title: Acceptability of a nurse-led non-pharmacological complex intervention for knee pain: Nurse and patient views and experiences

abstract:
ObjectivesThe overall purpose of this research programme is to develop and test the feasibility of a complex intervention for knee pain delivered by a nurse, and comprising both non-pharmacological and pharmacological interventions. In this first phase, we examined the acceptability of the non-pharmacological component of the intervention, issues faced in delivery, and resolve possible challenges.

MethodsEighteen adults with chronic knee pain were recruited from the community. The intervention comprised holistic assessment, education, exercise, weight-loss advice (where appropriate) and advice on adjunctive treatments such as hot/cold treatments, footwear modification and walking aids. After nurse training, the intervention was delivered in four sessions spread over five weeks. Participants had one to one semi-structured interview at the end of the intervention. The nurse was interviewed after the last visit of the last participant. These were audio recorded and transcribed verbatim. Themes were identified by one author through framework analysis of the transcripts, and cross-checked by another.

ResultsMost participants found the advice from the nurse easy to follow and were satisfied with the package, though some felt that too much information was provided too soon. The intervention changed their perception of managing knee pain, learning that it can be improved with self-management. However, participants thought that the most challenging part of the intervention was fitting the exercise regime into their daily routine. The nurse found discussion of goal setting to be challenging.

ConclusionThe nurse-led package of care is acceptable within a research setting. The results are promising and will be applied in a feasibility randomised-controlled trial.

category: rheumatology


title: Environmental impact and life cycle financial cost of hybrid (reusable/ single-use) instruments versus single-use equivalents in laparoscopic cholecystectomy

abstract:
BackgroundHybrid surgical instruments contain both single-use and reusable components, potentially bringing together advantages from both approaches. The environmental and financial costs of such instruments have not previously been evaluated.

MethodsWe used Life Cycle Assessment to evaluate the environmental impact of hybrid laparoscopic clip appliers, scissors and ports used for a laparoscopic cholecystectomy, comparing these with single-use equivalents. We modelled this using SimaPro and ReCiPe midpoint and endpoint methods to determine 18 midpoint environmental impacts including the carbon footprint, and three aggregated endpoint impacts. We also conducted life cycle cost analysis of products, taking into account unit cost, decontamination, and disposal costs.

ResultsThe environmental impact of using hybrid instruments for a laparoscopic cholecystectomy was lower than single-use equivalents across 17 midpoint environmental impacts, with mean average reductions of 60%. The carbon footprint of using hybrid versions of all three instruments was around one-quarter of single-use equivalents (1,756 g versus 7,194 g CO2e per operation), and saved an estimated 1.13 e-5 DALYs (disability associated life years, 74% reduction), 2.37 e-8 species.year (loss of local species per year, 76% reduction), and US $ 0.6 in impact on resource depletion (78% reduction). Scenario modelling indicated that environmental performance of hybrid instruments was better even if there was low number of reuses of instruments, decontamination with separate packaging of certain instruments, decontamination using fossil-fuel rich energy sources, or changing carbon intensity of instrument transportation. Total financial cost of using a combination of hybrid laparoscopic instruments was less than half that of single-use equivalents (GBP {pound}131 versus {pound}282).

ConclusionAdoption of hybrid laparoscopic instruments could play an important role in meeting carbon reduction targets for surgery, and also save money.

category: surgery


title: Towards adaptive deep brain stimulation: clinical and technical notes on a novel commercial device for chronic brain sensing

abstract:
BackgroundTechnical advances in deep brain stimulation (DBS) are crucial to improve therapeutic efficacy and battery life. A prerogative of new devices is the recording and processing of a given input signal to instruct the delivery of stimulation.

ObjectiveWe studied the advances and pitfalls of one of the first commercially available devices capable of recording brain local field potentials (LFP) from the implanted DBS leads, chronically and during stimulation.

MethodsWe collected clinical and neurophysiological data of the first 20 patients (14 with Parkinsons disease [PD], five with various types of dystonia, one with chronic pain) that received the Percept PC in our centers. We also performed tests in a saline bath to validate the recordings quality.

ResultsThe Percept PC reliably recorded the LFP of the implanted site, wirelessly and in real time. We recorded the most promising clinically useful biomarkers for PD and dystonia (beta and theta oscillations) with and without stimulation. Critical aspects of the system are presently related to contact selection, artefact detection, data loss, and synchronization with other devices. Furthermore, we provide an open-source code to facilitate export and analysis of data.

ConclusionNew technologies will soon allow closed-loop neuromodulation therapies, capable of adapting the stimulation based on real-time symptom-specific and task-dependent input signals. However, technical aspects need to be considered to ensure clean synchronized recordings. The critical use by a growing number of DBS experts will alert new users about the currently observed shortcomings and inform on how to overcome them.

category: neurology


title: Integration of proteomics with genomics and transcriptomics increases the diagnostic rate of Mendelian disorders

abstract: By lack of functional evidence, genome-based diagnostic rates cap at approximately 50% across diverse Mendelian diseases. Here, we demonstrate the effectiveness of combining genomics, transcriptomics, and, for the first time, proteomics and phenotypic descriptors, in a systematic diagnostic approach to discover the genetic cause of mitochondrial diseases. On fibroblast cell lines from 145 individuals, tandem mass tag labelled proteomics detected approximately 8,000 proteins per sample and covered over 50% of all Mendelian disease-associated genes. Aberrant protein expression analysis allowed the validation of candidate protein-destabilising variants, in addition to providing independent complementary functional evidence to variants leading to aberrant RNA expression. Overall, our integrative computational workflow led to genetic resolution for 22% of 121 genetically unsolved whole exome or whole genome negative cases and to the discovery of two novel disease genes. With increasing democratization of high-throughput omics assays, our approach and code provide a blueprint for implementing multi-omics based Mendelian disease diagnostics in routine clinical practice.

category: genetic and genomic medicine


title: Kinetics and seroprevalence of SARS-CoV-2 antibodies - a comparison of 3 different assays

abstract:
PurposeComparing seroprevalence and antibody kinetics in three different commercially available assays for SARS-CoV-2.

MethodsSerostatus of COVID-19 patients was analyzed 5 months and 10 months after their infection, using three different assays: Diasorin LIAISON(R), Euroimmun(R), Abbott Diagnostics(R) ARCHITECT.

ResultsSeropositivity at baseline differed significantly depending on the assay (Diasorin 81%, Euroimmun 83%, Abbott 59%). At follow-up antibody levels detected in the Diasorin assay were stable, while there was a significant loss in seropositivity in the Euroimmun and Abbott assays.

ConclusionThere are significant differences in SARS-CoV-2 antibody kinetics based on the specific assay used.

Trial registration number, date of registrationDRKS00022549, 29.07.2020 "retrospectively registered"

category: infectious diseases


title: Isofurans and isoprostanes as markers of delayed brain injury and mitochondrial dysfunction following aneurysmal subarachnoid hemorrhage. A prospective observational study

abstract:
IntroductionF2-Isoprostanes (F2-IsoPs) and Isofurans (IsoF), specific markers of lipid peroxidation in vivo, have been reported to be elevated and have prognostic implications following subarachnoid hemorrhage (SAH). Platelet activation and vasoconstriction are attributed to these compounds. Elevated IsoF: F2-IsoPs ratios have been previously suggested as indicative of mitochondrial dysfunction. In this small study we examined their performance as specific biomarkers for delayed brain injury (DBI) development following SAH. We also explored if evidence of mitochondrial dysfunction could be found in a cohort of SAH patients.

MethodsEighteen patients with SAH and 7 controls with normal neuroimaging and CSF analysis results underwent CSF sampling and abstraction of clinical, demographic, and laboratory data. Samples (two) of CSF were collected on day 1 and once on days 5-8 post-bleed. F2-IsoP and IsoF assays were performed at Vanderbilt Eicosanoid Core Lab by gas chromatography/mass spectroscopy. Levels are expressed in median (IQR) for non-parametric data. Repeated sample measurement were compared using the Wilcoxon signed-rank test, whereas the Mann Whitney test was used for other non-parametric data.

ResultsMean age was 61.2 + 15.7 (SAH cases) vs. 47.6 + 10 (controls) years, and 80% of SAH patients were female. Median Hunt-Hess score was 3 (2-4) and modified Fisher scale 3 (3-4). Thirty nine percent of patients developed DBI. F2-IsoP were significantly higher in SAH cases than in controls [47.5 (30.2-53.5) vs. 26.0 (21.2-34.5) pg/mL]. No significant differences were observed in patients with or without DBI [41 (33.5-52) vs. 44 (28.5-55.5) pg/mL]. IsoF were elevated in the second CSF sample in 9 patients, but undetectable in the remainder cases and all controls. Patients who developed DBI had significantly higher IsoF than cases who did not [(57 (34-72) vs. 0 (0-34) pg/mL]. Patients who met criteria for delayed injury had a significantly higher IsoF: F2IsoPs ratio on the late CSF sample [1.03 (1-1.38) vs. 0 (0-0.52)].

