title: Recent changes in COVID-19 Vaccine Hesitancy among Healthcare Workers

abstract:
IntroductionEarly COVID-19 vaccine acceptance rates suggest that up to one-third of HCWs may be vaccine-hesitant. However, it is unclear whether hesitancy among HCWs has improved with time and if there are temporal changes whether these differ by healthcare worker role.

MethodsIn October 2020, a brief survey was sent to all participants in the Healthcare Worker Exposure Response and Outcomes (HERO) Registry with a yes/no question regarding vaccination under emergency use authorization (EUA): "If an FDA emergency use-approved vaccine to prevent coronavirus/COVID-19 was available right now at no cost, would you agree to be vaccinated?" The poll was repeated in December 2020, with the same question sent to all registry participants. Willingness was defined as a "Yes" response, and hesitancy was defined as a "No" response. Participants were stratified into clinical care roles. Baseline demographics of survey respondents at each timepoint were compared using appropriate univariate statistics (chi-squared and t-tests). Analyses were descriptive, with frequencies and percentages reported for each category.

ResultsOf 4882 HERO active registry participants during September 1 - October 31, 2020, 2070 (42.4%) completed the October survey, and n=1541 (31.6%) completed the December survey. 70.2% and 67.7% who were in clinical care roles, respectively. In October, 54.2% of HCWs in clinical roles said they would take an EUA-approved vaccine, which increased to 76.2% in December. The largest gain in vaccine willingness was observed among physicians, 64.0% of whom said they would take a vaccine in October, compared with 90.5% in December. Nurses were the least likely to report that they would take a vaccine in both October (46.6%) and December (66.9%). We saw no statistically significant differences in age, race/ethnicity, gender, or medical role between time points. When restricting to the 998 participants who participated at both time points, 69% were vaccine-willing at both time points; 15% were hesitant at both time points, 13% who were hesitant in October were willing in December; and 2.9% who were willing in October were hesitant in December.

ConclusionsIn a set of cross-sectional surveys of vaccine acceptance among healthcare workers, willingness improved substantially over 2 calendar months during which the US had a presidential election and two vaccine manufacturers released top-line Phase 3 trial results. While improved willingness was observed in all role categories, nurses reported the most vaccine hesitancy at both time points.


title: Anti-tRNA synthetase syndrome interstitial lung disease: A single center experience

abstract:
BackgroundRecognition of Anti tRNA synthetase (ARS) related interstitial lung disease (ILD) is key to ensuring patients have prompt access to immunosuppressive therapies. The purpose of this retrospective cohort study was to identify factors that may delay recognition of ARS-ILD.

MethodsPatients seen at Vanderbilt University Medical Center (VUMC) between 9/17/2017-10/31/2018 were included in this observational cohort. Clinical and laboratory features were obtained via chart abstraction. Kruskal-Wallis ANOVA, Mann-Whitney U, and Fishers exact t tests were utilized to determine statistical significance.

ResultsPatients with ARS were found to have ILD in 51.9% of cases, which was comparable to the frequency of ILD in systemic sclerosis (59.5%). The severity of FVC reduction in ARS (53.2%) was comparable to diffuse cutaneous systemic sclerosis (56.8%, p=0.48) and greater than dermatomyositis (66.9%, p=0.005) or limited cutaneous systemic sclerosis (lcSSc, 71.8%, p=0.005). Frank honeycombing was seen with ARS antibodies but not other myositis autoantibodies. ARS patients were more likely to first present to a pulmonary provider in a tertiary care setting (53.6%), likely due to fewer extrapulmonary manifestations. Only 33% of ARS-ILD were anti-nuclear antibody, rheumatoid factor, or anti-cyclic citrullinated peptide positive. Patients with ARS-ILD had a two-fold longer median time to diagnosis compared to other myositis-ILD patients (11.0 months, IQR 8.5 to 43 months vs. 5.0 months, IQR 3.0 to 9.0 months, p=0.003).

ConclusionsARS patients without prominent extra-pulmonary manifestations are at high risk for not being recognized as having a connective tissue disease related ILD and miscategorized as UIP/IPF without comprehensive serologies.

category: respiratory medicine


title: Management Algorithm of External Fixation in Lower Leg Arterial Injury for Limb Salvages

abstract:
PurposeThe purpose of this study was to review the roles of using external fixation to rescue the patients who sustained arterial injuries in the lower legs.

MethodsDemographics, surgical treatment and outcomes in 88 patients with lower leg arterial injuries treated by external fixation at two trauma centers from 2009 to 2018 were reviewed. The primary outcome was the rate of successful lower leg salvage, while secondary outcomes were complications and functional recovery.

Results80 patients (90 legs) maintained a successful lower leg salvage. The patients were followed up for an average of 15.5{+/-}5.5 months. 6 patients (8 pins) experienced pin-tract infection, pins loosening happened in 2 patients (4 pins), 7 patients (7 legs) developed wound superficial infection, 3 patients (3 legs) with a deep infection developed osteomyelitis, 16 patients (17 legs) suffered the bone nonunion or bone defect. The average healing time of fracture was 5.6{+/-}4.3months. The maintain of external fixation average time was 5.8{+/-}3.6 months.

ConclusionWith correctly judging the condition of limb ischemia, mastering reasonably the operation indications, and preventing complications, good clinical effects can be achieved when external fixation is used.

Level of evidenceRetrospective cohort, level IV.

category: surgery


title: Searching for prognostic biomarkers of Parkinson's Disease development in the Spanish EPIC cohort through a multiplatform metabolomics approach

abstract:
ObjectiveThe lack of knowledge about the onset and progression of Parkinsons disease (PD) hampers its early diagnosis and treatment. Our aim was to determine the biochemical remodeling induced by PD in a really early and pre-symptomatic stage and unveiling early potential diagnostic biomarkers adopting a multiplatform (LC-MS, GC-MS, CE-MS) untargeted metabolomics approach.

Methods41,437 healthy volunteers from the European Prospective Study on Nutrition and Cancer (EPIC)-Spain cohort were followed for around 15 years to ascertain incident PD. For this study, baseline pre-clinical plasma samples of 39 randomly selected individuals (46% females, 41- 69 years old) that developed PD (Pre-PD group) and the corresponding control group (n=39, 46% females, 41-69 years old) were analyzed. The metabolic differences were investigated by univariate and multivariate data analyses, followed by pathway-based metabolite analyses to obtain possible clues on biological functions.

ResultsOur results exposed significantly lower levels of seven free fatty acids in the pre-PD subjects, together with alterations in other metabolite classes. Our finding revealed alterations in fatty acids metabolism, mitochondrial dysfunction, oxidative stress, and gut-brain axis dysregulation.

ConclusionsAlthough the biological purpose of these events is still unknown, the mechanisms involved in the remodelling of the suggested metabolic pathways seem to appear long before the development of PD hallmarks. These findings might be considered as worthy potential markers whose alteration might lead to the development of PD hallmarks in the future. Consequently, this study is of inestimable value since this is the first study conducted with samples collected many years before the disease development.

category: neurology


title: Elevated Neutrophil to Lymphocyte Ratio Predicts In-hospital Mortality Among Stroke Patients in a Metropolitan hospital in Australia, Universal Value-added measure in Stroke Care

abstract:
Neutrophil counts (innate immunity) and lymphocyte counts (adaptive immunity) are common markers of inflammation in the context of acute stroke, and Neutrophil lymphocyte ratio (NLR) is likely to be expected to predict the post-stroke outcome.

This study aimed to explore the predictive value of NLR to predict the very early mortality during the acute hospital admission (death within the first week of hospital stay) as this has management implications for the ongoing investigations, family discussions and resource allocation. This the first such study attempting at exploring the role of NLR in hyperacute in-patient mortality in the world to the best of our knowledge.

This retrospective study included 120 patients (60 acute stroke patients who died within the first week of the hospital stay and 60 age, sex-matched controls who were discharged within two weeks of the hospital admission, alive. We reviewed the total white cell counts of these patients (first 72 hours of the hospital admission) and NLR was calculated manually. While there was no statistically significant difference between mean neutrophil counts and mean lymphocyte counts between the two cohorts [neutrophil counts (mean, SD), 8.52(3.20) in the death cohort, 6.48(2.20) among survivors and lymphocyte (mean, SD), 1.83(1.48) in the death cohort,1.66 (0.69) among survivors], there was a statistically significant difference in NLR between the two cohorts. NLR (mean, SD) was 6.51 (4.98) in the death cohort while the survivors had mean NLR of 4.64 with an SD 2.90 with a p-value of 0.048. Hypertension, diabetes, atrial fibrillation, previous vascular events were common in both groups indicating the value of exploring the evidence of background compromised vascular system and metabolic syndrome and bringing the systems biology approach to the management of stroke.


title: The mass balance model perfectly fits both Hall et al. underfeeding data and Horton et al. overfeeding data

abstract:
Background & AimsRecently, the validity of mass balance model (MBM) was questioned based on two feeding studies. Thus, we simulated both of these feeding trials.

MethodsMBM describes the temporal evolution of body weight and body composition under a wide variety of feeding experiments. This computational study simulated, utilizing MBM, the underfeeding trial by Hall et al. (Cell Metab. 2015;22:427-36) and the overfeeding trial by Horton et al. (Am J Clin Nutr. 1995;62:19-29).

ResultsOur simulation results indicate that data from both of these feeding trials perfectly match MBM-based predictions, i.e., MBM gives a remarkably accurate description of experimental data.

ConclusionsIt is becoming increasingly clear that our model (MBM) is perfectly able to predict body weight and body composition fluctuations under a wide variety of feeding experiments.

