title: Antibody Response after Second-dose of ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) among Health Care Workers in India: Final Results of Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) study

abstract:
BackgroundWe assessed the humoral immune response after the completion of two doses of both ChAdOx1-nCOV (Covishield) and BBV-152 (Covaxin) vaccines in Indian health care workers (HCW).

MethodA Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study was conducted that measured SARS-CoV-2 anti-spike binding antibody quantitatively, 21 days or more after the first and second dose of two vaccines in both severe acute respiratory syndrome (SARS-CoV-2) naive and recovered HCW. Primary aim was to analyze antibody response (seropositivity rate and median [inter-quartile range, IQR] antibody titre) following each dose of both vaccines and its correlation to age, sex, blood group, body mass index (BMI) and comorbidities. Here we report the final results of anti-spike antibody response after the two completed doses.

ResultsAmong the 515 HCW (305 Male, 210 Female), 95.0% showed seropositivity after two doses of both vaccines. Of the 425 Covishield and 90 Covaxin recipients, 98.1% and 80.0% respectively, showed seropositivity. However, both seropositivity rate and median (IQR) rise in anti-spike antibody was significantly higher in Covishield vs. Covaxin recipient (98.1 vs. 80.0%; 127.0 vs. 53 AU/mL; both p<0.001). This difference persisted in 457 SARS-CoV-2 naive cohorts and propensity-matched (age, sex and BMI) analysis of 116 cohorts. While no difference was observed in relation to sex, BMI, blood group and any comorbidities; people with age >60 years or those with type 2 diabetes had a significantly lower seropositivity rates. Both vaccine recipients had similar solicited mild to moderate adverse events and none had severe or unsolicited side effects. In SARS-CoV-2 naive cohorts, sex, presence of comorbidities, and vaccine type were independent predictors of antibody positivity rate in multiple logistic regression analysis.

ConclusionsBoth vaccines elicited good immune response after two doses, although seropositivity rates and median anti-spike antibody titre was significantly higher in Covishield compared to Covaxin arm.

HighlightsO_LIThis study evaluated the humoral antibody response after 2 doses of SARS-CoV-2 vaccine Covishield and Covaxin in Indian health-care workers.
C_LIO_LICombined results of both vaccines showed 95% seropositivity to anti-spike antibody, 21-36 days after the second completed dose.
C_LIO_LISeropositivity rates were higher in Covishield recipients compared to Covaxin in the propensity-matched analysis of SARS-CoV-2 naive cohorts.
C_LIO_LIGender, presence of comorbidities and the type of vaccine received were independent predictors of antibody response after the second dose.
C_LI

category: allergy and immunology


title: Prenatal smoking, alcohol and caffeine exposure and offspring externalising disorders: A systematic review and meta-analysis

abstract:
Background and aimsSeveral studies have indicated that there is an association between maternal prenatal substance use and offspring externalising disorders. However, it is uncertain whether this relationship is causal. Therefore, we updated a previously conducted systematic review to determine if the literature supports 1) a causal role of maternal prenatal substance use on offspring externalising disorders and 2) whether these associations differ across externalising disorders.

MethodsWe searched Web of Science, Embase, PsycINFO and Medline databases. We included studies that examined smoking, alcohol or caffeine use during pregnancy as an exposure, and diagnosis of attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional-defiant disorder (ODD) in offspring as an outcome. Studies on non-English language, fetal alcohol syndrome and comorbid autism spectrum disorders were excluded. Risk of bias assessment was conducted using Newcastle Ottawa Scale (NOS) and where possible meta-analysis was conducted for studies classed as low risk of bias.

ResultsWe included 63 studies. All studies were narratively synthesised, and 7 studies were meta-analysed on smoking and ADHD. The majority of studies (46 studies) investigated the association between smoking and ADHD. Studies which accounted for genetic effects indicate that the association between smoking and ADHD is unlikely to be causal. Studies on alcohol exposure in all the outcomes reported inconsistent findings and no strong conclusions on causality can be made. Studies on caffeine exposure were mostly limited to ADHD and these studies do not support a causal effect.

ConclusionsThere is no causal relationship between maternal smoking during pregnancy and attention-deficit hyperactivity (ADHD) in offspring. However, given that the majority of identified studies investigated the association between ADHD and smoking exposure, findings with alcohol and caffeine exposures and conduct disorder (CD) and oppositional-defiant disorder (ODD) need more research, especially using more genetically sensitive designs.

category: epidemiology


title: Tracking deaths can provide an indicator of latent COVID19 cases

abstract:
BackgroundWith countries across the world facing repeated epidemic waves, it becomes critical to monitor, mitigate and prevent subsequent waves. Common indicators like active case numbers can flatter to deceive in the presence of systemic inefficiencies like insufficient testing or contact tracing. Test positivity rates are sensitive to testing strategies and cannot estimate the extent of undetected cases. Reproductive numbers estimated from logarithms of new incidences are inaccurate in dynamic scenarios and not sensitive enough to capture changes in efficiencies. Systemic fatigue results in lower testing, inefficient tracing and quarantining thereby precipitating the onset of the epidemic wave.

MethodsWe propose a novel indicator for detecting the slippage of test-trace efficiency based on the numbers of deaths/hospitalizations resulting from known and hitherto unknown infections. This can also be used to forecast an epidemic wave that is advanced or exacerbated due to drop in efficiency.

ResultsUsing a modified SEIRD epidemic simulator we show that (i) Ratio of deaths/hospitalizations from an undetected infection to total deaths converges to a measure of systemic test-trace inefficiency. (ii) This index forecasts the slippage in efficiency earlier than other known metrics. (iii) Mitigation triggered by this index helps reduce peak active caseload and eventual deaths.

ConclusionsDeaths/hospitalizations accurately track the systemic inefficiencies and detect latent cases. Based on these results we make a strong case that administrations use this metric in the ensemble of indicators. Further hospitals may need to be mandated to distinctly register deaths/hospitalizations due to previously undetected infections.

Key MessagesO_LIDeaths or Hospitalizations are unmissable events in an epidemic and this paper proposes a metric Dratio based on these numbers to monitor the inefficiencies in test-track-trace performance.
C_LIO_LIThe ratio of deaths(or hospitalizations) resulting from undetected infections to total deaths (or hospitalizations) detect the onset of laxity in regulations earlier than other conventional metrics like daily increase in active cases, daily deaths or even reproductive number estimates.
C_LIO_LIMitigation by tracking the Dratio reduces or truncates the epidemic wave intensity or delays it sufficiently.
C_LI


title: Tracking deaths from hitherto undetected infections can be an indicator of latent sars-cov-2 cases


title: Classifying Texas counties using ARIMA Models on COVID-19 daily confirmed cases: the impact of political affiliation and face covering orders

abstract: The aim of this paper is to investigate whether the 254 Texas counties in the United States can be grouped in a meaningful way according to the characteristics of the ARIMA or seasonal ARIMA models fitting the logarithm of daily confirmed cases of the Coronavirus Disease 2019 (COVID-19) for 254 counties in Texas of the United States. We analyze clusters of the models non-seasonal parameters (p, d, q), distinguishing between county-level political affiliations and face covering orders, and also consider county-level population and poverty rate. Using data from March 4, 2020 to March 15, 2021, we find that 223 of the total 254 counties are clustered into 23 model parameters (p, d, q), while the number of cases in the remaining 31 counties could not be successfully fitted to ARIMA models. We also find the impact of the county-level infection rate and the county-level poverty rate on clusters of counties with different political affiliations and face covering orders. Further, we find that the infection rate and the poverty rate had a significant high positive correlation, and Democrat-leaning counties, which tend to have large populations, had a higher correlation coefficient between infection rate and poverty rate. We also observe a significant high positive correlation between the infection rate and the number of cumulative cases in Republican counties that had not imposed a face covering order.


title: Semi-Supervised Medical Image Detection with Adaptive Consistency and Heterogeneous Perturbation

abstract: Semi-Supervised classification and segmentation methods have been widely investigated in medical image analysis. Both approaches can improve the performance of fully-supervised methods with additional unlabeled data. However, as a fundamental task, semi-supervised object detection has not gained enough attention in the field of medical image analysis. In this paper, we propose a novel Semi-Supervised Medical image Detector (SSMD). The motivation behind SSMD is to provide free yet effective supervision for unlabeled data, by regularizing the predictions at each position to be consistent. To achieve the above idea, we develop a novel adaptive consistency cost function to regularize different components in the predictions. Moreover, we introduce heterogeneous perturbation strategies that work in both feature space and image space, so that the proposed detector is promising to produce powerful image representations and robust predictions. Extensive experimental results show that the proposed SSMD achieves the state-of-the-art performance at a wide range of settings. We also demonstrate the strength of each proposed module with comprehensive ablation studies.

category: radiology and imaging


title: Efficacy of clarithromycin on COVID-19 pneumonia without oxygen administration; protocol for multicenter, open-label, randomized-controlled, 3-armed parallel group comparison, exploratory trial (CAME COVID study)

abstract:
IntroductionThe coronavirus disease 2019 (COVID-19) epidemic has been emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, no treatment strategy has been established for mild COVID-19 patients who do not require oxygen administration. The spread of SARS -CoV-2 has been mostly through patients with mild COVID-19; therefore, treating patients with mild COVID-19 is critical in society. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza infection. In this study, we aimed to evaluate the efficacy of clarithromycin in patients with mild COVID-19.

Methods and analysisThis is a multicenter, open-label, randomized controlled, 3-armed parallel group comparison, exploratory trial. Subjects with mild COVID-19 pneumonia who did not require oxygen administration were enrolled and randomly assigned in a 1:1:1 ratio to Group A (administration of clarithromycin 800 mg/day), Group B (administration of clarithromycin 400 mg/day), or Group C (standard treatment without clarithromycin). The primary endpoint was the number of days required to improve clinical symptoms as measured by the severity score. Secondary endpoints included days to recover the body temperature, proportion of subjects with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers, and pneumonia infiltrations.