ConclusionsPreliminary findings from this study suggest that IsoF may represent a specific biomarker predicting DBI following SAH and provide possible evidence of CNS mitochondrial dysfunction in SAH. Future studies to further explore the value of IsoF as biomarkers of secondary brain injury and the contribution of mitochondrial dysfunction and ferroptosis to clinical outcomes following SAH seem warranted.

category: intensive care and critical care medicine


title: Bayesian inference across multiple models suggests a strong increase in lethality of COVID-19 in late 2020 in the UK

abstract:
We apply Bayesian inference methods to a suite of distinct compartmental models of generalised SEIR type, in which diagnosis and quarantine are included via extra compartments. We investigate the evidence for a change in lethality of COVID-19 in late autumn 2020 in the UK, using age-structured, weekly national aggregate data for cases and mortalities. Models that allow a (step-like or graded) change in infection fatality rate (IFR) have consistently higher model evidence than those without. Moreover, they all infer a close to two-fold increase in IFR. This value lies well above most previously available estimates. However, the same models consistently infer that, most probably, the increase in IFR preceded the time window during which new variant B.1.1.7 became the dominant strain in the UK. Therefore, according to our models, the caseload and mortality data do not offer unequivocal evidence for higher lethality of a new variant. We compare these results for the UK with similar models for Germany and France, which also show increases in inferred IFR during the same period, despite the even later arrival of new variants in those countries. We argue that while the new variant(s) may be one contributing cause of a large increase in IFR in the UK in autumn 2020, other factors, such as seasonality, or pressure on health services, are likely to also have contributed.

SummaryO_ST_ABSModel structureC_ST_ABSWe study a family of non-geographic compartmented models structured by age, and by epidemiological and diagnostic state. They include stages within exposed (E) and infected (I) classes, and separation of symptomatic and asymptomatic infected individuals; E and I classes are subdivided according to whether they have had a positive test.

Disease transmission between compartments is modelled by contact matrices derived from survey data and previous Bayesian inference [1]. Non-pharmaceutical interventions are incorporated via time- and age-dependent transmission rates. This dependence is parameterised by functions that account for lockdowns, seasonal changes, etc., with parameters inferred from the data except where known a priori (e.g. lockdown dates).

The process of diagnosis is modelled explicitly through the subdivided compartments. The targeting of tests towards symptomatic individuals is controlled by a single inferred parameter. Tested individuals have reduced infectivity, as a model for self-isolation. The fraction of asymptomatic cases is presumed fixed. Most other parameters are inferred (including initial conditions in March 2020). Our models are stochastic at all stages, including the infection and the diagnosis processes.

Similar models are considered for Germany and France. All models are analysed with the same Bayesian methodology as outlined below.

DataWe analyse age-structured, weekly data for cases and mortalities for the UK, France and Germany starting in early March 2020. Our explicit modelling of diagnostic tests allows us to directly use data on the number of daily tests performed and their outcomes to inform parameter estimation. For the UK, the data we used are (i) ONS data for COVID deaths; (ii) PHE data for total numbers of tests; (iii) PHE data for numbers of positive tests. The time series analysed extends from March 2020 until January 2021.

MethodsIn line with the data used, we treat diagnosed cases and mortalities as the only observables; other compartments are treated as unobserved, with occupancies to be inferred from data. Parameters governing overdispersion for infection and death are likewise inferred.

We perform inference using a likelihood function that includes the stochasticity in all model transitions (infection, disease progression, testing, death). The likelihood of the observed data is computed in an approximation that becomes exact for large population sizes, taking into account all statistical dependencies in this limit. Inference is performed at the level of maximum a posteriori (MAP) estimates. Using these MAP estimates we approximate the evidence for each model, allowing us to compare the credibility of different models given the same set of data.

We use the software package PyRoss to build all the models and run the inference procedure [2, 3].

Model specificationsWe compare several distinct models that differ primarily in how interventions and fluctuations are addressed. Some of these variants (Type 1) allow for a time-dependent infection fatality rate (IFR) and some do not (Type 0). Most of our Type 1 models assume a step change in IFR but a ramped (tanh) variation is also studied. In Type 1 models, the values of IFR before and after the change are parameterised in terms of their log-ratio, whose prior is normal distributed with mean zero and standard deviation log(3). The prior for the time of the change is normal with mean 2020-12-12 and standard deviation 2 weeks.

For both Type 0 and Type 1 models we consider several possibilities for the time-dependence of model parameters other than the IFR. For the UK, these are (A) no dependence; (B) changing infectivity; (C) changing overdispersion: (BC) changing infectivity and overdispersion.

FindingsType 1 models for the UK consistently attain a significantly higher model evidence than Type 0 models. (Specifically, they show systematically larger values of the log-posterior.) For each Type 1 model, we separately infer that in the UK, the IFR rose by a factor of about two in late October or early November 2020: the MAP values vary between 1.9-2.2 depending on the model chosen. A similar change is also inferred in Germany and France, but is somewhat less pronounced.

Among the France/Germany models, the ratios of inferred IFRs before/after the step are smaller than in UK but still indicate significant changes, around 1.4 for France and 1.8 for Germany.

The IFR changes in UK are inferred to take place significantly before the B.1.1.7 variant became the dominant UK strain. The significant inferred IFR change in Germany is (to our knowledge) not associated with any new variant.

InterpretationThese findings support the hypothesis [4-6] that the lethality of COVID-19 in the UK increased significantly in late autumn 2020. The MAP estimates further suggest that a larger increase than previously suggested [4, 5], of roughly a factor 2, arose with an onset time in early November. However, the fact that this onset time precedes the rise to dominance of new variant B.1.1.7 suggests that this rise is not solely responsible for the change in IFR. Other factors, such as seasonality and/or pressure on health services, may also be important. If these factors came into play significantly before the arrival of B.1.1.7, then the MAP-estimated onset time of early November could represent a compromise between two successive episodes of increasing IFR within models that, as so far implemented, allow only one.

Note that the IFR depends on the true number of infections (not just diagnosed cases as in the case fatality rate) which, in our model, is itself estimated from the data for cases and testing. Underestimation of this number can lead to an overestimate of the IFR. However, to explain the factor-two increase in fitted IFR this way would require implausible assumptions to be made concerning change in testing efficacy in late autumn 2020 (models TT0, TT1, P0).

category: epidemiology


title: Disulfiram associated with lower risk of Covid-19: a retrospective cohort study

abstract:
In the global COVID-19 pandemic, there is a substantial need for effective, low-cost therapeutics. We investigated the potential effects of disulfiram on the incidence and outcomes of COVID-19 in an observational study in a large database of US Veterans Administration clinical records, the VA Corporate Data Warehouse (CDW). The study is motivated by the unique properties of disulfiram, which has been used as an anti-alcoholism drug since 1948, is non-toxic, easy to manufacture and inexpensive. Disulfiram reduces hyperinflammation in mammalian cells by inhibition of the gasdermin D pore. In a mouse model of sepsis, disulfiram reduced inflammatory cytokines and mortality. Disulfiram also is a low micromolar inhibitor of the Mpro and PLpro viral proteases of SARS-CoV-2.

To investigate the potential effects of disulfiram on the incidence and severity of COVID-19, we carried out an epidemiological study in the CDW. The VA dataset used has 944,127 patients tested for SARS-Cov-2, 167,327 with a positive test, and 2,233 on disulfiram, of which 188 had a positive SARS-Cov-2 test. A multivariable Cox regression adjusted for age, gender, race/ethnicity, region, a diagnosis of alcohol use disorders, and Charlson comorbidity score revealed a reduced incidence of COVID-19 with disulfiram use with a hazard ratio of 0.66 and 95% confidence interval of 0.57 to 0.76 (P < 0.001). There were no deaths among the 188 SARS-Cov-2 positive patients treated with disulfiram. The expected number of deaths would have been 5-6 according to the 3% death rate among the untreated (P-value 0.03).

Our finding of a lower hazard ratio and less severe outcomes for COVID-19 in patients treated with disulfiram compared to those not treated is a statistical association and does not prove any causative effect of disulfiram. However, the results of this study suggest that there is a pharmacological contribution to the reduced incidence and severity of COVID-19 with the use of disulfiram. Given the known anti-inflammatory and viral anti-protease effects of disulfiram, it is reasonable and urgent to initiate accelerated clinical trials to assess whether disulfiram reduces SARS-CoV-2 infection, disease severity and death.

STRUCTURED OUTLINEO_ST_ABSImportanceC_ST_ABSIdentifying already approved medications with well characterized antiviral or anti-inflammatory properties supported by real world evidence as candidates for clinical trials for repurposing is an important strategy to manage the pandemic given the ongoing challenges with producing and administering vaccines, the emergence of more infectious viral mutants and the paucity of approved therapies.

ObjectiveTo investigate the potential effects of disulfiram on the incidence and severity of COVID-19.

DesignRetrospective cohort study from February 20, 2020 to February 1, 2021.

SettingVeterans Health Administration. Veterans who had visited a VA primary care provider in the 18 months before their first SARS-CoV-2 test.

Participants2,233 Veterans with at least one SARS-CoV-2 laboratory (positive or negative) test result on or after February 20, 2020 and at least one pharmacy record for disulfiram on or after February 20, 2019 and 941,894 Veterans without a pharmacy record for disulfiram.

