title: Outcome Reporting bias in Exercise Oncology trials (OREO): a cross-sectional study

abstract:
BackgroundDespite evidence of selective outcome reporting across multiple disciplines, this has not yet been assessed in trials studying the effects of exercise in people with cancer. Therefore, the purpose of our study was to explore prospectively registered randomised controlled trials (RCTs) in exercise oncology for evidence of selective outcome reporting.

MethodsEligible trials were RCTs that 1) investigated the effects of at least partially supervised exercise interventions in people with cancer; 2) were preregistered (i.e. registered before the first patient was recruited) on a clinical trials registry; and 3) reported results in a peer-reviewed published manuscript. We searched the PubMed database from the year of inception to September 2020 to identify eligible exercise oncology RCTs clinical trial registries. Eligible trial registrations and linked published manuscripts were compared to identify the proportion of sufficiently preregistered outcomes reported correctly in the manuscripts, and cases of outcome omission, switching, and silently introduction of non-novel outcomes.

ResultsWe identified 31 eligible RCTs and 46 that were ineligible due to retrospective registration. Of the 405 total prespecified outcomes across the 31 eligible trials, only 6.2% were preregistered complete methodological detail. Only 16% (n=148/929) of outcomes reported in published results manuscripts were linked with sufficiently preregistered outcomes without outcome switching. We found 85 total cases of outcome switching. A high proportion (41%) of preregistered outcomes were omitted from the published results manuscripts, and many published outcomes (n=394; 42.4%) were novel outcomes that had been silently introduced (median, min-max=10, 0-50 per trial). We found no examples of preregistered efficacy outcomes that were measured, assessed, and analysed as planned.

ConclusionsWe found evidence suggestive of widespread selective outcome reporting and non-reporting bias (outcome switching, omitted preregistered outcomes, and silently introduced novel outcomes). The existence of such reporting discrepancies has implications for the integrity and credibility of RCTs in exercise oncology.

Preregistered protocolhttps://osf.io/dtkar/ (posted: November 19, 2019)

category: sports medicine


title: Early prediction of preeclampsia in pregnancy with circulating, cell-free RNA

abstract: Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an unprecedented opportunity to noninvasively study the development of pregnancy-related complications and to bridge gaps in clinical care. Here, we used 404 blood samples from 199 pregnant mothers to identify and validate cfRNA transcriptomic changes that are associated with preeclampsia (PE), a multi-organ syndrome which is the second largest cause of maternal death globally. We find that changes in cfRNA gene expression between normotensive (NT) and preeclamptic mothers are striking and stable early in gestation, well before the onset of symptoms. These changes are enriched for genes specific to neuromuscular, endothelial, and immune cell types and tissues that reflect important aspects of PE physiology and suggest new hypotheses for disease progression. This enabled identification and independent validation of a panel of 18 genes whose measurement between 5-16 weeks of gestation can form the basis of a liquid biopsy test that would identify mothers at risk of PE well before the clinical symptoms manifest themselves. Finally, we demonstrate that cfRNA changes reflect the multifactorial nature of PE and provide a means to non-invasively monitor maternal organ health. Tests based on these observations could help predict and manage who is at risk for PE, an important and until now unachieved objective for obstetric care.

category: obstetrics and gynecology


title: Early prediction of preeclampsia in pregnancy with circulating cell-free RNA


title: HIV service interruptions during the COVID-19 pandemic in China: the role of HIV service challenges and institutional response from healthcare professional's perspective

abstract:
BackgroundThe healthcare system in China was largely overwhelmed during the unprecedented pandemic of coronavirus disease (COVID-19). HIV-related services have been unavoidably interrupted and impacted. However, the nature and scope of HIV service interruptions due to COVID-19 has rarely been characterized in China and how HIV service challenges affect the service interruptions are also unclear. The current study aimed at characterize HIV service interruption levels and analyzed its associated factors related to service challenges and institutional response from HIV healthcare providers viewpoint.

MethodsA cross-sectional online survey was conducted among 1,029 HIV healthcare providers in Guangxi, China, from April to May 2020. Latent class analysis (LCA) was first used to identify HIV service interruption levels. Then hierarchical multinomial logistic regression was conducted to analyze the relationships of HIV care service challenges and institutional response with HIV service interruption levels. Simple slope analysis was employed to examine interaction effects between HIV service challenges and institutional response to COVID-19.

ResultsFour classes of HIV service interruption were identified using LCA, with 22.0% complete interruption (class 1), 15.4% moderate interruption (class 2), 21.9% minor interruption (class 3) and 40.7% almost no interruption (class 4). Using class 4 as a reference group, HIV care service challenges were positively associated with the probabilities of service interruptions (Class 1: AOR=1.23, 95%CI: 1.19[~]1.26; Class 2: AOR= 1.10, 95%CI: 1.08[~]1.13; Class 3: AOR= 1.10, 95%CI: 1.08[~]1.12). Institutional response to HIV healthcare delivery was negatively associated with the probabilities of being classified into Class 1 ("Complete interruption") (AOR=0.97, 95%CI: 0.93[~]1.00) and Class 3 ("minor interruption [Outreach service]") (AOR=0.96, 95%CI: 0.93[~]0.99) as compared to Class 4 ("almost no interruption"). Institutional response to HIV healthcare delivery moderated the association of HIV service challenges with complete interruption, but not with the moderate or minor interruption when comparing with no interruption group.

ConclusionsA substantial HIV service interruptions occurs due to the COVID-19 pandemic, particularly services that require face-to-face interactions, such as VCT counselling, follow up and outreach services. HIV service challenges largely hinder the HIV service delivery. Institutional response to HIV healthcare delivery could marginally buffer the negative effect of service challenges on complete HIV service interruptions. To maintain continuity of core HIV services in face of a pandemic, build a resilient health care system with adequate preparedness is necessary.

category: hiv aids


title: Determinants of losses in the latent tuberculosis infection cascade of care in Brazil: a prospective multicenter cohort study

abstract:
BackgroundFactors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients were investigated in a multicenter prospective cohort from highly endemic regions in Brazil.

MethodsClose contacts of 1,187 culture-confirmed pulmonary TB patients were prospectively studied between 2015 and 2019, with follow-up between 6 and 24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Stepwise multivariable models were used to identify determinants of losses in the LTBI cascade.

ResultsAmong 4,145 TB contacts initially identified, 1,901 were examined (54% loss). Within those individuals, 933 were people living with HIV, [≤]5 years-old and/or had positive IGRA results, therefore having recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (6% of all TB contacts) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy, and black/pardo (brown) race were independently associated with losses in cascade.

ConclusionThere were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts who are socially vulnerable and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil.

40-word summary of the articles main pointWe investigated factors associated with losses in the latent tuberculosis infection cascade of care in a large cohort of contacts in Brazil. Social vulnerability and HIV infection were the most relevant determinants of losses in the LTBI cascade of care.

category: infectious diseases


title: An update to the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model for prediction of individualized lifetime benefit from cardiovascular risk factor management in apparently healthy people

abstract:
IntroductionThe previously developed LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model can be used to predict lifetime cardiovascular disease risk, CVD-free life expectancy, and lifetime benefit from cardiovascular risk factor treatment in apparently healthy people aged 45 to 80 years. However, there was an unmet need to be able to apply the model in patients younger than 45 years, and to accurately estimate treatment effects in patients with a life expectancy exceeding 90 years.

AimUpdate the LIFE-CVD model to enable application of the model in people aged 35 to 89 years, and to allow more accurate estimation of treatment effects in patients with a life expectancy exceeding 90 years.

MethodsThe study was conducted using data from the same studies as were used for derivation and validation of the original model, including the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, Atherosclerosis Risk in Communities Study (ARIC) cohort, and the European Prospective Investigation into Cancer-Netherlands (EPIC-NL) and EPIC-Norfolk cohort studies. Age-specific baseline survivals were smoothed by predicting the progression of baseline survivals with age, using a local polynomial regression function and a exponential function for CVD, and non-CVD mortality baseline survivals respectively. Using these functions, baseline survivals were then extrapolated to the age range of 35 to 100 years. External validation using the newly updated baseline survivals was performed.

ResultsPerformance of the updated model was not dissimilar from the original model, with C-statistics for discrimination ranging from 0.70-0.76 in the external study populations. Calibration plots showed a good agreement between predicted and observed 10-year CVD risks. Estimation of treatment effects in patients with a life expectancy exceeding 90 years was improved.

ConclusionThis update of the LIFE-CVD model improves the clinical usability of the model by increasing the age range and improving the method of estimation of lifetime treatment effects.

category: cardiovascular medicine


title: Understanding SARS-CoV-2 Infection and Dynamics with Long Term Wastewater based Epidemiological Surveillance

abstract: Wastewater-based epidemiology (WBE) of SARS-CoV-2 emerged as an advantageous method to study the infection dynamics at substantial population level. A temporal glimpse at sewage viral genome helps as diagnostic tool to understand the viral spread at community level. In this study, for the long-term epidemiological surveillance, we monitored the SARS-CoV-2 genetic material in domestic sewage by adopting the longitudinal sampling to represent a selected community ([~]1.8 lakhs population which occupies 1.79% of the total population of Hyderabad city) to understand the dynamics of infection. Dynamics and spread of COVID-19 outbreak within the selected community were achieved by studying the longitudinal sampling for a specific period of time. WBE also promotes clinical scrutiny along with disease detection and management, in contrast to an advance warning signal to anticipate outbreaks.

category: epidemiology


title: Targeting Lyn Kinase in Chorea-Acanthocytosis: A Translational Treatment Approach in an Ultra-Rare Disease

abstract:
BackgroundChorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms and therefore represents a promising drug target.