Ethics and disseminationThe study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all participants. The results of this study will be reported as journal publications.

RegistrationThis study was registered at the Japan Registry of Clinical Trials (registration number: jRCTs071210011).

Strengths and limitations of this studyO_LIThis is the first randomized controlled trial to evaluate the efficacy of clarithromycin against COVID-19 pneumonia, especially in patients with mild COVID-19 pneumonia who do not require oxygen administration.
C_LIO_LITo date, no treatment strategy has been established for mild COVID-19 pneumonia.
C_LIO_LIThe major limitations of this study are its exploratory nature and relatively small sample size.
C_LIO_LIAnother limitation is the open-label study design and generalizability because this study was conducted only in Japan with Japanese patients.
C_LI

category: respiratory medicine


title: Subtle anomaly detection in MRI brain scans: Application to biomarkers extraction in patients with 'de novo' Parkinson's disease

abstract: With the advent of recent deep learning techniques, computerized methods for automatic lesion segmentation have reached performances comparable to those of medical practitioners. However, little attention has been paid to the detection of subtle physiological changes caused by evolutive pathologies such as neurodegenerative diseases. In this work, we investigated the ability of deep learning models to detect anomalies in magnetic resonance imaging (MRI) brain scans of recently diagnosed and untreated (de novo) patients with Parkinsons disease (PD). We evaluated two families of auto-encoders, fully convolutional and variational auto-encoders. The models were trained with diffusion tensor imaging (DTI) parameter maps of healthy controls. Then, reconstruction errors computed by the models in different brain regions allowed to classify controls and patients with ROC AUC up to 0.81. Moreover, the white matter and the subcortical structures, particularly the substantia nigra, were identified as the regions the most impacted by the disease, in accordance with the physio-pathology of PD. Our results suggest that deep learning-based anomaly detection models, even trained on a moderate number of images, are promising tools for extracting robust neuroimaging biomarkers of PD. Interestingly, such models can be seamlessly extended with additional quantitative MRI parameters and could provide new knowledge about the physio-pathology of neuro-degenerative diseases.

category: health informatics


title: Magnetic activated cell-sorting identifies a unique lung microbiome community associated with disease states

abstract:
RationaleThe advent of culture-independent, next-generation DNA sequencing has led to discovery of distinct lung bacterial communities. Studies of lung microbiome taxonomy often reveal only subtle differences between health and disease, but microbial host response may distinguish members of similar communities in different populations.

ObjectivesMagnetic-activated cell sorting (MACS) has been applied to the gut microbiome to identify numbers and types of bacteria eliciting a humoral response. We adapted this technique to examine populations of immunoglobulin-bound bacteria and investigate the lung microbiota in HIV as a representative disease.

Methods42 people living with HIV (PLWH) and 22 HIV-uninfected individuals underwent bronchoalveolar lavage (BAL). We separated immunoglobulin G-bound bacteria using MACS and sequenced the 16S rRNA gene on the Illumina MiSeq platform. We analyzed sequences and quantified BAL cytokines and bacterial rRNA copy numbers.

Measurements and Main ResultsImmunoglobulin G-bound bacteria were detectable in the healthy lung microbiota. Comparison of raw BAL by HIV status showed no significant taxonomic differences, but the immunoglobulin-bound lung microbiota differed by HIV status with greater abundance of Pseudomonas in PLWH. BAL cytokine levels were also higher in PLWH, which correlated with increased quantity of immunoglobulin G-bound bacteria.

ConclusionsWe report a novel application of magnetic-activated cell sorting to identify immunoglobulin G-bound bacteria in the lung. This technique identified distinct bacterial communities which differed in composition from raw BAL, revealing differences in health and disease not detected by traditional analyses. Cytokine response was also associated with differential immunoglobulin binding of lung bacteria, suggesting functional importance of these communities.

category: hiv aids


title: Reduced risk of placental parasitaemia associated with complement fixation on Plasmodium falciparum by antibodies among pregnant women

abstract:
BackgroundThe pathogenesis of malaria in pregnancy (MiP) involves accumulation of P. falciparum-infected red blood cells (pRBCs) in the placenta, contributing to poor pregnancy outcomes. Parasite accumulation is primarily mediated by P. falciparum erythrocyte membrane 1 (PfEMP1). Magnitude of IgG to pRBCs has been associated with reduced risk of MiP in some studies, but associations have been inconsistent. Further, antibody effector mechanisms are poorly understood, and the role of antibody complement interactions is unknown.

MethodsStudying a longitudinal cohort of pregnant women (n=302) from a malaria-endemic province in Papua New Guinea (PNG), we measured the ability of antibodies to fix and activate complement using placental binding pRBCs and PfEMP1 recombinant domains. We determined antibody-mediated complement inhibition of pRBC binding to the placental receptor, chondroitin sulfate A (CSA) and associations with protection against placental parasitaemia.

ResultsSome women acquired antibodies that effectively promoted complement fixation on placental-binding pRBCs. Complement fixation correlated with IgG1 and IgG3 antibodies, which dominated the response. There was, however, limited evidence for membrane attack complex activity or pRBC lysis or killing. Importantly, a higher magnitude of complement fixing antibodies was prospectively associated with reduced odds of placental infection at delivery. Using genetically-modified P. falciparum and recombinant PfEMP1 domains, we found that complement-fixing antibodies primarily targeted a specific variant of PfEMP1 (known as VAR2CSA). Furthermore, complement enhanced the ability of antibodies to inhibit pRBC binding to CSA, which was primarily mediated by complement C1q protein.

ConclusionThese findings provide new insights into mechanisms mediating immunity to MiP and reveal potential new strategies for developing malaria vaccines that harness antibody-complement interactions.

category: infectious diseases


title: A Cluster-based Model of COVID-19 Transmission Dynamics

abstract: Many countries have manifested COVID-19 trajectories where extended periods of constant and low daily case rate suddenly transition to epidemic waves of considerable severity with no correspondingly drastic relaxation in preventive measures. Such solutions are outside the scope of classical epidemiological models. Here we construct a deterministic, discrete-time, discrete-population mathematical model which can explain these non-classical phenomena. Our key hypothesis is that with partial preventive measures in place, viral transmission occurs primarily within small, closed groups of family members and friends, which we call clusters. Inter-cluster transmission is infrequent compared to intra-cluster transmission but it is the key to determining the course of the epidemic. If inter-cluster transmission is low enough, we see stable plateau solutions. Above a cutoff level however, such transmission can destabilize a plateau into a huge wave even though its contribution to the population-averaged spreading rate still remains small. We call this the cryptogenic instability. We also find that stochastic effects when case counts are very low may result in a temporary and artificial suppression of an instability; we call this the critical mass effect. Both these phenomena are absent from conventional infectious disease models and militate against the successful management of the epidemic.


title: Health care use up to 6 months after COVID-19 in 700.000 children and adolescents: a pre-post study

abstract:
ObjectivesTo explore whether, and for how long COVID-19 among children gives an increase in use of health care services, when compared to children with no COVID-19.

MethodsStudying all Norwegian residents aged 1-5, 6-15 and 16-19 years from August 1st 2020 to February 1st 2021 (N= 768 560), we contrasted rates of monthly all-cause primary and specialist health care use before and after testing for SARS-CoV-2 (% relative change), for children testing positive (non-hospitalized in the acute phase) (N=10 306) vs children with no COVID-19 (N=758 254).

ResultsWe found a substantial elevation in short-term primary care use for children testing positive for SARS-CoV-2 during the first month following positive test when compared to children testing negative (relative elevation 1-5 years: 325%, 95%CI=296-354; 6-15 years: 434%, 95%CI=415-453; 16-19 years: 360%, 95%CI=342-379). There was still elevated primary care use at 2 months (1-5 years: 21%, 95%CI= 4-38; 6-15 years: 13%, 95%CI=2-25) and at 3 months (1-5 years: 26%, 95%CI=7-45, 6-15 years: 15%, 95%CI=3-26) for young children, but not at 2 or 3 months for the older children (16-19 years: 10%, 95%CI=-1-22 and 6%, 95%CI=-5-18, respectively). The 1-5-year-olds also had a long-term (up to 6 months) increase of primary care (14%, 95%CI=1-26) that was not observed for older age groups, when compared to same-aged children testing negative. We observed no elevated use of specialist care.

ConclusionChildren in pre-school age used health services for a longer time (3-6 months) after COVID-19 than children in primary and secondary school age (1-3 months).


title: Effectiveness of mRNA COVID-19 Vaccines among Employees in an American Healthcare System

abstract:
BackgroundThe mRNA SARS-CoV-2 vaccines have shown great promise in clinical trials. The purpose of this study was to evaluate the effectiveness of these vaccines under real-world conditions in the USA.

MethodsEmployees of the Cleveland Clinic Health System, previously not infected with SARS-CoV-2, and working in Ohio on Dec 16, 2020, the day COVID-19 vaccination began, were included. The cumulative incidence of SARS-CoV-2 infection, over the next 5 months, was compared among those who received the vaccine and those who did not, by modeling vaccination as a time-dependent covariate in Cox proportional hazards regression analyses adjusted for the slope of the epidemic curve as a continuous time-dependent covariate.

ResultsOf the 46866 included employees, 28223 (60%) were vaccinated by the end of the study period. The cumulative incidence of SARS-CoV-2 infection was much higher among those not vaccinated than those vaccinated. Only 15 (0.7%) of the 2154 SARS-CoV-2 infections during the study occurred among those vaccinated. After adjusting for the slope of the epidemic curve, age, and job type, vaccination was associated with a significantly reduced risk of SARS-CoV-2 infection (HR 0.03, 95% C.I. 0.02 - 0.06, p < 0.001), corresponding to a vaccine effectiveness rate of 97.1% (95% CI 94.3 - 98.5). Vaccine effectiveness was 89.2% at 7 days and 95.0% at 14 days after the first vaccine dose.