ExposureTreatment with disulfiram

Main OutcomePositive test result for SARS-CoV-2

ResultsA multivariable Cox regression analysis adjusted for age, gender, race/ethnicity, region, diagnosis of an alcohol use disorder, and Charlson comorbidity score resulted in a reduced hazard of COVID-19 infection with disulfiram use, with a hazard ratio of 0.66 and 95% confidence interval of 0.57 to 0.76 (P < 0.001).

Conclusions and RelevanceThe results of this study suggest that disulfiram use contributes to a reduced incidence of COVID-19. Given the known anti-inflammatory and anti-protease effects of disulfiram, its low cost, low side effects, and general availability, it is reasonable and urgent to initiate accelerated clinical trials to assess the effect of disulfiram on infection and the development of advanced disease.


title: Repeated Testing Necessary: Assessing Negative Predictive Value of SARS-CoV-2 qPCR in a Population of Young Adults

abstract: Determining when individuals should be released from quarantine is critical for successfully managing a COVID-19 outbreak and local protocols frequently call for testing during the quarantine period, generally after a reasonable incubation period, which raises a question about the interpretation of test results during the quarantine period. We report the negative predictive value of SARS-CoV-2 qPCR tests based on a retrospective longitudinal analysis of 5349 qPCR tests collected from 1227 US service members infected with COVID-19 aboard the USS Theodore Roosevelt (CVN-71) aircraft carrier. In our retrospective evaluation of recovering qPCR-positive quarantined crew members undergoing repeated testing, the negative predictive value is 80% for tests occurring as late as seven weeks following an initial positive qPCR test result. Repeated qPCR testing is necessary to ensure that a once-infected person is no longer shedding viral RNA. When deciding the stringency of exit criteria, we recommend considering local operational and community risk factors.

category: pathology


title: Evaluating risk detection methods to uncover ontogenic-mediated adverse drug effect mechanisms in children

abstract:
BackgroundIdentifying adverse drugs effects (ADEs) in children is essential for preventing disability and death from marketed drugs. At the same time, however, detection is challenging due to dynamic biological processes during growth and maturation, called ontogeny, that alter pharmacokinetics and pharmacodynamics. As a result, current data mining methodologies have been limited to event surveillance and have not focused on investigating adverse event mechanisms. There is an opportunity to design data mining methodologies to identify and evaluate drug event patterns within observational databases for ontogenic-mediated adverse event mechanisms. The first step of which is to establish statistical models that can identify temporal trends of adverse effects across childhood.

ResultsUsing simulation, we evaluated a population stratification method (the proportional reporting ratio or PRR) and a population modeling method (the generalized additive model or GAM) to identify and quantify ADE risk at varying reporting rates and dynamics. We found that GAMs showed improved performance over the PRR in detecting dynamic drug event reporting across child developmental stages. Moreover, GAMs exhibited normally distributed and robust ADE risk estimation at all development stages by sharing information across child development stages.

ConclusionsOur study underscores the opportunity for using population modeling techniques, which leverages drug event reporting across development stages, to identify adverse drug effect risk resulting from ontogenic mechanisms.

category: pediatrics


title: Spread and sources of information and misinformation about COVID-19 early during the pandemic in a U.S. national cohort study

abstract:
BackgroundEarly in the pandemic, misinformation about COVID-19 was spread on social media. The purpose of this study was to describe trusted sources of COVID-19 information and claims seen and believed about COVID-19 early in the pandemic among U.S. adults. Then, we assessed the impact of believing such claims on engaging in personal protective actions (PPA).

MethodsWe used baseline data from the CHASING COVID Cohort (n = 7,070) collected March 28, 2020 to April 20, 2020 to describe trusted sources of COVID-19 information as well as claims circulating on social media that had been seen and believed. We used Poisson regression to determine the association of believing certain claims with engaging in a higher number of PPA.

ResultsThe top three trusted sources of COVID-19 information were the CDC (67.9%), the WHO (53.7%), and State Health Departments (53.0%). Several COVID-19 claims circulated on social media had been seen, e.g., that the virus was created in a laboratory (54.8%). Moreover, substantial proportions of participants indicated agreement with some of these claims. In multivariable regression, we found that belief in certain claims was associated with engaging in a higher number of PPA. For example, believing that paper masks would prevent transmission of the virus was associated with engaging in a higher number of protective actions ({beta} = 0.02, 95% CI: 0.004 - 0.046).

ConclusionsResults suggest the need for public health leadership on social media platforms to combat misinformation and supports social media as a tool to further public health interventions.

category: public and global health


title: Unplanned Hospital Visits after Ambulatory Surgical Care

abstract:
Structured AbstractO_ST_ABSObjectivesC_ST_ABSWe sought to assess the rate of unplanned hospital visits among patients undergoing ambulatory surgery.

Summary Background DataThe majority of surgeries performed in the United States now take place in outpatient settings. Post-discharge hospital visit rates have been shown to vary widely, suggesting variation in surgical or discharge care quality. Complicating efforts to address quality, most facilities and surgeons are unaware of their patients hospital visits after surgery since patients may present to a different hospital.

MethodsWe used state-level, administrative data from the Agency for Healthcare Research and Qualitys Healthcare Cost and Utilization Project from California to assess unplanned hospital visits after ambulatory surgery. To compare rates across centers, we determined the age, sex, and procedure-adjusted rates of hospital visits for each facility using 2-level, hierarchical, generalized linear models using methods similar to existing Centers for Medicare and Medicaid Services measures.

ResultsAmong a total of 1,260,619 ambulatory same-day surgeries from 440 surgical facilities, the risk adjusted 30-day rate of unplanned hospital visits was 4.8%, with emergency department visits of 3.1% and hospital admissions of 1.7%. Several patient characteristics were associated with increased risk of unplanned hospitals visits, including increased age, increased number of comorbidities (using the Elixhauser score), and type of procedure (p<0.001).

ConclusionsThe overall rate unplanned hospital visits within 30 days after same-day surgery is low but variable, suggesting a difference in the quality of care provided. Further, these rates are higher among specific patient populations and procedure types, suggesting areas for targeted improvement.

Mini-AbstractThe majority of surgeries performed in the United States now take place in outpatient settings with wide variation of post-discharge hospital visit rates. We used state-level, administrative data to assess the rate of unplanned hospital visits after ambulatory surgery and found a risk adjusted 30-day rate of 4.8%. Increased age, increased number of comorbidities (using the Elixhauser score), and type of procedure were associated with increased risk of unplanned hospitals visits, suggesting areas for targeted improvement.


title: The impact of headache disorders on COVID-19 survival: a world population-based analysis

abstract:
ImportanceCOVID-19 has not impacted people or countries uniformly. This disparity has prompted investigations to identify clinical and genetic predictors of COVID-19 mortality. Headache, a COVID-19 symptom, has been associated with positive disease prognosis. It is logical to consider whether primary headache disorders, among the most prevalent and disabling diseases globally, may also be associated with reduced viral mortality and thereby may have arisen as adaptive host defences

ObjectiveTo study the relationship between COVID-19 mortality and primary headache disorders.

Main outcome measureUsing a generalized additive model regression (GAM), we analysed data across 171 nations to identify variables which impact COVID-19 mortality rates (demographics, national wealth and government effectiveness, pandemic management indexes, latitude of the countrys capital, prevalence of headache disorders and other diseases). We performed similar analyses of seasonal influenza mortality. Separately, we meta-analysed studies of COVID-19 inpatient survival reporting headache, using PRISMA guidelines.

ResultsIn the global population-level analysis, we observed that a higher prevalence of headache disorders was associated with a higher COVID-19 mortality rate, and represented the main variable contributing to differences in COVID-19 mortality rates between countries (37.8%; F value=10.68). By contrast, we observed a negative trend between the prevalence of headache disorders and influenza death rates. Controversially, when considering headache as a symptom of COVID-19, in the 48 meta-analysed studies we observed a significantly higher risk ratio of survival (RR:2.178 [1.882-2.520], p<0.0001) among COVID-19 inpatients with headache.

Conclusions and RelevanceHeadache as a primary disorder is more prevalent in nations with higher COVID-19 mortality, whereas headache as a COVID-19 symptom is associated with enhanced survival. Further studies should clarify whether primary headache disorders represent a risk factor for mortality for COVID-19 or, rather, whether this association reflects evolutionary adaptive processes to enhance survival that, in the case of COVID-19, are insufficiently protective.


title: The Burden of and Factors Associated with Age-Related Eye Diseases in Arab American Adults

abstract:
PurposeTo estimate the age- and sex-adjusted proportions of cataract, diabetic retinopathy, glaucoma, and macular degeneration among the Arab American community, a notably understudied minority that is aggregated under whites.

MethodsThe Arab American Eye Study is a multicenter retrospective chart review involving ten years of electronic medical records (1/1/2010 through 1/1/2020). The study sample included 1,390 Arab Americans and 4,950 whites 45 years of age and older, totaling 6,340 subjects. Arab Americans were identified using an Arab American name algorithm. Subjects with race variables other than white or Arab American or those under age 45 were excluded from the study. Age- and sex-adjusted proportions of cataract, diabetic retinopathy, glaucoma, and macular degeneration were determined. Odds ratios with 95% confidence intervals were used to examine the association between race/ethnicity and eye diseases.

