title: Real World Performance of SARS-CoV-2 Antigen Rapid Diagnostic Tests in Various Clinical Settings

abstract:
BackgroundSeveral uses of Antigen rapid diagnostic tests (Ag-RDT) have been suggested. Analytical studies reported high specificity yet with lower sensitivity for detecting SARS-CoV-2 compared to qRT-PCR. Here, we present the use of these tests as a decision support tool in several settings.

MethodsSamples were collected for both Ag-RDT and qRT-PCR in three different clinical settings; 1. Symptomatic patients presenting at the Emergency Departments 2. Asymptomatic patients screened upon hospitalization and 3. Health-care workers (HCW) following SARS-CoV-2 exposure. Positive percent agreement (PPA), negative percent agreement (NPA), positive predictive value (PPV) and negative predictive value (NPV) were calculated. To estimate the association between Ct value, Ag-RDT and the number of days since SARS-CoV-2 exposure or symptomatic COVID-19, a mixed model was applied.

ResultsA total of 5172 samples were obtained from 4595 individuals, with Ag-RDT and qRT-PCR results. Of these, 485 samples were positive by qRT-PCR. The PPA of Ag-RDT was greater for lower Ct values, reaching 93% in cases where Ct value was lower than 25 and 85% where Ct value was lower than 30. PPA was similar between symptomatic and asymptomatic individuals. The NPV and PPV were 96.8% and 99.1%, respectively. We observed a significant correlation between Ct value and time from infection onset (p<0.001). Lower Ct values were significantly associated with a positive Ag-RDT (p=0.01).

ConclusionsAg-RDT can be used as a decision support tool in various clinical settings and play a major role in early detection of SARS-CoV-2 infected individuals, highly specific and with high sensitivity to the infectious stage of disease, whether symptomatic or asymptomatic.


title: An upsurge of SARS CoV-2 B.1.1.7 Variant in Pakistan

abstract: The emergence of a more transmissible variant of SARS-CoV-2 (B1.1.7) in the United Kingdom (UK) during late 2020 has raised major public health concerns. Several mutations have been reported in the genome of the B.1.1.7 variant including the N501Y and 69-70deletion in the Spike that has implications on virus transmissibility and diagnostics. Although the B.1.1.7 variant has been reported from several countries, only two cases have been identified through whole-genome sequencing from Pakistan. We used a two-step strategy for the detection of B.1.1.7 with initial screening through ThermoFisher TaqPath SARS-CoV-2 kit followed by partial sequencing of Spike (S) gene of samples having spike gene target failure (SGTF) on real-time PCR. From January 01, 2021, to February 21, 2021, a total of 2,650 samples were tested for the presence of SARS-CoV-2 using TaqPath kit and 70.4% (n=1,867) showed amplification of all the 3 genes (S, N, and ORF). Notably, 29.6% (n=783) samples had the spike gene target failure (SGTF). The SGTF cases were detected at a low frequency during the first three weeks of January (n=10, n=13, and n=1 respectively) however, the cases started to increase in the last week. During February, 726 (93%) cases of SGTF was reported with a peak (n=345) found during the 3rd week. Based on the partial sequencing of spike gene of SGTF samples (n=15), 93% (n=14) showed the characteristic N501Y, A570D, P681H, and T716I mutations found in the B.1.1.7 variant. Our findings highlight the high prevalence of B.1.1.7 in Pakistan and warrant large scale genomic surveillance and strengthening of laboratory network in the country.

category: infectious diseases


title: RT-RC-PCR: a novel and highly scalable next-generation sequencing method for simultaneous detection of SARS-COV-2 and typing variants of concern

abstract:
We describe a novel assay method: reverse-transcription reverse-complement polymerase chain reaction (RT-RC-PCR), which rationalises reverse transcription and NGS library preparation into a single closed tube reaction. By simplifying the analytical process and cross-contamination risks, RT-RC-PCR presents disruptive scalability and economy while using NGS and LIMS infrastructure widely available across health service, institutional and commercial laboratories.

We present a validation of RT-RC-PCR for the qualitative detection of SARS-CoV-2 RNA by NGS. The limit of detection is comparable to real-time RT-PCR, and no obvious difference in sensitivity was detected between extracted nasopharyngeal swab (NPS) RNA and native saliva samples.

The end point measurement of RT-RC-PCR is NGS of amplified sequences within the SARS-CoV-2 genome; we demonstrated its capacity to detect different variants using amplicons containing delH69-V70 and N501Y, both of which emerged in the UK Variant of Concern B.1.1.7 in 2020.

In summary, RT-RC-PCR has potential to facilitate accurate mass testing at disruptive scale and cost, with concurrent detection of variants of concern.


title: Characterizing all-cause excess mortality patterns during COVID-19 pandemic in Mexico

abstract:
BackgroundThe low testing rates, compounded by reporting delays, hinders the estimation of the mortality burden associated with the COVID-19 pandemic based on surveillance data alone. A more reliable picture of the effect of COVID-19 pandemic on mortality can be derived by estimating excess deaths above an expected level of death. In this study we aim to estimate the absolute and relative mortality impact of COVID-19 pandemic in Mexico in 2020 by gender and two geographic regions: Mexico City and the rest of the country.

MethodsWe obtained mortality time series due to all causes for Mexico, and by gender, and geographic region using epidemiological weeks from January to December 2020 and for preceding 5 years. We also compiled data on COVID-19 related morbidity and mortality to assess the timing and intensity of the pandemic in Mexico. We assembled weekly series of the number of tweets about  death from Mexico to assess the correlation between peoples media interaction about  death and the rise in pandemic deaths. We estimated all-cause excess mortality rates and mortality rate ratio increase over baseline by fitting Serfling regression models.

ResultsThe COVID-19 pandemic excess mortality rates per 10,000 population in Mexico between March 1, 2020 and January 2, 2021 was estimated at 26.10. The observed total number of deaths due to COVID-19 was 128,886 which is 38.64% of the total estimated excess deaths. Males had about 2-fold higher excess mortality rate (33.99) compared to females (18.53). The excess mortality rate for Mexico City (63.54) was about 2.7-fold higher than the rest of the country (23.25). Similarly, the mortality rate ratio relative to baseline was highest for Mexico City (RR: 2.09). There was no significant correlation between weekly number of tweets on  death and the weekly all-cause excess mortality rates ({rho}=0.309 (95% CI: 0.010, 0.558, p-value=0.043).

ConclusionThe excess mortality rate of 26.10 per 10,000 population corresponds to a total of 333,538 excess deaths in Mexico between March 1, 2020 to January 2, 2021. COVID-19 accounted for only 38.21% of the total excess deaths, which reflects either the effect of low testing rates in Mexico, or the surge in number of deaths due to other causes.


title: The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

abstract: The emergence and rapid rise in prevalence of three independent SARS-CoV-2 "501Y lineages, B.1.1.7, B.1.351 and P.1, in the last three months of 2020 prompted renewed concerns about the evolutionary capacity of SARS-CoV-2 to adapt to both rising population immunity, and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence, all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on various SARS-CoV-2 genes and gene segments (such as S, nsp2 and nsp6), that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition.


title: Factors associated with severe sepsis in diarrheal adults and their outcome at an urban hospital, Bangladesh: A retrospective analysis

abstract:
BackgroundClinical features of sepsis and severe diarrhea often overlap and create a dilemma among the clinicians. To describe factors associated with severe sepsis in diarrheal adults and their outcomes to understand their interplay as clinical features of sepsis and severe diarrhea often overlap.

Methods and resultsWe used this retrospective chart analysis employing a case-control design to study critically ill diarrheal adults aged [≥] 18 years treated in ICU Dhaka hospital, icddr,b between January 2011 to December 2015. Diarrheal adults with a diagnosis of severe sepsis were cases and an equal number of randomly selected non-septic patients were the controls. Of 8,863 in-patient adults, 350 fulfilled the criteria of cases. Cases died significantly more (9% vs 3%, p=0.002) than controls. 69% of the cases progressed to septic shock. In logistic regression analysis, steroid intake, ileus, acute kidney injury, metabolic acidosis, and hypocalcemia were significantly associated with severe sepsis in diarrheal adults (all, p<0.05). 12% of cases (40/335) had bacteremia. Streptococcus pneumoniae [9 (22.5%)] was the single most common pathogen and gram-negatives [27 (67.5%)] were prevailing as a group.

ConclusionDiarrheal adults who had ileus, AKI, metabolic acidosis, hypocalcemia, and also took steroids were prone to have severe sepsis. Strikingly, gram-negatives were the predominant bacteria among the diarrheal adults having severe sepsis.

category: intensive care and critical care medicine


title: SWIFT: A Deep Learning Approach to Prediction of Hypoxemic Events in Critically-Ill Patients Using SpO2 Waveform Prediction

abstract: Hypoxemia is a significant driver of mortality and poor clinical outcomes in conditions such as brain injury and cardiac arrest in critically ill patients, including COVID-19 patients. Given the host of negative clinical outcomes attributed to hypoxemia, identifying patients likely to experience hypoxemia would offer valuable opportunities for early and thus more effective intervention. We present SWIFT (SpO2 Waveform ICU Forecasting Technique), a deep learning model that predicts blood oxygen saturation (SpO2) waveforms 5 and 30 minutes in the future using only prior SpO2 values as inputs. When tested on novel data, SWIFT predicts more than 80% and 60% of hypoxemic events in critically ill and COVID-19 patients, respectively. SWIFT also predicts SpO2 waveforms with average MSE below .0007. SWIFT provides information on both occurrence and magnitude of potential hypoxemic events 30 minutes in advance, allowing it to be used to inform clinical interventions, patient triaging, and optimal resource allocation. SWIFT may be used in clinical decision support systems to inform the management of critically ill patients during the COVID-19 pandemic and beyond.


title: Disparities in outcomes among patients diagnosed with cancer associated with emergency department visits

abstract:
ImportanceDiagnosis of cancer in the emergency department (ED) may be associated with poor outcomes, related to socioeconomic (SES) disparities, however data are limited.