ConclusionsThe mRNA SARS-CoV-2 vaccines are over 97% protective against COVID-19 in the working-age population, with substantial protection possibly apparent within a few days of the first dose.

SummaryThe effectiveness of mRNA SARS-CoV-2 vaccines was evaluated among 46866 employees in an American healthcare system. After adjusting for age, job type, and the phase of the epidemic, vaccination was 97.1% effective in preventing COVID-19 among the fully vaccinated, and 89.2% protective within 7 days of the first dose.


title: Clinical cholera surveillance sensitivity in Bangladesh and implications for large-scale disease control

abstract:
IntroductionA surveillance system that is sensitive to detecting high burden areas is critical for achieving widespread disease control. In 2014, Bangladesh established a nationwide, facility-based cholera surveillance system for Vibrio cholerae infection. We sought to measure the sensitivity of this surveillance system to detect cases to assess whether cholera elimination targets outlined by the Bangladesh national control plan can be adequately measured.

MethodsWe overlaid maps of nationally-representative annual V. cholerae seroincidence onto maps of the catchment areas of facilities where confirmatory laboratory testing for cholera was conducted, and identified its spatial complement as surveillance greyspots, areas where cases likely occur but go undetected. We assessed surveillance system sensitivity and changes to sensitivity given alternate surveillance site selection strategies.

ResultsWe estimated that 69% of Bangladeshis (111.7 million individuals) live in surveillance greyspots, and that 23% (25.5 million) of these individuals live in areas with the highest V. cholerae infection rates.

ConclusionsThe cholera surveillance system in Bangladesh has the ability to monitor progress towards cholera elimination goals among 31% of the countrys population, which may be insufficient for accurately measuring progress. Increasing surveillance coverage, particularly in the highest risk areas, should be considered.


title: Group Testing Large Populations for SARS-CoV-2

abstract:
Group testing, the testing paradigm which combines multiple samples within a single test, was introduced in 1943 by Robert Dorfman. Since its original proposal for syphilis screening, group testing has been applied in domains such as fault identification in electrical and computer networks, machine learning, data mining, and cryptography. The SARS-CoV-2 pandemic has led to proposals for using group testing in its original context of identifying infected individuals in a population with few tests. Studies suggest that non-adaptive group testing - in which all the tests are determined in advance - for SARS-CoV-2 could help save 20% to 90% of tests depending on the prevalence. However, no systematic approach for comparing different non-adaptive group testing strategies currently exists.

In this paper we develop a software platform for evaluating non-adaptive group testing strategies in both a noiseless setting and in the presence of realistic noise sources, modelled on published experimental observations, which makes them applicable to polymerase chain reaction (PCR) tests, the dominant type of tests for SARS-CoV-2. This modular platform can be used with a variety of group testing designs and decoding algorithms. We use it to evaluate the performance of near-doubly-regular designs and a decoding algorithm based on an integer linear programming formulation, both of which are known to be optimal in some regimes. We find savings between 40% and 91% of tests for prevalences up to 10% when a small error (below 5%) is allowed. We also find that the performance degrades gracefully with noise. We expect our modular, user-friendly, publicly available platform to facilitate empirical research into non-adaptive group testing for SARS-CoV-2.


title: Vaccine nationalism and the dynamics and control of SARS-CoV-2

abstract: Vaccines provide powerful tools to mitigate the enormous public health and economic costs that the ongoing SARS-CoV-2 pandemic continues to exert globally, yet vaccine distribution remains unequal between countries. To examine the potential epidemiological and evolutionary impacts of  vaccine nationalism, we extend previous models to include simple scenarios of stockpiling. In general, we find that stockpiling vaccines by countries with high availability leads to large increases in infections in countries with low vaccine availability, the magnitude of which depends on the strength and duration of natural and vaccinal immunity. Additionally, a number of subtleties arise when the populations and transmission rates in each country differ depending on evolutionary assumptions and vaccine availability. Furthermore, the movement of infected individuals between countries combined with the possibility of increases in viral transmissibility may greatly magnify local and combined infection numbers, suggesting that countries with high vaccine availability must invest in surveillance strategies to prevent case importation. Dose-sharing is likely a high-return strategy because equitable allocation brings non-linear benefits and also alleviates costs of surveillance (e.g. border testing, genomic surveillance) in settings where doses are sufficient to maintain cases at low numbers. Across a range of immunological scenarios, we find that vaccine sharing is also a powerful tool to decrease the potential for antigenic evolution, especially if infections after the waning of natural immunity contribute most to evolutionary potential. Overall, our results stress the importance of equitable global vaccine distribution.


title: Dermatomyositis: Muscle Pathology According to Antibody Subtypes

abstract:
ImportanceCurrent pathological criteria of dermatomyositis (DM) do not recognize different features among DM subtypes classified by dermatomyositis-specific antibodies (DMSAs).

ObjectiveTo determine whether myopathological features differ among DM subtypes classified by DMSAs and whether the pathological features can be characterized by serologically defined DM subtype.

DesignRetrospective review of muscle pathology slides of 256 patients diagnosed with DM from January 2009 to December 2020.

SettingSingle center study in a tertiary laboratory for muscle diseases.

ParticipantsA total of 256 patients whose DM diagnosis was pathologically confirmed based on the sarcoplasmic expression of myxovirus resistant protein A (MxA) were included. Of these, 249 patients were positive for one of the 5 DMSAs (seropositive patients, anti-TIF1-{gamma}=87, anti-Mi-2=40, anti-MDA5=29, anti-NXP-2=83, and anti-SAE=10), and 7 were negative for all 5 DMSAs (seronegative patients).

ExposureHistochemical, enzyme histochemical, immunohistochemical staining, and ultrastructural study.

Main outcomes and measuresHistological features stratified according to four pathology domains: muscle fiber, inflammatory, vascular, and connective tissue domains, and histological features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy.

ResultsDMSAs significantly associated with characteristic histochemical and immunohistochemical features were as follows: anti-TIF1-{gamma} with vacuolated/punched out fibers (64.7%, P<.001) and perifascicular enhancement in HLA-ABC (75.9%, P<.001); anti-Mi-2 with prominent muscle fiber damage (score 4.8{+/-}2.1, P<.001), inflammatory cell infiltration (score 8.0{+/-}3.0, P=.002), perifascicular atrophy (67.5%, P=.02), perifascicular necrosis (52.5%, P<.001), increased perimysium alkaline phosphatase activity (70.0%, P<.001), central necrotic peripheral regenerating fibers (45.0%, P<.001), and sarcolemmal deposition of the membrane attack complex (67.5%, P<.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%, P<.001) with less muscle pathology and inflammatory features; and anti-NXP2 with microinfarction (26.5%, P<.001); and anti-SAE and seronegative DM with HLA-DR expression (50.0%, P=.02 and 57.1%, P=.02 respectively).

Conclusion and relevanceWe described an extensive study on serological-pathological correlation of DM primarily using MxA expression as an inclusion criterion. DMSAs was associated with distinctive myopathological features in our studied cohort, suggesting that different pathobiological mechanisms may underscore each subtype.

Key pointsO_ST_ABSQuestionC_ST_ABSAre myopathological features different among dermatomyositis (DM) subtypes classified by DM-specific autoantibodies (DMSAs)? If so what are the characteristic features of each subtype?

FindingsThis study enrolled 256 (249 DMSA-positive and 7 seronegative) patients whose DM diagnosis was made pathologically by confirming the expression of myxovirus resistant protein A in the sarcoplasm of muscle fibers in muscle biopsy samples. The DM subtypes classified by the positive DMSAs were associated with distinctively characteristic pathological features.

MeaningDifferent pathological features suggest different pathological mechanisms may well underly each DM subtype classified by DMSA.

category: neurology


title: LITE SABR M1: a phase I trial of Lattice SBRT for large tumors

abstract:
PurposeStereotactic body radiotherapy (SBRT) is an attractive treatment option for patients with metastatic and/or unresectable tumors, however its use is limited to smaller tumors. Lattice is a form of spatially fractionated radiotherapy that may offer safe delivery of SBRT for bulky tumors. We previously described Lattice SBRT, which delivers 20 Gy in 5 fractions with a simultaneous Lattice boost to 66.7 Gy. The goal of this study was to prospectively evaluate the acute toxicity and quality of life (QoL) of patients with large tumors (> 5 cm) treated with Lattice SBRT.

MethodsThis was a single-arm phase I trial conducted between October 2019 and August 2020. Patients with tumors >4.5 cm were eligible. Lattice SBRT was delivered every other day.. The primary outcome was the rate of 90-day treatment-associated (probably or definitely attributable) grade 3+ acute toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Other outcomes included changes in patient reported toxicity and QoL inventories, GTV, and peripheral blood cytokines.

ResultsTwenty patients (22 tumors) were enrolled. Median GTV was 783 cc (range: 64-3713 cc). Fifty percent of tumors were in the thorax, 45% abdomen/pelvis, and 5% extremity. There was no treatment-associated grade 3+ toxicity.. There was one case of grade 4 toxicity possibly associated with Lattice SBRT.

ConclusionsThis phase I study met its primary endpoint of physician reported safety. An ongoing phase II clinical trial of Lattice SBRT will evaluate late safety and efficacy of this novel technique.

category: oncology


title: Novel scotoma detection method using time required for fixation to the random targets

abstract:
We developed a novel scotoma detection system using time required for fixation to the random targets, or the" eye-guided scotoma detection method ". In order to verify the" eye-guided scotoma detection method ", we measured 78 eyes of 40 subjects, and examined the measurement results in comparison with the results of measurement by Humphrey perimetry. The results were as follows: (1) Mariotte scotomas were detected in 100% of the eyes tested; (2) The false-negative rate (the percentage of cases where a scotoma was evaluated as a non-scotoma) was less than 10%; (3) The positive point distribution in the low-sensitivity eyes was well matched. These findings suggested that the novel scotoma detection method in the current study will pave the way for the realization of mass screening to detect pathological scotoma earlier.