ResultsOf the 6,340 participants (4,950 whites and 1,390 Arab Americans), males comprised 46.3% and the median age group was 55-64 years. Arab Americans displayed higher age- and sex-adjusted proportions of cataracts (45.4% versus 40.7%), dry age-related macular degeneration (10% versus 8.9%), glaucoma (8% vs 6%), and diabetic retinopathy (11.7% versus 4.2%). Fully adjusted logistic regression revealed that Arab Americans were 19% more likely to have cataracts (OR = 1.19; 95% CI = 1.05, 1.35) and 272% more likely to have diabetic retinopathy (OR = 2.72; 95% CI = 2.17; 3.41).

ConclusionsResults from the Arab American Eye Study suggest that the burden of cataract and diabetic retinopathy is significantly higher among Arab Americans in comparison to whites.

category: ophthalmology


title: Mapping the human genetic architecture of COVID-19 by worldwide meta-analysis

abstract: The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 disease severity, host genetics may also be important. Identifying host-specific genetic factors indicate biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-COV-2 infection and COVID-19 severity. We describe the results of three genome-wide association meta-analyses comprising up to 49,562 COVID-19 patients from 46 studies across 19 countries worldwide. We reported 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases. They also represent potentially actionable mechanisms in response to infection. We further identified smoking and body mass index as causal risk factors for severe COVID-19. The identification of novel host genetic factors associated with COVID-19, with unprecedented speed, was enabled by prioritization of shared resources and analytical frameworks. This working model of international collaboration provides a blue-print for future genetic discoveries in the event of pandemics or for any complex human disease.


title: A Software Solution for Clinical Protocol Management

abstract:
Clinical treatments are mostly the result of consecutive success of medical procedures. The patterns in those procedures lead to creation of clinical guidelines which are currently essential to have better health treatments. The use of electronic health record systems (EHR) helps the patient management, but it fails in the treatment guidance due to the lack of clinical decision support systems. Although these systems have decision-making features incorporated, they are not designed for treatment management and guidance. In some top edge systems, this functionality was improved and integrated, but either they are tight to the typically complex EHR. Or, many times the independent solutions lack generality to support users and disease-specific protocols.

In this paper, we purpose a decision support web tool which works independently from EHR systems. This solution allows clinicians to build and manage rule-based clinical protocols, by facilitating health care treatments, reducing time, and increasing medication accuracy. Moreover, it also enables protocol sharing among distinct institutions and physicians, creating a larger database of clinical guidelines and a network of speciliased physicians in types of diseases.

The proposed system was evaluated with the implementation of distinct clinical protocols, from different medical fields. In this validation, we describe all the steps in the transformation of a clinical guideline, from the traditional format, into a ready-to-use protocol with guidance and recommendation features.

The purposed system was developed with the collaboration of health professionals from different Portuguese healthcare institutions, which helped in the identification of system requirements and gaps of the current systems.

category: health informatics


title: Differential Impacts of COVID-19 Lockdowns on PM2.5 across the United States

abstract: The COVID-19 pandemic has induced large-scale social, economic, and behavioral changes, presenting a unique opportunity to study how air pollution is affected by unprecedented societal shifts. At each of 455 PM2.5 monitoring sites across the United States, we conduct a causal inference analysis to determine the impacts of COVID-19 interventions and behavioral changes ("lockdowns") on PM2.5 concentrations. Our approach allows for rigorous confounding adjustment and provides highly spatio-temporally resolved effect estimates. We find that, with the exception of the Southwest, most of the US experienced increases in PM2.5 during lockdown, compared to the concentrations expected under business-as-usual. To investigate possible drivers of this phenomenon, we use regression to characterize the relationship of many environmental, geographical, meteorological, mobility, and socioeconomic factors with the lockdown-attributable changes in PM2.5. Our findings have immense environmental policy relevance, suggesting that large-scale mobility and economic activity reductions may be insufficient to substantially and uniformly reduce PM2.5.

category: health policy


title: Impact of close interpersonal contact on COVID-19 incidence: evidence from one year of mobile device data

abstract:
Close contact between people is the primary route for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). We sought to quantify interpersonal contact at the population-level by using anonymized mobile device geolocation data. We computed the frequency of contact (within six feet) between people in Connecticut during February 2020 - January 2021. Then we aggregated counts of contact events by area of residence to obtain an estimate of the total intensity of interpersonal contact experienced by residents of each town for each day. When incorporated into a susceptible-exposed-infective-removed (SEIR) model of COVID-19 transmission, the contact rate accurately predicted COVID-19 cases in Connecticut towns during the timespan. The pattern of contact rate in Connecticut explains the large initial wave of infections during March-April, the subsequent drop in cases during June-August, local outbreaks during August-September, broad statewide resurgence during September-December, and decline in January 2021. Contact rate data can help guide public health messaging campaigns to encourage social distancing and in the allocation of testing resources to detect or prevent emerging local outbreaks more quickly than traditional case investigation.

One sentence summaryClose interpersonal contact measured using mobile device location data explains dynamics of COVID-19 transmission in Connecticut during the first year of the pandemic.


title: High household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color

abstract:
BackgroundFew prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color.

Methods and FindingsThis is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05).

ConclusionsSARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance.

AUTHORS SUMMARYO_ST_ABSWhy was this study done?C_ST_ABSO_LIUnderstanding the secondary attack rate and the timing of transmission of SARS-CoV-2 within households is important to determine the role of household transmission in the larger pandemic and to guide public health policies about quarantine.
C_LIO_LIProspective studies looking at the determinants of household transmission are sparse, particularly studies including substantial racial and ethnic minorities in the United States and studies with adequate follow-up to detect sequential transmission events.
C_LIO_LIIdentifying individuals at high risk of transmitting and acquiring SARS-CoV-2 will inform strategies for reducing transmission in the household, or reducing disease in those exposed.
C_LI

What did the researchers do and find?O_LIBetween April-November 2020, the UNC CO-HOST study enrolled 102 households across the Piedmont region of North Carolina, including 45% with an index case who identified as racial or ethnic minorities.
C_LIO_LIOverall secondary attack rate was 60% with two-thirds of cases already infected at study enrollment.
C_LIO_LIDespite the potential for sequential transmission in the household, the majority of secondary cases were detected within 10 days of symptom onset of the index case.
C_LIO_LIViral loads were correlated within families, suggesting an inoculum effect.
C_LIO_LIHigh viral load in the index case was associated with a greater likelihood of household transmission.
C_LIO_LISpouses/partners of the COVID-positive index case and household members with obesity were at higher risk of becoming infected.
C_LIO_LIHigh household living density contributed to an increased risk of household transmission.
C_LIO_LIRacial/ethnic minorities had an increased risk of acquiring SARS-CoV-2 in their households in comparison to members of the majority (white) racial group.
C_LI

What do these findings mean?O_LIHousehold transmission often occurs quickly after a household member is infected.
C_LIO_LIHigh viral load increases the risk of transmission.
C_LIO_LIHigh viral load cases cluster within households - suggesting high viral inoculum in the index case may put the whole household at risk for more severe disease.
C_LIO_LIIncreased household density may promote transmission within racial and ethnic minority households.
C_LIO_LIEarly at-home point-of-care testing, and ultimately vaccination, is necessary to effectively decrease household transmission.
C_LI


title: A Dynamical Map to Describe Covid-19 Epidemics

abstract: Nonlinear dynamics perspective is an interesting approach to describe COVID-19 epidemics, providing information to support strategic decisions. This paper proposes a dynamical map to describe COVID-19 epidemics based on the classical susceptible-exposed-infected-recovered (SEIR) differential model, incorporating vaccinated population. On this basis, the novel map represents COVID-19 discrete-time dynamics by adopting three populations: infected, cumulative infected and vaccinated. The map promotes a dynamical description based on algebraic equations with a reduced number of variables and, due to its simplicity, it is easier to perform parameter adjustments. In addition, the map description allows analytical calculations of useful information to evaluate the epidemic scenario, being important to support strategic decisions. In this regard, it should be pointed out the estimation of the number death cases, infectious rate and the herd immunization point. Numerical simulations show the model capability to describe COVID-19 dynamics, capturing the main features of the epidemic evolution. Reported data from Germany, Italy and Brazil are of concern showing the map ability to describe different scenario patterns that include multi-wave and plateaus behaviors. The effect of vaccination is analyzed considering different campaign strategies, showing its importance to control the epidemics.


title: Type I, II, and III interferon signatures correspond to COVID-19 disease severity

abstract: We analyzed the plasma levels of interferons and cytokines, and the expression of interferon-stimulated genes in peripheral blood mononuclear cells in COVID-19 patients with different disease severity. Mild patients exhibited transient type I interferon responses, while ICU patients had prolonged type I interferon responses with hyper-inflammation mediated by interferon regulatory factor 1. Type II interferon responses were compromised in ICU patients. Type III interferon responses were induced in the early phase of SARS-CoV-2 infection, even in convalescent patients. These results highlight the importance of type I and III interferon responses during the early phase of infection in controlling COVID-19 progression.