MethodsWe evaluated an individual off-label treatment with the FDA-approved tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8-50.4 weeks) of three ChAc patients. Alongside with a thorough safety monitoring, we assessed motor and non-motor scales (e.g. MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g. serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells).

ResultsDasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels and acanthocyte count did not reveal consistent effects. However, reduction of initially elevated Lyn kinase activity and accumulated autophagy markers as well as partial restoration of actin cytoskeleton was found in red blood cells.

DiscussionWe report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for "clinical trial readiness". Here, we suggest a panel of outcome parameters for future clinical trials in ChAc.

category: neurology


title: Evaluation of RNA extraction free method for detection of SARS-COV-2 in salivary samples for mass screening for COVID-19

abstract: In this current COVID - 19 pandemic, there is a dire need for cost effective and less time-consuming alternatives for SARS-COV-2 testing. The RNA extraction free method for detecting SARS-COV-2 in saliva is a promising option, this study found that it has high sensitivity (85.34%), specificity (95.04%) and was comparable to the gold standard nasopharyngeal swab. The method showed good percentage of agreement (kappa coefficient) 0.797 between salivary and NPS samples. However, there are variations in the sensitivity and specificity based on the RT-PCR kit used. The Thermo Fischer-Applied biosystems showed high sensitivity, PPV and NPV but also showed higher percentage of invalid reports. Whereas the BGI kit showed high specificity, better agreement (kappa coefficient) between the results of saliva and NPS samples and higher correlation between the Ct values of saliva and NPS samples. Thus, the RNA extraction free method for salivary sample serves as an effective alternative for SARS-CoV 2-testing.


title: Using Machine Learning along with Data Science algorithms to pre-process and forecast COVID-19 Cases and Deaths

abstract: The Covid-19 pandemic has taken a major toll on the health and state of our global population. With tough decisions for allocating resources(i.e. vaccines)[1] are being made, forecasting through machine learning has become more important than ever. Moreover, as vaccines are being brought to the public and cases are going down, it is time that we reflect on where the pandemic has taken the most toll:for the purpose of future reform. This research illustrates two different models and algorithms for COVID-19 forecasting: Auto Regressive models and Recurrent Neural Networks(RNNs). The results show the true potential of RNNs to work with sequential and time-series data to forecast future cases and deaths in different states. As the paper utilizes the tanh activation function and multiple LSTM layers, the research will show the importance of machine learning and its ability to help politicians make decisions when it comes to helping states during the pandemic and future reform. The data will also pre-process the time-series data, using rolling statistics and will clean the data for the auto-regressive model and RNN layers. Thus, we show that along with Recurrent Neural Network layers, activation functions also play a crucial role in the accuracy of the forecast.


title: The Survey of the Health of Wisconsin (SHOW) Program: An infrastructure for Advancing Population Health Sciences in the 21st Century

abstract:
PurposeThe Survey of the Health of Wisconsin (SHOW) was established in 2008 by the University of Wisconsin (UW) School of Medicine and Public Health (SMPH) with the goals of 1) providing a timely and accurate picture of the health of the state residents; and 2) serving as an agile resource infrastructure for ancillary studies. Today SHOW continues to serve as a vital population health research infrastructure.

ParticipantsSHOW currently includes 5,846 adult and 980 minor participants recruited between 2008-2019 in four primary waves. WAVE I (2008-2013) includes annual statewide representative samples of 3,380 adults ages 21 to 74 years. WAVE II (2014-2016) is a triannual statewide sample of 1957 adults (age [≥]18 years) and 645 children. WAVE III (2017) consists of follow-up of 725 adults from the WAVE I and baseline surveys of 222 children in selected households. WAVEs II and III include stool samples collected as part of an ancillary study in a subset of 784 individuals. WAVE IV consist of 517 adults and 113 children recruited from traditionally under-represented populations in biomedical research including African Americans and Hispanics in Milwaukee county, WI.

Findings to DateThe SHOW provides extensive data to examine the intersectionality of multiple social determinants and population health. SHOW includes a large biorepository and extensive health data collected in a geographically diverse urban and rural population. Over 60 studies have been published covering a broad range of topics including, urban and rural disparities in cardio-metabolic disease and cancer, objective physical activity, sleep, green-space and mental health, transcriptomics, the gut microbiome, antibiotic resistance, air pollution, concentrated animal feeding operations and heavy metal exposures.

Future PlansThe SHOW cohort is available for continued longitudinal follow-up and ancillary studies including genetic, multi-omic and translational environmental health, aging, microbiome and COVID-19 research.

Article SummaryO_ST_ABSStrengths and limitationsC_ST_ABSO_LIThe Survey of the Health of Wisconsin (SHOW) is an infrastructure to advance population health sciences including biological sample collection and broader data on individual and neighborhood social and environmental determinants of health.
C_LIO_LIThe extensive data from diverse urban and rural populations offers a unique study sample to compare how socio-economic gradients shape health outcomes in different contexts.
C_LIO_LIThe objective health data supports novel interdisciplinary research initiatives and is especially suited for research in causes and consequences of environmental exposures (physical, chemical, social) across the life course on cardiometabolic health, immunity, and aging related conditions.
C_LIO_LIThe extensive biorepository supports novel omics research into common biological mechanisms underlying numerous complex chronic conditions including inflammation, oxidative stress, metabolomics, and epigenetic modulation.
C_LIO_LIAncillary studies, such as the Wisconsin Microbiome Study, have expanded the utility of the study to examine human susceptibility to environmental exposures and opportunities for investigations of the role of microbiome in health and disease.
C_LIO_LILong-standing partnerships and recent participation among traditionally under-represented populations in biomedical research offer numerous opportunities to support community-driven health equity work.
C_LIO_LINo biological samples were collected among children.
C_LIO_LIThe statewide sampling frame may limit generalizability to other regions in the United States.
C_LI


title: The Survey of the Health of Wisconsin (SHOW) Program: An infrastructure for Advancing Population Health Sciences


title: Safety of administering biologics to IBD patients at an outpatient infusion center In New York City during the COVID-19 pandemic: Sars-CoV-2 seroprevalence and clinical and social characteristics

abstract: Patients with immune-mediated inflammatory diseases (IMIDs) and acquired and genetic immunodeficiencies receiving therapeutic infusions are considered high risk for SARS-CoV-2 infection. However, the seroprevalance in this group and the safety of routine administrations at outpatient infusion centers are unknown. To determine the infection rate and clinical-social factors related to SARS-CoV-2 in asymptomatic patients with IMIDs and immunodeficiencies receiving routine non-cancer therapeutic infusions, we conducted a seroprevalence study at our outpatient infusion center. We report the first prospective SARS-CoV-2 sero-surveillance of 444 IBD/IMID, immunodeficiency, and immune competent patients at an outpatient infusion center in the U.S. showing lower seroprevalence in patients compared with the general population and provide clinical and social characteristics associated with seroprevalence in this group. These data suggest that patients can safely continue infusions at outpatient centers.

category: gastroenterology


title: A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance

abstract: The virus SARS-CoV-2 can exploit biological vulnerabilities in susceptible hosts that predispose to development of severe COVID-19. Previous reports have identified several host proteins related to the interferon response (e.g. OAS1), interleukin-6 signalling (IL-6R), and the coagulation cascade (linked via ABO) that were associated with risk of COVID-19. In the present study, we performed proteome-wide genetic colocalisation tests leveraging publicly available protein and COVID-19 datasets, to identify additional proteins that may contribute to COVID-19 risk. Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble FAS (colocalisation probability > 0.9, p = 1 x 10-4), implicating FAS-mediated apoptosis as a potential target for COVID-19 risk. We also undertook polygenic (pan) and cis-Mendelian randomisation analyses that showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal was associated with plasma concentrations of several proteins, with the strongest association observed with CD209 in several proteomic datasets. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.

category: pharmacology and therapeutics


title: The potential for bike riding across entire cities: quantifying spatial variation in interest in bike riding

abstract:
BackgroundRiding a bike is beneficial for health, the environment and for reducing traffic congestion. Despite this, bike riding participation in the state of Victoria, Australia, is low. To inform planning and practice, there is a need to understand the proportion of the population (the  near-market) that are interested in riding a bike, and how this varies across regions. The Geller typology classifies individuals into one of four groups, based on their confidence to ride a bike in various infrastructure types, and frequency of bike riding. The typology has been used at a city, state and country-wide scale, however not at a smaller spatial scale. We aimed to characterise and quantify the distribution of the Geller typology within Local Government Areas (LGAs) in the state of Victoria, Australia.