Author summaryConventional perimeters, such as the Goldmann perimeter and Humphrey perimeter, require experienced examiners and space occupying. With either perimeter, subjects eye movements need to be strictly fixed to the fixation target of the device. Other perimeters can monitor fixation and automatically measure the visual field. With the eye-guided scotoma detection method proposed in the current study, subjects feel less burdened since they do not have to fixate on the fixation target of the device and can move their eyes freely. Subjects simply respond to visual targets on the display; then, scotomas can be automatically detected. The novel method yields highly accurate scotoma detection through an algorithm that separates scotomas from non-scotomas.

category: ophthalmology


title: Multisystemic cellular tropism of SARS-CoV-2 in autopsies of COVID-19 patients

abstract:
BackgroundMultiorgan tropism of SARS-CoV-2 has previously been shown for several major organs.

MethodsWe have comprehensively analyzed 25 different formalin-fixed paraffin-embedded (FFPE) tissues/organs from autopsies of fatal COVID-19 cases (n=8), using detailed histopathological assessment, detection of SARS-CoV-2 RNA using polymerase chain reaction and RNA in situ hybridization, viral protein using immunohistochemistry, and virus particles using transmission electron microscopy. Finally, we confirmed these findings in an independent external autopsy cohort (n=9).

FindingsSARS-CoV-2 RNA was mainly localized in epithelial cells, endothelial and mesenchymal cells across all organs. Next to lung, trachea, kidney, heart, or liver, viral RNA was also found in tonsils, salivary glands, oropharynx, thyroid, adrenal gland, testicles, prostate, ovaries, small bowel, lymph nodes, skin and skeletal muscle. Viral RNA was predominantly found in cells expressing ACE2, TMPRSS2, or both. The SARS-CoV-2 replicating RNA was also detected in these organs. Immunohistochemistry and electron microscopy were not suitable for reliable and specific SARS-CoV-2 detection in autopsies. The findings were validated using in situ hybridization on external COVID-19 autopsy samples. Finally, apart from the lung, correlation of virus detection and histopathological assessment did not reveal any specific alterations that could be attributed to SARS-CoV-2.

InterpretationSARS-CoV-2 could be observed in virtually all organs, colocalizing with ACE2 and TMPRSS2 mainly in epithelial but also in mesenchymal and endothelial cells, and viral replication was found across all organ systems. Apart from the respiratory tract, no specific (histo-)morphologic alterations could be assigned to the SARS-CoV-2 infection.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSARS-CoV-2 has been shown to infect the respiratory tract and affect several other major organs. However, on a cellular level, the localization of SARS-CoV-2 and its targets ACE2 and TMPRSS2 have not been described comprehensively.

Added value of this studyWe have analyzed tissue SARS-CoV-2 RNA using RT-PCR and visualized its localization together with ACE2 and TMPRSS2 using in situ hybridization (ISH) in 25 different autopsy tissues. SARS-CoV-2 sense and antisense RNA were detected in 16 tissues/organs, mainly in epithelial cells and, to a lesser extent, in endothelial or stromal cells. Detection of viral protein using immunohistochemistry or viral particles using transmission electron microscopy did not yield specific results. Interestingly, apart from the respiratory tract and specifically the lungs, we have not found a specific pathology that would be associated with extrapulmonary viral spread.

Implications of all the available evidenceWe provide a recommendation on using these methods in autopsy diagnostics for SARS-CoV-2. Our data extend the current hypothesis of severe COVID-19 being multisystemic diseases. Our data also provide clear evidence of infection and replication of SARS-CoV-2 in the endothelial cell across all organs, extending the hypothesis on the (micro)vascular involvement in COVID-19.


title: Costs and predictors of early readmissions in patients with Infective Endocarditis. Utilizing the Nationwide Readmission Database.

abstract:
BACKGROUNDThere have been previous studies detailing the variables involved in readmissions in patients with a primary admission diagnosis of infective endocarditis - however those studies were done prior to the 2015 change in AHA guidelines and introduction to ICD-10 codes.

OBJECTIVESThe aim of this study was to describe the frequency, causes, factors, and costs associated with infective endocarditis encounters.

METHODSUtilizing the 2017 national readmission database (NRD), we identified all patients that were admitted with infective endocarditis. These patients were evaluated for the rates, predictors, and costs of unplanned 30 days readmissions. Weighted analysis was performed to obtain nationally representative data.

RESULTS56,357 patients were identified to have been admitted with a diagnosis of infective endocarditis of whom 13,004 patients (23%) were readmitted within 30 days of the index discharge. The most common causes of readmission were septicemia (15.1%), endocarditis and endocardial disease (10.5%), heart failure (9.5%), and complication of cardiovascular device, implant or graft, initial encounter (5.6%). Data showed that there were certain comorbidities that resulted in a higher risk of being readmitted, these include chronic kidney disease, COPD, tobacco use, and hepatic failure. Cost of readmissions per patient was approximately $22,059 (IQR $11,630 - $49,964).

CONCLUSIONSThirty-day unplanned readmissions remain a significant issue affecting nearly 1 in 6 patients with infective endocarditis. This is associated with significant mortality and financial burden. Multi-disciplinary approach may help decrease readmissions, reduce complications, and improve overall outcomes as well as the overall quality of life of our patients.

category: cardiovascular medicine


title: The Prevention and Control of Cancer by Metformin in Patients with Type 2 Diabetes: A Systematic Mapping Review

abstract:
ObjectiveMetformin is commonly used as a first line therapy for type 2 diabetes; however, existing evidence suggests an influence in oncology. The objective of this systematic mapping review was to describe current literature regarding metformin and its role in preventing and /or controlling cancer in patients with type 2 diabetes.

MethodWe searched PubMed, Cochrane Library, and ClinicalTrials.gov in February 2018 and April 2019 to identify research studies, systematic reviews and meta-analyses. Of the 318 citations identified, 156 publications were included in this analysis.

ResultsThe most common cancer types researched were colorectal, liver, prostate, lung and breast with the United States contributing the most to this data. Author teams averaged six members and most studies were funded. Only 68% of the articles were available open access. Ovarian and esophageal cancers were amongst the least studied, but the most costly for care.

category: endocrinology


title: Genotype-stratified GWAS meta-analysis reveals novel loci associated with alcohol consumption

abstract: An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis in up to 40,679 individuals from Japanese populations to uncover additional loci associated with alcohol consumption in an rs671-dependent manner. No loci satisfied the genome-wide significance threshold in wild-type homozygotes (GG), but six loci (ADH1B, ALDH1B1, ALDH1A1, ALDH2, GOT2, and MYOM1-MYL12A) did so in heterozygotes (GA). Of these, three loci (ALDH2, GOT2, and MYOM1-MYL12A) were novel, and two (ADH1B and ALDH1B1) showed genome-wide significant interaction with rs671. Our results identify a new genetic architecture associated with alcohol consumption, and shed additional light on the genetic characteristics of alcohol consumption among East Asians.


title: Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-related Mental Disorders (MIND-Set): a cross-sectional comorbidity study from an RDoC perspective

abstract:
BackgroundIt is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood on the basis of symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the MIND-Set study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). The main objective of the MIND-Set project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels.

MethodsThis is an observational, cross-sectional study. Data from different observational levels as defined in the research domain criteria (RDoC; genetics, physiology, neuropsychology, system level neuroimaging, behavior, self-report and experimental neurocognitive paradigms) are collected over four time points. Included are adult ([≥] 18 years), non-psychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder and/or addiction disorder) and/or a neurodevelopmental disorder (ASD and/or ADHD). Individuals with no current or past psychiatric diagnosis are included as controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 healthy controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with 1) Standardized clinical examination, physical examination, and blood sampling; 2) Psychological constructs, neuropsychological tests, and biological marker sampling; 3) Neuroimaging measures.

DiscussionThe MIND-Set study enables us to investigate the mechanistic underpinnings of non-psychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.

category: psychiatry and clinical psychology


title: A rare variant in D-amino acid oxidase implicates NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder

abstract:
Bipolar disorder is an often-severe mental health disorder characterized by alternation between extreme mood states of mania and depression. Despite strong heritability and the recent identification of 64 loci of small effect, pathophysiological mechanisms and much of the genetic risk remain unknown. Here, through genome sequencing and linkage and association analyses, we found that rare variants co-segregating with bipolar disorder in large multiply affected families cluster within gene networks enriched for synaptic and nuclear functions. The top variant in this analysis prioritized by statistical association, predicted deleteriousness, and network centrality was a missense variant in the gene encoding D-amino acid oxidase (DAOG131V). Heterologous expression of DAOG131V in human cells resulted in decreased DAO protein abundance and enzymatic activity. In a knock-in mouse harboring this human DAOG131V variant, DaoG130V/+, we similarly found decreased DAO protein abundance, as well as enhanced stress susceptibility and blunted behavioral responses to pharmacological inhibition of N-methyl-D-aspartate receptors (NMDARs). RNA sequencing of cerebellar tissue revealed that DaoG130V resulted in decreased expression of two gene networks that are enriched for synaptic functions and for genes expressed specifically in Purkinje cells and granule neurons. Similar expression changes in both of these gene networks were also identified in the cerebellum of bipolar disorder cases vs. controls. These findings implicate dysregulation of NMDAR signaling and of gene expression in cerebellar neurons in bipolar disorder pathophysiology and provide insight into its genetic architecture.

One Sentence SummaryFunctional studies of a rare hypofunctional variant in the D-amino acid oxidase gene implicate stress susceptibility, NMDA receptor signaling, and cerebellar circuits in risk for bipolar disorder.


title: Immunochemotherapy as induction treatment in Stage III (N2, N3) Non-small cell lung cancer

abstract:
BackgroundTo increase locoregional and systemic tumor control, a portion of patients with stage III (N2, N3) non-small cell lung cancer (NSCLC) received pulmonary resection after immunochemotherapy in our center. Herein, we assessed the real-world downstage (T, N stage) effectiveness of immunochemotherapy as induction treatment and explored the proper cycle number for stage III (N2, N3) NSCLC.