ObjectiveTo examine the morality and associated disparities for cancer diagnoses made less than six months after an ED visit.

DesignThis study is case-control analysis of the Indiana State Department of Health Cancer Registry, and the Indiana Network for Patient Care. First time diagnoses of ICD-"cancer" appearing in the registry between January 2013 and December 2017 were included. Cases were patients who had an ED visit in the 6 months before their cancer diagnosis; controls had no recent ED visits.

Main Outcome(s) and Measure(s)Primary outcome was mortality, comparing ED-associated mortality to non-ED-associated. Secondary outcomes include SES and demographic disparities.

Results134,761 first-time cancer patients were identified, including 15,432 (11.5%) cases. In cases and controls, the mean age was same at 65 and the Charlson Comorbidity Index (CCI) was the same at 2.0 in both groups. More of the ED cohort were Black than the non-ED cohort (12.4% vs 7.4%, P<.0001, Chi Square) and more were low income (36.4%. vs 29.3%). The top 3 ED-associated cancer diagnoses were lung (18.4%), breast (8.9%), and colorectal cancer (8.9%), vs. the non-ED cohort were breast (17%), lung (14.9%), and prostate cancer (10.1%). Regardless of type, all ED-associated cancers had an over three-fold higher mortality, with cumulative death rate of 32.9% for cases vs 9.0% for controls (P<.0001) over the entire study period. Regression analysis predicting mortality, clustering by city, controlling for age, gender, race, SES, drug/alcohol/tobacco use, and CCI score, produced an odds ratio of 4.12 (95% CI 3.72-4.56 for ED associated cancers).

Conclusion and RelevanceThis study found that an ED visit within 6 months prior to the first time of ICD-coded cancer is associated with Black race, low income and an overall three-fold increased risk of death. The mortality rates for ED-associated cancers are uniformly worse for all cancer types. These data suggest that additional work is needed in order to reduce disparities among ED-associated cancer diagnoses, including increased surveillance and improved transitions of care.

Key PointsO_ST_ABSQuestionC_ST_ABSDo patients diagnosed with cancer, shortly after an emergency department (ED) visit have worsened outcomes than patients with diagnoses not associated with an ED visit.

FindingsIn this retrospective, epidemiological assessment, 134,761 patients were diagnosed with cancer, 11.5% (15,432) were seen in the ED within 6 months prior to their diagnosis. They had increased mortality, associated with racial and socioeconomic disparities.

MeaningThese findings imply an urgent need for improved transitions of care for minority and low-income patients with suspected cancer in the ED.

category: emergency medicine


title: Modeling transmission dynamics and effectiveness of worker screening programs for SARS-CoV-2 in pork processing plants

abstract: Pork processing plants were apparent hotspots for SARS-CoV2 in the spring of 2020. As a result, the swine industry was confronted with a major occupational health, financial, and animal welfare crisis. The objective of this work was to describe the epidemiological situation within processing plants, develop mathematical models to simulate transmission in these plants, and test the effectiveness of routine PCR screening at minimizing SARS-CoV2 circulation. Cumulative incidence of clinical (PCR-confirmed) disease plateaued at [~]2.5% to 25% across the three plants studied here. For larger outbreaks, antibody prevalence was approximately 30% to 40%. Secondly, we developed a mathematical model that accounts for asymptomatic, pre-symptomatic, and background "community" transmission. By calibrating this model to observed epidemiological data, we estimated the initial reproduction number (R) of the virus. Across plants, R generally ranged between 2 and 4 during the initial phase, but subsequently declined to [~]1 after two to three weeks, most likely as a result of implementation/compliance with biosecurity measures in combination with population immunity. Using the calibrated model to simulate a range of possible scenarios, we show that the effectiveness of routine PCR-screening at minimizing disease spread was far more influenced by testing frequency than by delays in results, R, or background community transmission rates. Testing every three days generally averted about 25% to 40% of clinical cases across a range of assumptions, while testing every 14 days typically averted 7 to 13% of clinical cases. However, the absolute number of additional clinical cases expected and averted was influenced by whether there was residual immunity from a previous peak (i.e., routine testing is implemented after the workforce had experienced an initial outbreak). In contrast, when using PCR-screening to prevent outbreaks or in the early stages of an outbreak, even frequent testing may not prevent a large outbreak within the workforce. This research helps to identify protocols that minimize risk to occupational safety and health and support continuity of business for U.S. processing plants. While the model was calibrated to meat processing plants, the structure of the model and insights about testing are generalizable to other settings where large number of people work in close proximity.

category: epidemiology


title: A Two-Sample Robust Bayesian Mendelian Randomization Method Accounting for Linkage Disequilibrium and Idiosyncratic Pleiotropy With Applications to the COVID-19 Outcome

abstract: Mendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample MR methods based on genome-wide association study summary level data, however, those methods could suffer from potential power loss or/and biased inference when the chosen genetic variants are in linkage disequilibrium (LD), and also have relatively large direct effects on the outcome whose distribution might be heavy-tailed which is commonly referred to as the idiosyncratic pleiotropy phenomenon. To resolve those two issues, we propose a novel Robust Bayesian Mendelian Randomization (RBMR) model that uses the more robust multivariate generalized t-distribution (Arellano-Valle and Bolfarine, 1995) to model such direct effects in a probabilistic model framework which can also incorporate the LD structure explicitly. The generalized t-distribution can be represented as a Gaussian scaled mixture so that our model parameters can be estimated by the EM-type algorithms. We compute the standard errors by calibrating the evidence lower bound using the likelihood ratio test. Through extensive simulation studies, we show that our RBMR has robust performance compared to other competing methods. We also apply our RBMR method to two benchmark data sets and find that RBMR has smaller bias and standard errors. Using our proposed RBMR method, we find that coronary artery disease is associated with increased risk of critically ill coronavirus disease 2019 (COVID-19). We also develop a user-friendly R package RBMR (https://github.com/AnqiWang2021/RBMR) for public use.


title: SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing

abstract:
BackgroundHigh frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing.

MethodsDuring the fall 2020 semester, athletes and staff in both programs were tested daily using Quidels Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks.

ResultsIn Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition.

ConclusionsThese findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings.

SummaryHigh frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester.


title: Direct detection of microorganisms responsible for the sexually transmitted infection on the mobile real-time PCR device without treating in advance

abstract:
As WHO reported, four curable STIs-chlamydia, gonorrhoea, syphilis and trichomoniasis occur more than 1 million per each day globally almond 2016. For this reason, it is important to control these STIs, one of which is "to detect". The general methods in order to detect STIs are nucleic acid amplification tests (NAATs). One of the reasons why NAATs are utilized in many tests is that it is possibly to be more sensitive than other test. However, there needs to treat extraction of nucleic acids in advance and amplify specific regions by NAATs, and hence it must take much labour and much time. In this work, for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Treponema pallidum (TP) which is each etiological agent of chlamydia, gonorrhoea and syphilis, we evaluate and propose "quicker and simpler" NAATs. Specifically, utilizing mobile real-time PCR device "PCR1100" and PCR reagent kit "KAPA3G Plant PCR Kit", it was considered whether real-time direct PCR could be performed or not without treating DNA extraction in advance so-called "direct".

As a result, firstly, we established that real-time direct PCR could be performed in all of CT, NG, and TP, and moreover, each Ct value correlated with the concentration of each organism similarly to detection of genome DNA (each correlation coefficient R2 > 0.95). Moreover, each assay demonstrated a limit of detection (LOD) of the follows; CT was 10^0.86 = 7.24 IFU/reaction, NG was 10^-0.19 = 0.65 CFU/reaction, and TP was 10^1.4 = 25.1 organisms/reaction. However, it appeared the sensitivity was a little low, especially for CT and TP.

Secondly, we found that even as without treating sample in advance, the time of detection was required more less 15 minutes at any of case, which was very quick compared with other current methods for real-time PCR. Additionally, compared with other commercial devices, it was easier to operate the PCR1100 device, for example, start, analysis of Ct value.

In conclusion, the present study has demonstrated that it is possible for real-time direct PCR to perform with combination of the PCR1100 device and the PCR reagent kit in 3 kinds of microorganisms-CT, NG and TP. Furthermore, we propose "quicker and simpler" methods for NAATs, which it would not take labour and time. Further studies are needed in order to contribute to control STIs.


title: CNBP, REL, and BHLHE40 variants are associated with IL-12 and IL-10 responses and tuberculosis risk

abstract:
RationaleThe major human genes regulating M. tuberculosis (Mtb)-induced immune responses and tuberculosis (TB) susceptibility are poorly understood. Although IL-12 and IL-10 are critical for TB pathogenesis, the genetic factors that regulate their expression are unknown. CNBP, REL, and BHLHE40 are master regulators of IL-12 and IL-10 signaling.

ObjectivesTo determine whether common human genetic variation in CNBP, REL and BHLHE40 is associated with IL-12 and IL-10 expression, adaptive immune responses to mycobacteria, and susceptibility to TB.