MethodsAn online survey was conducted in 37 LGAs in Victoria, including all LGAs in Greater Melbourne, and a selection of six key regional centres. Participants were recruited from an opt-in online research company panel with the objective of recruiting a representative sample of adults across each LGA. The Geller typology classified individuals as either:  Strong and Fearless,  Enthused and Confident,  Interested but Concerned, or  No Way No How.  Interested but Concerned participants are those that would ride a bike if protected infrastructure were provided.

ResultsThe survey was completed by 3999 individuals. Most participants owned a bike (58%), however only 20% rode at least once per week. The distribution of the Geller groups was:  Strong and Fearless (3%),  Enthused and Confident (3%),  Interested but Concerned (78%), and  No Way No How (16%). While variation in the distributions of the Geller groups was observed between LGAs within Greater Melbourne., the  Interested but Concerned group, reflecting people who are comfortable riding only in protected lanes or off-road paths, was high across all LGAs and all demographic sub-groups. Even though the frequency of riding a bike was lower in women, interest in riding a bike was high and comparable to men. Participants who resided in the outer urban fringe regions of Greater Melbourne had high interest, but low participation in bike riding.

ConclusionsWhile there was variation in interest in bike riding across an entire metropolitan region and across population groups, interest was high across all areas and demographics. Our results show the potential for substantial increases in cycling participation, but only when high-quality cycling infrastructure is provided. Further research is required to understand the policy and practice barriers to equitable provision of protected infrastructure.

category: public and global health


title: Motor Unit Number Index (MUNIX) of the Upper Trapezius: Reliability and Meta-Analysis

abstract: Motor unit number index (MUNIX) of the upper trapezius is a candidate biomarker for lower motor neuron function of the bulbar region; however, only a few studies have explored this measure in neuromuscular diseases and reliability data is incomplete. We conducted a systematic review and meta-analysis of this measure in control participants and assessed its reliability in twenty healthy volunteers. Four studies were included with heterogeneous mean-MUNIX estimates, moderated by variability in the populations age and MUNIX sampling technique. We demonstrated an inter- and intra-rater intraclass correlation of 0.86 and 0.94, respectively. Upper trapezius MUNIX is a reliable measure with in-between study variability moderated by age and MUNIX technique.


title: KidneyNetwork: Using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease

abstract:
BackgroundGenetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for the disorder as potentially pathogenic variants can reside in genes that are not yet known to be involved in kidney disease. To help identify these genes, we have developed KidneyNetwork, that utilizes tissue-specific expression to predict kidney-specific gene functions.

MethodsKidneyNetwork is a co-expression network built upon a combination of 878 kidney RNA-sequencing samples and a multi-tissue dataset of 31,499 samples. It uses expression patterns to predict which genes have a kidney-related function and which (disease) phenotypes might result from variants in these genes. We applied KidneyNetwork to prioritize rare variants in exome sequencing data from 13 kidney disease patients without a genetic diagnosis.

ResultsKidneyNetwork can accurately predict kidney-specific gene functions and (kidney disease) phenotypes for disease-associated genes. Applying it to exome sequencing data of kidney disease patients allowed us to identify a promising candidate gene for kidney and liver cysts: ALG6.

ConclusionWe present KidneyNetwork, a kidney-specific co-expression network that accurately predicts which genes have kidney-specific functions and can result in kidney disease. We show the added value of KidneyNetwork by applying it to kidney disease patients without a molecular diagnosis and consequently, we propose ALG6 as candidate gene in one of these patients. KidneyNetwork can be applied to clinically unsolved kidney disease cases, but it can also be used by researchers to gain insight into individual genes in order to better understand kidney physiology and pathophysiology.

Significance statementGenetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for the patients disorder. Potentially pathogenic variants can reside in genes not yet known to be involved in kidney disease, making it difficult to interpret the relevance of these variants. This reveals a clear need for methods to predict the phenotypic consequences of genetic variation in an unbiased manner. Here we describe KidneyNetwork, a tool that utilizes tissue-specific expression to predict kidney-specific gene functions. Applying KidneyNetwork to a group of undiagnosed cases identified ALG6 as a candidate gene in cystic kidney and liver disease. In summary, KidneyNetwork can aid the interpretation of genetic variants and can therefore be of value in translational nephrogenetics and help improve the diagnostic yield in kidney disease patients.

category: genetic and genomic medicine


title: Lessons learned from the resilience of Chinese hospitals to the COVID-19 pandemic: a scoping review.

abstract:
As the SARS-CoV-2 pandemic has brought huge strain on hospitals worldwide, the resilience shown by Chinas hospitals appears to have been a critical factor in their successful response to the pandemic. This paper aims to determine the key findings, recommendations and lessons learned in terms of hospital resilience during the pandemic, as well as the quality and limitations of research in this field at present.

We conducted a scoping review of evidence on the resilience of hospitals in China during the COVID-19 crisis in the first half of 2020. Two online databases (the CNKI and WHO databases) were used to identify papers meeting the eligibility criteria, from which we selected 59 publications (English: n= 26; Chinese: n= 33). After extracting the data, we present an information synthesis using a resilience framework.

We found that much research was rapidly produced in the first half of 2020, describing certain strategies used to improve hospital resilience, particularly in three key areas: human resources; management and communication; and security, hygiene and planning. Our search revealed that considerable attention was focused on interventions related to training, healthcare worker well-being, e-health/ telemedicine, and work organization, while other areas, such as hospital financing, information systems and healthcare infrastructure, were less well represented in the literature.

We identified a number of lessons learned regarding how Chinas hospitals have maintained resilience when confronted with the SARS-CoV-2 pandemic. However, we also noted that the literature was dominated by descriptive case studies, often lacking consideration of methodological limitations, and that there was a lack of both highly-focused research on individual interventions and holistic research that attempted to unite the topics within a resilience framework. Research on Chinese hospitals would benefit from a greater range of analysis in order to draw more nuanced and contextualised lessons from the responses to the crisis.

category: health systems and quality improvement


title: Real-World Effectiveness and Tolerability of Monoclonal Antibodies for Ambulatory Patients with Early COVID-19

abstract:
ImportanceInterventions to reduce hospitalization of patients with COVID-19 are urgently needed. Randomized trials for efficacy suggest that anti-SARS-CoV2 neutralizing monoclonal antibodies (MAb) may reduce medically-attended visits and hospitalization but effectiveness has not been confirmed in a real-world setting.

ObjectiveEstimate the effectiveness of MAb infusion in a real-world cohort of ambulatory patients with early symptomatic COVID-19 at high risk for hospitalization.

DesignQuasi-experimental observational cohort study using target trial emulation and causal inference methodology in pre-and post-implementation groups.

SettingInfusion centers and urgent care clinics within an integrated healthcare system in the United States

Participants13,534 high-risk adult outpatients with symptomatic, laboratory-confirmed COVID-19 within 7 days of symptom onset.

ExposuresA single intravenous infusion of either bamlanivimab 700 mg or casirivimab/imdevimab 1200 mg/1200 mg.

Main Outcomes and MeasuresThe primary outcome was emergency department visit or hospitalization within 14 days of positive test. Patients who received MAb infusion were compared to contemporaneous controls using inverse probability of treatment weighting, and to a pre-implementation cohort using propensity-weighted interrupted time series analysis. An exploratory analysis compared effectiveness of casirivimab/imdevimab and bamlanivimab.

Results7404 patients who would have been MAb-eligible were identified in a pre-implementation cohort (July 1-November 27, 2020). In the post-implementation period (November 28, 2020-January 28, 2021), 594 received MAb treatment and 5536 MAb-eligible patients did not. Among Mab recipients, 479 (80.6%) received bamlanivimab and 115 (19.4%) casirivimab/imdevimab. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls, and 1525 (20.6%) patients in the pre-implementation cohort. MAb treatment was associated with fewer subsequent emergency department visits and hospitalizations (odds ratio estimating the average treatment effect 0.69, 95% CI 0.60-0.79). After implementation, propensity-weighted probability of emergency department visit or hospitalization decreased by 0.7% per day (95% CI 0.03-0.10%, p<0.001). Overall, 7 (1.2%) MAb patients experienced an adverse event; two (0.3%) were considered serious. In the exploratory analysis, the effect of casirivimab/imdevimab versus bamlanivimab was not significant (OR 0.52, 95% CI 0.17-1.63, p=0.26).

Conclusions and RelevanceMAb treatment of high-risk ambulatory patients with early COVID-19 was well-tolerated and effective at preventing the need for subsequent medically-attended care.

Key Points SectionO_ST_ABSQuestionC_ST_ABSWhat is the real-world effectiveness of COVID-19 monoclonal neutralizing antibody (MAb) infusions in high-risk, ambulatory patients?

Findings594 high-risk, early-symptomatic adults with COVID-19 treated with MAb infusion were compared to 5536 contemporaneous controls using inverse probability of treatment weighting, and to 7404 patients in a pre-implementation cohort using propensity-weighted interrupted time series analysis. MAb treatment was associated with fewer subsequent emergency department visits and hospitalizations (odds ratio 0.69 (95% CI 0.60-0.79). After MAb implementation the probability of emergency department visit or hospitalization decreased by 0.7% per day, 95% CI 0.03-0.10%, p<0.001).