MethodsBiopsy confirmed stage III (N2, N3) NSCLC patients who underwent immunochemotherapy between January 1st, 2018, to August 30th, 2019, were identified. Tumor radiologic regression, lymph node down-staging, and pathological response information were collected.

ResultsIn total, 16 patients with stage IIIA NSCLC, 30 with stage IIIB NSCLC, 9 with stage IIIC NSCLC (N2, N3 metastasis) were included. After immunochemotherapy, 25/55 (45.5%) patients achieved an objective response. Ultimately, 33/55 (60.0%) patients received lobectomy plus systemic lymphadenectomy, of whom 18/33 (54.5%) obtained major pathological response (MPR) of the primary lesion, and 24 (72.7%) had pathological-confirmed lymph node downstage (N2-3 to N0-1). Notably, four patients had MPR of the primary lesion but without lymph node downstage. At the time of data cutoff (December 30th, 2020), the median follow-up duration was 9.2 months (IQR 8.0-11.7), 24/33 (72.7%) of patients that had pulmonary resection were progression-free, with 30 of them alive. Binary logistics analysis showed that 3-4 induction cycles were favorably associated with MPR than 1-2 cycles (p = 0.017).

ConclusionsImmunochemotherapy as induction treatment showed encouraging MPR and lymph nodes down-staging rates in stage III (N2, N3) NSCLC in this study. Prolonged (3-4) cycles of immunochemotherapy were recommended for a better pathological response.


title: Direct comparison of venipuncture serum draws versus whole blood finger-stick specimens by anti-COVID-19 IgG/IgM rapid lateral flow immunoassay and ELISA.

abstract: During the COVID-19 pandemic, manufacturers have developed several diagnostic test kits that include lateral flow immunoassays (LFIA) also known as rapid cassette testing. Rapid cassette testing provides qualitative test results indicating the presence or absence of IgG and IgM antibodies to determine COVID-19 (SARS-CoV-2) infection among individuals. Venipuncture blood draws have been the traditional and widely proposed sample collection method but is costly and not applicable to point-of-care testing (POC) and in remote settings. Whole blood finger-stick blood collections traditionally used by diabetics for glucose level testing is an ideal scenario, but raises concerns regarding the outcome of test results in regards to specificity and sensitivity. In this study we directly compare simultaneous collections of venipuncture serum (SST) blood draws and whole blood finger-sticks (n = 75) to detect human Anti-COVID-19 IgG and IgM antibodies using an EUA-approved lateral flow immunoassay, showing equal to enhanced performance characteristics for this specimen type.


title: Development of a multiplex real-time PCR assay for BCG and validation in a clinical laboratory

abstract: Mycobacterium bovis bacille Calmette-Guerin (BCG) is a live attenuated vaccine which can result in local or disseminated infection, most commonly in immunocompromised individuals. Differentiation of BCG from other members of the Mycobacterium tuberculosis complex (MTBC) is required to diagnose BCG disease, which requires specific management. Current methods for BCG diagnosis are based on mycobacterial culture and conventional PCR; the former is time-consuming and the latter often unavailable. Further, there are reports that certain BCG strains may be associated with a higher rate of adverse events. This study describes the development of a two-step multiplex real-time PCR assay which uses single nucleotide polymorphisms to detect BCG and identify early or late BCG strains. The assay has a limit of detection of 1 pg BCG boiled lysate DNA and was shown to detect BCG in both pure cultures and experimentally infected tissue. Performance was assessed on 19 suspected BCG clinical isolates at Christian Medical College in Vellore, India taken from January 2018 to August 2020. Of these 19 isolates, 10 were identified as BCG (6 early and 4 late strains) and 9 were identified as other MTBC members. Taken together, the results demonstrate the ability of this assay to identify and characterize BCG disease from cultures and infected tissue. The capacity to identify BCG may improve patient management and the ability to discriminate between BCG strains may enable BCG vaccine pharmacovigilance.


title: Clinical performance of two EUA-approved anti-COVID-19 IgG/IgM rapid lateral flow immunoassays using whole blood finger-sticks

abstract: Serological, or antibody, tests detect immunoglobulins produced by the hosts plasma B cells following exposure to foreign antigens. Venipuncture blood draws to collect human venous whole blood, plasma from anticoagulated blood (Li+ heparin, K2EDTA and sodium citrate), or serum are commonly utilized and require refrigerated temperatures during transport to the testing facility. Subsequent laboratory testing by enzyme-linked immunosorbent assays (ELISA) or chemiluminescence immunoassays (CLIA) can take an additional 2-5 hours. In the context of the COVID-19 pandemic, rapid diagnostic tests (RDT) to be used in point-of-care (POC) and remote settings have become essential during mandatory quarantine and isolation periods. RDTs allowed for more cost-effective testing using less collection materials with an immediate (5-10 minutes) test result. However, the majority of emerging RDTs receiving Emergency Use Authorization (EUA) approval by the Food and Drug Administration (FDA) for qualitative detection and differentiation of IgM and IgG antibodies to SARS-CoV-2 were only approved for use in human venous whole blood, plasma or serum. In this study we summarize performance characteristics of one RDT (COVID-19 IgG/IgM lateral flow immunoassay rapid cassette) to another by simultaneous application of whole blood finger-stick specimens (n = 32). The study was performed over 5 different days, with daily quality controls consisting of serum previously verified to be positive or negative by COVID-19 IgG/IgM ELISA testing.


title: Classification of Fetal State through the application of Machine Learning techniques on Cardiotocography records: Towards Real World Application.

abstract:
ObjectiveAnticipating fetal risk is a major factor in reducing child and maternal mortality and suffering. In this context cardiotocography (CTG) is a low cost, well established procedure that has been around for decades, despite lacking consensus regarding its impact on outcomes.

Machine learning emerged as an option for automatic classification of CTG records, as previous studies showed expert level results, but often came at the price of reduced generalization potential.

With that in mind, the present study sought to improve statistical rigor of evaluation towards real world application.

Materials and MethodsIn this study, a dataset of 2126 CTG recordings labeled as normal, suspect or pathological by the consensus of three expert obstetricians was used to create a baseline random forest model.

This was followed by creating a lightgbm model tuned using gaussian process regression and post processed using cross validation ensembling.

Performance was assessed using the area under the precision-recall curve (AUPRC) metric over 100 experiment executions, each using a testing set comprised of 30% of data stratified by the class label.

ResultsThe best model was a cross validation ensemble of lightgbm models that yielded 95.82% AUPRC.

ConclusionsThe model is shown to produce consistent expert level performance at a less than negligible cost. At an estimated 0.78 USD per million predictions the model can generate value in settings with CTG qualified personnel and all the more in their absence.

category: obstetrics and gynecology


title: Transmission of SARS-CoV-2 associated with aircraft travel: a systematic review (Version 1)

abstract:
BackgroundAir travel may be associated with the spread of viruses via infected passengers and potentially through in-flight transmission. Given the novelty of the SARS-CoV-2 virus, transmission associated with air travel is based on what is known about the dynamics of transmission of other respiratory virus infections, especially those due to other coronaviruses and influenza. Our objective was to provide a rapid summary and evaluation of relevant data on the transmission of SARS-CoV-2 aboard aircraft, report important policy implications, and highlight research gaps requiring urgent attention.

MethodsThis review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We searched LitCovid, medRxiv, Google Scholar, and the WHO Covid-19 database from 1 February 2020 to 27 January 2021 and included studies on the transmission of SARS-CoV-2 aboard aircraft. We assessed study quality based on five criteria and reported important findings.

ResultsWe included 18 studies on in-flight transmission of SARS-CoV-2, representing 130 unique flights and two studies on wastewater from aircraft. The overall quality of reporting was low. Two wastewater studies reported PCR-positive SARS-CoV-2 samples, but with relatively high Cycle threshold values ranging from 36 to 40. The definition of an index case was very heterogeneous across the studies. The proportion of contacts traced ranged from 0.68% to 100%. In total, the authors successfully traced 2800/19729 passengers, 140/180 crew members, and 8/8 medical staff. Altogether, 273 index cases were reported, with 64 secondary cases. No secondary cases were reported in three studies, each investigating one flight. The secondary attack rate among the studies that followed up >80% of the passengers and crew (including data on 10 flights) varied between 0% and 8.2%. The included studies reported on the possibility of SARS-CoV-2 transmission from asymptomatic, pre-symptomatic, and symptomatic individuals. Viral cultures were performed in two studies, with 10 positive results reported. Genomic sequencing and phylogenetic analysis were performed in individuals from four flights, with the completeness of genomic similarity ranging from 81-100%.

ConclusionCurrent evidence suggests that SARS-CoV-2 can be transmitted during aircraft travel, but the published data do not permit any conclusive assessment of the likelihood and extent. Furthermore, the quality of evidence from most published studies is low. The variation in study design and methodology restricts the comparison of findings across studies. Standardized guidelines for conducting and reporting future studies of transmission on aircrafts should be developed.


title: Normal mean oral temperature is 98F, not 98.2F or 98.6F

abstract:
Background98.6{degrees}F is generally accepted as normal body temperature as defined by Wunderlich (1868) and later challenged by Mackowiak (1992) and Protsiv (2020) who concluded as 98.2{degrees}F based on cross-sectional studies. Hence, the normal body temperature at present needs quantification?

MethodsA longitudinal study on the healthy population of Northen-India were followed-up over 1-year. Participants were advised for self-monitoring of oral temperature with a standard digital thermometer in either left or right sublingual pocket and record it in the thermometry diary. The study was considered complete if the participant had all the three phases of the study (i.e. non-febrile, febrile, and post-febrile phases) or completed the duration of the study.