"There is a stupid humility that is not at all rare, and those afflicted with it are altogether unfit to become devotees of knowledge. As soon as a person of this type perceives something striking, he turns on his heel, as it were, and says to himself: "You have made a mistake. What is the matter with your senses? This cannot, may not, be the truth." And then, instead of looking and listening again, more carefully, he runs away from the striking thing, as if he had been intimidated, and tries to remove it from his mind as fast as he can. For his inner canon says: "I do not want to see anything that contradicts the prevalent opinion. Am I called to discover new truths? There are too many old ones, as it is..."

- Friedrich Nietzsche, The Gay Science (1882)

category: nutrition


title: A comprehensive digital phenotype for postpartum hemorrhage

abstract:
ObjectiveWe aimed to establish a comprehensive digital phenotype for postpartum hemorrhage (PPH). Current guidelines rely primarily on estimates of blood loss, which can be inaccurate and biased, and ignore a suite of complementary information readily available in electronic medical records (EMR). Inaccurate and incomplete phenotyping contribute to ongoing challenges to track PPH outcomes, develop more accurate risk assessments, and identify novel interventions.

MethodsWe constructed a cohort of 71,944 deliveries from the Mount Sinai Health System, 2011-2019. Estimates of postpartum blood loss, shifts in hematocrit intra- and postpartum, administration of uterotonics, surgical treatments, and associated diagnostic codes were combined to identify PPH retrospectively. All clinical features were extracted from structured EMR data and mapped to common data models for maximum interoperability across hospitals. Blinded chart review was done on a randomly selected subset of cases and controls for validation and performance was compared to alternate PPH phenotypes.

ResultsWe identified 6,639 cases (9% prevalence) using our phenotype - more than three times as many as using blood loss alone (N=1,747), supporting the need to incorporate other diagnostic and treatment data. Blinded chart review revealed our phenotype had 96% sensitivity, 89% precision, 77% specificity, and 89% accuracy to detect PPH. Alternate phenotypes were less accurate, including a common blood loss-based definition (67%) and a previously published digital phenotype (74%).

ConclusionWe have developed a scalable, accurate, and valid digital phenotype that may be of significant use for tracking outcomes and ongoing clinical research to deliver better preventative interventions for PPH.

category: obstetrics and gynecology


title: Day by day symptoms following positive and negative PCR tests for SARS-CoV-2 in non-hospitalized health-care workers: a 90-day follow-up study

abstract:
BackgroundLittle is known about the long-term course of symptoms for mild coronavirus disease 2019 (COVID-19) when accounting for symptoms due to other causes. We aimed to compare symptoms day by day for non-hospitalised individuals who tested positive and negative with polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

MethodsWe followed 210 test-positive and 630 individually matched test-negative health-care workers of the Central Denmark Region up to 90 days after the test, April-June 2020. They daily reported seven COVID-19 related symptoms. Symptom courses were compared graphically and by conditional multivariable logistic regression.

ResultsThirty % of test-positive and close to zero of test-negative participants reported a reduced sense of taste and smell during all 90 days of follow-up (adjusted odds ratio [aOR] 86.07, 95% CI 22.86-323). Dyspnoea was reported by an initial 20% of test-positive with a gradual decline to about 5% after 30 days without ever reaching the level of the test-negative participants (aOR 6.88, 95% CI 2.41-19.63). Cough, headache, sore throat, muscle aches, and fever were temporarily more prevalent among the test positive participants, but after 30 days, no increases were seen. Women and participants aged 45 years or older tended to be more susceptible to SARS-CoV-2 infection.

ConclusionPrevalence of long-lasting reduced sense of taste and smell is highly increased after being diagnosed with mild COVID-19. This pattern is also seen for dyspnoea at a low level but not for cough, sore throat, headache, muscle ache or pain, or fever.

Key messagesO_LIReduced sense of taste and smell is present at a highly increased level of 30% during 90 days after testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2).
C_LIO_LITest-positive participants experience dyspnoea persistently more often than test-negative participants but affect only few.
C_LIO_LIThe prevalence of cough, sore throat, headache, muscle ache or pain, and fever following a positive test reach the level seen after a negative test within 30 days.
C_LIO_LIWomen and participants aged 45 years or older tend to be more susceptible to symptoms following SARS-CoV-2 infection.
C_LI

category: occupational and environmental health


title: Strong and Significant Associations of Single Nucleotide Variants (SNVs) in the Promoter and 3'-Untranslated Region (3'-UTR) of Vascular Endothelial Growth Factor (VEGF) Gene with Head and Neck Cancers

abstract:
BackgroundVascular Endothelial Growth Factor (VEGF) has a potent role in tumorigenesis and metastasis. However, data for the role of common single nucleotide variants (SNVs) in the highly polymorphic VEGF gene in head and neck cancers (HNCs) is limited in general and unavailable in South Asian populations.

The present study addresses this shortfall. It investigates the association of two VEGF SNVs, -2578 C/A (rs699947) in the promoter region and +936 C/T (rs3025039) in 3-UTR, with the risk of HNCs and tumour characteristics.

MethodsThe study comprised 323 participants with 121 HNC patients and 202 controls. Germline DNA was isolated from peripheral blood samples. PCR-RFLP methods were optimized and validated by Sanger sequencing. After Hardy-Weinberg evaluation, the independent associations were analyzed by applying genetic models. The {chi}2 test of independence or Fishers Exact test (significant p-values at <0.05) were performed and ORs (odds ratios) with 95% confidence interval were tabulated.

ResultsVEGF -2578 A-allele, A-carrier and AA genotypes had significant protective association against HNCs. The respective ORs were: 0.651 (0.469 - 0.904), 0.613 (0.381 - 0.985), and 0.393 (0.193 - 0.804). VEGF +936 T-allele, CT and T-carrier genotypes had significantly increased susceptibility for HNCs. The respective ORs were 1.882 (1.001 - 3.536), 2.060 (1.035 - 4.102), and 2.023 (1.032 - 3.966). Additionally, VEGF +936 CT and T-carrier genotypes showed significant associations with higher tumour grade (p-value <0.029, and <0.037, respectively).

ConclusionThe present study is the foremost report of independent and unique associations of the investigated VEGF SNVs with HNCs.

category: genetic and genomic medicine


title: redBERT: A Topic Discovery and Deep SentimentClassification Model on COVID-19 OnlineDiscussions Using BERT NLP Model

abstract: A Natural Language Processing (NLP) method was used to uncover various issues and sentiments surrounding COVID-19 from social media and get a deeper understanding of fluctuating public opinion in situations of wide-scale panic to guide improved decision making with the help of a sentiment analyser created for the automated extraction of COVID-19 related discussions based on topic modelling. Moreover, the BERT model was used for the sentiment classification of COVID-19 Reddit comments. These findings shed light on the importance of studying trends and using computational techniques to assess human psyche in times of distress.

category: health informatics


title: State minimum wage, paid sick leave, and food insufficiency during the COVID-19 pandemic

abstract:
IntroductionPeople in low-income households face a disproportionate burden of health and economic consequences brought on by the COVID-19 pandemic, including COVID-19 and food insufficiency. State minimum wage and paid sick leave policies may affect whether people are vulnerable to employment and health shocks to income and affect food insufficiency.

MethodsWe evaluated the relationship between state minimum wage policies and the outcome of household food insufficiency among participants younger than 65 during the COVID-19 pandemic. We used data from biweekly, state representative Census Pulse surveys conducted between August 19 and December 21, 2020. We conducted analyses in the full population under age 65 years, who are most likely to work, and in households with children. The primary exposure was state minimum wage policies in four categories: less than $8.00, $8.00 to $9.99, $10.00 to $11.99, and $12.00 or more. A secondary exposure was missing work due to COVID-19, interacted with whether participants reported not having paid sick leave. Food insufficiency was defined as sometimes or often not having enough to eat in the past seven days. Very low child food sufficiency was defined as children sometimes or often not eating enough in the past seven days because of inability to afford food. We conducted a multivariable modified Poisson regression analysis to estimate adjusted prevalence ratios and marginal effects. We clustered standard errors by state. To adjust for state health and social programs, we adjusted for health insurance and receipt of supplemental nutrition assistance program benefits, unemployment insurance, and stimulus payments as well as for population demographic characteristics associated with food insufficiency. We conducted subgroup analyses among populations most likely to be affected by minimum wage policies: Participants who reported any work in the past seven days, who reported <$75,000 in 2019 household income, or who had a high school education or less. We conducted falsification tests among participants less likely to be directly affected by policies, [≥]65 years or with >$75,000 in 2019 household income.

ResultsIn states with a minimum wage of less than $8.00, 14.3% of participants under age 65 and 16.6% of participants in households with children reported household food insufficiency, while 10.3% of participants reported very low child food sufficiency. A state minimum wage of $12 or more per hour was associated with a 1.83 percentage point reduction in the proportion of households reporting food insufficiency relative to a minimum wage of less than $8.00 per hour (95% CI: -2.67 to -0.99 percentage points). In households with children, a state minimum wage of $12 or more per hour was associated with a 2.13 percentage point reduction in household food insufficiency (95% CI: -3.25 to -1.00 percentage points) and in very low child food sufficiency (-1.16 percentage points, 95% CI: -1.69 to -0.63 percentage points) relative to a state minimum wage of less than $8.00 per hour. Minimum wages of $8.00 to $9.99 and $10.00 to $11.99 were not associated with changes in child food insufficiency or very low child food sufficiency relative to less than $8.00 per hour. Subgroup analyses and sensitivity analyses were consistent with the main results. Estimates were of a lesser magnitude (<0.6 percentage points) in populations that should be less directly affected by state minimum wage policies. Missing work due to COVID-19 without paid sick leave was associated with a 5.72 percentage point increase in the proportion of households reporting food insufficiency (95% CI: 3.59 to 7.85 percentage points).