MeaningMonoclonal antibody infusion within seven days of symptom onset in high-risk ambulatory adults with COVID-19 appears to prevent subsequent emergency department visits and hospitalization. Further evaluation of the differences between specific Mab products is warranted.


title: Hospitalisation rates differed by city district and ethnicity during the first wave of COVID-19 in Amsterdam, the Netherlands

abstract:
BackgroundIt is important to gain insight into the burden of COVID-19 at city district level to develop targeted prevention strategies. We examined COVID-19 related hospitalisations by city district and migration background in the municipality of Amsterdam, the Netherlands.

MethodsWe used surveillance data on all PCR-confirmed SARS-CoV-2 hospitalisations in Amsterdam until 31 May 2020, matched to municipal registration data on migration background. We calculated directly standardised (age, sex) rates (DSR) of hospitalisations, as a proxy of COVID-19 burden, per 100,000 population by city district and migration background. We calculated standardised rate differences (RD) and rate ratios (RR) to compare hospitalisations between city districts of varying socio-economic and health status and between migration backgrounds. We evaluated the effects of city district and migration background on hospitalisation after adjusting for age and sex using Poisson regression.

ResultsBetween 29 February and 31 May 2020, 2326 cases (median age 57 years [IQR=37-74]) were notified in Amsterdam, of which 596 (25.6%) hospitalisations and 287 (12.3%) deaths. 526/596 (88.2%) hospitalisations could be matched to the registration database. DSR were higher in individuals living in peripheral (South-East/New-West/North) city districts with lower economic and health status, compared to central districts (Centre/West/South/East) (RD=36.87,95%CI=25.79-47.96;RR=1.82,95%CI=1.65-1.99), and among individuals with a non-Western migration background compared to ethnic-Dutch individuals (RD=57.05,95%CI=43.34-70.75; RR=2.36,95%CI=2.17-2.54). City district and migration background were independently associated with hospitalisation.

ConclusionCity districts with lower economic and health status and those with a non-Western migration background had the highest burden of COVID-19 during the first wave of COVID-19 in Amsterdam.


title: Long-term sequelae of Pneumococcal Sepsis in children: a systematic review

abstract:
BackgroundLong-term sequelae associated with pneumococcal sepsis (PS) in pediatric patients in existing literature is currently unclear.

AimTo review the evidence on sequelae and prognostic factors associated with PS among pediatric patients.

MethodWe conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened six databases from their inception to January 15, 2021. Study population were neonates, infants, children and adolescents less than 18 years old with suspected or confirmed PS disease. Outcomes included sequelae types, prognostic factors, pooled death estimate and length of hospital stay (LOS) for survivors and deceased patients. Quality of studies was assessed using Joanna Briggs Institute appraisal checklists.

ResultsWe screened 981 abstracts, and 24 full-text articles for final review. Septic shock was the most prevalent physical sequelae reported (13%, n=1492 patients). No functional, cognitive or neurological sequelae were reported in included studies. Meta-analysis of pooled mortality estimate was 14.6% (95%CI: 9.9 -19.4%). Prognostic factors associated with increased risk of PS sequelae and death included pediatric risk of mortality score [≥] 10 and co-infection with meningitis. LOS for survivors and non-survivors ranged between 5-30 days and 1-30 days. Nine included studies met at least 50% of the quality assessment criteria.

ConclusionPhysical sequelae and death are the PS sequelae types currently identified in existing literature. Lack of information about other possible sequelae types suggests the long-term consequences of PS disease maybe underreported, especially in resource-limited settings. Future studies should consider exploring reasons for the existing of this knowledge gap.


title: Faecal shedding models for SARS-CoV-2 RNA amongst hospitalised patients and implications for wastewater-based epidemiology

abstract: The concentration of SARS-CoV-2 RNA in faeces is not well established, posing challenges for wastewater-based surveillance of COVID-19 and risk assessments of environmental transmission. We develop versatile hierarchical models for faecal RNA shedding and apply them to data collected in six studies. We find that the mean number of gene copies per mL of faeces is 1.9x106 (2.3x105--2.0x108 95% credible interval) amongst hospitalised patients. We find no evidence for a subpopulation of patients who do not shed RNA: limits of quantification can account for negative stool samples. Our models indicate that hospitalised patients represent the tail of the shedding profile with a half-life of 34 hours (28--43 95% credible interval), suggesting that wastewater-based surveillance signals are more indicative of incidence than prevalence and can be a leading indicator of clinical presentation. Shedding amongst inpatients cannot explain high RNA concentrations observed in wastewater, consistent with more abundant shedding during the early infection course.


title: A bibliometric analysis of COVID-19 research in Africa

abstract:
BackgroundThe ongoing COVID-19 pandemic has led to an unprecedented global research effort to build a body of knowledge that can inform mitigation strategies. We carried out a bibliometric analysis to describe the COVID-19 research output in Africa.

MethodsWe searched for articles published between 1st December 2019 and 3rd January 2021 from various databases including PubMed, African Journals Online, MedRxiv, BioRxiv, Collabovid, the World Health Organisation global research database and Google for grey literature. Editorial type publications and papers reporting original research done in Africa and were included. Data analysis was done using Microsoft Excel.

ResultsA total of 1296 articles were retrieved. 46.6% were primary research articles, 48.6% were editorials type articles while 4.6% were secondary research articles. 20.3% articles used the entire continent of Africa as their study setting while South Africa (15.4%) was the most common country focused setting. 90.3% of the articles had at least one African researcher as author, 78.5% had an African researcher as first author, while 63.5% had an African researcher as last author. The University of Cape Town tops the list with the greatest number of first and last authors. Over 13% of the articles were published in MedRxiv and of the studies that declared funding, the Wellcome Trust was the top funding body. The most common research topics include "country preparedness and response" (24.9%) and "the direct and indirect health impacts of the pandemic" (21.6%). However, only 1.0% of articles focus on therapeutics and vaccines.

ConclusionsThis study sheds light on the contribution of African researchers to COVID-19 research in Africa and highlights Africas existing capacity to carry out research that addresses local problems. However, the uneven distribution of research productivity amongst African countries emphasizes the need for increased investment where needed.


title: Epidemiological and clinical insights from SARS-CoV-2 RT-PCR cycle amplification values

abstract: The SARS-CoV-2 pandemic has led to an unprecedented daily use of molecular RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of amplification cycles (Ct), is debated because of strong potential biases. We analyze a national database of tests performed on more than 2 million individuals between January and November 2020. Although we find Ct values to vary depending on the testing laboratory or the assay used, we detect strong significant trends with patient age, number of days after symptoms onset, or the state of the epidemic (the temporal reproduction number) at the time of the test. These results suggest that Ct values can be used to improve short-term predictions for epidemic surveillance.


title: PD-1highCXCR5-CD4+ Peripheral Helper T (Tph) cells Promote Tissue-Homing Plasmablasts in COVID-19

abstract: A dysregulated immune response against coronavirus-2 (SARS-CoV-2) plays a critical role in the outcome of patients with coronavirus disease 2019 (COVID-19). A significant increase in circulating plasmablasts is characteristic of COVID-19 though the underlying mechanisms and its prognostic implications are not known. Here, we demonstrate that in the acute phase of COVID-19, activated PD-1highCXCR5-CD4+ T cells, peripheral helper T cells, (Tph) are significantly increased and promote inflammatory tissue-homing plasmablasts in patients with stable but not severe COVID-19. Analysis of scRNA-seq data revealed that plasmablasts in stable patients express higher levels of tissue-homing receptors including CXCR3. The increased Tph cells exhibited "B cell help" signatures similar to that of circulating T follicular helper (cTfh) cells and promoted B cell differentiation in vitro. Compared with cTfh cells, Tph cells produced more IFN{gamma}, inducing tissue-homing chemokine receptors on plasmablasts. Finally, expansion of activated Tph cells was correlated with the frequency of CXCR3+ plasmablasts in the acute phase of patients with stable disease. Our results demonstrate a novel role for Tph cells in acute viral immunity by inducing ectopic, antibody secreting plasmablasts.

category: allergy and immunology


title: COVID-19 with early neurological and cardiac thromboembolic phenomena--timeline of incidence and clinical features

abstract:
BackgroundAt our tertiary care public hospital, we saw COVID-19 presenting with thromboembolic phenomena, indicating a possible early thrombo-inflammatory pathology.

ObjectivesWe documented patients with cardiac and neurological thromboembolic phenomena as a primary presentation of COVID-19, and compared a subset of COVID associated strokes against COVID-19 patients without thrombotic manifestations.

MethodsWe included all COVID-Stroke and COVID-ACS (COVID-19, with ischemic arterial stroke/Acute Coronary Syndrome presenting prior to/simultaneous with/within 72 hours of systemic/respiratory COVID manifestations) admitted from April to November 2020. In the nested case control analysis, we used unpaired T-test and chi-square test to study differences between COVID-Strokes (case group) and non-thrombotic COVID controls.