ResultsThe mean oral temperature of the participants (n=144) during the non-febrile and post-febrile phases (temperature readings=6543) were 98{degrees}F (SD, 0.61) and 98.01{degrees}F (SD, 0.60) respectively (P<0.001). The mean oral temperature during post-febrile phase was found to be 0.01{degrees}F higher than non-febrile phase. With the diurnal variability, the morning (AM), noon (AN), and afternoon (PM) mean temperatures were 97.91, 98.08, and 98.27{degrees}F (P<0.001) respectively during the non-febrile phase. Similar trends were observed in variability among men and women, and seasons.

ConclusionsThe mean oral temperature is 98{degrees}F (SD, 0.61). The temperature is as low as 96.90F and as high as 99.10F. The temperature during post-febrile phase was found to be higher than the non-febrile phase temperature like PM over AN & AM, women over men, summer over other seasons in the non-febrile phase, spring over others in the post-febrile phase.

category: public and global health


title: Virtual care and the impact of COVID-19 on nursing: A single centre evaluation

abstract:
AimsThe overall aim of this evaluation was to look at the impact of the changes in working practices during the pandemic on nurses. This secondary analysis provided an evaluation of virtual care and being able/required to work from home.

DesignThis was secondary analysis of an evaluation using semi-structured interviews.

MethodsConducted at a single National Health Service (NHS) university hospital in the United Kingdom between May-July 2020. Forty-eight operational leads and nurses participated in semi-structured interviews which were digitally recorded, transcribed verbatim and analysed using a framework analysis.

ResultsTwo overarching themes emerged relating to the patient experience and nursing experience. There were both positive and negative elements associated with virtual care and remote working related to these themes. However, the majority of nurses found virtual clinics were useful when proper resources were provided, and managerial strategies were put in place to support them. Participants felt virtual care could benefit many but not all patient groups moving forward, and that flexibility around working from home would be desirable in the future.

ConclusionVirtual care and remote working were implemented to accommodate the restrictions imposed because of the pandemic. The benefits of these changes to nurses and patients support these being business as usual. However, clear policies are needed to ensure nurses feel supported when working remotely and there are robust assessments in place to ensure virtual care is provided to patients who have access to the necessary technology.

ImpactThis was a study of the move to virtual care and remote working during the COVID-19 pandemic. Telemedicine and flexible working were not common in the NHS prior to the pandemic but the current evaluation supports the role out of these as standard care with policies in place to ensure nurses and patients are appropriately supported.

category: nursing


title: Small Area Estimation of Food Insecurity in the Eastern Indo-Gangetic Plain

abstract:
Achieving food security for all citizens is an important policy issue in India. While the existing data based on socio-economic surveys provide accurate estimates of food insecurity indicators at state and national level, due to small sample sizes, the surveys cannot be used directly to produce reliable estimates at the district or lower administrative levels. The availability of reliable and representative disaggregated measures of food insecurity is necessary for effective policy planning and monitoring, as food insecurity is often distributed unevenly within relatively small areas.

This article explores a small area estimation (SAE) approach to derive reliable and representative estimates of food insecurity prevalence (FIP), gap (FIG), and severity (FIS) among people in different districts of the rural areas of the Eastern Indo-Gangetic Plain (EIGP) region by linking the latest round of available data from the Household Consumer Expenditure Survey collected by the National Sample Survey Office of India as well as the latest available Indian Population Census data. District-specific food insecurity indictors such as FIP, FIG, and FIS were estimated based on a recommended threshold of per capita caloric intake of 2400 kilocalories per day, as defined by the Ministry of Health and Family Welfare, Government of India. Spatial maps showing district level inequality in the distribution of the indicators of food insecurity among the population in EIGP region are also produced. Our disaggregated estimates can provide district-specific focused insights into food insecurity to policy-analysts and decision-makers, and could thereby prove to be useful and relevant to the U.N. Sustainable Development Goal Indicator 2.1.2.

category: nutrition


title: Inferring SARS-CoV-2 RNA shedding into wastewater relative to time of infection

abstract: Since the start of the COVID-19 pandemic, there has been interest in using wastewater monitoring as an approach for disease surveillance. A significant uncertainty that would improve interpretation of wastewater monitoring data is the intensity and timing with which individuals shed RNA from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into wastewater. By combining wastewater and case surveillance data sets from a university campus during a period of heightened surveillance, we inferred that individual shedding of RNA into wastewater peaks on average six days (50% uncertainty interval (UI): 6 - 7; 95% UI: 4 - 8) following infection, and that wastewater measurements are highly overdispersed (negative binomial dispersion parameter, k = 0.39 (95% credible interval: 0.32 - 0.48)). This limits the utility of wastewater surveillance as a leading indicator of secular trends in SARS-CoV-2 transmission during an epidemic, and implies that it could be most useful as an early warning of rising transmission in areas where transmission is low or clinical testing is delayed or of limited capacity.


title: ASSESSMENT OF PERFORMANCE AND IMPLEMENTATION CHARACTERISTICS OF RAPID POINT OF CARE SARS-CoV-2 ANTIGEN TESTING IN KENYA

abstract:
BackgroundThe COVID-19 pandemic has resulted in a need for rapid identification of infectious cases. Testing barriers have prohibited adequate screening for SARS COV2, resulting in significant delays in treatment provision and commencement of outbreak control measures. This study aimed to generate evidence on the performance and implementation characteristics of the BD Veritor rapid antigen test as compared to the gold standard test for diagnosis of SARS COV2 in Kenya.

MethodsThis was a field test performance evaluation in symptomatic and asymptomatic adults undergoing testing for SARS COV2. Recruited participants were classified as SARS-CoV2-positive based on the locally implemented gold standard reverse transcription polymerase chain reaction (RT-PCR) test performed on nasopharyngeal swabs. 272 antigen tests were performed with simultaneous gold standard testing, allowing us to estimate sensitivity, specificity, positive and negative predictive values for the BD Veritor rapid antigen test platform. Implementation characteristics were assessed using the Consolidated Framework for Implementation Research for feasibility, acceptability, turn-around time, and ease-of-use metrics.

Results and DiscussionWe enrolled 97 PCR negative symptomatic and 128 PCR negative asymptomatic, and 28 PCR positive symptomatic and 19 PCR positive asymptomatic participants. Compared to the gold standard, the sensitivity of the BD Veritor antigen test was 94% (95% confidence interval [CI] 86.6 to 100.0) while the specificity was 98% (95% confidence interval [CI] 96 to 100). The sensitivity of BD Veritor antigen test was higher among symptomatic (100%) compared to asymptomatic (84%) participants, although this difference was not statistically significant. There was also a lack of association between cycle threshold value and sensitivity of BD Veritor test. The BD Veritor test had quick turnaround time and minimal resource requirements, and laboratory personnel conducting testing felt that it was easier to use than the gold standard RT-PCR.

ConclusionThe BD Veritor rapid antigen test exhibited excellent sensitivity and specificity when used to detect SARS-CoV-2 infection among both symptomatic and asymptomatic individuals in varied population settings in Kenya. It was feasible to implement and easy to use, with rapid turnaround time.


title: Breadth of neutralising antibody responses to SARS-CoV-2 variants of concern is augmented by vaccination following prior infection: studies in UK healthcare workers and immunodeficient patients

abstract: Approximately 75% of the UK population has received only one dose of a 2-dose COVID-19 vaccine regime in the face of circulating SARS-CoV-2 Variants of Concern (VOCs). We aimed to determine the levels of vaccine-induced neutralising antibodies to SARS-CoV-2 variants B.1.1.7, B.1.351 and P.1. To do so, we undertook a single-centre cross-sectional study of health care workers (HCWs) and outpatients with immunodeficiencies (IDP) based at the same critical care tertiary NHS Trust, following a single dose of either BNT162b2 or AZD1222 vaccines. Data revealed low neutralising antibodies (nAbs) in IDPs, with only 5% and 3% showing detectable neutralisation of B.1.1.7 and B.1.351, respectively. In contrast, healthy HCWs without a prior SARS-CoV-2 infection demonstrated a wide range of nAb titres post-vaccination with responses significantly lower than HCWs with prior SARS-CoV-2 infection. Neutralisation of VOCs with the E484K mutation (B.1.351 and P.1) were consistently lower in HCWs in the absence of evidence of prior SARS-CoV-2 infection (p<0.001). Notably, in vaccinated HCWs with prior SARS-CoV-2 infection, there was a significant increase of neutralising titres post-vaccination to all variants, compared to their pre-vaccination neutralisation titres. This underscores the importance of vaccination to boost neutralising antibody breadth to VOCs, and also provides support for the hypothesis that repeated immunisations will boost protective immunity in individuals without prior SARS-CoV-2 exposure.


title: Lead exposure and serum metabolite profiles in pregnant women in Mexico City

abstract:
BackgroundLead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes. Yet, the mechanisms of Pb toxicology remain incompletely understood, especially during pregnancy. To uncover biological pathways impacted by Pb exposure, this study investigated serum metabolomic profiles during the third trimester of pregnancy that are associated with blood Pb and bone Pb.

MethodsWe used data and specimens collected from 99 women enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort based in Mexico City. Maternal Pb exposure was measured in whole blood samples from the third trimester of pregnancy and in the tibia and patella bones at 1 month postpartum. Third-trimester serum samples underwent metabolomic analysis; metabolites were identified based on matching to an in-house analytical standard library. A metabolome-wide association study was performed with all three Pb measurements using multiple linear regression models, adjusted for confounders and batch effects. Class enrichment analyses were also conducted.

ResultsThe median (interquartile range) blood Pb concentration was 2.9 (2.6) g/dL. Median bone Pb, measured in the patella and tibia, were 2.5 (7.3) g/g and 3.6 (9.5) g/g, respectively. Of 248 total metabolites identified in serum, 31 were associated with blood Pb (p<0.05). Class enrichment analysis identified significant overrepresentation of metabolites classified as fatty acids and conjugates, amino acids and peptides, and purines. Tibia and patella Pb were associated with 14 and 11 metabolites, respectively (p<0.05). Comparing results from bone and blood Pb, glycochenodeoxycholic acid and glycocholic acid were negatively associated with blood Pb and tibia Pb, while 5-aminopentanoic acid and 7-methylguanine were negatively associated with blood Pb and patella Pb. One metabolite, 5-aminopentanoic acid, was associated with all three Pb measures.