title: Specific allelic discrimination of N501Y and other SARS-CoV-2 mutations by ddPCR detects B.1.1.7 lineage in Washington State

abstract: Real-time epidemiological tracking of variants of interest can help limit the spread of more contagious forms of SARS-CoV-2, such as those containing the N501Y mutation. Typically, genetic sequencing is required to be able to track variants of interest in real-time. However, sequencing can take time and may not be accessible in all laboratories. Genotyping by RT-ddPCR offers an alternative to sequencing to rapidly detect variants of concern through discrimination of specific mutations such as N501Y that is associated with increased transmissibility. Here we describe the first cases of the B.1.1.7 lineage of SARS-CoV-2 detected in Washington State by using a combination of RT-PCR, RT-ddPCR, and next-generation sequencing. We screened 1,035 samples positive for SARS-CoV-2 by our CDC-based laboratory developed assay using ThermoFishers multiplex RT-PCR COVID-19 assay over four weeks from late December 2020 to early January 2021. S gene dropout candidates were subsequently assayed by RT-ddPCR to confirm four mutations within the S gene associated with the B.1.1.7 lineage: a deletion at amino acid (AA) 69-70 (ACATGT), deletion at AA 145, (TTA), N501Y mutation (TAT), and S982A mutation (GCA). All four targets were detected in two specimens, and follow-up sequencing revealed a total of 10 mutations in the S gene and phylogenetic clustering within the B.1.1.7 lineage. As variants of concern become increasingly prevalent, molecular diagnostic tools like RT-ddPCR can be utilized to quickly, accurately, and sensitively distinguish more contagious lineages of SARS-CoV-2.


title: SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

abstract:
BackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.

MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.

ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).

ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.

SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.


title: Brain connectivity and motor improvements after ballet intervention in multiple sclerosis: pilot

abstract:
Background and PurposeA pilot study to determine feasibility of detecting changes in structural connectivity (SC) and resting-state functional connectivity (RSFC) occur alongside motor improvements after participation in the Targeted Ballet Program (TBP) in adults with relapsing-remitting multiple sclerosis (RRMS).

MethodsFive participants (four female) with RRMS between the ages of 38-64 with the following characteristics at baseline: Expanded Disability Status Scale 2.0-6.0, International Cooperative Ataxia Rating Scale (ICARS) > 7, Symbol-Digit Modality Test > 22, and no relapses or initiation of medications indicated to affect mobility within the past 30 days. Participants were asked to complete 12 weeks (one hour, twice per week) of the TBP. Magnetic resonance imaging data was collected pre- and post-intervention for SC and RSFC network analysis.

ResultsIncreases in two RRMS-related graph theoretical measures (mean strength and mean clustering coefficient) for RSFC (p < 0.05) are detectable alongside significant reduction in ataxia (ICARS: p = 0.01012, Smoothness Index: p = 0.04995), and increase in balance (Mini-BESTest: p = 0.01474) following participation in the well-tolerated TBP.

Discussion and ConclusionsSignificant increases in mean strength and mean clustering coefficient of RSFC suggest functional neurological improvements after participation in the TBP. The relationship between these network changes and clinical improvements in balance and amelioration of ataxia after participation in the TBP requires a larger randomized-controlled clinical trial of the TBP in persons with RRMS.

category: rehabilitation medicine and physical therapy


title: A tale of three SARS-CoV-2 variants with independently acquired P681H mutations in New York State

abstract: Several SARS-CoV-2 variants of concern have independently acquired some of the same Spike protein mutations - notably E484K, N501Y, S477N, and K417T - associated with increased viral transmission and/or reduced sensitivity to neutralization by antibodies. Repeated evolution of the same mutations, particularly in variants that are now rapidly spreading in various regions of the world, suggests a fitness advantage. Mutations at position P681 in Spike - possibly affecting viral transmission - have also evolved multiple times, including in two variants of concern. Here, we describe three variants circulating in New York State that have independently acquired a P681H mutation and the different trajectories they have taken. While one variant rose to high prevalence since later summer 2020 it appears to be in decline. The other two variants were more recently detected in New York and harbor additional Spike mutations that might be cause for continued monitoring. The latter two P681H variants have shown moderate increases in prevalence but ultimately all might be subject to the same fate as more competitive variants come to dominate the scene.


title: Acceptance and intake of COVID-19 vaccines among older Germans

abstract: The main aim of this study was to investigate the various factors influencing COVID-19 vaccination acceptance and actual intake among older Germans aged over 75 years old (N = 1037). We found that the intention to get vaccinated or intake of the COVID-19 vaccine were positively related to the perceptions of becoming infected, perceptions of the severity of the potential long-term effects, the vaccines efficacy, and the benefits of vaccination. Meanwhile, the intention to get the vaccine or vaccine intake were decreased by perceptions of the negative side-effects and the general impediments to vaccination.


title: MRI versus mammography plus ultrasound in women at intermediate breast cancer risk: study design and protocol of the MRIB multicentre randomized controlled trial

abstract:
BackgroundIn women at high/intermediate lifetime risk of breast cancer (BC-LTR), contrast-enhanced magnetic resonance imaging (MRI) added to mammography {+/-}ultrasound (Mx{+/-}US) increases sensitivity but decreases specificity. An alternative strategy, MRI alone, potentially more cost-effective, has never been explored. This study aims to assess the characteristics of women who participated in a randomized trial offering MRI alone.

MethodsIn this feasibility multicentre randomized controlled trial we compared MRI alone versus Mx+US in women at intermediate BC-risk (allocation ratio 1:1). Eligible women were aged 40 -59, with a 15-30% LTR and/or extremely dense breasts. Two screening rounds per woman were planned in ten centres experienced in MRI screening. Primary endpoint: rate of cancers detected in the two arms after 5 years of follow-up. Secondary endpoints: distribution of the risk profiles among the women enrolled in the trial; distribution of pathological stages and histology of cancers detected; interval cancer rate in the two arms.

ResultsFrom 07/2013 to 11/2015, 1,254 women (mean age 47 years) were enrolled: 624 were assigned to Mx+US, 630 to MRI. Most of them were aged below 50 (72%) and premenopausal (45%), 52% used oral contraceptives. Among postmenopausal women, 15% had used hormone replacement therapy. Breast and/or ovarian cancer in mother and/or sisters were reported by 37% of enrolled women, extreme breast density was recorded for 79%, 41% had a 15-30% BC-LTR.

ConclusionsThe distribution of BC-risk profile major determinants (breast density and family of breast and ovarian cancer) of enrolled women varied across centres.

Trial registrationNCT02210546

Key pointsO_LIMammography plus ultrasound are commonly used to screen women with dense breasts
C_LIO_LISupplemental ultrasound increases BC detection rate but also false-positives and potential overdiagnosis
C_LIO_LIWhether increased BC detection by US translates into reduced mortality is unknown
C_LIO_LIMRI alone could be more risk- and cost-effective than mammography plus ultrasound
C_LI

category: radiology and imaging


title: Genome-wide association study identifies two new loci associated with anti-NMDAR encephalitis

abstract:
ObjectiveTo investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis.

MethodsWe performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls followed by a colocalization analysis to identify putatively causal genes.

ResultsWe identified two independent risk loci harboring genome-wide significant variants (P < 5 x 10-8, OR [≤] 2.2), one on chromosome 15, harboring only the LRRK1 gene, and one on chromosome 11 centered on the ACP2 and NR1H3 genes in a larger region of high linkage-disequilibrium. Colocalization signals with expression quantitative trait loci (eQTL) for different brain regions and immune cell types suggested ACP2, NR1H3, MADD, DDB2, and C11orf49 as putatively causal genes. The best candidate genes in each region are LRRK1, encoding Leucine-Rich Repeat Kinase 1, a protein involved in B-cell development, and NR1H3 liver x receptor alpha, a transcription factor whose activation inhibits inflammatory processes.

ConclusionThis study provides evidence for relevant genetic determinants of antibody-mediated autoimmune encephalitides outside the HLA-region. The results suggest that future studies with larger sample sizes will successfully identify additional genetic determinants and contribute to the elucidation of the pathomechanism.


title: Risk, clinical course and outcome of ischemic stroke in patients hospitalized with COVID-19: a multicenter cohort study

abstract:
Background and purposeThe frequency of ischemic stroke in patients with COVID-19 varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

MethodsWe included patients with a laboratory confirmed SARS-CoV-2 infection admitted in 16 hospitals participating in the international CAPACITY-COVID registry between March 1st and August 1st, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

ResultsWe included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit (ICU). Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older, but did not differ in sex or cardiovascular risk factors. Median time between onset of COVID-19 symptoms and diagnosis of stroke was two weeks. The incidence of ischemic stroke was higher among patients who were treated at an ICU (16/586; 2.7% versus 22/1561; 1.4%; p=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted RR: 2.08; 95%CI:1.52-2.84). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functional dependent at discharge and in-hospital mortality. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted RR 1.56; 95%CI:1.13-2.15) than patients without stroke.