Results and ConclusionsWe noted 68 strokes and 122 ACS associated with COVID-19. ACS peaked in May-June, while stroke admissions peaked later in September-October, possibly because severe strokes may have expired at home during the lockdown.

In the case-control analysis, cases (n=43; 12F:31M; mean age 51.5 years) had significantly higher D-Dimer values than controls (n=50; 9F:41M; mean age 51.6 years). Mortality was significantly higher in cases (51.2% vs. 26.0%; p = 0.018). We noted 7.5 times higher mortality in cases versus controls even among patients needing minimal oxygen support. Imaging in 37 patients showed both anterior and posterior circulation territories affected in seven, with almost half of Carotid territory strokes being large hemispherical strokes. Additionally, CT/MRI angiography in 28 strokes showed large vessel occlusions in 19 patients. Death in cases thus probably occurred before progression to intense respiratory support, due to severe central nervous system insult.

Binary logistic regression analysis showed respiratory support intensity to be the sole independent predictor of mortality among cases. Respiratory distress could have been due to COVID-19 lung infection or aspiration pneumonia resulting from obtunded sensorium. In controls, mortality was predicted by increasing age, female sex, and respiratory support intensity.


title: The course of the UK COVID 19 pandemic; no measurable impact of new variants.

abstract:
IntroductionIn November 2020, a new SARS-COV-2 variant or the  Kent variant emerged in the UK, and became the dominant UK SARS-COV-2 variant, demonstrating faster transmission than the original variant, which rapidly died out. However, it is unknown if this altered the overall course of the pandemic as genomic analysis was not common place at the outset and other factors such as the climate could alter the viral transmission rate over time. We aimed to test the hypothesis that the overall observed viral transmission was not altered by the emergence of the new variant, by testing a model generated earlier in the pandemic based on lockdown stringency, temperature and humidity.

MethodsFrom 1/1/20 to 4/2/21, the daily incidence of SARS-COV-2 deaths and the overall stringency of National Lockdown policy on each day was extracted from the Oxford University Government response tracker. The daily average temperature and humidity for London was extracted from Wunderground.com.

The viral reproductive rate was calculated on a daily basis from the daily mortality data for each day. The correlation between log10 of viral reproductive rate and lockdown stringency and weather parameters were compared by Pearson correlation to determine the time lag associated with the greatest correlation.

A multivariate model for the log10 of viral reproductive rate was constructed using lockdown stringency, temperature and humidity for the period 1/1/20 to 30/9/20. This model was extrapolated forward from 1/10/20 to 4/2/21 and the predicted viral reproductive rate, daily mortality and cumulative mortality were compared with official data.

ResultsOn multivariate linear regression, the optimal model had and R2 0f 0.833 for prediction of log10 viral reproductive rate 13 days later in the model construction period, with (coefficient, probability) lockdown stringency (-0.0109, p=0.0000), humidity (0.0038, p=0.0041) and temperature (-0.0035, p=0.0008). When extrapolated to the validation period (1/10/20 to 4/2/21), the model was highly correlated with daily (Pearson coefficient 0.88, p=0.0000) and cumulated SARS-COV-2 mortality (Pearson coefficient 0.99, p=0.0000).

ConclusionThe course of the SARS-COV-2 pandemic in the UK seems highly predicted by an earlier model based on the lockdown stringency, humidity and temperature and unaltered by the emergence of a newer viral genotype.


title: Identifying hidden Zika hotspots in Pernambuco, Brazil: A Spatial Analysis

abstract: Northeast Brazil has the worlds highest rate of Zika-related microcephaly. Yet, in this hard-hit region, traditional case counts of Zika cannot accurately describe Zika risk. Reporting of Zika cases only became mandatory after its association with microcephaly in neonates, when the Zika epidemic was already declining in the region. To advance the study of the Brazilian Zika epidemic and its impacts, we identified hotspots of Zika in Pernambuco state, Northeast Brazil, using Aedes-borne diseases (dengue, chikungunya and Zika) and microcephaly data. We used the Kulldorffs Poisson purely spatial scan statistic to detect low- and high-risk clusters and combined the results to identify the municipalities most affected by the Zika epidemic. Municipalities were classified as hotspots if they were part of any high-risk cluster, and classified according to a gradient of Zika burden during the epidemic, considering the strength of the evidence. In Pernambuco, officials confirmed 123,934 dengue cases, 167 Zika cases, and 32,983 chikungunya cases between 2014-2017, and 800 microcephaly cases between 2015-2017. We identified 26 Aedes-borne diseases clusters (11 high-risk), and 5 microcephaly cases clusters (3 high-risk). Combining the results, sixty-three out of 184 municipalities were identified as hotspots for Zika. The northeast of Pernambuco and the Sertao region were hit hardest by the Zika epidemic. The first is the most populous area, while the second has one of the highest rates of social and economic inequality in Brazil. The identification of Sertao as a Zika hotspot was only possible because the clusters results were combined. The under-reporting of acute infectious diseases is expected to be higher in poor areas. Therefore, using only Aedes-borne data does not correctly identify the high-risk areas. We successfully identified hidden Zika hotspots using a simple methodology combining Aedes-borne diseases and microcephaly information.


title: Age specific COVID-19 undercount in Spain from the regional breakdown of 52-week accumulated mortality rates

abstract:
Spanish NUTS3 region records of age specific weekly deaths since the year 2020, records of age specific COVID-19 deaths and age specific population since the year 2020 are used to estimate first age specific all-cause death rates and age specific COVID-19 undercount.

Results shows a statistically significant impact of the pandemic in excess deaths for population aged 40 and elder. Statistically significant COVID-19 undercount is identified only for population aged 80 and elder. Very likely this is the result of the impact of the pandemic in institutionalized population at the early stages of the pandemic.


title: U.S. adolescents' mental health and COVID-19-related changes in technology use, Fall 2020

abstract: Preliminary reports suggest that during COVID-19, adolescents mental health has worsened while technology and social media use has increased. Much data derives from early in the pandemic, when schools were uniformly remote and personal/family stressors related to the pandemic were limited. This cross-sectional study, conducted during Fall 2020, examines the correlation between mental wellbeing and COVID-19-related changes in technology use, along with influence of COVID-19-related stressors, school status (in-person versus remote), and social media use for coping purposes, among 978 U.S. adolescents. Results suggest self-reported daily social media and technology use increased significantly from prior to COVID-19 through Fall 2020. Increased social media use was significantly associated with higher levels of anxiety and depressive symptoms regardless of other theoretical moderators or confounders of mental health (e.g., demographics, school status, importance of technology, COVID-19-related stress). Despite literature suggesting that remote learning may result in adverse mental health outcomes, we did not find local school reopening to be associated with current depressive/anxiety symptoms, nor with COVID-19-related increases in technology use. Self-reported use of social media for coping purposes moderated the association between increased social media use and mental health symptoms; in other words, some social media use may have positive effects. Although much prior research has focused on social media use as a marker of stress, we also found that increased video gaming and TV/movie watching were also associated with internalizing symptoms, in accordance with others' work. Future research should explore in more granular detail what, if any, social media and technology use is protective during a pandemic, and for whom, to help tailor prevention efforts.

category: psychiatry and clinical psychology


title: Female gender and knowing a person positive for COVID-19 significantly increases fear levels in the Cuban population

abstract: The objective of this study was to explore the relationship between sociodemographic factors and fear of COVID-19 in a Cuban population. A web-based study with a cross-sectional design was conducted. The sample comprised 1145 participants. To explore fear, the Fear of COVID-19 Scale was used. Our results suggest that women were more likely to experience medium to high levels fear compared to men. Additionally, knowing a person positive to COVID-19 significantly increases fear levels in Cuban participants.


title: Characterizing altruistic motivation in potential volunteers for SARS-CoV-2 challenge trials

abstract: In human challenge trials, volunteers are deliberately infected with a pathogen to accelerate vaccine development and answer key scientific questions. In the U.S., preparations for challenge trials with the novel coronavirus are complete, and in the U.K., challenge trials have recently begun. However, ethical concerns have been raised about the potential for invalid consent or exploitation. These concerns largely reflect worries that challenge trial volunteers may be unusually risk-seeking or too economically vulnerable to refuse the payments these trials provide, rather than being motivated primarily by altruistic goals. We conducted the first large-scale survey of intended human challenge trial volunteers and found that SARS-CoV-2 challenge trial volunteers exhibit high levels of altruistic motivations without any special indication of poor risk perception or economic vulnerability. Findings indicate that challenge trials with the novel coronavirus can attract volunteers with background conditions, attitudes, and motivations that should allay key ethical concerns.