ConclusionThis study identified serum metabolites in pregnant women associated with Pb measured in blood (31 metabolites) and bone (tibia: 14 metabolites, patella: 11 metabolites). These findings provide insights on the metabolic profile around Pb exposure in pregnancy and may provide important links to guide detailed studies of toxicological effects for both mothers and children.


title: NEW CORONAVIRUS IN PREGNANT WOMEN. Maternal and perinatal outcomes.

abstract:
ObjectivesTo report the maternal and neonatal results of patients infected with COVID-19 in Panama.

MethodsThe study is based on the analysis of pregnant women with COVID-19, in 5 hospitals in the Republic of Panama. The inclusion criteria were: Patients with or without symptoms, positive RT-PCR for SARS-CoV-2 in the period from March 23 to 6 months after, whose births were attended in one of those 5 hospitals and who signed the consent. Data was obtained at the time of diagnosis of the infection and at the time of termination of pregnancy for the mother and newborn.

Results253 patients met the inclusion criteria. Most were diagnosed in the third trimester (89.3%). 10.3% of the patients presented in a severe form of COVID-19. The most frequent complication was pre-eclampsia and if we add gestational hypertension they represent 21.2%; most of the patients terminated the pregnancy by caesarean section (58%). 26.9% (95% CI 21.3-32.9%) of the births were premature, and perinatal mortality was 5.4% (95% CI 3.0-9.0%). There was a need for mechanical ventilation in 5.9% (95% CI 3.6-9.6%) of the cohort and there were four maternal deaths (1.6% - 95% CI 0.6-4.0%).

ConclusionsThis study of pregnant women infected with COVID-19 and diagnosed with RT-PCR shows serious maternal complications such as high admission to the ICU, need for mechanical ventilation and one death in every 64 infected. Frequent obstetric complications such as hypertension, premature rupture of membranes, high rate of prematurity and perinatal lethality were also seen.


title: Alcov: Estimating Variant of Concern Abundance from SARS-CoV-2 Wastewater Sequencing Data

abstract: Detection of SARS-CoV-2 in wastewater is an important strategy for community level surveillance. Variants of concern (VOCs) can be detected in the wastewater samples using next generation sequencing, however it can be challenging to determine the relative abundance of different VOCs since the reads cannot be assembled into complete genomes. Here, we present Alcov (abundance learning of SARS-CoV-2 variants), a tool that uses mutation frequencies in SARS-CoV-2 sequencing data to predict the distribution of VOC lineages in the sample. We used Alcov to predict the distributions of lineages from three wastewater samples which agreed well with clinical data. By predicting not just which VOCs are present, but their relative abundances in the population, Alcov extracts a more complete snapshot of the variants which are circulating in a community.


title: The role of HIV infection in the clinical spectrum of COVID-19: a population-based cohort analysis based on US National COVID Cohort Collaborative (N3C) Enclave data

abstract: The authors have withdrawn this manuscript because of the accidental low cell size in the supplementary materials. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.


title: Individual-based modeling of COVID-19 transmission in college communities

abstract:
The ongoing COVID-19 pandemic has created major public health and socio-economic challenges across the United States. Among them are challenges to the educational system where college administrators are struggling with the questions of how to reopen in-person activities while prioritizing student safety. To help address this challenge, we developed a flexible computational framework to model the spread and control of COVID-19 on a residential college campus. The modeling framework accounts for heterogeneity in social interactions, activities, disease progression, and control interventions. The relative contribution of classroom, dorm, and social activities to disease transmission was explored. We observed that the dorm has the highest contribution to disease transmission followed by classroom and social activities. Without vaccination, frequent (weekly) random testing coupled with risk reduction measures (e.g. facial mask,) in classroom, dorm, and social activities is the most effective control strategy to mitigate the spread of COVID-19 on college campuses. Moreover, since random screening testing allows for the successful and early detection of both asymptomatic and symptomatic individuals, it successfully reduces the transmission rate such that the maximum quarantine capacity is far lower than expected to further reduce the economic burden caused from quarantine. With vaccination, herd immunity is estimated to be achievable by 50% to 80% immunity coverage. In the absence of herd immunity, simulations indicate that it is optimal to keep some level of transmission risk reduction measures in classroom, dorm, and social activities, while testing at a lower frequency. Though our quantitative results are likely provisional on our model assumptions, extensive sensitivity analysis confirms the robustness of their qualitative nature.

HighlightsO_LIIndividual-based model for college communities with structured students interactions.
C_LIO_LIWe evaluated COVID-19 control measures needed for in-person college reopening.
C_LIO_LIWithout vaccination, high testing frequency is paramount for outbreak control.
C_LIO_LIWith high vaccination coverage, some NPIs are still needed for outbreak control.
C_LIO_LIGeneral access website tool was developed for the public to explore simulations.
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title: Temporal association of reduced serum vitamin D with COVID-19 infection: A single-institution case-control and historical cohort study

abstract:
ObjectivesVitamin D supplementation has been proposed for the prevention and treatment of COVID-19, but the relationship between the two is inconclusive: Reduced serum vitamin D may predispose to COVID-19, but it may also be a secondary consequence of infection. The objective of this study was to assess the temporal association between serum vitamin D levels and COVID-19.

DesignA single-institution case-control study and a historical cohort study

SettingUniversity of California San Diego (UCSD) Health System in San Diego, California

ParticipantsPatients testing positive for COVID-19 from January 1, 2020 to September 30, 2020 with serum 25-hydroxy-vitamin D (25(OH)D) measured within 180 days of diagnosis. Patients were separated based on whether 25(OH)D was measured before (n=107; "pre-diagnosis") or after (n=203; "post-diagnosis") COVID-19 diagnosis. Subjects with 25(OH)D assessments prior to COVID-19 diagnosis were evaluated using a case-control study design, while subjects with 25(OH)D measured after COVID-19 diagnosis were analyzed with a historical cohort study design.

Primary and Secondary Outcome MeasuresIn the pre-diagnosis study, a conditional logistic regression was performed using COVID-19 infection status as the binary dependent variable. In the post-diagnosis study, an ordinary least squares regression was performed using serum 25(OH)D levels as the continuous dependent variable.

ResultsSerum 25(OH)D levels were not associated with the odds of subsequently testing positive for COVID-19 (OR 1.00, 95% CI: 0.98 to 1.02, p = 0.982). However, COVID-19 positive individuals had serum 25(OH)D measurements that were lower by 2.70 ng/mL (95% CI: -5.19 to -0.20, p = 0.034) compared to controls.

ConclusionsIn our study population, serum 25(OH)D levels were not associated with risk of testing positive for COVID-19 but were reduced in subjects after being diagnosed with COVID-19 infection. These results raise the possibility that reduced serum 25(OH)D may be a consequence and not a cause of COVID-19 infection.


title: Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

abstract:
SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence ( first wave), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease.

One Sentence SummaryT cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells.


title: Comparison of antigen- and RT-PCR-based testing strategies for detection of Sars-Cov-2 in two high-exposure settings

abstract: Surveillance testing for infectious disease is an important tool to combat disease transmission at the population level. During the SARS-CoV-2 pandemic, RT-PCR tests have been considered the gold standard due to their high sensitivity and specificity. However, RT-PCR tests for SARS-CoV-2 have been shown to return positive results when administered to individuals who are past the infectious stage of the disease. Meanwhile, antigen-based tests are often treated as a less accurate substitute for RT-PCR, however, new evidence suggests they may better reflect infectiousness. Consequently, the two test types may each be most optimally deployed in different settings. Here, we present an epidemiological model with surveillance testing and coordinated isolation in two congregate living settings (a nursing home and a university dormitory system) that considers test metrics with respect to viral culture, a proxy for infectiousness. Simulations show that antigen-based surveillance testing coupled with isolation greatly reduces disease burden and carries a lower economic cost than RT-PCR-based strategies. Antigen and RT-PCR tests perform different functions toward the goal of reducing infectious disease burden and should be used accordingly.


title: Prevalence of long-term effects in individuals diagnosed with COVID-19: a living systematic review

abstract:
ObjectivePost COVID-19 condition refers to persisting or recurring symptoms weeks after acute COVID-19 illness which can significantly impact quality of life and health systems. It is important to understand the manifestation and magnitude of this condition. The objective of this living systematic review is to summarize the prevalence of symptoms and sequelae reported by people [≥]4 weeks after COVID-19 diagnosis.

DesignSystematic review, meta-analysis and narrative synthesis.

Data sourcesEmbase, Medline, PsychInfo, Cochrane Central and select grey literature up to April 14, 2021.

MethodsWe adapted a previous search strategy used by the U.K. National Institute for Health and Care Excellence and updated it to search for new literature. Two reviewers screened references independently; one extracted data and assessed risk of bias and certainty of the evidence while another verified them. Prevalence data from laboratory-confirmed populations were meta-analyzed using a random effects model and synthesized separately in the short-term (4-12 weeks) and long-term (>12 weeks) periods after diagnosis. Data from clinically-diagnosed populations were synthesized narratively.

ResultsOf the 4444 unique citations, 84 observational studies met our inclusion criteria. Over 100 post COVID-19 symptoms and sequelae were reported. Sixty-one percent (95% CI: 44-76%, low certainty) and 53% (95% CI: 41-65%, low certainty) of laboratory-confirmed individuals reported persistence or presence of one or more symptoms in the short- and long-term periods, respectively. The most prevalent symptoms in both periods included: fatigue, general pain or discomfort, shortness of breath, cognitive impairment and mental health symptoms.