DiscussionFood insufficiency is high in all households and even more so in households with children during the COVID-19 pandemic. Living in a state with at least a $12 minimum wage was associated with a decrease in the proportion of people reporting food insufficiency during the COVID-19 pandemic. Not having paid leave was associated with increases in food insufficiency among people who reported missing work due to COVID-19 illness. Policymakers may wish to consider raising the minimum wage and paid sick leave as approaches to reducing food insufficiency during and after the COVID-19 pandemic.

category: health policy


title: Accounting for health inequities in the design of contact tracing interventions: a rapid review

abstract:
ContextContact tracing has been a central COVID-19 transmission control measure. However, without the consideration of the needs of specific populations, public health interventions can exacerbate health inequities.

PurposeThe purpose of this rapid review was to determine if and how health inequities were included in the design of contact tracing interventions in epidemic settings.

MethodWe conducted a search of the electronic databases MEDLINE and Web of Science. Our inclusion criteria included articles that: (i) described the design of contact tracing interventions, (ii) have been published between 2013 and 2020 in English, French, Spanish, Chinese, or Portuguese, (iii) and included at least 50% of empiricism, according to the Automated Classifier of Texts on Scientific Studies (ATCER) tool. We relied on various tools to extract data.

ResultFollowing the titles and abstracts screening of 230 articles, 39 articles met the inclusion criteria. Only seven references were retained after full text review. None of the selected studies considered health inequities in the design of contact tracing interventions.

ConclusionThe use of tools/concepts for incorporating health inequities, such as the REFLEX-ISS tool, and "proportionate universalism" when designing contact tracing interventions, would enable practitioners, decision makers, and researchers to better consider health inequities.


title: Years of Life Lost Associated with COVID-19 Deaths in the United States During the First Year of the Pandemic

abstract:
BackgroundYears of Life Lost (YLL) measure the shortfall in life expectancy due to a medical condition and have been used in multiple contexts. Previously it was estimated that there were 1.2 million YLLs associated with COVID-19 deaths in the United States through July 11, 2020. The aim of this study is to update YLL estimates for the first full year of the pandemic.

MethodsWe employed data regarding COVID-19 deaths in the United States through January 31, 2021 by jurisdiction, gender, and age group. We used actuarial life expectancy tables by gender and age to estimate YLLs.

ResultsWe estimated roughly 3.9 million YLLs due to COVID-19 deaths, which corresponds to roughly 9.2 YLLs per death. We observed a large range across states in YLLs per 10,000 capita, with New York City at 298 and Vermont at 12. Nationally, males had a higher number of YLLs per death than females (9.5 versus 8.8), but there was significant variation in gender differences across states.

ConclusionsOur estimates provide further insight into the mortality effects of COVID-19. The observed differences across states and genders demonstrate the need for disaggregated analyses of the pandemics effects.

category: infectious diseases


title: Genetic variation of IFNL4 is associated with COVID-19

abstract: COVID-19 currently represents a major public health problem. The causes that underlying susceptibility to infection in have not yet been determined. Interferons (IFNs) are intensively being investigated because of their antiviral properties. Among them, Interferon lambda 4 (IFNL4) has been reported to have antiviral activity against viral infections of the upper respiratory tract, Hepatitis virus C (HCV), and coronaviruses. The importance of this cytokine was shown by the fact that genetic variants of IFNL4 have been associated with viral clearance and response to IFNs-based therapies in HCV and other infections by RNA virus. In this study, we have investigated whether the rs12979860 polymorphism within the IFNL4 was also associated with COVID-19. Our findings show that the presence of the CC allele of rs12979860 was significantly lower in SARS-CoV-2 infected patients with regard to non-COVID-19 controls (38% vs 55%, p<0001). These results were not affected by sex, age, and severity of disease. These findings suggest that the CC allele may also confer protection against COVID-19. They may contribute to understanding the mechanisms of disease, the response to IFN-based treatments, and the racial differences observed in the disease.


title: IFNL4 genetic variant can predispose to COVID-19


title: A single dose of SARS CoV 2 FINLAY FR 1A dimeric RBD recombinant vaccine enhances neutralization response in COVID19 convalescents, with excellent safety profile. A preliminary report of an open-label phase 1 clinical trial

abstract: We evaluated response to a single dose of the FINLAY-FR-1A recombinant dimeric-RBD base vaccine during a phase I clinical trial with 30 COVID-19 convalescents, to test its capacity for boosting natural immunity. This short report shows: a) an excellent safety profile one month after vaccination for all participants, similar to that previously found during vaccination of naive individuals; b) a single dose of vaccine induces a >20 fold increase in antibody response one week after vaccination and remarkably 4-fold higher virus neutralization compared to the median obtained for Cuban convalescent serum panel. These preliminary results prompt initiation of a phase II trial in order to establish a general vaccination protocol for convalescents.


title: Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients

abstract:
BackgroundSustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.

MethodsNinety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.

ResultsViral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI [≥] 25kg/m2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044).

ConclusionsWe demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.


title: On the Environmental Determinants of COVID-19 Seasonality

abstract:
Viral respiratory diseases (VRDs), such as influenza and COVID-19, are thought to spread faster over winter than during summer. It has been previously argued that cold and dry conditions were more conducive to the transmission of VRD than warm and humid climates, although this relationship appears restricted to temperate regions, and the causal relationship is not well understood. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has emerged as a serious global public health problem after the first COVID-19 reports in Wuhan, China, in late 2019. It is still unclear whether this novel respiratory disease will ultimately prove to be a seasonal endemic disease. Here, we suggest that Air Drying Capacity (ADC; an atmospheric state-variable known to control the fate/evolution of the virus-laden droplets) and ultraviolet radiation (UV) are probable environmental determinants in shaping the transmission of COVID-19 at the seasonal time scale. These variables, unlike temperature and humidity, provide a physically-based framework consistent with the apparent seasonal variability in COVID-19 prevalence across a broad range of climates (e.g., Germany and India). Since this disease is known to be influenced by the compounding effect of social, biological, and environmental determinants, this study does not claim that these environmental determinants exclusively shape the seasonality of COVID-19. However, we argue that ADC and UV play a significant role in COVID-19 dynamics at the seasonal scale. These findings could help guide the development of a sound adaptation strategy against the pandemic over the coming seasons.

Plain Language SummaryThere is growing scientific interest in the potential seasonality of COVID-19 and its links to climate variables. This study aims to determine whether four environmental variables, namely temperature, humidity, Air Drying Capacity (ADC), and ultraviolet radiation (UV), are probable environmental determinants for the observed seasonal dynamics of COVID-19 prevalence, based on extensive country-level data spanning the first year of the pandemic. Although the influence of socio-economic factors may be dominant, we here suggest that ADC and UV are key environmental determinants of COVID-19 and can potentially affect the transmission and seasonality of the disease across a wide range of climates.

Key PointsO_LIThe seasonality of COVID-19 appears to follow seasonality of some environmental variables.
C_LIO_LISeasonality of air drying capacity and ultraviolet radiation consistently match seasonality of COVID-19, across climatic zones.
C_LIO_LISeasonality of air humidity and temperature, match seasonality of COVID-19 in temperate climates, but not in tropical monsoon climates.
C_LI


title: Towards Understanding the COVID-19 Case Fatality Rate

abstract: An important parameter for COVID-19 is the case fatality rate (CFR). It has been applied to wide applications, including the measure of the severity of the infection, the estimation of the number of infected cases, risk assessment etc. However, there remains a lack of understanding on several aspects of CFR, including population factors that are important to CFR, the apparent discrepancy of CFRs in different countries, and how the age effect comes into play. We analyze the CFRs at two different time snapshots, July 6 and Dec 28, with one during the first wave and the other a second wave of the COVID-19 pandemic. We consider two important population covariates, age and GDP as a proxy for the quality and abundance of public health. Extensive exploratory data analysis leads to some interesting findings. First, there is a clear exponential age effect among different age groups, and, more importantly, the exponential index is almost invariant across countries and time in the pandemic. Second, the roles played by the age and GDP are a little surprising: during the first wave, age is a more significant factor than GDP, while their roles have switched during the second wave of the pandemic, which may be partially explained by the delay in time for the quality and abundance of public health and medical research to factor in.


title: THE PERFORMANCE COMPARISON OF sPLA2-IIA WITH HIGH-SENSITIVE CRP, PCT, NEUTROPHIL PERCENTAGE, LACTATE TO IDENTIFY BACTERIAL INFECTION IN LOW- AND MIDDLE-INCOME COUNTRY: A PROSPECTIVE STUDY

abstract: Early bacterial infection (BI) identification in resource-limiting Emergency Departments (ED) is challenging especially in low- and middle-income counties (LMIC). Misdiagnosis predisposes to antibiotic overuse and propagates antimicrobial resistance. This study evaluates new emerging biomarkers, secretory phospholipase A2 group IIA (sPLA2-IIA), and compares with other biomarkers on their performance characteristic of BI detection in Malaysia, an LMIC. A prospective cohort study was conducted involving 151 consecutive patients admitted to the ED. A single measurement was taken upon patient arrival in ED and was analysed for serum levels of sPLA2-IIA, high-sensitive C-reactive protein (CRP), procalcitonin (PCT), neutrophil percentage (N%), and lactate. All biomarkers performance was compared for the outcomes using area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. The performance of sPLA2-IIA (AUROC 0.93 [95% CI: 0.89-0.97]; Sn 80% [95% CI: 72-87] Sp 94% [95% CI: 81-89]) was the highest among all. It was comparable with high-sensitive CRP (AUROC 0.93 [95% CI: 0.88-0.97]; Sn 75% [95% CI: 66-83]; Sp 91 [95% CI: 77-98]) but had a higher Sn and Sp. The sPLA2-IIA was also found superior to N%, PCT, and lactate. This finding suggested sPLA2-IIA was recommended biomarkers for BI detection in LMIC.

category: emergency medicine


title: COMPARISON OF sPLA2-IIA PERFORMANCE WITH HIGH-SENSITIVE CRP, NEUTROPHIL PERCENTAGE, PCT AND LACTATE TO IDENTIFY BACTERIAL INFECTION: A PROSPECTIVE STUDY


title: 365 days with COVID-19 in Iran: data analysis and epidemic curves

abstract:
BackgroundThe first confirmed cases of COVID-19 in Iran were reported on February 19, 2020. This study aimed to analyze the epidemic curves and to investigate the correlation between epidemic parameters and furthermore to analyze the impact of control measures on the spread of COVID-19 in Iran during 365 days of the epidemic.