Methods and Main MeasurementsWe characterized the association between common variants in CNBP, REL, and BHLHE40 and innate immune responses in dendritic cells and monocyte-derived macrophages (MDM), BCG-specific T cell responses, and susceptibility to pediatric and adult TB.

ResultsSNP BHLHE40 rs4496464 was associated with increased BHLHE40 expression in MDMs and increased IL-10 from both peripheral blood dendritic cells and MDMs after LPS and TB whole cell lysate stimulation. SNP BHLHE40 rs11130215, in linkage disequilibrium with rs4496464, was associated with increased BCG-specific IL2+CD4+ T cell responses and decreased risk for pediatric TB in South Africa. SNPs REL rs842634 and CNBP rs11709852 were associated with increased IL-12 production from dendritic cells, and SNP REL rs842618, in linkage disequilibrium with rs842634, was associated with increased risk for TB meningitis.

ConclusionsGenetic variation in CNBP, REL, and BHLHE40 is associated with IL-12 and IL-10 cytokine response and TB clinical outcomes. Common human genetic regulation of well-defined intermediate cellular traits provides insights into mechanisms of TB pathogenesis.


title: The COVID-19 health equity twindemic: Statewide epidemiologic trends of SARS-CoV-2 outcomes among racial minorities and in rural America

abstract:
BackgroundEarly studies on COVID-19 identified unequal patterns in hospitalization and mortality in urban environments for racial and ethnic minorities. These studies were primarily single center observational studies conducted within the first few weeks or months of the pandemic. We sought to examine trends in COVID-19 morbidity and mortality over time for minority and rural populations, especially during the U.S. fall surge.

MethodsStatewide cohort of all adult residents in Indiana tested for SARS-CoV-2 infection between March 1 and December 31, 2020, linked to electronic health records. Primary measures were per capita rates of infection, hospitalization, and death. Age adjusted rates were calculated for multiple time periods corresponding to public health mitigation efforts.

ResultsMorbidity and mortality increased over time with notable differences among sub-populations. Initially, per capita hospitalizations among racial minorities were 3-4 times higher than whites, and per capita deaths among urban residents were twice those of rural residents. By fall 2020, per capita hospitalizations and deaths in rural areas surpassed those of urban areas, and gaps between black/brown and white populations narrowed. Cumulative morbidity and mortality were highest among minority groups and in rural communities.

ConclusionsBurden of COVID-19 morbidity and mortality shifted over time, creating a twindemic involving disparities in outcomes based on race and geography. Health officials should explicitly measure disparities and adjust mitigation and vaccination strategies to protect vulnerable sub-populations with greater disease burden.


title: Timing of parental depression on risk of child depression and poor educational outcomes: a population based routine data cohort study from Born in Wales, UK.

abstract:
BackgroundMaternal depression is a risk factor for depression in children, though the influence of paternal depression has been less well examined. We examined the association between maternal and paternal depression, and the timing of their depression (before or after the childs birth) and outcomes for the child including incidence of child depression and poor educational attainment.

MethodsA linked routine data cohort study linking General Practitioner(GP), hospital and education records of young people (aged 0 to 30 years) in Wales. Parental and child diagnosis of depression was identified from GP data. Regression analysis examined the association of maternal and paternal depression with time to diagnosis of depression in the child and odds of attaining educational milestones.

OutcomesIn adjusted models, the relative risk of offspring developing depression was 1.22 if the mother had depression before the child was born, 1.55 if the mother had depression after the child was born and 1.73 if she had depression both before and after the child was born (chronic depression), compared to those were there was no maternal depression history. For achieving milestones at end of primary school, odds were 0.92, 0.88 and 0.79 respectively. Association of depression in the child was similar if the male living in the household had depression with risk ratios of 1.24 (before), 1.43 (after) and 1.27 (before and after) for child diagnosed depression and 0.85, 0.79 and 0.74 for achieving age 11 milestones.

InterpretationChildren who live with a parent who has depression are more likely to develop depression and not achieve educational milestones, compared to children who live with a parent who has a history of depression (but no active depression in childs lifetime) and compared to those with no depression. This finding suggests that working closely with families where depression (particularly chronic depression) is present in either parent and treating parental depression to remission is likely to have long-term benefits for childrens mental health and educational attainment.

FundingThis study had no specific funding. The infrastructure to enable the study was funded by Health Care Research Wales (https://healthandcareresearchwales.org/) which funded; the National Centre for Population Health and Wellbeing Research (https://ncphwr.org.uk/) enabling the involvement of SB, CT, MAR, TK, the National Centre for Mental Health Wales (https://www.ncmh.info/), which supported the involvement of FR, and the Secure Anonymised Information Linkage Database (https://saildatabank.com/)


title: Comparing the Evidential Strength for Psychotropic Drugs: A Bayesian Meta-Analysis

abstract:
ObjectiveApproval and prescription of drugs should be informed by the strength of evidence for efficacy. While there is no formal policy towards different standards for drug approval, the typical strength of evidence might differ for different psychotropic drug groups. Using a Bayesian framework, we examine (1) whether psychotropic drugs are supported by substantial evidence (at the time of Food and Drug Administration [FDA] approval), and (2) whether there are systematic differences across drug groups.

MethodsData from short-term, placebo-controlled phase II/III clinical trials for 15 antipsychotics, 16 antidepressants for depression, nine antidepressants for anxiety, and 20 drugs for ADHD were extracted from FDA reviews evaluating efficacy prior to marketing approval. Bayesian model-averaged meta-analysis was performed and strength of evidence was quantified with the Bayes factor (BFBMA).

ResultsWe observed substantial variation in strength of evidence and trialling between approved psychotropic drugs: Median evidential strength was extremely strong for ADHD medication (BFBMA = 1820.4), but considerably lower and more frequently classified as weak or moderate for antidepressants for both depression (BFBMA = 94.2) and anxiety (BFBMA = 49.8). Differences might be accounted for by varying median effect sizes (schizophrenia: ESBMA = 0.45, depression: ESBMA = 0.30, anxiety: ESBMA = 0.37, ADHD: ESBMA = 0.72), sample sizes (schizophrenia: N = 324, depression: N = 218, anxiety: N = 254, ADHD: N = 189.5), and numbers of trials (schizophrenia: Nr = 3, depression: Nr = 5.5, anxiety: Nr = 3, ADHD: Nr = 2).

LimitationsThe analysis only included pre-marketing studies.

ConclusionEvidential strength varied across drug groups: Although most psychotropic drugs were supported by strong evidence at the time of approval, some drugs only had moderate or even ambiguous evidence. These results show the need for more systematic quantification and classification of statistical evidence for psychotropic drugs, and for transparent and clear communication of evidential strength toward clinical decision makers.

Registrationhttps://osf.io/5jn2d

category: pharmacology and therapeutics


title: Risk of hospitalization and risk of death for healthcare workers with COVID-19 in nine European Union/European Economic Area countries, January 2020 - January 2021

abstract:
We assessed the impact of COVID-19 on healthcare workers (HCWs) from data on 2.9 million cases reported from nine countries in the EU/EEA. Compared to non-HCWs, HCWs had a higher adjusted risk of hospitalization (IRR 3.0 [95% CI 2.2-4.0]), but not death (IRR 0.9, 95% CI 0.4-2.0).

Article Summary LineHealthcare workers are hospitalized more frequently than non-healthcare workers when adjusting for age, sex, and comorbidities.

category: public and global health


title: Prevalence of vitamin D is not associated with the COVID-19 epidemic in Europe. A judicial update of the existing evidence.

abstract:
BackgroundCOVID-19 has emerged as a global pandemic, affecting nearly 104 million people worldwide as of February 4th 2021. In previous published studies, the association between the mean Vit D status of each country and COVID-19 infection rate, and mortality among the adult population in European countries was examined. The aim of this study was to re-examine the relationship between the Vit D status of each country and COVID-19 infection, recovery, and mortality using updated data and a different methodological approach.

MethodsInformation only form the last decade on Vit D concentration/deficiency for each country was retrieved through literature search on PubMed(R) database. As of February, 4th 2021, COVID-19 infections and mortalities per one million population as well as total recoveries were extracted from the Worldometer website. The association between vitamin D deficiency and COVID-19 infection, recovery, and mortality were explored using correlation coefficients and scatterplots.

FindingsThe prevalence of vitamin D deficiency among European countries ranged from 6.0 (Finland) to 75.5% (Turkey), with several countries facing more than 50% of vitamin D deficiency among their population. Non-significant correlations were observed between the number of COVID-19 infections (r=0.190; p=0.374), recoveries (rs=0.317, p=0.131), and mortalities (r=0.129; p=0.549) per one million population, with the prevalence of vitamin D deficiency.

InterpretationPrevalence of vitamin D deficiency was not significantly associated with either number of infections, recoveries or mortality rate of COVID-19 among European countries. Thus, it is an important parameter to be considered when implementing preventive measures to face COVID-19.

FundingNone

category: nutrition


title: Prevalence of vitamin D is not associated with the COVID-19 epidemic in Europe. A critical update of the existing evidence.


title: Characterization of patients that can continue conservative treatment for adenomyosis

abstract:
IntroductionHistorically, hysterectomy has been the radical treatment for adenomyosis. However, some patients do not wish to hysterectomy. Nevertheless, patients often required hysterectomy during the course of conservative treatment, but the factors involved remain unknown. The purpose of this study was to determine which patients can continue conservative treatment for adenomyosis.