title: Factors associated with the stigma-discrimination complex towards healthcare workers among university students during the coronavirus pandemic in Mexico

abstract: The COVID-19-related stigma towards healthcare workers negatively influences their performance and job satisfaction, and well-being. The frequency of COVID-19-related stigma towards healthcare workers and its associated factors has not been sufficiently investigated. The objective was to determine the frequency and variables associated with COVID-19-related stigmatisation towards health workers in emerging-age university adults in Mexico. Analytical and cross-sectional study using an online questionnaire in 1,054 students between 18 and 29 years of age. Demographic variables, religiosity, fear of COVID-19 and stigma-discrimination related to COVID-19 towards healthcare workers were analysed. The latter was set as the dependent variable, while demographic variables, religiosity and high fear of COVID-19 were the independent variables. For the association between the variables, a binomial and logarithmic generalised linear model was designed to calculate the adjusted prevalence ratios. The proportion of high stigma-discrimination was 12.4%, and this was associated with a high fear of COVID-19 (APR 1.51, 95% CI 1.06 to 2.23). The main limitations were the cross-sectional nature, social desirability bias, non-probabilistic sampling. The results highlight the importance of establishing programmes to reduce COVID-19-related stigmatisation towards healthcare workers.


title: A Longitudinal Analysis of COVID-19 Lockdown Stringency on Sleep and Resting Heart Rate Measures across 20 Countries

abstract: Lockdowns imposed to stem the spread of COVID-19 massively disrupted the daily routines of many worldwide, but studies to date are mostly confined to observations within a limited number of countries, based on subjective reports and survey from specific time periods during the pandemic. We investigated associations between lockdown stringency and objective sleep and resting-heart rate measures in 113,000 users of a consumer sleep tracker across 20 countries from Jan-Jul 2020. With stricter lockdown measures, midsleep times were universally delayed, particularly on weekdays, while midsleep variability and resting heart rate declined. These shifts (midsleep: +0.09 to +0.58 hours; midsleep variability: -0.12 to -0.26 hours; resting heart rate: -0.35 to -2.08 bpm) correlated with the severity of lockdown across different countries and highlight the graded influence of mobility restriction and social isolation on human physiology.


title: COVID-19 and Cognitive Impairment: Severity, Evolution, and Functional Impact during Inpatient Rehabilitation

abstract: Cognitive impairment is increasingly recognized as a sequela of COVID-19. It is unknown how cognition changes and relates to functional gain during inpatient rehabilitation. We administered the Montreal Cognitive Assessment (MoCA) at admission to 77 patients undergoing inpatient rehabilitation for COVID-19 in a large U.S. academic medical center. 45 patients were administered the MoCA at discharge. Functional gain was assessed by change in the Quality Indicator for Self-Care (QI-SC). In the full sample, 80.5% of patients exhibited cognitive impairment on admission, which was associated with prior delirium. Among 45 patients with retest data, there were significant improvements in MoCA and QI-SC. QI-SC score gain was higher in patients who made clinically meaningful changes on the MoCA, an association that persisted after accounting for age and delirium history. Cognitive impairment is frequent among COVID-19 patients, but improves over time and is associated with functional gain during inpatient rehabilitation.

category: rehabilitation medicine and physical therapy


title: Cognitive impairment and functional change in COVID-19 patients undergoing inpatient rehabilitation


title: Post-viral parenchymal lung disease of COVID-19 and viral pneumonitis: A systematic review and meta-analysis.

abstract:
BackgroundApproximately half of COVID-19 survivors present persisting breathlessness, which may include development of pulmonary fibrosis.

Research QuestionWhat is the prevalence of long-term radiological and functional pulmonary sequelae of parenchymal lung disease following hospitalisation with COVID-19 and other viral pneumonia?

Study design and methodsWe performed systematic review and random effects meta-analysis of studies in adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV, or Influenza pneumonia and followed within 12 months from discharge. Searches were run on MEDLINE and Embase, updated 29 July 2021. Primary outcomes were proportion of 1) radiologic sequelae at CT scans; 2) restrictive impairment; 3) impaired gas transfer. Heterogeneity was explored in meta-regression.

ResultsNinety-five studies were included for qualitative synthesis, of which 70 were suitable for meta-analysis, including 60 studies of SARS-CoV-2 with a median follow up of 3 months. In SARS-CoV-2 the overall estimated proportion of inflammatory changes during follow up was 0.50 (95%CI 0.41 to 0.58, I2=94.6%), whilst fibrotic changes were estimated at 0.29 (95%CI 0.22 to 0.37, I2=94.1%). Inflammatory changes reduced compared with CTs performed during hospitalisation (-0.47; 95%CI -0.56 to -0.37), whereas no significant resolution was observed in fibrotic changes (-0.09; 95%CI -0.25 to 0.07). Impaired gas transfer was estimated at 0.38 (95%CI 0.32 to 0.44, I2=92.1%), which was greater than estimated restrictive impairment (0.17; 95%CI 0.13 to 0.23, I2=92.5%). High heterogeneity means that estimates should be interpreted with caution. Confidence in the estimates was deemed low due to the heterogeneity and because studies were largely observational without controls.

InterpretationA substantial proportion of radiological and functional sequelae consistent with parenchymal lung disease are observed following COVID-19 and other viral pneumonitis. Estimates of prevalence are limited by differences in case mix and initial severity. This highlights the importance of extended radiological and functional follow-up post hospitalisation.

PROSPERO registrationCRD42020183139 (April 2020)

category: respiratory medicine


title: Post-viral parenchymal lung disease following COVID-19 and viral pneumonitis hospitalisation: A systematic review and meta-analysis


title: Systematic review of imaging tests to predict the development of rheumatoid arthritis in people with unclassified arthritis

abstract:
ObjectivesTo estimate and compare the diagnostic accuracy of magnetic resonance imaging (MRI) and ultrasound, for the prediction of rheumatoid arthritis (RA) in unclassified arthritis (UA).

MethodsMEDLINE, Embase and BIOSIS were searched from 1987 to May 2019. Studies evaluating any imaging test in participants with UA were eligible. Reference standards were RA classification criteria or methotrexate initiation. Two authors independently extracted data and assessed validity using QUADAS-2. Sensitivities and specificities were calculated for each imaging characteristic and joint area. Summary estimates with 95% confidence intervals (CI) were estimated where possible.

ResultsNineteen studies were included; 13 evaluated MRI (n=1,143; 454 with RA) and 6 evaluated ultrasound (n=531; 205 with RA). Studies were limited by unclear recruitment procedures, inclusion of patients with RA at baseline, differential verification, lack of blinding and consensus grading. Study heterogeneity largely precluded meta-analysis, however summary sensitivity and specificity for MRI synovitis in at least one joint were 93% (95% CI 88%, 96%) and 25% (95% CI 13%, 41%) (3 studies). Specificities may be higher for other MRI characteristics but data are limited. Ultrasound results were difficult to synthesise due to different diagnostic thresholds and reference standards.

ConclusionsThe evidence for MRI or ultrasound as single tests for predicting RA in people with UA is heterogeneous and of variable methodological quality. Larger studies using consensus grading and consistently defined RA diagnosis are needed to identify whether combinations of imaging characteristics, either alone or in combination with other clinical findings, can better predict RA in this population.

Systematic review registrationPROSPERO CRD42020158239.

Key messagesO_LITo date, the diagnostic accuracy of imaging tests for the earlier identification of RA has not been systematically assessed. We conducted a systematic review to estimate, and if possible compare, the accuracy of MRI and ultrasound for predicting the diagnosis of rheumatoid arthritis in people with unclassified arthritis.
C_LIO_LIIn this systematic review of 13 studies of MRI (1,143 participants) and 6 studies of ultrasound (531 participants), study quality was highly variable with considerable variation in populations, diagnostic thresholds and reference standards limiting potential for meta-analysis.
C_LIO_LIIndividual MRI imaging characteristics demonstrated either high sensitivity (with low specificity) or high specificity (with low sensitivity) with inconsistent results between studies. Similar heterogeneity in results was observed for ultrasound but with considerably fewer data.
C_LIO_LIImaging can identify subclinical inflammatory changes in joint areas where no synovitis is apparent, which may be useful in identifying the aetiology of symptoms. However, larger studies using consistent scoring systems for imaging interpretation and definition of RA are needed to identify the extent to which imaging findings alone can predict the development of RA. Until then, imaging should be interpreted in light of other findings.
C_LI

category: rheumatology


title: Geospatial approach to investigate spatial clustering and hotspots of blood lead levels in children within Kabwe, Zambia

abstract:
BackgroundCommunities around Kabwe/Zambia are exposed to lead due to deposits from an old lead (Pb) and zinc (Zn) mining site. Children are particularly more vulnerable than adults, presenting with greatest risk of health complications because of their increased oral uptake due to their hand to mouth activities. Spatial analysis of childhood lead exposure is useful in identifying specific areas with highest risk of pollution. The objective of the current study was to use a geospatial approach investigate spatial clustering and hotspots of blood lead levels in children within Kabwe.

MethodsWe analysed data on blood lead levels (BLL) for 363 children below the age of 15 from Kabwe town. We used spatial autocorrelation methods involving the global Morans I and local Getis-Ord Gi*statistic in ArcMap 10.5.1, to test for spatial dependency among the blood lead levels in children.