MethodsWe used data from February 20, 2020, to February 18, 2021, on the number of COVID-19 cases reported by Iranian governments. Pearson correlation coefficient was applied to investigate the correlation between different epidemic parameters. The number of daily deaths per daily new cases was averaged to calculate daily death rate and the same method was used to investigate the rate of daily positive tests. Furthermore, we employed two different methods to calculate the effective reproduction number using reported data.

ResultsThe results showed that there was a strong correlation between the number of daily deaths and the number of daily new cases (specially the admitted cases). The results also indicated that the mean of daily death rate of COVID-19 during 365 days was 4.9 percent, and averagely 13.9 percent of daily tests results were positive. Furthermore, epidemic curves showed that implementing strict social distancing measures effectively reduced the number of confirmed cases. The effective reproduction curve indicated that social distancing is still necessary to control the spread of COVID-19 in Iran.

ConclusionsAnalyzing the prevention and control measures indicated that the strict social distancing implemented by the government effectively reduces the number of new cases and deaths. The curve of reproduction number also showed that effective reproduction number is still above one; hence, it is necessary to continue strict social distancing and control travelling to prevent causing another wave of outbreak especially in Persian New Year.

category: epidemiology


title: Long-term Exposures to Air Pollutants Affect FeNO in Children: A Longitudinal Study

abstract:
Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation shown to be responsive to short-term air pollution exposures; however, effects of long-term exposures are uncertain. Using longitudinal assessments of FeNO and air pollutant exposures, we aimed to determine whether FeNO is a marker for chronic effects of air pollution exposures after accounting for short-term exposures effects.

FeNO was assessed up to six times 2004-2012 in 3607 schoolchildren from 12 communities in the Southern California Childrens Health Study. Within-community long-term ambient air pollution exposures (PM2.5, PM10, NO2, O3) were represented by differences between community-specific annual averages and the eight-year average spanning the study period. Linear mixed-effect models estimated within-participant associations of annual average air pollution with current FeNO, controlling for previous FeNO, prior seven-day average pollution, potential confounders, and community-level random intercepts. We considered effect modification by sex, ethnicity, asthma, and allergy at baseline.

We found FeNO was positively associated with annual average air pollution, after accounting for short-term exposures. One standard deviation higher annual PM2.5 and NO2 exposures (PM2.5:2.0 g/m3 ; NO2:2.7 ppb) were associated, respectively, with 4.6% (95%CI:2.3%-6.8%) and 6.5% (95%CI:4.1%-8.9%) higher FeNO. These associations were larger among females. We found little evidence supporting association with PM10 or O3.

Annual average PM2.5 and NO2 levels were associated with FeNO in schoolchildren, adding new evidence that long-term exposure affects FeNO beyond the well-documented short-term effects. Longitudinal FeNO measurements may be useful as an early marker of chronic respiratory effects of long-term PM2.5 and NO2 exposures in children.

Key messagesO_LIWe show strong evidence that long-term exposures to air pollutants affect FeNO, independent of the well-documented associations with short-term exposures to air pollution
C_LIO_LILongitudinal FeNO measurements may be useful as an early marker of chronic respiratory effects of long-term air pollution exposures in children.
C_LI

Capsule summaryAnnual average PM2.5 and NO2 were associated with FeNO in schoolchildren, adding new evidence that long-term exposure affects FeNO beyond the well-documented short-term effects.


title: A Nonlinear Observer to Estimate the Effective Reproduction Number of Infectious Diseases

abstract: In this paper, we design a Nonlinear Observer (NLO) to estimate the effective reproduction number ([R]t) of infectious diseases. The NLO is designed from a discrete-time augmented Susceptible-Infectious-Removed (SIR) model. The observer gain is obtained by solving a Linear Matrix Inequality (LMI). The method is used to estimate[R] t in Jakarta using epidemiological data during COVID-19 pandemic. If the observer gain is tuned properly, this approach produces similar result compared to existing approach such as Extended Kalman filter (EKF).


title: Massive Open Online Course (MOOC) Opportunities on Health Education (HE) during of mandatory social isolation context

abstract:
BackgroundRoutine care for prevention and health promotion has reduced significantly due to the Covid-19 pandemic and mandatory social isolation measures. In this context, it is necessary to identify and describe Massive Open Online Courses (MOOCs) that provide opportunities for health education, promotion, and prevention aimed at the general population. The study is a systematic review of MOOCs on health education, health promotion, and prevention for the general population in a pandemic context.

MethodsWe developed a search for MOOC courses aimed at the general population on health education, health promotion, and prevention in different MOOC available platforms. We executed a descriptive analysis of the main characteristics of the selected MOOCs.

ResultsThere were 117 MOOCs chosen on Health education, promotion, and prevention for the general population. Coursera (40.3%) was the platform that offered the highest quantity of MOOCs; more than half of MOOCs language was in English (52.9%). The median duration time in hours of the selected MOOCs was 11 (IR 6-15). The predominant themes were "Health promotion" (43%) and "Food and nutrition" (31%), and the origin was mainly from Europe (37.8%).

ConclusionsMOOCs offerings in Health Education (HE) is diverse, predominantly in English, of European origin, and in health promotion issues. This study opens an opportunity to multiply initiatives in different territories, considering other languages and topics more akin to each territorial reality, allowing it to be a more equitable learning opportunity in times of pandemic and compulsory social isolation.

FUNDINGNone.

category: primary care research


title: Maternal psychiatric diagnosis and comorbidities around pregnancy

abstract:
IMPORTANCEComorbidity between mental and physical health is a frequent problem, resulting in greater morbidity than the sum of the effects of individual diseases. Despite pervasive physiological and behavioral changes during pregnancy, the pattern of comorbidities among pregnant women is not well-understood.

OBJECTIVESystematically examine the associations between mental and physical diagnoses around pregnancy.

DESIGN, SETTING, PARTICIPANTSPopulation-based sample, containing all children born between January 1st, 1997 and December 31st, 2008 within a health maintenance organization (HMO) in Israel. Cohort children were linked to their mothers health information, creating mother-child dyads.

MAIN OUTCOMES AND MEASURESThe primary outcome was any ICD-9 mental health diagnosis within the pregnancy period or the preceding 12 months. The secondary outcomes were specific ICD-9 mental health diagnoses. Exposures were all ICD-9 physical (non-mental) health diagnoses received during the exposure period. We used logistic regression to test the risk of physical health diagnoses in pregnant women associated with mental health diagnoses. The covariates for this study included maternal age, birth year, socioeconomic status and total number of ICD-9 diagnoses during the exposure period.

RESULTSThe analytical sample included 76,783 mother-child dyads, with 30,084 unique mothers. The mean age at birth was 29.8 years, with 4.4% of mothers diagnosed with a mental health disorder during the pregnancy period. Of the 18 major ICD-9 diagnostic categories, 10 were positively associated with mental health disorders, including ICD categories of e.g., symptoms, signs, and ill-defined conditions (OR=1.69; 95% CI=1.50, 1.89), musculoskeletal (OR=1.33; 95% CI=1.22,1.45) and digestive system diseases (OR=1.25; 95% CI=1.15, 1.37). Comorbidity between mental and physical health diagnoses was higher than that observed between various physical health diagnoses. Associations between physical health diagnoses and specific mental health conditions were consistent with the results of the general mental health and physical health comorbidity.

CONCLUSION AND RELEVANCEWe observed that associations between maternal diagnoses and mental health stand out from the general pattern of comorbidity between non-mental health diseases. The high co-occurrence of mental health and physical health diagnoses has implications for diagnoses and management of morbidity among pregnant women, with potential impact on pregnancy and child health outcomes.

category: psychiatry and clinical psychology


title: Experiences of COVID-19 Recovered Patients - A Qualitative Case Study from a Hotspot in Saudi Arabia

abstract:
BackgroundCOVID-19 is highly contagious and can have fatal outcomes in the elderly and those with comorbidities. Social distancing is highly recommended by the World Health Organization to prevent the spread of the disease. However, it is difficult to maintain social distancing in highly populated areas where people live in close proximity. Such high-risk areas have the potential to become hotspots for the disease spread, should one person therein contract the disease. Nakkasah is one such area in the Makkah city of Saudi Arabia which has been a hotspot in this pandemic. This study aims to qualitatively explore the experiences of COVID-19 recovered patients residing in this area.