Materials and MethodsWe selected women diagnosed with adenomyosis and provided with conservative treatment at the Kindai University Hospital and Osaka Red Cross Hospital. Age at diagnosis, parity, uterine size, subtype of adenomyosis, type of conservative treatment, and timing of hysterectomy for cases with difficulty continuing conservative treatment were examined retrospectively.

ResultsA total of 885 patients were diagnosed with adenomyosis, and 124 started conservative treatment. Conservative treatment was continued in 96 patients (77.4%) and hysterectomy was required in 28 patients (22.6%). The cumulative hysterectomy rate was 32.4%, and all women had hysterectomy within 63 months. In the decision tree analysis, 82% (23/28) of women aged 46 years or younger were able to continue conservative treatment when parity was zero or one. If parity was two and over, 95% (20/21) of those aged 39 years and older had hysterectomy.

ConclusionsPatients that continue conservative treatment for approximately 5 years are more likely to have successful preservation of the uterus. Multipara and higher age of diagnosis are factors that contribute to hysterectomy after conservative treatment. Parity and age at diagnosis may be stratifying factor in future clinical trials on hormone therapy.

category: obstetrics and gynecology


title: Digital Health-Enabled Community-Centered Care (D-CCC): A Scalable Model to Empower Future Community Health Workers utilizing Human-in-the-Loop AI

abstract: Digital Health-Enabled Community-Centered Care (D-CCC) represents a pioneering vision for the future of community-centered care. Utilizing an artificial intelligence-enabled closed-loop digital health platform designed for, and with, community health workers, D-CCC enables timely and individualized delivery of interventions by community health workers to the communities they serve. D-CCC has the potential to transform the current landscape of manual, episodic and restricted community health worker-delivered care and services into an expanded, digitally interconnected and collaborative community-centered health and social care ecosystem which centers around a digitally empowered community health workforce of the future.

category: health informatics


title: Cost-Sharing in Medical Care Can Increase Adult Mortality Risk in Lower-Income Countries

abstract:
Patient cost-sharing in medical care constrains total health spending, presumably with little harm to underlying patient health. This paper re-evaluates the link between cost-sharing and health, studying Colombias entire formal sector workforce with individual-level health care utilization records linked to payroll data and vital statistics. Given discrete breaks in outpatient cost-sharing imposed at multiple income thresholds by Colombias national health system, we use a regression discontinuity design and find that outpatient cost-sharing reduces use of outpatient care, resulting in fewer diagnoses of common chronic diseases and increasing subsequent emergency room visits and hospitalizations. Ultimately, these effects measurably increase mortality, and disproportionately so among the poor - raising the absolute difference in 7-year mortality risk by 0.80 and 0.23 deaths per 1,000 individuals at lower- and higher-income thresholds, respectively. To the best of our knowledge, this study is the first to show a relationship between cost-sharing and adult mortality risk in lower-income countries, a relationship important to incorporate into social welfare analyses of cost-sharing policies.

One Sentence SummaryOutpatient cost-sharing in medical care discourages use - but over time, also increases costly hospital service use and raises mortality risk.

category: health policy


title: Knowledge transfer to enhance the performance of deep learning models for automated classification of B-cell neoplasms

abstract: Multi-parameter flow cytometry (MFC) is a cornerstone in clinical decision making for hematological disorders such as leukemia or lymphoma. MFC data analysis requires trained experts to manually gate cell populations of interest, which is time-consuming and subjective. Manual gating is often limited to a two-dimensional space. In recent years, deep learning models have been developed to analyze the data in high-dimensional space and are highly accurate. Such models have been used successfully in histology, cytopathology, image flow cytometry, and conventional MFC analysis. However, current AI models used for subtype classification based on MFC data are limited to the antibody (flow cytometry) panel they were trained on. Thus, a key challenge in deploying AI models into routine diagnostics is the robustness and adaptability of such models. In this study, we present a workflow to extend our previous model to four additional MFC panels. We employ knowledge transfer to adapt the model to smaller data sets. We trained models for each of the data sets by transferring the features learned from our base model. With our workflow, we could increase the models overall performance and more prominently, increase the learning rate for very small training sizes.

category: hematology


title: Estimating the long-term effects of population-wide screening for latent and active tuberculosis in the Republic of the Marshall Islands

abstract:
BackgroundAmbitious population-based screening programs for latent and active tuberculosis (TB) were implemented in the Republic of the Marshall Islands (RMI) in 2017 and 2018.

MethodsWe used a transmission dynamic model of TB informed by local data to capture the historical dynamics of the RMI epidemic. We then used the model to project the future epidemic trajectory following the active screening interventions, as well as considering a counterfactual scenario with no intervention. We also simulated future scenarios including periodic interventions similar to those previously implemented, to assess their ability to reach the End TB Strategy targets and TB pre-elimination in RMI.

FindingsThe screening activities conducted in 2017 and 2018 were estimated to have reduced TB incidence and mortality by more than one third in 2020, and are predicted to achieve the End TB Strategy milestone of 50% incidence reduction by 2025 compared to 2015. Screening interventions had a considerably greater impact when latent TB screening and treatment was included, compared to active case finding alone. Such combined programs implemented at the national level could achieve TB pre-elimination around 2035 if repeated every two years, and around 2045 if repeated every five years.

InterpretationOur model suggests that it would be possible to achieve TB pre-elimination by 2035 in RMI through periodic repetition of the same interventions as those already implemented in the country. It also highlights the importance of including latent infection testing in active screening activities.

FundingAustralian National Health and Medical Research Council and World Health Organization.


title: Long-term effects of mass screening for latent and active tuberculosis in the Marshall Islands


title: Rapid increase of SARS-CoV-2 variant B.1.1.7 detected in sewage samples from England between October 2020 and January 2021

abstract: SARS-CoV-2 variants with multiple amino acid mutations in the spike protein are emerging in different parts of the world raising concerns on their possible impact on human immune response to the virus and vaccine efficacy against them. Recently, a variant named lineage B.1.1.7 was detected and shown to be rapidly spreading across the UK since November 2020. As surveillance for these SARS-CoV-2 variants of concern (VOCs) becomes critical, we have investigated the use of environmental surveillance (ES) for the rapid detection and quantification of B.1.1.7 viruses in sewage as a way of monitoring its expansion that is independent on the investigation of identified clinical cases. B.1.1.7 mutations in viral sequences from sewage were first identified in a sample collected in London on 10th November 2020 and shown to rapidly increase in frequency to >95% in January 2021, in agreement with clinical data over the same period. We show that ES can provide an early warning of VOCs becoming prevalent in the population and that, as well as B.1.1.7, our method can potentially detect VOCs B.1.351 and P.1, first identified in South Africa and Brazil, respectively, and other viruses also carrying critical spike mutation E484K, known to have an effect on virus antigenicity.


title: Multi-Omic Profiling of Plasma Identify Biomarkers and Pathogenesis of COVID-19 in Children

abstract:
Although children usually develop less severe disease responding to COVID-19 than adults, little is known about the pathogenesis of COVID-19 in children. Herein, we conducted the plasma proteomic and metabolomic profiling of a cohort of COVID-19 pediatric patients with mild symptoms. Our data show that numerous proteins and metabolites involved in immune as well as anti-inflammatory processes were up-regulated on a larger scale in children than in adults. By developing a machine learning-based pipeline, we prioritized two sets of biomarker combinations, and identified 5 proteins and 5 metabolites as potential children-specific COVID-19 biomarkers. Further study showed that these identified metabolites not only inhibited the expression of pro-inflammatory factors, but also suppressed coronaviral replication, implying that these factors played key roles in protecting pediatric patients from both viral infection and infection-induced inflammation. Together, our study uncovered a protective mechanism responding to COVID-19 in children, and sheds light on potential therapies.

TeaserAnti-inflammatory metabolites were highly elevated in the plasma of COVID-19 pediatric patients with mild symptoms.


title: Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naive and Recovered Individuals Following mRNA Vaccination

abstract:
Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naive subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naive subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naive and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naive individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naive individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.

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title: REACT-1 round 9 final report: Continued but slowing decline of prevalence of SARS-CoV-2 during national lockdown in England in February 2021

abstract:
BackgroundEngland will start to exit its third national lockdown in response to the COVID-19 pandemic on 8th March 2021, with safe effective vaccines being rolled out rapidly against a background of emerging transmissible and immunologically novel variants of SARS-CoV-2. A subsequent increase in community prevalence of infection could delay further relaxation of lockdown if vaccine uptake and efficacy are not sufficiently high to prevent increased pressure on healthcare services.

MethodsThe PCR self-swab arm of the REal-time Assessment of Community Transmission Study (REACT-1) estimates community prevalence of SARS-CoV-2 infection in England based on random cross-sections of the population ages five and over. Here, we present results from the complete round 9 of REACT-1 comprising round 9a in which swabs were collected from 4th to 12th February 2021 and round 9b from 13th to 23rd February 2021. We also compare the results of REACT-1 round 9 to round 8, in which swabs were collected mainly from 6th January to 22nd January 2021.

ResultsOut of 165,456 results for round 9 overall, 689 were positive. Overall weighted prevalence of infection in the community in England was 0.49% (0.44%, 0.55%), representing a fall of over two thirds from round 8. However the rate of decline of the epidemic has slowed from 15 (13, 17) days, estimated for the period from the end of round 8 to the start of round 9, to 31 days estimated using data from round 9 alone (lower confidence limit 17 days). When comparing round 9a to 9b there were apparent falls in four regions, no apparent change in one region and apparent rises in four regions, including London where there was a suggestion of sub-regional heterogeneity in growth and decline. Smoothed prevalence maps suggest large contiguous areas of growth and decline that do not align with administrative regions.