ConclusionsA substantial proportion of individuals reported a variety of symptoms [≥]4 weeks after COVID-19 diagnosis. Due to gaps in the research base, and the low certainty of the evidence currently available, further research is needed to determine the true burden of post COVID-19 condition in the general population and in specific subgroups.

PROSPERO registration numberCRD42021231476.


title: Prevalence of long-term effects in individuals diagnosed with COVID-19: an updated living systematic review


title: Field evaluation of specificity and sensitivity of a standard SARS-CoV-2 antigen rapid diagnostic test: A prospective study at a teaching hospital in Northern Ghana

abstract:
BackgroundThe testing capacity for SARS-CoV-2 in Africa is rather limited. Antigen-detection rapid diagnostic tests (Ag-RDTs) are a cheap and rapid alternative to reverse transcriptase-polymerase chain reaction (RT-PCR) tests, but there is little data about their performance under real life conditions in tropical countries.

ObjectiveTo evaluate the performance of a standard Ag-RDT in a population of a major hospital in northern Ghana.

MethodsProspective, cross-sectional, blinded verification of the performance of the SD Biosensor Standard Q SARS-CoV-2 Ag-RDT under real life conditions in 135 symptomatic patients and 58 contacts of RT-PCR positives at Tamale Teaching Hospital in February 2021. Nasopharyngeal samples were taken under standard conditions and tested against RT-PCR in the hospital laboratory.

Results193 participants (median age 35 years, 109 male) were included into the study for which both RT-PCR test and Ag-RDT results were available. A total of 42 (22%) were RT-PCR positive. Of the 42 RT-PCR positives, 27 were Ag-RDT positive, resulting in a sensitivity of 64% (95% CI 49-79). Sensitivity among symptomatic patients was 58% (95% CI 38-78). 123 were identified Ag-RDT negatives of the 151 RT-PCR negatives, resulting in a specificity of 81% (95% CI 75-87).

ConclusionsSARS-CoV-2 Ag-RDTs appear to have a rather low sensitivity and particularly a low specificity under real life conditions in Africa. The role of existing Ag-RDTs in countries with high-temperature climates and limited resources still needs more data and discussion.


title: Implementation of COVID-19 Preventive Measures in Primary and Secondary Schools Following Reopening of Schools in Autumn 2020; A Cross-Sectional Study of Parents' and Teachers' Experiences in England

abstract:
ObjectiveThe main objective was to assess implementation of and ease of implementation of control measures in schools as reported by staff and parents.

DesignCross-sectional study.

SettingStaff and parents/guardian participants in the 132 primary schools and 20 secondary schools participating in sKIDs and sKIDsPLUS surveillances.

Main outcome measurePrevalence of control measures implemented in Autumn 2020, parental and staff perception of ease of implementation and acceptability of conducting school surveillance studies.

ResultsIn total, 56/152 (37%) schools participating in Public Health Englands sKIDs study of COVID in schools accepted the invitation to participate in the survey. By 28 December 2020, 1,953 parent and 986 staff respondents had completed the online questionnaire. While more than half the parents were positive about their children returning to school, roughly a third reported being a little anxious. 90% and 82% of primary and secondary school parents were either completely or partly reassured by the preventive measures implemented in their schools. Among staff, 80% of primary staff and 87% of secondary school staff felt that they were at higher risk of COVID-19 because of their profession; only 52% of primary school staff and 38% of secondary school staff reportedly felt safe. According to the teaching staff, most preventive measures were well-implemented apart from requiring 2-metre distancing between staff. For students, maintaining the 2-metre distance was reported to be particularly difficult. By extension, secondary schools also struggled to maintain small groups at all times or ensuring that the same staff were assigned to each student group (a problem also commonly reported by parents).

ConclusionsVariable implementation of infection control measures was reported by staff and parents. Whilst the majority were not worried about returning to school, some parents and staff, were concerned about returning to school and the risks posed to children, staff and household members.

Strengths and limitations of this studyO_ST_ABSStrengthsC_ST_ABSO_LIThis study is one of the few to investigate school staff and parents perceptions of the implementation of control measures implemented following the reopening of schools in England.
C_LIO_LIThe early establishment of COVID-19 surveillance in primary and secondary schools in the summer term 2020 provided a cohort to rapidly evaluate the experiences of parents and school staff during the autumn term before schools were required to close for the subsequent national lockdown.
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LimitationsO_LIAs the questionnaire and information provided was available in English only, there is likely to be an under-representation of families for whom English was not their main language.
C_LIO_LISome school responses were only provided by one participant so may not necessarily be representative of the whole school.
C_LIO_LIAlthough the surveillance included schools recruited nationally, a convenience sample was used and as such may not be representative of all primary and secondary schools in England.
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title: Language systems from lesion-symptom mapping in aphasia: A meta-analysis of voxel-based lesion mapping studies

abstract:
BackgroundAphasia is one of the most common causes of post-stroke disabilities. As the symptoms and impact of post-stroke aphasia are heterogeneous, it is important to understand how topographical lesion heterogeneity in patients with aphasia is associated with different domains of language impairments. Here, we aim to provide a comprehensive overview of neuroanatomical basis in post-stroke aphasia through coordinate based meta-analysis of voxel-based lesion-symptom mapping studies.

MethodsWe performed a meta-analysis of lesion-symptom mapping studies in post-stroke aphasia. We obtained coordinate-based functional neuroimaging data for 2,007 individuals with aphasia from 25 studies that met predefined inclusion criteria.

ResultsOverall, our results revealed that the distinctive patterns of lesions in aphasia are associated with different language functions and tasks. Damage to the insular-motor areas impaired speech with preserved comprehension and a similar pattern was observed when the lesion covered the insular-motor and inferior parietal lobule. Lesions in the frontal area severely impaired speaking with relatively good comprehension. The repetition-selective deficits only arise from lesions involving the posterior superior temporal gyrus. Damage in the anterior-to-posterior temporal cortex was associated with semantic deficits.

ConclusionThe association patterns of lesion topography and specific language deficits provide key insights into the specific underlying language pathways. Our meta-analysis results strongly support the dual pathway model of language processing, capturing the link between the different symptom complexes of aphasias and the different underlying location of damage.


title: Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review

abstract:
BackgroundPregnant women with COVID-19 are at an increased risk of severe COVID-19 illness as well as adverse pregnancy and birth outcomes. Many countries are vaccinating or considering vaccinating pregnant women with limited available data about the safety of this strategy. Early identification of safety concerns of COVID-19 vaccines, including their components, or their technological platforms is therefore urgently needed.

MethodsWe conducted a rapid systematic review, as the first phase of an ongoing full systematic review, to evaluate the safety of COVID-19 vaccines in pregnant women, including their components, and their technological platforms (whole virus, protein, viral vector or nucleic acid) used in other vaccines, following the Cochrane methods and the PRISMA statement for reporting (PROSPERO-CRD42021234185).

We searched literature databases, COVID-19 and pregnancy registries from inception February 2021 without time or language restriction and explored the reference lists of relevant systematic reviews retrieved. We selected studies of any methodological design that included at least 50 pregnant women or pregnant animals exposed to the vaccines that were selected for review by the COVAX MIWG in August 2020 or their components or platforms included in the COVID-19 vaccines, and evaluated adverse events during pregnancy and the neonatal period.

Pairs of reviewers independently selected studies through the COVIDENCE web software and performed the data extraction through a previously piloted online extraction form. Discrepancies were resolved by consensus.

ResultsWe identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals) and 12 pregnancy registries were included.

Most studies (89%) were conducted in high-income countries. The most frequent study design was cohort studies (n=21), followed by surveillance studies, randomized controlled trials, and registry analyses. Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures during the three trimesters of pregnancy.

The most frequent exposure was to AS03 adjuvant in the context of A/H1N1 pandemic influenza vaccines (n=24), followed by aluminum-based adjuvants (n=11). Aluminum phosphate was used in Respiratory Syncytial Virus Fusion candidate vaccines (n=3) and Tdap vaccines (n=3). Different aluminum-based adjuvants were used in hepatitis vaccines. The replication-deficient simian adenovirus ChAdOx1 was used for a Rift Valley fever vaccine. Only one study reported exposure to messenger RNA (mRNA) COVID-19 vaccines that also used lipid nanoparticles. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03) - corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns.

ConclusionThis rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines that were selected for review by the COVAX MIWG or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted given their novelty. Our findings support current WHO guidelines recommending that pregnant women may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.


title: Characterisation of Staphylococcus argenteus carried by healthy Royal Marines: a molecular epidemiology case-study

abstract:
ObjectivesDuring a prospective study of S. aureus carriage in Royal Marines (RM) recruits, six S. argenteus strains were identified in four recruits undertaking military training together. As S. argenteus sepsis leads to mortality similar to S. aureus, we determined the potential for person-to-person transmission, to evaluate future outbreak risk.

MethodsWe used whole-genome sequencing to characterise S. argenteus and investigate phylogenetic relationships between isolates. Participant colonisation with S. aureus and skin and soft tissue infection acquisition were recorded.

ResultsAll six S. argenteus strains were spa-type t5078, ST2250. Strains were detected in 4/40 recruits in the same troop (training cohort) in weeks 1, 6 or 15 of training. No mec, tsst or LukPV genes were detected. We identified differences of 10-35 core SNPs between S. argenteus from different recruits. In two recruits, two S. argenteus strains were isolated; these could be distinguished by 3 and 15 core SNPs in each case. S. argenteus was not identified in any one of the other 21 participating troops (1,012 recruits).

ConclusionsThe identification of S. argenteus within a single troop from the total recruit population supports a common source for transmission, supported by SNP analysis. The high number of SNPs between some isolates may indicate a common source of diverse isolates or a high level of S. argenteus mutation in carriage. S. argenteus ST2250 is a newly recognised lineage; a better understanding of the frequency of genetic changes during transmission and transition from asymptomatic carriage to disease is required.