MethodsWe employed semi-structured face-to-face interviews with people living in Nakkasah, above 18 years of age, and recovered from COVID-19. An interview guide was developed, validated, piloted, and minor changes were made. Two trained students conducted the interviews in the Arabic language in a semi-private area of the community center. The interviews were audio-recorded, with informed consent from interviewees, transcribed verbatim, and thematically analyzed later.

ResultsEleven eligible COVID-19 recovered people (two female and nine male) agreed to be interviewed, and their verbal informed consent was audio recorded. The mean interview time was 24 minutes. Thematic analysis generated 30 subthemes, which were categorized into seven overarching themes: information about COVID-19; life during COVID-19 illness; spreading of COVID-19; precautionary measures; interventions that helped in recovery; impact of COVID-19 on life; support received during COVID-19 illness.

ConclusionExperiences of people from the hotspot who had recovered from COVID-19 highlighted how life had been like in the hotspot under lockdown especially with having been afflicted with the infection, factors that facilitated their recovery, and the way their lives were and have been affected due to COVID-19.

category: public and global health


title: A mixed methods study of seasonal influenza vaccine hesitancy in adults with chronic respiratory conditions

abstract:
BackgroundSeasonal influenza vaccination is recommended for patients with chronic respiratory conditions, but uptake is suboptimal. We undertook a comprehensive mixed methods study in order to examine the barriers and enablers to influenza vaccination in patients with chronic respiratory conditions.

MethodsMixed methods including a survey (n=429) which assessed socio-demographics and the psychological factors associated with vaccine uptake (i.e. confidence, complacency, constraints, calculation and collective responsibility) with binary logistic regression analysis. We also undertook focus groups and interviews (n=59) to further explore barriers and enablers to uptake using thematic analysis.

ResultsThe survey analysis identified that older participants were more likely to accept the vaccine, as were those with higher perceptions of collective responsibility around vaccination, lower levels of complacency, and lower levels of constraints. Thematic analysis showed that concerns over vaccine side effects, lack of tailored information and knowledge, and a lack of trust and rapport with healthcare professionals were key barriers. In contrast, the importance of feeling protected, acceptance of being part of an at-risk group, and feeling a reduced sense of vulnerability after vaccination were seen as key enablers.

ConclusionsOur findings showed that the decision to accept a vaccine against influenza is influenced by multiple sociodemographic and psychological factors. Future interventions should provide clear and transparent information about side effects and be tailored to patients with chronic respiratory conditions. Interactions between patients and their healthcare providers have a particularly important role to play in helping patients address their concerns and feel confident in vaccination.


title: An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis

abstract: The National COVID-19 Chest Imaging Database (NCCID) is a centralised database containing chest X-rays, chest Computed Tomography (CT) scans and cardiac Magnetic Resonance Images (MRI) from patients across the UK, jointly established by NHSX, the British Society of Thoracic Imaging (BSTI), Royal Surrey NHS Foundation Trust (RSNFT) and Faculty. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and development of machine learning (ML) technologies that will improve care for patients hospitalised with a severe COVID-19 infection. The NCCID is now accumulating data from 20 NHS Trusts and Health Boards across England and Wales, with a total contribution of approximately 25,000 imaging studies in the training set (at time of writing) and is actively being used as a research tool by several organisations. This paper introduces the training dataset, including a snapshot analysis performed by NHSX covering: the completeness of clinical data, the availability of image data for the various use-cases (diagnosis, prognosis and longitudinal risk) and potential model confounders within the imaging data. The aim is to inform both existing and potential data users of the NCCIDs suitability for developing diagnostic/prognostic models. In addition, a cohort analysis was performed to measure the representativeness of the NCCID to the wider COVID-19 affected population. Three major aspects were included: geographic, demographic and temporal coverage, revealing good alignment in some categories, e.g., sex and identifying areas for improvements to data collection methods, particularly with respect to geographic coverage. All analyses and discussions are focused on the implications for building ML tools that will generalise well to the clinical use cases.

category: radiology and imaging


title: Developing a psychological support intervention to help injured athletes get Back in the Game

abstract:
BackgroundAfter serious knee injury, up to half of athletes do not return to competitive sport, despite recovering sufficient physical function. Athletes often desire psychological support to return to sport, but rehabilitation clinicians feel ill-equipped to deliver adequate support.

ObjectiveTo design and develop an Internet-delivered psychological support programme for athletes recovering from knee ligament surgery.

MethodOur work developing and designing the Back in the Game intervention was guided by a blend of theory & evidence-based and target population-based strategies to developing complex interventions. We systematically searched for qualitative evidence related to athletes experiences, perspectives and needs for recovery and return to sport after anterior cruciate ligament (ACL) injury. Two reviewers coded and synthesised the results using thematic meta-synthesis. We systematically searched for randomised controlled trials (RCTs) reporting on psychological support interventions for improving ACL rehabilitation outcomes in athletes. One reviewer extracted the data (including effect estimates); a second reviewer checked the data for accuracy. The results were synthesised descriptively. We conducted feasibility testing in two phases: (1) technical assessment, and (2) feasibility and useability testing. For phase 1, we recruited clinicians and people with lived experience of ACL injury. For phase 2, we recruited patients aged between 15 and 30 years, who were within 8 weeks of ACL reconstruction surgery. Participants completed a 10-week version of the intervention, and semi-structured interviews evaluating acceptability, demand, practicality and integration. The project was approved by the Swedish Ethical Review Authority (2018/45-31).

ResultsThree analytic themes emerged from the meta-synthesis (n = 16 studies, 164 participants): (1) tools/strategies to support rehabilitation progress, (2) barriers and facilitators for physical readiness to return to sport, and (3) barriers and facilitators to psychological readiness to return to sport. Coping strategies, relaxation and goal setting may have a positive effect on rehabilitation outcomes after ACL reconstruction (n = 7 RCTs, 430 participants). There were no trials of psychological support interventions for improving return to sport. Eleven people completed phase 1 of feasibility testing (technical assessment) and identified 4 types of software errors that we fixed. Six participants completed feasibility and useability testing. Their feedback suggested the intervention was easy to access and addressed the needs of athletes who want to return to sport after ACL reconstruction. We refined the intervention to include more multimedia content, and support to access and use the intervention features.

ConclusionThe Back in the Game intervention is a 24-week Internet-delivered self-guided programme comprising 7 modules that complements usual rehabilitation, changes focus as rehabilitation progresses, is easy to access and use, and includes different psychological support strategies.

category: sports medicine


title: Knowledge syntheses in medical education: Examining author gender, geographic location, and institutional affiliation

abstract:
PurposeAuthors of knowledge syntheses make many subjective decisions during their review process. Those decisions, which are guided in part by author characteristics, can impact the conduct and conclusions of knowledge syntheses, which assimilate much of the evidence base in medical education. Therefore, to better understand the evidence base, this study describes the characteristics of knowledge synthesis authors, focusing on gender, geography, and institution.

MethodIn 2020, the authors conducted a case study of authors of 963 knowledge syntheses published between 1999 and 2019 in 14 core medical education journals using a publicly accessible dataset.

ResultsThe authors of the present study identified 4,110 manuscript authors across all authorship positions. On average there were 4.3 authors per knowledge synthesis (SD=2.51, Median=4, Range=1-22); 79 knowledge syntheses (8%) were single-author publications. Over time, the average number of authors per synthesis increased (M=1.80 in 1999; M=5.34 in 2019). Knowledge syntheses were authored by slightly more females (n=2047; 50.5%) than males (n=2005; 49.5%) across all author positions (Pearson X2=22.02, p<.001). Authors listed affiliations in 58 countries, and 58 knowledge syntheses (6%) included authors from low- or middle-income countries (LMIC). Authors from the United States (n=366; 38%), Canada (n=233; 24%), and the United Kingdom (n=180; 19%) published the most knowledge syntheses. Authors listed affiliation at 617 unique institutions, and first authors represented 362 unique institutions with greatest representation from the University of Toronto (n=55, 6%) and the Mayo Clinic (n=31, 3%). Across all authorship positions, the large majority of knowledge syntheses (n=753; 78%) included authors at top 200 ranked institutions.

ConclusionsKnowledge synthesis author teams have grown over the past 20 years, and while there is near gender parity across all author positions, authorship has been dominated by North American researchers located at highly ranked institutions. This suggests a potential overrepresentation of certain authors with particular characteristics, which may impact the conduct and conclusions of knowledge syntheses in medical education.

category: medical education


title: A multicentre point prevalence survey of patterns and quality of antibiotic prescribing in Indonesian hospitals

abstract:
SynopsisO_ST_ABSBackgroundC_ST_ABSAntibiotic misuse and overuse are a major driver of antimicrobial resistance, but systematic data in Indonesia are scarce.

ObjectivesTo evaluate patterns and quality indicators of antibiotic prescribing in six acute-care hospitals in Jakarta, Indonesia.

MethodsWe conducted a hospital-wide point prevalence survey (PPS) between March and August 2019, using Global-PPS and WHO-PPS protocols. The analysis focused on antibacterials for systemic use (antibiotics).