Prevalence fell by 50% or more across all age groups in round 9 compared to round 8, with prevalence (round 9) ranging from 0.21% in those aged 65 and over to 0.71% in those aged 13 to 17 years. Round 9 prevalence was highest among Pakistani participants at 2.1% compared to white participants at 0.45% and Black participants at 0.83%. There were higher adjusted odds of infection for healthcare and care home workers, for those working in public transport and those working in education, school, nursery or childcare and lower adjusted odds for those not required to work outside the home.

ConclusionsCommunity prevalence of swab-positivity has declined markedly between January and February 2021 during lockdown in England, but remains high; the rate of decline has slowed in the most recent period, with a suggestion of pockets of growth. Continued adherence to social distancing and public health measures is required so that infection rates fall to much lower levels. This will help to ensure that the benefits of the vaccination roll-out programme in England are fully realised.


title: Learning to Treat Hypotensive Episodes in Sepsis Patients Using a Counterfactual Reasoning Framework

abstract: The optimal treatment strategy for volume resuscitation and vasopressor dosing to combat hypotensive episodes in septic patients remains a subject of ongoing controversy and can vary from clinician to clinician. We develop a machine learning approach to guide a fluid and vasopressor dosing strategy that adapts to patient-specific clinical states to improve the survival of septic patients. We adopt a model-free reinforcement learning (RL) framework in a continuous action space with a clinically significant reward function, and use a Switching Generalized Linear Model (SGLM) to characterize patient-specific clinical states. We use retrospective data from the MIMIC III database to train this model to learn volume resuscitation and vasopressor dosing strategies among the 5,366 patients (totalling 352,328 unique hourly measurements) with ICU-onset sepsis or septic shock, as diagnosed by the Sepsis-3 definition. The RL agent receives short- and long-term rewards associated with optimizing in-hospital survival and avoiding end-organ damage to learn volume resuscitation and vasopressor dosing strategies. On average, the RL agent learns to resuscitate patients earlier than clinicians with a fluid bolus (one hour vs. four hours after the diagnosis of sepsis), and improves the expected survival by {approx} 3%. Our preliminary results indicate that adherence to RL-based individualized fluid and vasopressor dosing recommendations is associated with a significant mortality reduction in septic patients, even after adjusting for severity of illness.


title: Comparison of clinical course and outcomes of critically ill patients with SARS-CoV2 infection managed in traditional ICU and "Flex" ICU during the surge of the pandemic in the Bronx.

abstract:
BACKGROUNDAs part of the response to increase critical care capacity during the unprecedented surge of COVID-19 infections, NYC Health + Hospital systems identified and resourced areas in the hospital that could deliver critical care as "Flex" ICUs to complement the traditional ICUs to manage the rapid influx of critically ill patients.

OBJECTIVEComparison of clinical features and outcomes of mechanically ventilated COVID-19 patients admitted to the traditional and "Flex" ICUs during the surge of the pandemic

METHODSRetrospective comparative cohort study of patients with confirmed SARS-CoV-2 infection on mechanical ventilation admitted to traditional ICU and  Flex ICU. Univariate and multivariate analysis to detect factors associated with death from COVID-19 patients in mechanical ventilation were performed with the Cox proportional hazards regression model

RESULTSOut of the 312 patients on mechanical ventilation, 111 were admitted to the traditional ICU and 201 to the  Flex ICU. The mortality rate was higher in the  Flex ICU compared with the traditional ICU, but the adjusted risk model was not significantly associated with increased mortality

CONCLUSION"Flex" ICUs played a crucial role in the management of critically ill patients during the pandemic. Mortality risk of patients in the "Flex" ICUs were comparable to traditional ICUs in the adjusted analysis. While there is enough evidence for Intensivist managed ICUs to have better outcomes, our study demonstrates the feasibility of non-intensivist led Flex" ICUs during a crisis.


title: We also deserve help during the pandemic: The effect of the COVID-19 pandemic on foreign domestic workers in Hong Kong

abstract: The coronavirus disease 2019 (COVID-19) pandemic poses particular challenges for migrant workers around the world. This study explores the unique experiences of foreign domestic workers (FDWs) in Hong Kong, and how COVID-19 impacted their health and economic wellbeing. Interviews with FDWs (n = 15) and key informants (n = 3) were conducted between May and August 2020. FDWs reported a dual-country experience of the pandemic, where they expressed concerns about local transmission risks as well as worries about their family members in their home country. Changes to their current work situation included how their employers treated them, as well as their employment status. FDWs also cited blind spots in the Hong Kong policy response that also affected their experience of the pandemic, including a lack of support from the Hong Kong government. Additional support is needed to mitigate the particularly negative effects of the pandemic on FDWs.


title: Self-reported real-world safety and reactogenicity of COVID-19 vaccines: An international vaccine-recipient survey.

abstract:
BackgroundThe safety of COVID-19 vaccines has been demonstrated in selected populations in recent studies, but more data in specific groups is needed to inform vaccine choice and health policy.

ObjectivesAn international, online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups.

MethodsThis survey was launched in February 2021, for 11 days. Recipients of a first COVID-19 vaccine dose [≥]7 days prior to survey completion were eligible. The incidence and severity of vaccination side effects were assessed.

ResultsSurvey was completed by 2,002 respondents, of whom 26.6% had prior COVID-19 infection (68.8% laboratory confirmed). Prior COVID-19 infection was associated with increased risk of any side effect (risk ratio 1.08, 95% confidence intervals [1.05-1.11]), fever (2.24 [1.86-2.70]), breathlessness (2.05 [1.28-3.29]), flu-like illness (1.78 [1.51-2.10]), fatigue (1.34 [1.20-1.49]) and local reactions (1.10 [1.06-1.15]). It was also associated with increased risk of severe side effects, leading to hospital care (1.56 [1.14-2.12]).

While mRNA vaccines were associated with a higher incidence of any side effect (1.06 [1.01-1.11]) compared to viral vector-based vaccines, these were generally milder (p<0.001), mostly local reactions. Importantly, mRNA vaccine-recipients reported considerably lower incidence of systemic reactions (RR<0.6) including anaphylaxis, swelling, flu-like illness, breathlessness and fatigue, and of side effects requiring hospital care (0.42 [0.31-0.58]).

ConclusionFor the first time, our study links prior COVID-19 illness with increased incidence of vaccination side effects and demonstrates that mRNA vaccines cause milder, less frequent systemic side effects, but more local reactions.

Key messages- People with prior COVID-19 illness appear to experience significantly increased incidence and severity of side effects after receiving the COVID-19 vaccine.
- In this first head-to-head comparison of the safety and reactogenicity of different types of vaccines, it was demonstrated that mRNA vaccines cause milder, less frequent systemic side effects, compared to viral vector vaccines, but more local reactions.

Tweetable SummaryA survey of >2000 COVID-19 vaccine-recipients links prior COVID-19 illness with increased incidence of vaccination side effects; mRNA vaccines cause milder, less frequent systemic side effects, but more local reactions.


title: Recommendations for COVID-19 Vaccination in People with Rheumatic Disease: Developed by the Singapore Chapter of Rheumatologists

abstract:
AimPeople with rheumatic diseases (PRD) remain vulnerable in the era of the COVID-19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS-CoV-2 in PRD.

MethodsSystematic literature reviews were performed to evaluate (1) outcomes in PRD with COVID-19; (2) efficacy, immunogenicity and safety of COVID-19 vaccination; and (3) published guidelines/recommendations for non-live, non-COVID-19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology.

ResultsThe consensus comprises two overarching principles and seven recommendations. Vaccination against SARS-CoV-2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommended that eligible PRD and household contacts be vaccinated against SARS-CoV-2. We conditionally recommended that the COVID-19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommended that the COVID-19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post-vaccination antibody titres against SARS-CoV-2 need not be measured. Any of the approved COVID-19 vaccines may be used, with no particular preference.

ConclusionThese recommendations provide guidance for COVID-19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low-level evidence. (words 247)

category: rheumatology


title: Effect of Eight-Week Online Cognitive Training in Parkinson's Disease: A Randomized Controlled Trial

abstract:
BackgroundCognitive training (CT) has been proposed as a non-pharmacological treatment option for the frequent cognitive impairments occurring in PD.

ObjectiveAssess the efficacy of CT on cognitive function in PD.

MethodsIn this double-blind, randomized controlled trial we enrolled 140 PD patients with significant subjective cognitive complaints. In eight weeks, participants underwent 24 sessions of computerized multi-domain CT or an active control condition for 45 minutes each (n=70 vs. n=70). The primary outcome was the accuracy on a computerized Tower of London task; secondary outcomes included effects on other neuropsychological outcomes and subjective cognitive complaints. Outcomes were assessed before and after training and at six-months follow-up, and were analyzed with multivariate mixed-model analyses.

ResultsThe intention-to-treat population consisted of 136 participants. Multivariate mixed-model analyses showed no group difference on the Tower of London accuracy corrected for baseline performance: B: -0.06, 95% CI: -0.27 to 0.15, p=0.562. Participants in the CT group were on average 0.30 SD (i.e., 1.5 seconds) faster on the Tower of London, difficulty load 4 (secondary outcome): 95% CI: -0.55 to -0.06, p=0.015. CT had similar positive effects on other processing speed-related executive function tasks, although these did not reach statistical significance. At follow-up, no group differences were present.