ConclusionsIn this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was approximately 2%, with a higher risk in patients treated at an ICU. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.


title: Lung function changes of divers after single deep heliox diving

abstract: ObjectivesThis study detects the changes in pulmonary function of divers after 80m, 100 m, and 120 m helium-oxygen (heliox) dive. Methods: A total of 26 divers participated in the experiment, of which 15 divers performed the 80m dive, 5 divers performed the 100m dive, and 6 divers performed the 120m dive. The exposure phases included breathing heliox or air in water and O2 in the hyperbaric chamber. Pulmonary function (forced flow-volume) was measured twice before diving, within 30 minutes after diving, and 24 hours after diving. The parameters examined were forced vital capacity (FVC), forced expired volume in 1 second (FEV1), forced expired flow from 25% to 75% volume expired (FEF25-75%), 25-75 percent maximum expiratory flow as compared with vital capacity (MEF 25-75%) and peak expiratory flow (PEF). Results: FEV1/FVC and MEF25% markedly decreased (p = 0.0395, p = 0.0496) within 30min after the 80m dive, but returned to base values at 24h after the dive. Other indicators showed a downward trend within 30min after 80m heliox diving (no statistical difference). Interestingly, FEV1, FEV1/FVC, PEF, MEF decreased after 100m heliox dives, but there was no statistical difference. However, in the 120m heliox dive, FEV1/FVC and MEF75% significantly decreased again after diving (p = 0.0098, p = 0.0073). The relatively small number and more proficient diving skills of divers in 100m and 120m diving may be responsible for the inconsistent results. But when the diving depth reached 120m, results again showed a significant statistical change. Conclusion: Single deep heliox diving can cause temporary expiratory and small airway dysfunction, which can be recovered at 24h after diving.

category: occupational and environmental health


title: Are vaccines safe in patients with Long COVID? A prospective observational study.

abstract:
IntroductionAlthough the efficacy of SARS-CoV-2 vaccination to prevent symptomatic COVID-19 is well established, there are no published studies on the impact on symptoms in patients with Long Covid. Anecdotal reports have suggested both a potential benefit and worsening of symptoms post vaccination with the uncertainty leading to some vaccine hesitancy amongst affected individuals.

MethodsPatients initially hospitalised with COVID-19 were prospectively recruited to an observational study with clinical follow-up at 3 months (June-July 2020) and 8 months (Dec 2020-Jan 2021) post-admission. Participants who received the Pfizer-BioNTech (BNT162b2) or Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccine between January to February 2021 were identified and matched 2:1 (in terms of 8-month symptoms) with participants from the same cohort who were unvaccinated. All were re-assessed at 1 month post vaccination (or matched timepoint for unvaccinated cohort). Validated quality of life (SF-36), mental wellbeing (WEMWBS) and ongoing symptoms were assessed at all timepoints. Formal statistical analysis compared the effect of vaccination on recent quality of life using baseline symptoms, age, and gender in linear regression.

ResultsForty-four vaccinated participants were assessed at a median of 32 days (IQR 20-41) post vaccination with 22 matched unvaccinated participants. Most were highly symptomatic of Long Covid at 8 months (82% in both groups had at least 1 persistent symptom), with fatigue (61%), breathlessness (50%) and insomnia (38%) predominating. There was no significant worsening in quality-of-life or mental wellbeing metrics pre versus post vaccination. Nearly two-thirds (n=27) reported transient (<72hr duration) systemic effects (including fever, myalgia and headache).

When compared to matched unvaccinated participants from the same cohort, those who had receive a vaccine had a small overall improvement in Long Covid symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated) (p=0.035). No difference in response was identified between Pfizer-BioNTech or Oxford-AstraZeneca vaccines.

ConclusionsReceipt of vaccination with either an mRNA or adenoviral vector vaccine was not associated with a worsening of Long Covid symptoms, quality of life, or mental wellbeing. Individuals with prolonged COVID-19 symptoms should receive vaccinations as suggested by national guidance.


title: Reducing the Cost of Rapid Antigen Tests through Swab Pooling and Extraction in a Device

abstract: The COVID-19 pandemic places a significant stress on the viral testing capabilities of many countries. The value of rapid point-of-care (PoC) antigen tests is becoming increasingly clear, but implementing frequent large scale testing is costly. We have developed an inexpensive device for pooling swabs, extracting specimens, and detecting viral antigens with a commercial lateral flow assay detecting the nucleocapsid protein of SARS-CoV-2 as antigen. The holder of the device can be produced locally through 3D printing. The extraction and the elution can be performed with the entire set-up encapsulated in a transparent bag, minimizing the risk of infection for the operator. With 6 swabs holding approx. 0.1 mL specimen each and 0.35 mL extraction buffer, 43{+/-}6 % (n= 8) of the signal for an individual extraction of a positive control standard was obtained. Image analysis still showed a signal-to-noise ratio of [≥] 7 upon further eight-fold dilution. Our current total cost of materials is below $ 2 per tested person or 20% of our cost for an individual PoC test. These findings suggest that pooling can make frequent testing more affordable for schools, universities and other institutions, without decreasing sensitivity to an unacceptable level. Further validation of the method is required.


title: Analysis of Accumulated SARS-CoV-2 Seroconversion in North Carolina: The COVID-19 Community Research Partnership

abstract:
IntroductionThe COVID-19 Community Research Partnership is a population-based longitudinal syndromic and sero-surveillance study. The study includes over 17,000 participants from six healthcare systems in North Carolina who submitted over 49,000 serology results. The purpose of this study is to use these serology data to estimate the cumulative proportion of the North Carolina population that has either been infected with SARS-CoV-2 or developed a measurable humoral response to vaccination.

MethodsAdult community residents were invited to participate in the study between April 2020 and February 2021. Demographic information was collected and daily symptom screen was completed using a secure, HIPPA-compliant, online portal. A portion of participants were mailed kits containing a lateral flow assay to be used in-home to test for presence of anti-SARS-CoV-2 IgM or IgG antibodies. The cumulative proportion of participants who tested positive at least once during the study was calculated. A standard Cox proportional hazards model was constructed to illustrate the probability of seroconversion over time up to December 20, 2020 (before vaccines available). A separate analysis was performed to describe the influence of vaccines during an extended period through February 15, 2021.

Results17,688 participants contributed at least one serology result. Approximately two-thirds of the population were female and almost three-quarters were between 30 and 64 years of age. The average number of serology test results submitted per participant was 3.0 ({+/-}1.9). At December 20, 2020, the overall probability of seropositivity in the CCRP population was 32.6%. At February 15, 2021 the probability among healthcare workers and non-healthcare workers was 83% and 49%, respectively. An inflection upward in the probability of seropositivity was demonstrated around the end of December, suggesting an influence of vaccinations, especially for healthcare workers. Among healthcare workers, those in the oldest age category (60+ years) were 38% less likely to have seroconverted by February 15, 2021.

ConclusionsResults of this study suggest more North Carolina residents may have been infected with SARS-CoV-2 than the number of documented cases as determined by positive RNA or antigen tests. The influence of vaccinations on seropositivity among North Carolina residents is also demonstrated. Additional research is needed to fully characterize the impact of seropositivity on immunity and the ultimate course of the pandemic.


title: Optimal vaccination strategies for COVID-19 based on dynamical social networks with real-time updating

abstract: Vaccination strategy is crucial in fighting the COVID-19 pandemic. Since the supply is still limited in many countries, contact network-based interventions can be most powerful to set an efficient strategy by identifying high-risk individuals or communities. However, due to the high dimension, only partial and noisy network information can be available in practice, especially for dynamic systems where contact networks are highly time-variant. Furthermore, the numerous mutations of SARS-CoV-2 have a significant impact on the infectious probability, requiring real-time network updating algorithms. In this study, we propose a sequential network updating approach based on data assimilation techniques to combine different sources of temporal information. We then prioritise the individuals with high-degree or high-centrality, obtained from assimilated networks, for vaccination. The assimilation-based approach is compared with the standard method (based on partially observed networks) and a random selection strategy in terms of vaccination effectiveness in a SIR model. The numerical comparison is first carried out using real-world face-to-face dynamic networks collected in a high school, followed by sequential multi-layer networks generated relying on the Barabasi-Albert model emulating large-scale social networks with several communities.


title: Real-time Updating of Dynamic Social Networks for COVID-19 Vaccination Strategies


title: Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination

abstract:
BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy and early infancy can result in severe disease. Evaluating the serologic response after maternal vaccination during pregnancy and subsequent transplacental antibody transfer has important implications for maternal care and vaccination strategies.

ObjectiveTo assess maternal and neonatal SARS-CoV-2 antibody levels after antenatal mRNA vaccination.

Design, Setting, and ParticipantsThis study took place at Hadassah Medical Center in Jerusalem, Israel in February 2021. Maternal and cord blood sera were collected for antibody measurement from mother/newborn dyads following antenatal vaccination.

ExposureSARS-CoV-2 BNT162b2 mRNA vaccination.

Main outcome and measuresSpike protein (S) and receptor binding domain (RBD) - specific, IgG levels were evaluated in maternal and cord blood sera.