ResultsOf 1602 inpatients, 993 (62.0%) received [≥]1 antimicrobials. Of 1666 antimicrobial prescriptions, 1273 (76.4%) were antibiotics. Most common reasons for prescribing were pneumonia (27.7%), skin and soft tissue infections (8.3%), gastrointestinal prophylaxis (7.9%), and gastrointestinal infections (5.4%). The most common indication was community-acquired infection (42.6%), followed by surgical prophylaxis (22.6%), hospital-acquired infection (18.5%), medical prophylaxis (9.6%), unknown (4.6%) and other indications (2.1%). The most prescribed antibiotic classes were third-generation cephalosporins (44.3%), fluoroquinolones (13.5%), carbapenems (7.4%), penicillins with B-lactamase inhibitor (6.8%) and aminoglycosides (6.0%). According to the WHO AWaRe classification, Watch antibiotics accounted for 67.4%, followed by 28.0% Access, 2.4% Reserve, and 2.2% Unclassified. Reason for prescribing, stop/review date and planned duration were poorly documented. Hospital antibiotic guidelines were not available for 28.1% of prescriptions, and guideline compliance was 52.2% (478/915). Parenteral administration was high (85.1%). Targeted (non-empirical) prescriptions comprised 8.1% (44/542) for community-acquired infections and 26.8% (63/235) for hospital-acquired infections.

ConclusionsOur data indicate a high rate of parenteral, empiric use of broad-spectrum antibiotics in Indonesian hospitals, coupled with poor documentation and guideline adherence. The findings suggest important areas for antimicrobial stewardship interventions.


title: Estimation of secondary household attack rates for emergent SARS-CoV-2 variants detected by genomic surveillance at a community-based testing site in San Francisco

abstract:
BackgroundSequencing of the SARS-CoV-2 viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.

MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during November 22-December 2, 2020 and January 10-29, 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.

ResultsA total of 12,124 tests were performed yielding 1,099 positives. From these, 811 high quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.9% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to "West Coast" variants were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.357 vs 0.294, RR=1.29; 95% CI:1.01-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.1%).

ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants; however, additional laboratory and epidemiological studies are required to better understand differences between these variants.

SummaryWe observed a growing prevalence and elevated attack rate for "West Coast" SARS-CoV-2 variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.


title: Recent Gains in Life Expectancy Reversed by the COVID-19 Pandemic

abstract: Variations in the age patterns and magnitudes of excess deaths, as well as differences in population sizes and age structures make cross-national comparisons of the cumulative mortality impacts of the COVID-19 pandemic challenging. Life expectancy is a widely-used indicator that provides a clear and cross-nationally comparable picture of the population-level impacts of the pandemic on mortality. Life tables by sex were calculated for 29 countries, including most European countries, Chile, and the USA for 2015-2020. Life expectancy at birth and at age 60 for 2020 were contextualised against recent trends between 2015-19. Using decomposition techniques, we examined which specific age groups contributed to reductions in life expectancy in 2020 and to what extent reductions were attributable to official COVID-19 deaths. Life expectancy at birth declined from 2019 to 2020 in 27 out of 29 countries. Males in the USA and Lithuania experienced the largest losses in life expectancy at birth during 2020 (2.2 and 1.7 years respectively), but reductions of more than an entire year were documented in eleven countries for males, and eight among females. Reductions were mostly attributable to increased mortality above age 60 and to official COVID-19 deaths. The COVID-19 pandemic triggered significant mortality increases in 2020 of a magnitude not witnessed since WW-II in Western Europe or the breakup of the Soviet Union in Eastern Europe. Females from 15 countries and males from 10 ended up with lower life expectancy at birth in 2020 than in 2015.


title: Quantifying impacts of the COVID-19 pandemic through life expectancy losses


title: Quantifying impacts of the COVID-19 pandemic through life expectancy losses: a population-level study of 29 countries


title: Contextual Embeddings from Clinical Notes Improves Prediction of Sepsis

abstract: Sepsis, a life-threatening organ dysfunction, is a clinical syndrome triggered by acute infection and affects over 1 million Americans every year. Untreated sepsis can progress to septic shock and organ failure, making sepsis one of the leading causes of morbidity and mortality in hospitals. Early detection of sepsis and timely antibiotics administration is known to save lives. In this work, we design a sepsis prediction algorithm based on data from electronic health records (EHR) using a deep learning approach. While most existing EHR-based sepsis prediction models utilize structured data including vitals, labs, and clinical information, we show that incorporation of features based on clinical texts, using a pre-trained neural language representation model, allows for incorporation of unstructured data without an explicit need for ontology-based named-entity recognition and classification. The proposed model is trained on a large critical care database of over 40,000 patients, including 2805 septic patients, and is compared against competing baseline models. In comparison to a baseline model based on structured data alone, incorporation of clinical texts improved AUC from 0.81 to 0.84. Our findings indicate that incorporation of clinical text features via a pre-trained language representation model can improve early prediction of sepsis and reduce false alarms.

category: intensive care and critical care medicine


title: Aging-induced isoDGR-modified fibronectin activates monocytic and endothelial cells to promote atherosclerosis

abstract:
Background and AimsAging is the primary risk factor for cardiovascular disease (CVD), but the mechanisms underlying age-linked atherosclerosis remain unclear. We previously observed that long-lived vascular matrix proteins can acquire  gain-of-function isoDGR motifs that might play a role in atherosclerotic pathology.

MethodsIsoDGR-specific mAb were generated and used for ELISA-based measurement of motif levels in plasma samples from patients with coronary artery diseases (CAD) and non-CAD controls. Functional consequences of isoDGR accumulation in age-damaged fibronectin were determined by bioassay for capacity to activate monocytes, macrophages, and endothelial cells (signalling activity, pro-inflammatory cytokine expression, and recruitment/adhesion potential). Mice deficient in the isoDGR repair enzyme PCMT1 were used to assess motif distribution and macrophage localisation in vivo.

ResultsIsoDGR-modified fibronectin and fibrinogen levels in patient plasma were significantly enhanced in CAD and further associated with smoking status. Functional assays demonstrated that isoDGR-modified fibronectin activated both monocytes and macrophages via integrin receptor  outside in signalling, triggering an ERK:AP-1 cascade and expression of pro-inflammatory cytokines MCP-1 and TNF to drive additional recruitment of circulating leukocytes. IsoDGR-modified fibronectin also induced endothelial cell expression of integrin {beta}1 to further enhance cellular adhesion and matrix deposition. Analysis of murine aortic tissues confirmed accumulation of isoDGR-modified proteins co-localised with CD68+ macrophages in vivo.

ConclusionsAge-damaged fibronectin features isoDGR motifs that increase binding to integrins on the surface of monocytes, macrophages, and endothelial cells. Subsequent activation of  outside-in signalling elicits a range of potent cytokines and chemokines that drive additional leukocyte recruitment to the developing atherosclerotic matrix.

Graphical Abstract

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/21252419v1_ufig1.gif" ALT="Figure 1">
View larger version (20K):
org.highwire.dtl.DTLVardef@1e53c2dorg.highwire.dtl.DTLVardef@d1b682org.highwire.dtl.DTLVardef@251a75org.highwire.dtl.DTLVardef@1ebfa79_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LIIsoDGR-modified plasma proteins are associated with CAD.
C_LIO_LIIsoDGR binding to integrin receptors on monocytes, macrophage, and endothelial cells promotes  outside-in signalling, monocyte infiltration, and endothelial binding.
C_LIO_LIIsoDGR-modified fibronectin may initiate vascular inflammation in atherosclerotic CVD.
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category: cardiovascular medicine


title: 40Hz sensory stimulation induces gamma entrainment and affects brain structure, sleep and cognition in patients with Alzheimer's dementia

abstract: Non-invasive Gamma ENtrainment Using Sensory stimuli (GENUS) at 40Hz reduced Alzheimers disease (AD) pathology, prevented cerebral atrophy and improved performance during behavioral testing in mouse models of AD. We report data from a safety study (NCT04042922) and a randomized, placebo-controlled trial in participants with probable mild AD dementia after 3 months of one-hour daily 40Hz light and sound GENUS (NCT04055376) to assess safety, compliance, entrainment and possible effects on brain structure, function, sleep and cognitive function. GENUS was well-tolerated and compliance was high in both groups. Electroencephalography recordings show that our GENUS device safely and effectively induced 40Hz entrainment in cognitively normal subjects and participants with mild AD. After 3 months of daily stimulation, participants with mild AD in the 40Hz GENUS group showed less ventricular enlargement and stabilization of the hippocampal size compared to the control group. Functional connectivity increased in both the default mode network and the medial visual network after 3 months of stimulation. Circadian rhythmicity also improved with GENUS. Compared to controls, the active group performed better on the face-name association delayed recall test. These results suggest that 40Hz GENUS can be used safely at home daily and shows favorable outcomes on cognitive function, daily rhythms, and structural and functional MRI biomarkers of AD-related degeneration. These results support further evaluation of GENUS in larger and longer clinical trials to evaluate its potential as a disease modifying therapeutic for Alzheimers disease.