ConclusionsThe results show tentative but consistent positive effects of CT on processing speed during executive functioning. Future studies should investigate booster sessions to increase durability, optimize training duration, and study different sub-groups of PD patients along the continuum of cognitive decline towards PD dementia.

category: neurology


title: Measuring the exposure of Black, Asian and other ethnic groups to Covid-infected neighbourhoods in English towns and cities

abstract: Drawing on the work of The Doreen Lawrence Review - a report on the disproportionate impact of Covid-19 on Black, Asian and minority ethnic communities in the UK - this paper develops an index of exposure, measuring which ethnic groups have been most exposed to Covid-19 infected residential neighbourhoods during the first and second waves of the pandemic in England. The index is based on a Bayesian Poisson model with a random intercept in the linear predictor, allowing for extra-Poisson variation at neighbourhood and town/city scales. This permits within-city differences to be decoupled from broader regional trends in the disease. The research finds that members of ethnic minority groups tend to be living in areas with higher infection rates but also that the risk of exposure is distributed unevenly across these groups. Initially, in the first wave, the disease disproportionately affected Black residents. As the pandemic has progressed, especially the Pakistani but also the Bangladeshi and Indian groups have had the highest exposure. This higher exposure of the Pakistani group is not straightforwardly a function of neighbourhood deprivation because it is present across a range of average house prices. However, we find evidence to support the view, expressed in The Doreen Lawrence Review, that it is linked to occupational and environmental exposure, particularly residential density.

category: occupational and environmental health


title: Evaluation of Junior Doctors Knowledge of Corneal Donation and the New Opt-Out System in England

abstract:
ObjectivesTo evaluate the knowledge of corneal donation and the new opt-out system among junior doctors in the East Midlands, UK.

MethodsThis was a cross-sectional study performed during June-September 2020. A 26-item questionnaire-based survey was disseminated to all 340 junior doctors working in the East Midlands, UK. Relevant data, including participants background, knowledge of corneal donation and the new opt-out system introduced in England, were analysed.

ResultsA total of 143 responses were received (response rate=42.1%). Nineteen (13.3%) junior doctors had previously discussed about corneal donation. The majority (100, 69.9%) of them perceived the importance of obtaining consent for corneal donation as junior doctors, but only 24 (16.8%) felt comfortable in discussing corneal donation. The knowledge of corneal donation was low, with a mean correct response rate of 33.3+/-20.8%. Only 28 (19.6%) doctors were aware of the 24-hour death-to-enucleation time limit. The majority (116, 81.1%) of doctors would consider certifying a death on the ward quicker if they knew it could potentially compromise the quality of corneas. Most (103, 72%) doctors were aware of the new opt-out system but only 56 (39.2%) doctors correctly stated that donation can only proceed with family consent.

ConclusionJunior doctors working at the frontline services serve as valuable members in contributing to the process of obtaining consent for organ/tissue donation. Our study highlights the lack of knowledge of corneal donation and the opt-out system amongst junior doctors in the UK. Targeted postgraduate training during the induction process may potentially enhance the donation rate.

category: ophthalmology


title: De-novo FAIRification via an Electronic Data Capture system by automated transformation of filled electronic Case Report Forms into machine-readable data

abstract:
IntroductionExisting methods to make data Findable, Accessible, Interoperable, and Reusable (FAIR) are usually carried out in a post-hoc manner: after the research project is conducted and data are collected. De-novo FAIRification, on the other hand, incorporates the FAIRification steps in the process of a research project. In medical research, data is often collected and stored via electronic Case Report Forms (eCRFs) in Electronic Data Capture (EDC) systems. By implementing a de-novo FAIRification process in such a system, the reusability and, thus, scalability of FAIRification across research projects can be greatly improved. In this study, we developed and implemented a novel method for de-novo FAIRification via an EDC system. We evaluated our method by applying it to the Registry of Vascular Anomalies (VASCA).

MethodsOur EDC and research project independent method ensures that eCRF data entered into an EDC system can be transformed into machine-readable, FAIR data using a semantic data model (a canonical representation of the data, based on ontology concepts and semantic web standards) and mappings from the model to questions on the eCRF. The FAIRified data are stored in a triple store and can, together with associated metadata, be accessed and queried through a FAIR Data Point. The method was implemented in Castor EDC, an EDC system, through a data transformation application. The FAIRness of the output of the method, the FAIRified data and metadata, was evaluated using the FAIR Evaluation Services.

ResultsWe successfully applied our FAIRification method to the VASCA registry. Data entered on eCRFs is automatically transformed into machine-readable data and can be accessed and queried using SPARQL queries in the FAIR Data Point. Twenty-one FAIR Evaluator tests pass and one test regarding the metadata persistence policy fails, since this policy is not in place yet.

ConclusionIn this study, we developed a novel method for de-novo FAIRification via an EDC system. Its application in the VASCA registry and the automated FAIR evaluation show that the method can be used to make clinical research data FAIR when they are entered in an eCRF without any intervention from data management and data entry personnel. Due to the generic approach and developed tooling, we believe that our method can be used in other registries and clinical trials as well.


title: Estimating the super-spreading rate at workplaces using bluetooth technology

abstract: Workplaces deploy internal guidelines to remain operational during the ongoing COVID-19 pandemic. It is challenging to assess whether those interventions will prevent super-spreading events, where an infected individual transmits the disease to 10 or more secondary cases. Here we provide a model of infectious disease at the level of a workplace to address that problem. We take as input proximity contact records based on bluetooth technology and the infectious disease parameters from the literature. Using proximity contact data for a case-study workplace and an infection transmission model, we estimate the SARS-CoV-2 transmission rate as 0.014 per proximity contact, going up to 0.041 for the SARS-CoV-2 B.1.1.7 variant first detected in the UK. Defining super-spreading as events with 10 or more secondary infections, we obtain a super-spreading event rate of 2.3 per 1000 imported SARS-CoV-2 cases, rising up to 13.7 for SARS-CoV-2 B.1.1.7. This methodology provides the means for workplaces to determine their internal super-spreading rate or other infection related risks.


title: Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected persons

abstract:
ObjectiveTo compare anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG antibody concentrations and antibody-mediated neutralization of spike-ACE2 receptor binding in vitro following vaccination of non-hospitalized participants by sero-status and acute virus diagnosis history.

MethodsParticipants were studied before and after mRNA vaccination in a community-based, home-collected, longitudinal serosurvey; none reported hospitalization for COVID-19. Prior to vaccination, some reported prior positive acute viral diagnostic testing and were seropositive (COVID-19+). Participants who did not report acute viral diagnostic testing were categorized as seropositive or seronegative based on anti-spike RBD IgG test results. Primary measures were anti-spike RBD IgG concentration and percent antibody-mediated neutralization of spike protein-ACE2 interaction prior to vaccination, and after one or two doses of vaccine.

ResultsOf 290 unique vaccine recipients, 42 reported a prior COVID-19 diagnosis and were seropositive (COVID-19+). Of the 248 with no history of acute viral diagnostic testing, 105 were seropositive and 143 seronegative before vaccination. The median age was 38yrs (range 21-83) with 65% female and 35% male; 40% were non-white. Responses were evaluated after one (n=140) or two (n=170) doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. After one dose, median post-vaccine IgG concentration and percent neutralization were each significantly higher among the COVID-19+ group (median 47.7 {micro}g/ml, IgG; >99.9% neutralization) compared to the seropositives (3.4 {micro}g /ml IgG; 62.8% neutralization) and seronegatives (2.2 {micro}g /ml IgG; 39.5% neutralization). The latter two groups reached >95% neutralization after the second vaccine dose.

ConclusionsA prior outpatient COVID-19 diagnosis was associated with strong anti-spike RBD IgG and in vitro neutralizing responses after one vaccine dose. Persons seropositive for anti-spike RBD IgG in the absence of acute viral diagnostic testing, and those who were seronegative, required two doses to achieve equivalently high levels of IgG and neutralization activity. One mRNA vaccine dose is not sufficient to generate in vitro evidence of strong protection against COVID-19 among most persons previously infected with SARS-CoV-2, nor among seronegative persons.


title: Estimation and optimal control of the multi-scale dynamics of the Covid-19

abstract: This work aims at a better understanding and the optimal control of the spread of the new severe acute respiratory corona virus 2 (SARS-CoV-2). We first propose a multi-scale model giving insights on the virus population dynamics, the transmission process and the infection mechanism. We consider 10 compartments in the human population in order to take into accounts the effects of different specific mitigation policies: susceptible, infected, infectious, quarantined, hospitalized, treated, recovered, non-infectious dead, infectious dead, buried. The population of viruses is also partitioned into 10 compartments corresponding respectively to each of the first nine human population compartments and the free viruses available in the environment. Indeed, we have human to human virus transmission, human to environment virus transmission, environment to human virus transmission and self infection by susceptible individuals. We show the global stability of the disease free equilibrium if a given threshold[T] 0 is less or equal to 1 and we provide how to compute the basic reproduction number[R] 0. A convergence index[T] 1 is also defined in order to estimate the speed at which the disease extincts and an upper bound to the time of extinction is given. The existence of the endemic equilibrium is conditional and its description is provided. We evaluate the sensitivity of[R] 0,[T] 0 and[T] 1 to control parameters such as the maximal human density allowed per unit of surface, the rate of disinfection both for people and environment, the mobility probability, the wearing mask probability or efficiency, and the human to human contact rate which results from the previous one. Except the maximal human density allowed per unit of surface, all those parameters have significant effects on the qualitative dynamics of the disease. The most significant is the probability of wearing mask followed by the probability of mobility and the disinfection rate. According to a functional cost taking into consideration economic impacts of SARS-CoV-2, we determine and discuss optimal fighting strategies. The study is applied to real available data from Cameroon and an estimation of model parameters is done. After several simulations, social distancing and the disinfection frequency appear as the main elements of the optimal control strategy.


title: Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study

abstract:
BackgroundBromhexine hydrochloride has been suggested as a TMPRSS2 protease blocker that precludes the penetration of SARS-CoV-2 into cells. We aimed to assess the preventive potential of regular bromhexine hydrochloride intake for COVID-19 risk reduction in medical staff actively involved in the evaluation and treatment of patients with confirmed or suspected SARS-CoV-2 infection.