ResultsThe study cohort consisted of 20 parturients, with a median maternal age of 32 y ears and a median gestational age of 393/7 weeks at the time of delivery. The median time lapsed from the first and second doses of vaccine administration until delivery was 33 [IQR 30-37] and 11 [IQR 9-15] days, respectively. Of the 20 dyads, all women an d infants were positive for anti S- and anti-RBD-specific IgG. Anti-S and anti-RBD-specific IgG levels in maternal sera were positively correlated to their respective concentrations in cord blood ({rho}s= 0.72; P<0.001 and {rho}s= 0.72; P <0.001, respectively). Anti-S and anti-RBD-specific IgG titers in cord blood were directly correlated with time lapsed since the administration of the first vaccine dose ({rho}s= 0.71; P =0.001 and {rho}s= 0.63; P=0.004, respectively).

Conclusion and RelevanceIn this study, SARS-CoV-2 mRNA vaccine administered during pregnancy induced adequate maternal serologic response with subsequent efficient transplacental transfer. Our findings highlight that vaccination of pregnant women may provide maternal and neonatal protection from SARS-CoV-2 infection.


title: Evolution of antibodies against SARS-CoV-2 over seven months: experience of the Nationwide Seroprevalence ENE-COVID Study in Spain

abstract:
ObjectivesTo analyse temporal trends in SARS-CoV-2 anti-nucleocapsid IgG throughout the four rounds of the nationwide seroepidemiologic study ENE-COVID (April-November 2020), and to compare the fourth-round results of two immunoassays detecting antibodies against nucleocapsid and to S protein receptor-binding domain (RBD).

MethodsA chemiluminescent microparticle immunoassay (CMIA) was offered to all participants in the first three rounds (Abbott; anti-nucleocapsid IgG). In the fourth round we offered this test and a chemiluminescence immunoassay (CLIA) (Beckman; anti-RBD IgG) to i) a randomly selected sub-cohort, ii) participants who were IgG-positive in any of the three first rounds; and iii) participants who were IgG-positive in the fourth round by point-of-care immunochromatography.

ResultsImmunoassays involving 10,153 participants (82.2% of people invited to donate samples) were performed in the fourth round. A total of 2595 participants (35.1% of participants with immunoassay results in the four rounds) were positive for anti-nucleocapsid IgG in at least one round. Anti-nucleocapsid IgG became undetectable in 43.3% of participants with positive first-round results. Pneumonia was more frequent in participants with anti-nucleocapsid IgG in all four rounds (11.2%) than those in which IgG became undetectable (2.4%).

In fourth round, anti-nucleocapsid and anti-RBD IgG were detected in 5.5% and 5.4% participants of the randomly selected sub-cohort, and in 26.6% and 25.9% participants with at least one previous positive result, respectively. Agreement between techniques was 90.3% (kappa: 0.72).

ConclusionsThe response of IgG to SARS-CoV-2 is heterogeneous and conditioned by infection severity. A substantial proportion of the SARS-CoV-2 infected population may have negative serologic results in the post-infection months.


title: Characterizing the COVID-19 illness experience to inform the study of post-acute sequalae and recovery: a qualitative study

abstract: We aimed to characterize the variability in the illness experience and recovery process from COVID-19. We conducted in-depth individual interviews with participants enrolled in the Long-term Immunological Impact of Novel Coronavirus (LIINC) cohort study in San Francisco, California from June through October of 2020. Participants were adults who had a previously confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations at our clinical research center. We purposefully sampled 24 English- and Spanish-speaking adults with asymptomatic, mild and severe symptomatic infection, including those who were hospitalized, and those with HIV co-infection. Half of our sample (50.0%) identified as Latinx/Hispanic and most of the participants were men (62.5%). We used thematic analysis to characterize the illness experience, recovery process, and mental health impact of experiencing COVID-19 and present clinical data for each participant. Emergent themes were: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress, (2) among participants with symptomatic infection, the illness experience was characterized by uncertainty in terms of managing symptoms and recovery, and (3) despite wide-ranging illness experiences, participants shared many common characteristics, including health information-seeking behavior facilitated by access to medical care, and uncertainty regarding the course of their illness and recovery. COVID-19 was associated with elevated levels of psychological distress, regardless of symptoms.


title: Characterizing the COVID-19 illness experience to inform the study of post-acute sequelae and recovery: a qualitative study


title: Evaluation of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients in outbreak on a cruise ship

abstract:
BackgroundA few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 (COVID-19) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 patients.

MethodsBlood samples were collected from 143 COVID-19 patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured using the enzyme-linked immunosorbent assay to compare false-negative-with positive-result samples.

ResultsSensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein, were significantly lower in blood samples with false-negative results than in those with positive results.

ConclusionsThese findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 patients than required in the guidelines, and situations in which it is useful are limited.


title: A novel whole-blood stimulation assay to detect and quantify memory T-cells in COVID-19 patients

abstract: SARS-CoV-2 specific T-cells responses are essential for virus clearance. We present a novel and simple whole-blood assay allowing the detection of interferon-gamma-producing antiviral T-cells following peptide stimulation. We show that unlike neutralizing antibodies, antiviral memory T-cells persist at least 6 months in convalescent Covid-19 individuals.


title: Pre-existing health conditions and severe COVID-19 infection: Analysis of commercial health insurance data from 690,000 infected patients

abstract: The development and distribution of new vaccines promises an end to the COVID-19 pandemic. With the elderly and front line workers first in line, the vaccination strategy for the general population remains unclear. In this study we identified 690,000 patients infected with COVID-19 with commercial health insurance coverage across the country between April 1, 2020 and September 30, 2020. From prior health care claims, we determined each persons pre-existing diseases among 26 common chronic diseases. Across age-sex strata we determined the relationships between these conditions and severe COVID-19 infections: ICU admission and extended in-patient stay. We classify disease according to risk, develop multivariable models to predict infection outcomes, and created an online risk assessment tool to estimate risk of ICU admission based on pre-existing health conditions. Our results could be used to help guide risk, vaccination health policy, and personal decision-making as these become available to the general population.


title: An international comparison of age and sex dependency of COVID-19 Deaths in 2020 - a descriptive analysis

abstract: COVID-19 mortality, the number of reported COVID-19 deaths per 100,000 persons observed so far, is described in 15 European countries and the USA depending on age groups and sex for the full year 2020. It is contrasted to the corresponding historic all-cause mortality per year depending on age and sex observed in these countries. Although there are substantial differences in the age and sex dependency of COVID-19 mortality between countries, there are some common features: Exponential increase with age is a good model to describe and analyse both COVID-19 and all-cause mortality above an age of 40 years, where almost all COVID-19 death occur. Age dependency is stronger for COVID-19 mortality than for all-cause mortality, males have an excess risk compared to women which flattens off with increasing age. Also with regard to calendar time, there were differences in the age and sex dependency between countries with the common tendency that male excess risk of COVID-19 mortality was smaller in the second half of the year.


title: Clinical presentation, disease course and outcome of COVID-19 in hospitalized patients with and without pre-existing cardiac disease: a cohort study across sixteen countries

abstract:
AimsPatients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality.

Method and resultsWe used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existent heart disease and in-hospital mortality. 16,511 patients with COVID-19 were included (21.1% aged 66 - 75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male and often had other comorbid conditions when compared to those without. Mortality was higher in patients with cardiac disease (29.7%; n=1545 versus 15.9%; n=1797). However, following multivariable adjustment this difference was not significant (adjusted risk ratio (aRR) 1.08 [95% CI 1.02 - 1.15; p-value 0.12 (corrected for multiple testing)]). Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure aRR (1.19 [1.10 - 1.30]; p-value <0.018) particularly for severe NYHA III/IV) heart failure (aRR 1.41 [95% CI 1.20 - 1.64; p-value <0.018]. None of the other heart disease subtypes, including ischemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in <1% of patients.

ConclusionConsiderable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare.


title: Clinical presentation, disease course and outcome of COVID-19 in hospitalized patients with and without pre-existing cardiac disease: a cohort study across eighteen countries


title: Smartphone-based videoconference visits are easy to implement, effective, and feasible in Crohn's Disease Patients: A Prospective Cohort Study

abstract:
BackgroundCrohns Disease patients require life-long follow-up resulting frequent hospital visits. Usefulness of telehealth has been established in remote management of Crohns disease but mobile technologys role is missing. We aimed to determine the feasibility and effectiveness of smartphone-based real-time video visits.

MethodsWe prospectively studied 139 patients either at a traditional (FTF) or online clinic (OLV) in a university hospital between March 2020-September 2020. We measured patients satisfactions, disease activity, visit outcomes, socioeconomic parameters, and travel expenses to assess the effectiveness and acceptance of OLV.

ResultsSatisfaction scores were significantly higher at OLV compared to FTF (89.58{+/-}9.93 vs 70.85{+/-}18.51, p<0.001). The Cronbach Alpha reliability coefficient of the VSQ9 scale was 0.878. Median 47km travel distance and 49 minutes travel time per visit saved with OLV. An average of US$12.24 potential travel costs were saved per appointment. Eighty-five per cent of the patients met the needs at online visits and did not require a face-to-face visit.