category: neurology


title: Gamma Frequency Sensory Stimulation in Probable Mild Alzheimer's Dementia Patients: Results of a Preliminary Clinical Trial


title: A novel, multiplexed RT-qPCR assay to distinguish lineage B.1.1.7 from the remaining SARS-CoV-2 lineages

abstract: The emergence of a novel SARS-CoV-2 variant called lineage B.1.1.7 sparked global alarm due to evidence of increased transmissibility, mortality, and uncertainty about vaccine efficacy, thus accelerating efforts to detect and track the variant. Current approaches to detect lineage B.1.1.7 include sequencing and RT-qPCR tests containing a target assay that fails or results in reduced sensitivity towards the B.1.1.7 variant. Since many countries lack robust genomic surveillance programs and failed assays detect multiple unrelated variants containing similar mutations as B.1.1.7, we sought to develop an RT-qPCR test that can accurately and rapidly differentiate the B.1.1.7 variant from other SARS-CoV-2 variants. We used bioinformatics, allele-specific PCR, and judicious placement of LNA-modified nucleotides to develop a test that differentiates B.1.1.7 from other SARS-CoV-2 variants. We validated the test on 106 clinical samples with lineage status confirmed by sequencing. Our room temperature-stable, multiplexed RT-qPCR test consists of two assays that target either the common SARS-CoV-2 spike gene or spike gene deletions specific to lineage B.1.1.7. A simple relative comparison of the Ct values of the two assays permits not only identification of the B.1.1.7 variant but also its differentiation from other variants that harbor only the {Delta}H69/{Delta}V70 deletion.The test showed 97% clinical sensitivity at detecting lineage B.1.1.7. This test can easily be implemented in labs to rapidly scale B.1.1.7 surveillance efforts and is particularly useful in countries with high prevalence of variants possessing only the {Delta}H69/{Delta}V70 deletion because current strategies using target failure assays incorrectly identify these as putative B.1.1.7 variants.


title: Surveillance of SARS-CoV-2 lineage B.1.1.7 in Slovakia using a novel, multiplexed RT-qPCR assay


title: Ethnicity and COVID-19 outcomes among healthcare workers in the United Kingdom: UK-REACH ethico-legal research, qualitative research on healthcare workers' experiences, and stakeholder engagement protocol

abstract:
IntroductionAs the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The UK-REACH project has been initiated to understand ethnic differentials in COVID-19 outcomes among healthcare workers (HCWs) in the United Kingdom (UK) through five inter-linked work packages. The ethico-legal work package (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the healthcare workers experiences work package (Work Package 4) is a qualitative study exploring healthcare workers experiences during COVID-19 and; the stakeholder engagement work package (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations.

Methods and AnalysisWork Package 3 has two different research strands: (a) desk-based doctrinal research; and (b) empirical qualitative research with key opinion leaders. For the empirical research, in-depth interviews will be conducted digitally and recorded with participants permission. Recordings will be transcribed, coded and analysed using thematic analysis. In Work Package 4, online in-depth interviews and focus groups will be conducted with approximately 150 HCWs, from across the UK, and these will be recorded with participants consent. The recordings will be transcribed, coded and data will be analysed using thematic analysis. Work Package 5 will achieve its objectives through regular group meetings and in-group discussions.

Ethics and DisseminationEthical approval has been received from the London - Brighton & Sussex Research Ethics Committee of the Health Research Authority (Ref No. 20/HRA/4718). Results of the study will be published in open access journals, and disseminated through conference presentations, project website, stakeholder organisations, media and scientific advisory groups.

Registration DetailsRegistered with the International Standard Randomised Controlled Trial Number registry (ISRCTN11811602).

STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThe dual approach of doctrinal and empirical research (Work Package 3) on the use of personal data by UK-REACH will give a comprehensive understanding of the ethical and legal implications of the study, and perceptions about its use of data.
C_LIO_LIQualitative research with healthcare workers in the UK on their experiences during the COVID-19 pandemic (Work Package 4) will provide insight into personal behaviour, perceptions of risk and coping mechanisms adopted both inside and outside of the work environment.
C_LIO_LIStakeholder engagement (Work Package 5) from professional regulatory bodies and staff groups is embedded within the UK-REACH study to provide feedback on project activities and support with project recommendations.
C_LIO_LIThe target participants (key opinion leaders) for Work Package 3 empirical study will likely come from predominantly White backgrounds which may limit the breadth of views obtained in interviews. This limitation will be mitigated by active recruitment of opinion leaders from a wide variety of ethnic backgrounds and active interaction with Work Package 5.
C_LIO_LIDue to the pandemic restrictions, interviews and focus group discussions will be conducted via online methods as a substitute for face-to-face meetings, posing practical and technological challenges for dynamic interaction with participants.
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title: Modeling University Reopening in Low Risk Countries During COVID-19

abstract: The safety of students worldwide remains a key issue during COVID-19. The reopening of universities in high risk countries during Fall 2020 resulted in numerous outbreaks. While regular screening and testing on campus can prevent the transmission of SARS-CoV-2, they are extremely challenging to implement due to various reasons such as cost and logistics. However, for low risk countries with minimal to no community spread, our study suggests that universities can fully reopen without testing, if students self-quarantine for 14 days on arrival and adopt proper nonpharmaceutical interventions (NPIs). This alternative strategy might save institutions millions of dollars. We adopt agent-based simulation to model virus transmission on campus and test the effectiveness of several NPIs when school reopens. Assuming one initially infected student, results indicate that transmission between roommates causes the most infections with visitors, ground floors, and elevators, being the next main contributors. Limiting density and/or population are not impactful at flattening the curve. However, adopting masks, minimizing movement, and increasing the frequency of cleaning can effectively minimize infection and prevent outbreak, allowing for classes and activities to resume as normal.


title: Reopening Universities without Testing During COVID-19: Evaluating a Possible Alternative Strategy in Low Risk Countries


title: Upper respiratory tract SARS-CoV-2 RNA loads in symptomatic and asymptomatic children and adults

abstract:
ObjectivesThere is limited information comparing SARS-CoV-2 RNA load in the upper respiratory tract (URT) between children and adults, either presenting with COVID-19 or asymptomatic. Here we conducted a retrospective, single center study involving a large cohort of SARS-CoV-2 infected individuals to address this issue.

Patients and MethodsA total of 1,184 consecutive subjects (256 children and 928 adults) testing positive for SARS-COV-2 RNA in nasopharyngeal exudates (NP) were included, of whom 424 (121 children and 303 adults) had COVID-19 not requiring hospitalization and 760 (135 children and 625 adults) were asymptomatic close contacts of COVID-19 patients. SARS-CoV-2 RNA testing was carried out using the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, MS, USA). The AMPLIRUN(R) TOTAL SARS-CoV-2 RNA Control (Vircell SA, Granada, Spain) was used for estimating SARS-CoV-2 RNA loads (in copies/mL).

ResultsMedian SARS-COV-2 RNA loads were comparable between adults and children with COVID-19 (7.14 log10 copies/ml vs. 6.98 log10 copies/ml; P=0.094). Median SARS-CoV-2 RNA load in asymptomatic children and adults was similar (6.20 log10 copies/ml vs. 6.48 log10 copies/ml; P=0.97). Children with COVID-19 symptoms displayed SARS-CoV-2 RNA loads comparable to their asymptomatic counterparts (P=0.61). Meanwhile in adults, median SARS-CoV-2 RNA load was significantly higher in symptomatic than in asymptomatic subjects (P=<0.001), yet comparable (P=0.61) when the analysis excluded patients sampled within 48 h after symptoms onset.

ConclusionsThe data suggest that children may be drivers of SARS-CoV-2 transmission in the general population at the same level as adults.


title: SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

abstract:
BackgroundBoth SARS-CoV-2 reinfection and persistent infection have been described, but a systematic assessment of mutations is needed. We assessed sequences from published cases of COVID-19 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection.

MethodsA systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistent infection with available sequences. Amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent COVID-19 to community-driven evolution.

ResultsFourteen reinfection and five persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 9 amino acid changes with enrichment of changes in the S, ORF8 and N genes. The number of amino acid changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of mutations than seen with community-driven evolution with continued viral changes during convalescent plasma or monoclonal antibody treatment.

ConclusionsSARS-CoV-2 reinfection does not require an unusual set of circumstances in the host or virus, while persistent COVID-19 is largely described in immunosuppressed individuals and is associated with accelerated viral evolution as measured by clock rates.


title: Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome: a randomized, controlled trial

abstract:
BackgroundMass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities.

MethodsThis study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.

FindingsThe proportion of bacteria carrying macrolide resistance increased after azithromycin treatment; the effect was enhanced in children treated within six months of sampling. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.

InterpretationThe impacts of MDA with azithromycin, including increased carriage of macrolide-resistant bacteria, were enhanced in children treated more recently, suggesting effects may be transient. Increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage.

FundingBill and Melinda Gates Foundation


title: Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support: REACT-SCOT case-control study

abstract:
BackgroundClinically vulnerable individuals have been advised to shield themselves during the COVID-19 epidemic. The objectives of this study were to investigate: (1) the risk of severe COVID-19 in those eligible for shielding, and (2) the relation of severe COVID-19 to transmission-related factors in those in shielding and the general population.

MethodsAll 178578 diagnosed cases of COVID-19 in Scotland from 1 March 2020 to 18 February 2021 were matched for age, sex and primary care practice to 1744283 controls from the general population. This dataset (REACT-SCOT) was linked to the list of 212702 individuals identified as eligible for shielding. Severe COVID-19 was defined as cases that entered critical care or were fatal.

ResultsWith those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 3.21 (95% CI 3.01 to 3.41) in those with moderate risk conditions and 6.3 (95% CI 5.8 to 6.8) in those eligible for shielding. The highest rate was in solid organ transplant recipients: rate ratio 13.4 (95% CI 9.6 to 18.8). Risk of severe COVID-19 increased with the number of adults but decreased with the number of school-age children in the household. Severe COVID-19 was strongly associated with recent exposure to hospital (defined as 5 to 14 days before presentation date): rate ratio 12.3 (95% CI 11.5 to 13.2) overall. To test for causality, a case-crossover analysis was undertaken; with less recent exposure only (15 to 24 days before first testing positive) as reference category, the rate ratio associated with recent exposure only was 5.9 (95% CI 3.6 to 9.7). The population attributable risk fraction for recent exposure to hospital peaked at 50% in May 2020 and again at 65% in December 2020.