MethodsIn a single-center randomized open-label study, medical staff managing patients with suspected and confirmed COVID-19 were enrolled and followed up for 8 weeks. The study began at the initiation of COVID-19 management in the clinic. The study was prematurely terminated after the enrollent of 50 participants without a history of SARS-CoV-2 infection: 25 were assigned to bromhexine hydrochloride treatment (8 mg 3 times per day), and 25 were controls. The composite primary endpoint was a positive nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV-2 or signs of clinical infection within 28 days and at week 8. Secondary endpoints included: time from the first contact with a person with COVID-19 to the appearance of respiratory infection symptoms; the number of days before a first positive SARS-CoV-2 test; the number of asymptomatic participants with a positive nasopharyngeal swab test; the number of symptomatic COVID-19 cases; adverse events.

ResultsThe rate of the combined primary endpoint did not differ significantly between the active treatment group (2/25 [8%]) and control group (7/25 [28%]); P=0.07. A fewer number of participants developed symptomatic COVID-19 in the treatment group compared to controls (0/25 vs 5/25; P = 0.02).

ConclusionAlthough the study was underpowered, it showed that Bromhexine hydrochloride prophylaxis was associated with a reduced rate of symptomatic COVID-19. The prophylactic treatment was not associated with a lower combined primary endpoint rate, a positive swab PCR test, or COVID-19. (ClinicalTrials.gov number, NCT04405999)


title: Development and Implementation of a scalable and versatile test for COVID-19 diagnostics in rural communities

abstract: Rapid and widespread testing of severe acute respiratory coronavirus 2 (SARS-CoV-2) is essential for an effective public health response aimed at containing and mitigating the coronavirus disease 2019 (COVID-19) pandemic. Successful health policy implementation relies on early identification of infected individuals and extensive contact tracing.However, rural communities, where resources for testing are sparse or simply absent, face distinctive challenges to achieving this success. Accordingly, we report the development of an academic, public land grant University laboratory-based detection assay for the identification of SARS-CoV-2 in samples from various clinical specimens that can be readily deployed in areas where access to testing is limited. The test, which is a quantitative reverse transcription polymerase chain reaction (RT-qPCR)-based procedure, was validated on samples provided by the state laboratory and submitted for FDA Emergency Use Authorization. Our test exhibits comparable sensitivity and exceeds specificity and inclusivity values compared to other molecular assays. Additionally, this test can be re-configured to meet supply chain shortages, modified for scale up demands, and is amenable to several clinical specimens. Test development also involved 3D engineering critical supplies and formulating a stable collection media that allowed samples to be transported for hours over a dispersed rural region without the need for a cold-chain. These two elements that were critical when shortages impacted testing and when personnel needed to reach areas that were geographically isolated from the testing center. Overall, using a robust, easy-to-adapt methodology, we show that an academic laboratory can supplement COVID-19 testing needs and help local health departments assess and manage outbreaks. This additional testing capacity is particularly germane for smaller cities and rural regions that would otherwise be unable to meet the testing demand.


title: Mouth-to-mouth ventilation through cardiopulmonary resuscitation, is there any other way?

abstract:
objectiveto provide and explore possibility of new idea that perform mouth-to-mouth ventilation through cardiopulmonary resuscitation.

Methodsstage one is establishing the ventilation technique using cola bottle, stage two is measuring the tidal volume when different sized cola bottles were used.

Resultthe smallest sized cola bottle(500ml) can also make obvious thorax rise in manikin CPR model. The tidal volume is 174.5+9.1ml, 220+7.6ml and 447+15.9ml respectively for 500ml, 600ml and 1.25L cola bottles when using single hand performance. There are statistical differences (0.001) in tidal volume of different sized cola bottle by using one hand performance and two hands.

Conclusionlarger sized cola bottles(600ml,1.25L) could be used as substitute ventilation technique for mouth-to-mouth ventilation in special circumnutates.


title: The use of a participatory patient engagement research project to meaningfully engage those with lived experience of diabetes and homelessness

abstract:
IntroductionParticipatory research is a study method that engages patient partners in research programs from study design through to completion. It has seldom been used in diabetes health services research. Our objectives were to describe the process and challenges of conducting a patient-engagement project and to highlight the experiences of patient participants and academic researchers.

Research Design & MethodsWe recruited PWLEH and diabetes in Toronto, Canada to be patient partners. Group members were asked to commit to attending biweekly meetings. We undertook two major research projects: Concept mapping to choose a research focus; and photovoice to explore accessing healthy food while homeless. We used a convergent mixed methods design to evaluate their experience.

ResultsA diverse group of 8 PWLEH had an average attendance of 82% over 21 meetings - despite this success, we encountered a number of challenges to conducting this research. Group members reported that participation improved their ability to be self-advocates in their diabetes care and provided them with tangible skills and social benefits. Group members stated that they valued being involved in all aspects of the research, in particular knowledge translation activities, including advocating for nutritious food at shelters; presenting to stakeholders; and meeting with policy makers.

ConclusionsThe use of participatory patient engagement research methods enables academic researchers to support community members in pursuing research that is pertinent to them and which has a positive impact. In our study, group members contributed in meaningful ways and also valued the experience.

What is already known about this subject?O_LIPatient oriented research is important to public health research as it helps with the development of relevant interventions and knowledge translation.
C_LIO_LIParticipatory research is a form of research that maximally involves patients in all phases of the research.
C_LIO_LIParticipatory research has rarely been used in research on diabetes and diabetes-related interventions.
C_LI

What are the new findings?O_LIPatient engagement is important for studies involving socially disadvantaged populations with diabetes.
C_LIO_LICommunity members involved in research contribute substantially to research projects but also find the experience to be enriching and valuable.
C_LI

How might these results change the focus of research or clinical practice?O_LIThose who conduct research with and develop programs to provide diabetes care, especially to socially disadvantaged populations, should involve community members through all phases of the process to ensure the intervention is maximally useful for patients.
C_LI

category: endocrinology


title: Predictive Capacity of COVID-19 Test Positivity Rate

abstract: COVID-19 infections can spread silently, due to the simultaneous presence of significant numbers of both critical and asymptomatic to mild cases. While for the former reliable data are available (in the form of number of hospitalization and/or beds in intensive care units), this is not the case of the latter. Hence, analytical tools designed to generate reliable forecast and future scenarios, should be implemented to help decision makers planning ahead (e.g. medical structures and equipment). Previous work of one of the authors shows that an alternative formulation of the Test Positivity Rate (TPR), i.e. the proportion of the number of persons tested positive in a given day, exhibits a strong correlation with the number of patients admitted in hospital and intensive care units. In this paper, we investigate the lagged correlation structure between the newly defined TPR and the hospitalized people time series, exploiting a rigorous statistical model, the Seasonal Auto Regressive Moving Average (SARIMA). The rigorous analytical framework chosen, i.e. the stochastic processes theory, allowed for a reliable forecasting about 12 days ahead, of those quantities. The proposed approach would also allow decision makers to forecast the number of beds in hospitals and intensive care units needed 12 days ahead. The obtained results show that a standardized TPR index is a valuable metric to monitor the growth of the COVID-19 epidemic. The index can be computed on daily basis and it is probably one of the best forecasting tools available today for predicting hospital and intensive care units overload, being an optimal compromise between simplicity of calculation and accuracy.


title: Trends in SARS-CoV-2 detection during social relaxation measures over ten months of COVID-19 pandemic in the metropolitan area of Rio de Janeiro, Brazil

abstract: We analyzed the effects of sequential reopening events during COVID-19 pandemic, based on 76,419 SARS-CoV-2 molecular tests performed from April 2020 to January 2021 in Rio de Janeiro metropolitan area, Brazil, third largest in South America. Post-opening events provoked different impacts on cases and deaths, but showing limited temporary effect.


title: A systematic review and meta-analysis of longitudinal cohort studies comparing mental health before versus during the COVID-19 pandemic

abstract:
BackgroundIncreases in mental health problems have been observed in some studies during the COVID-19 pandemic. It is unclear whether changes have been large and experienced by most population sub-groups, persisted over time or been symptom specific.

MethodsWe systematically reviewed and meta-analysed longitudinal cohort studies that examined changes in mental health among the same group of participants before and during the pandemic (PROSPERO: CRD42021231256). Searches for published and unpublished studies were conducted in January 2021. Changes in mental health (standardised mean change; SMC) were examined using meta-analyses.