ConclusionsSmartphone-based real-time video visit telehealth model for distant management of Crohn disease had high acceptance. The model was easy to implement, effective and saved travel cost and time.

category: gastroenterology


title: Day Camp in the Time of COVID-19: What Went Right?

abstract:
ObjectiveTo evaluate whether a successful camp experience can be achieved with implementation of COVID-19 education, screening and hygiene protocols, and designated cohorts during the summer of 2020.

Study DesignA survey study of summer day camp directors in the metro-New York area was conducted in September, 2020. The survey inquired about camper demographics, COVID-10 related policies, and the number of COVID-19 cases and exposures at each camp.

ResultsResponses were received from 77% (23/30) of camp directors at the completion of the 2020 summer. There were 8,480 camper children and 3,698 staff across the 23 camps surveyed. A variety of precautions were taken to limit COVID-19 incidence among campers and staff, most often including COVID-19 screening at entry, cohorting campers, maximizing outdoor activities, mandating mask use when indoors, and frequent hand sanitizing. Six staff and one camper tested positive for COVID-19. There was no secondary spread within the staff or campers in any of the camps.

ConclusionCamps successfully stayed open in the summer of 2020. The low level of COVID-19 in the community was critical to the initial success of camp opening. Policies that were consistent and maintained among the camps helped prevent further spread.


title: Oxygen provision to severely ill COVID-19 patients at the peak of the 2020 pandemic in a Swedish district hospital: medical records-based cohort study

abstract:
Oxygen is a low-cost and life-saving therapy for patients with COVID-19. Yet, it is a limited resource in many hospitals in low income countries and in the 2020 pandemic even hospitals in richer countries reported oxygen shortages. An accurate understanding of oxygen requirements is needed for capacity planning. The World Health Organization estimates the average flow-rate of oxygen to severe COVID-19-patients to be 10 l/min. However, there is a lack of empirical data about the oxygen provision to patients. This study aimed to estimate the oxygen provision to COVID-19 patients with severe disease in a Swedish district hospital.

A retrospective, medical records-based cohort study was conducted in March to May 2020 in a Swedish district hospital. All adult patients with severe COVID-19 - those who received oxygen in the ward and had no ICU-admission during their hospital stay - were included. Data were collected on the oxygen flow-rates provided to the patients throughout their hospital stay, and summary measures of oxygen provision calculated.

One-hundred and twenty six patients were included, median age was 70 years and 43% were female. On admission, 27% had a peripheral oxygen saturation of [≤]91% and 54% had a respiratory rate of [≥]25/min. The mean oxygen flow-rate to patients while receiving oxygen therapy was 3.0 l/min (SD 2.9) and the mean total volume of oxygen provided per patient admission was 16,000 l (SD 23,000).

In conclusion, the provision of oxygen to severely ill COVID-19-patients was lower than previously estimated. Further research is required before global estimates are adjusted.


title: Oxygen provision to severely ill COVID-19 patients at the peak of the 2020 pandemic in a Swedish district hospital


title: Seroprevalence of SARS-CoV-2 Infection in Cincinnati Ohio USA from August to December 2020

abstract: The world is currently in a pandemic of COVID-19 (Coronavirus disease-2019) caused by a novel positive-sense, single-stranded RNA {beta}-coronavirus referred to as SARS-CoV-2. Fortunately, most infected individuals recover and are then resistant to re-infection for a period, indicating that a vaccination approach can be successful. Elucidation of rates of past SARS-CoV-2 infection within select regions across the United States of America (USA) will help direct vaccination efforts and together will inform our approach towards achieving herd immunity. Here we investigated rates of SARS-CoV-2 infection in the greater Cincinnati, Ohio, USA metropolitan area from August to December 2020, just prior to initiation of the national vaccination program. Examination of 9,550 adult blood donor volunteers for serum IgG antibody positivity against the SARS-CoV-2 Spike protein showed an overall prevalence of 8.40%, measured as 7.56% in the first 58 days of this time frame, versus a significant increase to 9.24% in the last 58 days, and a final rate of 12.86% in December 2020. Approximately 56% of Spike seropositive individuals also had immunoreactivity against the receptor binding domain (RBD) within the Spike protein, which is associated with viral neutralization. Males and females in the Cincinnati area showed nearly identical rates of past infection, and rates among Hispanics, African Americans and Caucasians were not significantly different. Interestingly, donors under 30 years of age had the highest rates of past infection, while those over 60 had the lowest. Geographic analysis showed that the West side of Cincinnati had a rate of 9.63% versus 8.13% on the East side (demarcated by Interstate-75), while the adjoining area of Kentucky was 7.04% (as demarcated by the Ohio River). These results among healthy blood donors will be critical in calculating the time needed to achieve regional herd immunity in conjunction with the national vaccination campaign.


title: Airborne Transmission of COVID-19 and Mitigation Using Box Fan Air Cleaners in a Poorly Ventilated Classroom

abstract: Many indoor places, including aged classrooms and offices, prisons, homeless shelters, etc., are poorly ventilated but resource-limited to afford expensive ventilation upgrade or commercial air purification systems, raising concerns on the safety of opening activities in these places in the era of COVID-19 pandemic. To address this challenge, using computational fluid dynamics, we conducted a systematic investigation of airborne transmission in a classroom equipped with a single horizontal unit ventilator (HUV) and evaluate the performance of low-cost box fan air cleaner for risk mitigation. Our study shows that placing box fan air cleaners in the classroom results in a substantial reduction of airborne transmission risk across the entire space. The air cleaner can achieve optimal performance when placed near the asymptomatic patient. However, without knowing the location of the patient, the performance of the cleaner is optimal near the HUV with the air flowing downwards. In addition, we find that it is more efficient in reducing aerosol concentration and spread in the classroom by adding air cleaners in comparison with raising the flow rate of HUV alone. The number and placement of air cleaners need to be adjusted to maintain its efficacy for larger classrooms and to account for the thermal gradient associated with human thermal plume and hot ventilation air during cold seasons. Overall, our study shows that box fan air cleaners can serve as an effective low-cost alternative for mitigating airborne transmission risks in poorly ventilated spaces.


title: Sleep quality mediates the relationship between risk of obstructive sleep apnea and acute stress in young adults

abstract:
PurposeIntermittent hypoxia and transient arousals in obstructive sleep apnea (OSA) can lead to poor sleep quality and acute stress. Rising levels of obesity and increased incidence of OSA in young adults predisposes them to acute stress. We propose a mediation model to assess if risk of OSA is associated with acute stress and if the relationship between risk for OSA and acute stress is mediated by sleep quality.

Methods493 healthy individuals (F=237, M=256) from 18-25 years of age (mean age=20.3{+/-}1.53 years) were screened for OSA, sleep quality and acute stress using STOP-BANG questionnaire, Pittsburg Sleep Quality Index and American Psychiatry Associations National Stressful Events Survey Acute Stress Disorder Short Scale (NSESS-S) respectively. Binary and logistic regression were used establish the relationships between the variables. Sobel test for mediation analysis was conducted.

Results73 participants (17.3%) were found at an intermediate and high risk of OSA by STOP BANG questionnaire. 79 (16%) participants reported level of stress as  None. Mild, moderate and severe stress was present in 248 (50.3%), 109 (22.1%), 51 (10.3%) and 16 (3.2%) participants respectively. The odds of having severe and extreme stress among those at risk of sleep apnea is 2.18 times higher than that among those not at risk of sleep apnea (OR: 2.18, 95% Confidence Interval: 1.37-3.51). Sobel test established that the relationship between OSA and acute stress is mediated by sleep quality.

ConclusionSleep quality mediates the relationship between risk for sleep apnea and acute stress. This highlights the importance of screening for OSA in young adults, particularly young men with high BMI, presenting with high stress levels.


title: Acceptability of COVID-19 vaccination among health care workers in Ghana

abstract: The acceptance or otherwise of the COVID-19 vaccine by health care workers can influence the uptake of COVID-19 vaccines among the general population as they are a reliable source of health information. In this study, we sought to determine the acceptability of COVID-19 vaccines among health care workers in Ghana. Using a cross-sectional design, we collected data from 234 health care workers through a self-administered online survey from 16 January to 15 February 2021. Descriptive, bivariate and multivariate analyses using binary logistic regression were performed using STATA version 15. The results showed that 39.3% of health care workers had the intention of receiving the COVID-19 vaccine. Factors such as sex, category of health care workers, relative being diagnosed with COVID-19, and trust in the accuracy of the measures taken by the government in the fight against COVID-19 proved to be significant predictors of the acceptability of the COVID-19 vaccine. Concerns about the safety of vaccines and the adverse side effects of the vaccine were identified as the main reasons why health care workers would decline uptake of the COVID-19 vaccine in Ghana. The self-reported low intention of health care workers to accept the COVID-19 vaccine in Ghana requires the urgent call of the Government of Ghana and other stakeholders to critically address health care workers concerns about the safety and adverse side effects of COVID-19 vaccines, as this would increase vaccine uptake. Interventions must also take into consideration sex and the category of health care workers to achieve the desired results.