ConclusionsThe effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household. For solid organ transplant recipients, in whom the efficacy of vaccines is uncertain, these results support a policy of offering vaccination to household contacts. Mitigating the impact of the epidemic requires control of nosocomial transmission.


title: Impact of COVID-19 pre-test probability on positive predictive value of high cycle threshold SARS-CoV-2 real-time reverse transcription PCR test results

abstract:
BackgroundPerformance characteristics of SARS-CoV-2 nucleic acid detection assays are understudied within contexts of low pre-test probability, including screening asymptomatic persons without epidemiological links to confirmed cases, or asymptomatic surveillance testing. SARS-CoV-2 detection without symptoms may represent resolved infection with persistent RNA shedding, presymptomatic or asymptomatic infection, or a false positive test. This study assessed clinical specificity of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) assays by retesting positive specimens from five pre-test probability groups ranging from high to low with an alternate assay.

Materials and MethodsA total of 122 rRT-PCR positive specimens collected from unique patients between March and July 2020 were retested using a laboratory-developed nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene followed by Sanger sequencing.

ResultsSignificantly less positive results in the lowest pre-test probability group (facilities with institution-wide screening having [≤] 3 positive asymptomatic cases) were reproduced with the nested RdRp gene RT-PCR assay than in all other groups combined (5/32, 15{middle dot}6% vs 61/90, 68%; p <0{middle dot}0001), and in each subgroup with higher pre-test probability (individual subgroup range 50{middle dot}0% to 85{middle dot}0%).

ConclusionsA higher proportion of false-positive test results are likely with lower pre-test probability. Positive SARS-CoV-2 PCR results should be interpreted within the context of patient history, clinical setting, known exposure, and estimated community disease prevalence. Large-scale SARS-CoV-2 screening testing initiatives among low pre-test probability populations should be evaluated thoroughly prior to implementation given the risk of false positives and consequent potential for harm at the individual and population level.


title: Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil

abstract:
Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

One-Sentence SummaryWe report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.


title: Impact of COVID-19 pandemic on Black, Asian and Minority Ethnic (BAME) communities: a qualitative study on the perspectives of BAME community leaders

abstract:
ObjectivesThe aim of this study was to explore the perspectives of BAME community leaders in relation to - the impact of the COVID-19 pandemic on their communities; and BAME communitys perception, understanding and adherence to Government guidelines on COVID-19 public health measures.

DesignA phenomenological approach was adopted using qualitative semi-structured interviews.

SettingsCommunity organisations and places of worships in the West Midlands region of England.

ParticipantsCommunity leaders were recruited through organisations representing BAME communities and religious places of worship.

ResultsA total of 19 participants took part. Participants alluded to historical and structural differences for the observed disparities in COVID-19 morbidity and mortality. Many struggled with lockdown measures which impeded cultural and religious gatherings that were deemed to be integral to the community. Cultural and social practices led to many suffering on their own as discussion of mental health was still deemed a taboo within many communities. Many expressed their communitys reluctance to report symptoms for the fear of financial and physical health implications. They reported increase in hate crime which was deemed to be exacerbated due to perceived insensitive messaging from authority officials and historical structural biases. Access and adherence to government guidelines was an issue for many due to language and digital barriers. Reinforcement from trusted community and religious leaders encouraged adherence. Points of support such as food banks were vital in ensuring essential supplies during the pandemic. Many could not afford masks and sanitisers.

ConclusionThe study highlights the perceived impact of COVID-19 pandemic on BAME communities. Government agencies and public health agencies need to integrate with the community, and community leaders to penetrate the key messages and deliver targeted yet sensitive public health advice which incorporates cultural and religious practices. Addressing route cause of disparities is imperative to mitigate current and future pandemics.

Strengths and limitations of this studyO_LITo our knowledge, this is the first study in England to investigate the understanding of risk and impact of COVID-19 using the perspectives of BAME community leaders.
C_LIO_LIParticipants represented diverse BAME community organisations and places of worship.
C_LIO_LIParticipant recruitment was limited to one of the seven regions within England with the highest proportion of BAME populations.
C_LIO_LIResults may not be generalizable to any BAME communities not represented in the data.
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title: Saliva testing is accurate for early-stage and presymptomatic COVID-19

abstract:
BackgroundAlthough nasopharyngeal (NP) samples have been considered the gold standard for COVID-19 testing, variability in viral load across different anatomical sites could theoretically cause NP samples to be less sensitive than saliva or nasal samples in certain cases. Self-collected samples also have logistical advantages over NP samples, making them amenable to population-scale screening.

MethodsTo evaluate sampling alternatives for population screening, we collected NP, saliva, and nasal samples from two cohorts with varied levels and types of symptoms.

ResultsIn a mixed cohort of 60 symptomatic and asymptomatic participants, we found that saliva had 88% concordance with NP when tested in the same testing lab (n = 41), and 68% concordance when tested in different testing labs (n = 19). In a second cohort of 20 participants hospitalized for COVID-19, saliva had 74% concordance with NP tested in the same testing lab, but detected virus in two participants that tested negative with NP on the same day. Medical record review showed that the saliva-based testing sensitivity was related to the timing of symptom onset and disease stage.

ConclusionsWe find that no sample site will be perfectly sensitive for COVID-19 testing in all situations, and the significance of negative results will always need to be determined in the context of clinical signs and symptoms. Saliva retained high clinical sensitivity while allowing easier collection, minimizing the exposure of healthcare workers and need for personal protective equipment, and making it a viable option for population-scale testing.


title: Comparing SARS-CoV-2 case rates between pupils, teachers and the general population: results from Ger-many

abstract: Given the inconsistent state of research regarding the role of pupils and teachers during the SARS-CoV-2 pandemic in Germany, statewide and nationwide data of infection case rates were analyzed to contribute to the discourse. Infection data from official sources ranging from mid to late 2020 were collected, prepared and analyzed to answer the question if pupils, teachers and general population differed in active case rates or not. The data showed that pupils and teachers case rates didnt exceeded those of the general population. In conclusion, it seems appropriate to appraise school-related measures to mitigate the SARS-CoV-2 pandemic sufficiently. Data-quality is a yet to overcome obstacle to provide good evidence-based recommendations regarding the management around infection cases in schools.


title: Comparing SARS-CoV-2 case rates between pupils, teachers and the general population: results from Germany


title: Designing research studies in writer's cramp dystonia: an analysis of automated writing measures

abstract:
BackgroundWriters cramp (WC) dystonia presents with abnormal postures during the task of writing and is an ideal dystonia subtype to study disease mechanisms for all forms of focal dystonia. Development of novel therapies is contingent on identifying sensitive and specific measures that can relate to the clinical syndrome and achieve a realistic sample size to power clinical research study for a rare disease. Although there have been prior studies employing automated measures of writing kinematics, it remains unclear which measures can distinguish WC subjects with high sensitivity and specificity and how these measures relate to clinician rating scales and patient-reported disability. The goal of this study was to: 1-identify automated writing measures that distinguish WC from healthy subjects, 2-measure sensitivity and specificity of these automated measures as well as their association with established dystonia rating scales, and 3-determine the sample size needed for each automated measure to power a clinical research study.

Methods21 WC dystonia and 22 healthy subjects performed a sentence-copying assessment on a digital tablet in a kinematic software and hand recognition software. The sensitivity and specificity of automated measures was calculated using a logistic regression model. Measures were then correlated with examiner and patient rating scales. Power analysis was performed for 2 clinical research designs using these automated measures.

ResultsOf the 23 automated writing measures analyzed, only 3 measures showed promise for use in a clinical research study. The automated measures of writing legibility, duration, and peak acceleration were able to distinguish WC from healthy controls with high sensitivity and specificity, correlated with examiner-rated dystonia sub-score measures and demonstrated relatively smaller sample sizes suitable for research studies in a rare disease population.

DiscussionWe identified novel automated writing outcome measures for use in clinical research studies of WC subjects which capture key aspects of the clinical disease and can serve as important readout of dystonia disease mechanism as well as future disease interventions.


title: Subjective sleep quality and objective sleep physiology in migraineurs: a meta-analysis

abstract:
ObjectivesSleep disturbance is often associated with migraine. However, there is a paucity of research investigating objective and subjective measures of sleep in migraineurs. This meta-analysis aims to determine whether there are differences in subjective sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) and objective sleep physiology measured using polysomnography between adult and pediatric migraineurs, and healthy controls.

MethodsA systematic search of five databases was conducted to find case-controlled studies which measured polysomnography and/or PSQI in migraineurs. Effect sizes (Hedges g) were entered into a random effects model meta-analysis.

Results32 separate studies were eligible. Overall, adult migraineurs had higher PSQI scores than healthy controls (g = 0.75, p < .001). This effect was larger in chronic than episodic migraineurs (g = 1.03, p < .001, g = 0.63, p < .001 respectively). For polysomnographic studies, adult and pediatric migraineurs displayed a lower percentage of REM sleep (g = -0.22, p = 0.017, g = -0.71, p = 0.025 respectively) than healthy controls. Pediatric migraineurs also displayed less total sleep time (g = -1.37, p = 0.039), more wake (g = 0.52, p < .001) and shorter sleep onset latency (g = -0.37, p < .001) than healthy controls.

ConclusionMigraineurs have significantly poorer subjective sleep quality, and altered sleep compared to healthy individuals - a finding which is particularly evident in children. This has implications for developing appropriate treatments. Further longitudinal empirical studies are required to enhance our understanding of this relationship.