FindingsSixty-five studies were included. There was an overall increase in mental health symptoms that was most pronounced during March-April 2020 (SMC = .102 [95% CI: .026 to .192], p = 0.03) before significantly declining over time (May-July SMC = .067 [95% CI: -.022 to .157], p = .141). Compared to measures of anxiety (SMC = 0.13, p = 0.02) and general mental health (SMC = -.03, p = 0.65), increases in depression and mood disorder symptoms tended to be larger (SMC = 0.22, p < .001) and reductions over time appeared less pronounced. Increased mental health symptoms were observed across most population subgroups examined but there was no evidence of any change in symptoms among samples with a pre-existing mental health condition.

InterpretationThere was a small increase in mental health symptoms soon after the outbreak of the COVID-19 pandemic that decreased and was comparable to pre-pandemic levels by mid-2020 among most population sub-groups and symptom types.

FundingN/A

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere have been reported increases in mental health problems during the outbreak of the COVID-19 pandemic. However, it is unclear whether changes in mental health problems have been symptom specific, how changes have differed across populations and whether increased mental health problems have persisted over time. We systematically reviewed and meta-analysed longitudinal cohort studies that examined mental health among the same participants prior to and during the pandemic in 2020. This approach allowed us to quantify the mental health burden associated with the outbreak of the pandemic and how it has changed over time. We searched Pubmed, SCOPUS, Web of Science and PsychInfo from January 2020 to January 11, 2021 and identified eligible unpublished articles available on pre-print servers.

Added value of this studyWe identified 65 eligible articles that reported 201 comparisons of mental health pre vs. post pandemic outbreak. Meta-analysis indicated that longitudinal cohort studies that examined mental health prior to and during the COVID-19 pandemic in 2020 showed a significant but statistically small increase in mental health symptoms. The overall increase in mental health symptoms was most pronounced during the early stages of the pandemic (March-April), before decreasing and being generally comparable to pre-pandemic levels by mid-2020.

Compared to anxiety and general measures of mental health functioning, increases tended to be larger in depressive symptoms and although statistically small, remained elevated past the early stages of the pandemic. Increases in mental health symptoms were observed across most population sub-groups, but there was no evidence of a change in mental health symptoms among samples of participants with a pre-existing mental health condition.

Implications of all the available evidenceFindings confirm that the initial outbreak of the pandemic was associated with a significant but statistically small increase in mental health symptoms. Given that small effects may have meaningful cumulative consequences at the population level, there is a need for continued mental health provision and monitoring particularly during periods of the pandemic when infection rates and deaths are high. Further into the pandemic, mental health problems decreased significantly, which indicated recovery and resilience in overall mental health. Contrary to predictions made early in the pandemic, there was also no evidence of a worsening of mental health symptoms among samples of participants with a pre-existing mental health condition. Overall the results of the present analyses suggest that the pandemic may not have caused an unprecedented and long lasting mental health crisis, instead there appears to have been resilience in mental health.

category: psychiatry and clinical psychology


title: An increase in willingness to vaccinate against COVID-19 in the US between October 2020 and February 2021: longitudinal evidence from the Understanding America Study

abstract:
BackgroundRecent evidence suggests that willingness to vaccinate against COVID-19 has been declining throughout the pandemic and is low among ethnic minority groups.

MethodsObservational study using a nationally representative longitudinal sample (N =7,840) from the Understanding America Study (UAS). Changes in the percentage of respondents willing to vaccinate, undecided, or intending to refuse a COVID-19 vaccine were examined over 20 survey waves from April 1 2020 to February 15 2021.

ResultsAfter a sharp decline in willingness to vaccinate against COVID-19 between April and October 2020 (from 74.0% to 52.7%), willingness to vaccinate increased by 8.1% (p <.001) to 60.8% between October 2020 and February 2021. A significant increase in willingness to vaccinate was observed across all demographic groups examined and Black (15.6% increase) and Hispanic participants (12.1% increase) showed particularly large changes.

ConclusionsWillingness to vaccinate against COVID-19 increased in the US from October 2020 to February 2021.

Funding statementN/A


title: An increase in willingness to vaccinate against COVID-19 in the US: longitudinal evidence from the Understanding America Study


title: Analysis of the Factors Affecting the Adoption and Compliance of the NHS COVID-19 Mobile Application

abstract:
ObjectivesTo conduct an independent study investigating how adults perceive the usability, and functionality of the "NHS COVID-19" app. This study aims to highlight strengths, and provide recommendations to improve adoption of future contact tracing developments.

DesignA 60-item, anonymous online questionnaire, disseminated through social media outlets and email-lists by a team from Imperial College London.

SettingEngland

ParticipantsConvenience sample of 1036 responses, from participants aged 18 and above, between December 2020 to February 2021.

Primary Outcome MeasuresEvaluate the compliance and public attitude towards the "NHS COVID-19" app, regarding its functionality and features. This included whether participants expectations were met, and their thoughts on the app privacy and security. Furthermore, to distinguish how usability, perception, and adoption differed with varying demographics and user values.

ResultsFair app compliance was identified, with the app meeting expectations of 62.1% of participants who stated they downloaded it after weighted analysis. However, participants finding the interface challenging were less likely to read information in the app and had a lesser understanding of its functionality. Furthermore, lack of understanding regarding the apps functionality and privacy concerns were possibly reasons why users did not download it. A readability analysis of the text revealed that app information was conveyed at a level which might only be accessible to under 60% of the population. The study highlighted issues related to the potential of false positives caused by the design choices in the "Check-In" feature.

ConclusionThis study showed that while the "NHS COVID-19" app was viewed positively, there remained issues regarding participants perceived knowledge of the app functionality, potentially affecting compliance. Therefore, we recommended improvements regarding the delivery and presentation of the apps information, and highlighted the potential need for the ability to check out of venues to reduce the number of false positive contacts.

Strengths and LimitationsO_LIThis is the first study assessing the perceived usability and functionality of the "NHS COVID-19" app directly from app users.
C_LIO_LIDiverse sample size, with representation from all major regions of England.
C_LIO_LIStatistical analysis to compare perceived app usability and functionality across demographics and the participants values regarding privacy and information.
C_LIO_LIStudy was conducted during lockdown where app use may have been minimal.
C_LIO_LIStudy may have missed potential participants who were not active on the relevant social media channels and email mailing lists which were used to disseminate the survey.
C_LI


title: Analysis of the Factors Affecting the Adoption and Compliance of the NHS COVID-19 Mobile Application: A National Online Questionnaire Survey in England


title: Social-distancing Fatigue: Evidence from Real-time Crowd-sourced Traffic Data

abstract:
IntroductionTo mitigate the COVID-19 pandemic and prevent overwhelming the healthcare system, social-distancing policies such as school closure, stay-at-home orders, and indoor dining closure have been utilized worldwide. These policies function by reducing the rate of close contact within populations and results in decreased human mobility. Adherence to social distancing can substantially reduce disease spread. Thus, quantifying human mobility and social-distancing compliance, especially at high temporal resolution, can provide great insight into the impact of social distancing policies.

MethodsWe used the movement of individuals around New York City (NYC), measured via traffic levels, as a proxy for human mobility and the impact of social-distancing policies (i.e., work from home policies, school closure, indoor dining closure etc.). By data mining Google traffic in real-time, and applying image processing, we derived high resolution time series of traffic in NYC. We used time series decomposition and generalized additive models to quantify changes in rush hour/non-rush hour, and weekday/weekend traffic, pre-pandemic and following the roll-out of multiple social distancing interventions.

ResultsMobility decreased sharply on March 14, 2020 following declaration of the pandemic. However, levels began rebounding by approximately April 13, almost 2 months before stay-at-home orders were lifted, indicating premature increase in mobility, which we term social-distancing fatigue. We also observed large impacts on diurnal traffic congestion, such that the pre-pandemic bi-modal weekday congestion representing morning and evening rush hour was dramatically altered. By September, traffic congestion rebounded to approximately 75% of pre-pandemic levels.

ConclusionUsing crowd-sourced traffic congestion data, we described changes in mobility in Manhattan, NYC, during the COVID-19 pandemic. These data can be used to inform human mobility changes during the current pandemic, in planning for responses to future pandemics, and in understanding the potential impact of large-scale traffic interventions such as congestion pricing policies.

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title: Impact of social support, loneliness & social isolation on sustained physical activity during the COVID-19 pandemic

abstract:
COVID-19 lockdown introduced substantial barriers to physical activity, providing a unique  natural experiment to understand the social factors associated with sustained physical activity.

ObjectivesThe objectives of this study were to identify the proportion of people who successfully sustained physical activity during lockdown and to explore whether social support, loneliness and social isolation were associated with maintenance of physical activity during COVID-19 lockdown

MethodLongitudinal data from the COVID-19 Social Study was used to identify a sample of participants who maintained their physical activity despite lockdown.

Results16% were consistently active while 44% were completely inactive. After adjustment for multiple confounders high social support was associated with a 39% (95% CI, 12-74%) increased odds of sustaining physical activity. Associations between physical activity and loneliness and social isolation were not found.

ConclusionThis study supports previous research showing the importance of social support for the long-term maintenance of physical activity behaviour but shows that such effects extend to contexts of social restrictions.


title: Social support & sustained physical activity during the COVID-19 pandemic


title: Genome sequencing and detection of Philippine SARS-CoV-2 infections with viruses classified under the B.1.1.7 lineage

abstract: We report the sequencing and detection of 39 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage (UK variant) in the Philippines.


title: Detection and genome sequencing of SARS-CoV-2 belonging to the B.1.1.7 lineage in the Philippines