civil Servant Medical Benefit Scheme (CSMBS; N=1397, 46.2%) and UCS (N=1333, 44.1%). After 36 months of follow-up, 248 patients died (8.2%), 95 suffered from ischemic stroke (3.1%), and 136 suffered from major bleeding (4.5%). AF patients with no formal education lost 1.78 months before they died (adjusted RMST difference -1.78; 95% CI, -3.25 to -0.30; P =.02) and 1.04 months before they developed ischemic stroke (adjusted RMST difference -1.04; 95% CI, -2.03 to -0.04; P =.04) compared to those with higher education. Educational attainment level was not associated with major bleeding. Across all types of insurance plan, RMSTs to all three clinical outcomes were essentially similar.

ConclusionO_LIEducation attainment level was independently associated with all-cause mortality and ischemic stroke in AF patients.
C_LIO_LIHealth insurance plans were not associated with adverse clinical outcomes.
C_LI

Clinical Trial RegistrationThai Clinical Trial Registration; Study ID: TCTR20160113002

Strengths and limitations of this studyO_LIThe study links two of the most important of sociodemographic factors, education and health insurance plan, and clinical outcomes of atrial fibrillation (AF), one of the most common cardiovascular conditions.
C_LIO_LIData is derived from a large prospective and nationwide cohort.
C_LIO_LIThe study evaluates healthcare quality in universal health coverage system.
C_LIO_LICausal relationship cannot be assumed from a cohort trial.
C_LIO_LIEnrollment took place in the medical center, thus, excluding patients who could not access the healthcare facilities.
C_LI


title: SARS-CoV-2 virus transfers to skin through contact with contaminated solids

abstract: Transfer of SARS-CoV-2 from solids to fingers is one step in infection via contaminated solids, and the possibility of infection from this route has driven calls for increased frequency of handwashing during the COVID-19 pandemic. To analyze this route of infection, we measured the percentage of SARS-CoV-2 that was transferred from a solid to an artificial finger. A droplet of SARS-CoV-2 suspension (1 {micro}L) was placed on a solid, and then artificial skin was briefly pressed against the solid with a light force (3 N). Transfer from a variety of solids was detected, and transfer from the non-porous solids, glass, stainless steel, and Teflon, was substantial (13-16 %) when the droplet was still wet. Transfer still occurred after the droplet evaporated, but it was smaller. We found a lower level of transfer from porous solids but did not find a significant effect of solid wettability for non-porous solids.


title: Music and Dance in respiratory disease management in Uganda: A qualitative study of patient and healthcare professional perspectives

abstract:
IntroductionMusic and dance are increasingly used as adjunctive arts-in-health interventions in high-income settings, with a growing body of research suggesting biopsychosocial benefits. Such low-cost, low-resource interventions may have application in low-resource settings such as Uganda. However, research on perceptions of patients and healthcare professionals regarding such approaches is lacking.

MethodsWe delivered taster music and dance for chronic respiratory disease (CRD) sessions to patients and healthcare professionals. We then conducted an exploratory qualitative study, using thematic analysis of semi-structured interviews with the healthcare professionals and patients regarding i) the role of music and dance in Ugandan life and ii) the perceived acceptability and feasibility of using music and dance in CRD management in Uganda.

ResultsEleven patients with long-term respiratory conditions and eight healthcare professionals were interviewed after selection by purposeful convenience sampling. Four key themes were identified from (interview) analysis: Music and dance: 1) were central components of daily life; 2) had an established role supporting health and wellbeing; 3) had strong therapeutic potential in respiratory disease management; 4) the importance of modulating demographic considerations of culture and religion, and age.

ConclusionMusic and dance are central to life in Uganda, with established roles supporting health and wellbeing. These roles could be built on in the development of music and dance interventions as adjuncts to established components of CRD disease management like pulmonary rehabilitation. Through consideration of key contextual factors, and co-development and adaptation of interventions, such approaches are likely to be well received.

Summary Box: Key QuestionsO_ST_ABSWhat is already known?C_ST_ABSMusic and dance are increasingly being used as adjunctive components of CRD management in high resource settings, with a growing body of research suggesting such approaches are effective, well-received, and can be delivered at low cost. However, the perceptions of patients and healthcare professionals about potential application of such approaches in low-resource settings, such as Uganda, is not known.

What are the new findings?Music and dance have central roles in the social, religious and cultural life in Uganda, including a clear view that participation supports both collective and individual health and wellbeing. In this study, both healthcare professionals and patients saw great potential for the use of music and dance as interventions for people with CRD, and highlighted important factors for consideration for successful implementation.

What do the new findings imply?Music and dance interventions for people with long-term respiratory conditions in Uganda are likely to be accepted with enthusiasm due to the existing role of such activities in daily life. Delivery is likely to be feasible, but interventions would need to be co-developed with patients, their family members, and healthcare professionals, considering a number of key factors. Suggested approaches to address these considerations are provided. More generally, this study highlights how genuine co-design processes can provide valuable insights into health intervention development.

category: respiratory medicine


title: Evolving Phenotypes of non-hospitalized Patients that Indicate Long Covid

abstract: For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection. In this retrospective electronic health records (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston metropolitan area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized. We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients medical records two months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR: 2.60, 95% CI [1.94 - 3.46]), alopecia (OR: 3.09, 95% CI [2.53 - 3.76]), chest pain (OR: 1.27, 95% CI [1.09 - 1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22 - 1.64]), pneumonia (OR 1.66, 95% CI [1.28 - 2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22 - 1.64]) are some of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65. Our approach avoids a flood of false positive discoveries while offering a more robust probabilistic approach compared to the standard linear phenome-wide association study (PheWAS). The findings of this study confirm many of the post-COVID symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63 percent of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.