ResultsBLL in children from Kabwe are spatially autocorrelated with a Morans Index of 0.62 (p<0.001). We found distinct hot spots in communities close to the old lead and zinc-mining site, lying on its western side. We observed lower levels of BLL in areas distant to the mine and located at its eastern side. This pattern suggests a possible association between BLL and distance from the abandoned lead and zinc mine, and prevailing winds.

ConclusionUsing geocoded data, we found clustering of childhood blood lead and identified distinct hot spot areas with particular high lead levels for Kabwe town. The geospatial approach used is especially valuable in resource-constrained settings like Zambia, where the precise identification of the locations of risk areas allows to initiate targeted remedial and treatment programs.

category: occupational and environmental health


title: Electronic health record enabled track and trace inan urban hospital network: implications for infectionprevention and control

abstract: Healthcare-associated infections represent one of the most significant challenges for modern medicine as they can significantly impact patientslives. Carbapenemase-producing Enterobacteriaceae (CPE) pose the greatest clinical threat, given the high levels of resistance to carbapenems, which are considered as agents of  last resort against life-threatening infections. Understanding patterns of CPE infection spreading in hospitals is paramount to design effective infection control protocols to mitigate the presence of CPE in hospitals. We used patient electronic health records from three urban hospitals to: i) track microbiologically confirmed carbapenemase producing Escherichia coli (CP-Ec) carriers and ii) trace the patients they shared place and time with until their identification. We show that yearly contact networks in each hospital consistently exhibit a core-periphery structure, highlighting the presence of a core set of wards where most carrier-contact interactions occured before being distributed to peripheral wards. We also identified functional communities of wards from the general patient movement network. The contact networks projected onto the general patient movement community structure showed a comprehensive coverage of the hospital. Our findings highlight that infections such as CP-Ec infections can reach virtually all parts of hospitals through first-level contacts.

category: health informatics


title: Understanding Convergence Between Non-Hispanic Black and White COVID-19 Mortality: A County-Level Approach

abstract:
BackgroundNon-Hispanic Black populations have suffered greater per capita COVID-19 mortality at more than 1.5 times that of White populations. Previous work has established that, over time, rates of Black and White mortality have converged; however, some studies suggest that regional shifts in COVID-19 prevalence may play a role in the relative change between racial groups. This studys objective was to investigate changes in Black and White COVID-19 mortality over time and uncover potential mechanisms driving these changes.

Methods and FindingsUsing county-level COVID-19 mortality data stratified by race, we investigate the trajectory of non-Hispanic Black mortality, White mortality, and the Black/White per capita mortality ratio from June 2020-January 2021. Over this period, in the counties studied, cumulative mortality rose by 56.7% and 82.8% for Black and White populations respectively, resulting in a decrease in mortality ratio of 0.369 (23.8%). These trends persisted even when a county-level fixed-effects model was used to estimate changes over time within counties (controlling for all time-invariant county level characteristics and removing the effects of changes in regional distribution of COVID-19). Next, we leverage county-level variation over time in COVID-19 prevalence to show that the decline in the Black/White mortality ratio can be explained by changes in COVID-19 prevalence. Finally, we study heterogeneity in the time trend, finding that convergence occurs most significantly in younger populations, areas with less dense populations, and outside of the Northeast. Limitations include suppressed data in counties with fewer than 10 deaths in a racial category, and the use of provisional COVID-19 death data that may be incomplete.

ConclusionsThe results of this study suggest that convergence in Black/White mortality is not driven by county-level characteristics or changes in the regional dispersion of COVID-19, but instead by changes within counties. Further, declines in the Black/White mortality ratio appear strongly linked to changes in COVID-19 prevalence, rather than a time-specific effect. Further studies on changes in exposure by race over time, or on the vulnerability of individuals who died at different points in the pandemic, may provide crucial insight on mechanisms and strategies to further reduce COVID-19 mortality disparities.

category: health policy


title: Tocilizumab Effect in COVID-19 Hospitalized Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials

abstract:
Since the emergence of the first cases of COVID-19 viral pneumonia late 2019 several studies evaluated the benefits of different treatment modalities. Early in the pandemic, the interleukin 6 (IL-6) receptor antibody Tocilizumab was considered in view of the cytokine release syndrome associated with COVID-19 infection. Several early observational studies showed beneficial effect of treatment with Tocilizumab on mortality, however, results from well-designed randomized clinical trials (RCT) were contradicting.

ObjectivesTo perform a systematic literature review and meta-analysis of RCTs utilizing Tocilizumab in the treatment of COVID-19 pneumonia, with in-hospital mortality as a primary objective, while secondary objectives included composite outcome of mortality, intubation, or ICU admission, another secondary outcome was super added infection.

MethodThis was a random effects model (DerSimonian and Laird) model of relative risk (RR), along with corresponding 95% confidence intervals, p values, and forest plots of both primary and secondary outcomes. A fixed effect sensitivity test was performed for the primary outcome, in addition to subgroup and meta-regression analyses with predefined criteria.

ResultsThe primary outcome of mortality showed statistically insignificant reduction of mortality with Tocilizumab (RR = 0.9, 95% CI: 0.8 - 1.01; p = 0.09) although with an unmistakable apparent clinical benefit. There was a significant reduction in the RR of the secondary composite outcome (RR = 0.83, 95% CI: 0.76 - 0.9; p < 0.001), and no difference between groups in super-added infection (RR = 0.77, 95% CI: 0.51 - 1.19; p = 0.24). Treatment protocol allowing a second dose was the only significant predictor of improved mortality in the meta-regression analysis. Certainty of evidence was reduced to moderate for the primary outcome and the secondary outcome of clinical deterioration, while it was reduced to low for the secondary outcome of super-added infection.

ConclusionModerate certainty of evidence suggest no statistically significant improvement of 28-30 day all-cause mortality of hospitalized COVID-19 patients treated with TCZ, although there may be clinically important value. Moderate certainty of evidence suggest lowered relative risk of a composite outcome of death or clinical deterioration, while, low grade evidence indicate no increase in the risk of super-added infection associated with TCZ treatment. A protocol allowing two doses of TCZ shows evidence of improved mortality as compared to a strictly single dose protocol.

category: infectious diseases


title: Rapid base-specific calling of SARS-CoV-2 variants of concern using combined RT-PCR melting curve screening and SIRPH technology

abstract: The emergence of novel variants of concern of SARS-CoV-2 demands a fast and reliable detection of such variants in local populations. Here we present a cost-efficient and fast workflow combining a pre-screening of SARS-CoV-2 positive samples using RT-PCR melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions (SIRPH). The entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 h. We applied the sensitive method to monitor the local VOC outbreaks in a few hundred positive samples collected in a confined region of Germany.


title: Associations of the BNT162b2 COVID-19 vaccine effectiveness with patient age and comorbidities

abstract: Vaccinations are considered the major tool to curb the current SARS-CoV-2 pandemic. A randomized placebo-controlled trial of the BNT162b2 vaccine has demonstrated a 95% efficacy in preventing COVID-19 disease. These results are now corroborated with statistical analyses of real-world vaccination rollouts, but resolving vaccine effectiveness across demographic groups is challenging. Here, applying a multivariable logistic regression analysis approach to a large patient-level dataset, including SARS-CoV-2 tests, vaccine inoculations and personalized demographics, we model vaccine effectiveness at daily resolution and its interaction with sex, age and comorbidities. Vaccine effectiveness gradually increased post day 12 of inoculation, then plateaued, around 35 days, reaching 91.2% [CI 88.8%-93.1%] for all infections and 99.3% [CI 95.3%-99.9%] for symptomatic infections. Effectiveness was uniform for men and women yet declined mildly but significantly with age and for patients with specific chronic comorbidities, most notably type 2 diabetes. Quantifying real-world vaccine effectiveness, including both biological and behavioral effects, our analysis provides initial measurement of vaccine effectiveness across demographic groups.


title: Associations of the BNT162b2 COVID-19 vaccine effectiveness with patient age and comorbidities at daily resolution


title: Quantitative Comparison of SARS-CoV-2 Nucleic Acid Amplification Test and Antigen Testing Algorithms: A Decision Analysis Simulation Model

abstract:
BackgroundAntigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations continue to recommend different strategies for utilizing NAATs and antigen tests in various settings. There has not yet been a quantitative comparison of the expected performance of these strategies.

MethodsWe utilized a decision analysis approach to simulate the expected outcomes of six algorithms for implementing NAAT and antigen testing, analogous to testing strategies recommended by public health organizations. Each algorithm was simulated 50,000 times for four SARS-CoV-2 infection prevalence levels ranging from 5% to 20% in a population of 100000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported.

ResultsAlgorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Substituting repeat antigen testing in lieu of NAAT confirmation of all initial negative antigen tests resulted in 2,280 missed cases (95% UR: 1,507-3,067) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case at 10% prevalence compared to exclusive use of antigen tests.

ConclusionsNo single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities; each presents a trade-off between prioritized outcomes and resource constraints. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and constraints.

DisclaimerThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.


title: Seroreactivity to SARS-CoV-2 in individuals attending a university campus in Bogota Colombia

abstract: Most community-specific serological surveys for SARS-CoV-2 antibodies have been performed in healthcare workers and institutions. In this study, IgG antibodies specific to the virus were evaluated in individuals working at a university campus in Bogota, Colombia. The aim of this work was to determine previous exposure to SARS-CoV-2 in those attending the campus during city lockdown. A total of 237 individuals, including 93 women and 144 men were evaluated using chemiluminescent detection of IgG anti N-viral protein between November and December 2020. There were 32 positives individuals corresponding to a seroprevalence of 13.5% (10 women and 22 men) and mostly asymptomatic (68.75%) and three cluster of seropositive individuals were identified. Only 13 of the seropositive individuals had previous positive detection of SARS-CoV-2 RNA by RT-qPCR performed in average 91 days before serological test. Seropositive individuals did not come from boroughs having higher percentages of SARS-CoV-2 cases in the city. This survey was carried out after the first peak of SARS-CoV-2 transmission in the city, and before the preparedness to reopening the campus for students in 2021, demonstrating a low seroprevalence in high percentage of asymptomatic. These results will help to evaluate some of the strategies stablished to control virus spread in the campus or other similar communities.


title: Acute Respiratory Distress Syndrome is associated with impaired alveolar macrophage efferocytosis

abstract:
BackgroundAlveolar macrophage dysfunction may contribute to Acute Respiratory Distress Syndrome (ARDS) pathogenesis, however this has been little studied. Objective: To investigate the pathophysiological link between alveolar macrophage efferocytosis, alveolar neutrophil apoptosis and clinical outcomes in ARDS patients, and to determine whether efferocytosis can be restored.

MethodsVentilated sepsis patients with or without ARDS underwent broncho-alveolar lavage. Apoptosis of alveolar neutrophils was assessed using flow cytometry. Alveolar macrophages were isolated and used in flow cytometric efferocytosis assays with labelled apoptotic neutrophils. Alveolar macrophages were also isolated from the lung tissue of lobectomy patients, then treated with pooled ARDS BAL fluid prior to functional assessment. Rac1 gene expression was assessed using RT-qPCR.

ResultsPatients with sepsis-related ARDS have decreased alveolar macrophage efferocytosis and increased alveolar neutrophil apoptosis compared to control ventilated sepsis patients. Across all ventilated sepsis patients, alveolar macrophage efferocytosis correlated negatively with alveolar cytokines (IL-8, IL-1ra), duration of ventilation and mortality. ARDS BAL treatment of alveolar macrophages decreased efferocytosis and Rac1 gene expression, however bacterial phagocytosis was preserved. Unexpectedly, alveolar macrophage efferocytosis receptor expression (MerTK, CD206) decreased and expression of the anti-efferocytosis receptor SIRP increased following ARDS BAL treatment. Rho-associated kinase inhibition partially restored alveolar macrophage efferocytosis in an in vitro model of ARDS.

ConclusionsPatients with sepsis-related ARDS have impaired AM efferocytosis, which potentially contributes to ARDS pathogenesis and negatively impacts clinical outcomes, including mortality. Strategies to upregulate AM efferocytosis may be of value for attenuating inflammation in ARDS.

category: intensive care and critical care medicine


title: The Effects of Pericapsular nerve group (PENG) block on Postoperative Recovery in Elderly Patients with Hip fracture: a study protocol for randomized, parallel controlled, double-blind trial

abstract:
IntroductionHip fracture is a common and serious emergency in the elderly, it is associated with severe pain, significant postoperative morbidity and mortality. Featuring peripheral nerve block in Enhanced recovery after surgery (ERAS) pathway may have significantly effect on shortening length of hospital stay, decreasing complications and costs, particular in improvement in dynamic pain and reducing the use of opioid. Pericapsular Nerve Group Block(PENG), suggested by Arango et al, may provide a effective blockade to the articular branches of the anterior hip joint,which innervate the most section of the hip capsule richly, with a potential motor-sparing effect.The purpose of this trail is to investigate whether PENG is effective to enhanced recovery in elderly patients with hip fracture.

Methods and analysisThis study will be a single centre,randomized, parallel controlled, double-blind trail. 92 elderly patients scheduled for hip fracture surgery will be divided into two groups randomly to receive ultrasound-guided PENG block or ultrasound-guided femoral nerve(FN) block. The primary outcome will be compare the quality of recovery-15(QoR-15) score at 24h postoperatively between two groups.The secondary outcomes include the strength of quadriceps, the visual analogue scale(VAS) at rest and on movement, the total morphine consumption, the rescue analgesic, the first time of postoperative out-of-bed mobilization, the complications.

Ethics and disseminationThis study has been approved by the Medical Science Research Ethics Committees of The First Affiliated Hospital of Guangzhou University of Chinese Medicine on 15 December 2020 (Reference K2020-110). The results of this study will be published in peer-reviewed international journals.

Trial registration numberChiCTR2100042341.

category: anesthesia


title: A First Analysis of Excess Mortality in Switzerland in 2020

abstract:
ObjectiveTo quantify the excess all-cause mortality in Switzerland in 2020, a key indicator for assessing direct and indirect consequences of the COVID-19 pandemic.

MethodsUsing official data on deaths in Switzerland, all-cause mortality in 2020 was compared with that of previous years using directly standardized mortality rates, age- and sex-specific mortality rates, and life expectancy.

ResultsThe standardized mortality rate was 8.6% higher in 2020 than in 2019, returning to the level observed 5-6 years ago. This increase was greater for men (10.4%) than for women (7.0%), and was statistically significant only for men over 70 years of age, and for women over 75 years of age. The decrease in life expectancy in 2020 compared to 2019 was about 1%, with a loss of 9.4 months for men and 5.1 months for women.

ConclusionsThere was an excess mortality in Switzerland in 2020, linked to the COVID-19 pandemic. However, as this excess only concerned the elderly, the resulting loss of life expectancy was restricted to a few months.

category: epidemiology


title: Patterns of compliance with COVID-19 preventive behaviours: a latent class analysis of 20,000 UK adults

abstract:
BackgroundGovernments have implemented a range of measure to tackle COVID-19, primarily focusing on changing citizens behaviours in order to lower transmission of the virus. Few studies have looked at the patterns of compliance with different measures within individuals: whether people comply with all measures or selectively choose some but not others. Such research is important for designing interventions to increase compliance.

MethodsWe used cross-sectional data from 20,947 UK adults in the COVID-19 Social Study collected 17 November - 23 December 2020. Self-report compliance was assessed with six behaviours: mask wearing, hand washing, indoor household mixing, outdoor household mixing, social distancing, and compliance with other guidelines. Patterns of compliance behaviour were identified using latent class analysis, and multinomial logistic regression was used to assess demographic, socioeconomic and personality predictors of behaviour patterns.

ResultsWe selected a four latent class solution. Most individuals reported similar levels of compliance across the six behaviour measures. High levels of compliance was the modal response. Lower self-reported compliance was related to young age, high risk-taking behaviour, low confidence in government, and low empathy, among other factors. Looking at individual behaviours, mask wearing had the highest level of compliance whilst compliance with social distancing was relatively low.

ConclusionResults suggest that individuals choose to comply with all guidelines, rather than some but not others. Strategies to increase compliance should focus on increasing general motivations to comply alongside specifically encouraging social distancing.


title: SARS-CoV-2 Epidemiology on a Public University Campus in Washington State

abstract:
BackgroundTesting programs have been utilized as part of SARS-CoV-2 mitigation strategies on university campuses, and it is not known which strategies successfully identify cases and contain outbreaks.

ObjectiveEvaluation of a testing program to control SARS-CoV-2 transmission at a large university.

DesignProspective longitudinal study using remote contactless enrollment, daily mobile symptom and exposure tracking, and self-swab sample collection. Individuals were tested if the participant was (1) exposed to a known case, developed new symptoms, or reported high-risk behavior, (2) a member of a group experiencing an outbreak, or (3) at baseline upon enrollment.

SettingAn urban, public university during Autumn quarter of 2020

ParticipantsStudents, staff, and faculty.

MeasurementsSARS-CoV-2 PCR testing was conducted, and viral genome sequencing was performed.

ResultsWe enrolled 16,476 individuals, performed 29,783 SARS-CoV-2 tests, and detected 236 infections. Greek community affiliation was the strongest risk factor for testing positive. 75.0% of positive cases reported at least one of the following: symptoms (60.8%), exposure (34.7%), or high-risk behaviors (21.5%). 88.1% of viral genomes (52/59) sequenced from Greek-affiliated students were genetically identical to at least one other genome detected, indicative of rapid SARS-CoV-2 spread within this group, compared to 37.9% (11/29) of genomes from non-Greek students and employees.

LimitationsObservational study.

ConclusionIn a setting of limited resources during a pandemic, we prioritized testing of individuals with symptoms and high-risk exposure during outbreaks. Rapid spread of SARS- CoV-2 occurred within outbreaks without evidence of further spread to the surrounding community. A testing program focused on high-risk populations may be effective as part of a comprehensive university-wide mitigation strategy to control the SARS-CoV-2 pandemic.


title: Vaccine escape in a heterogeneous population: insights for SARS-CoV-2 from a simple model

abstract:
As a counter measure to the SARS-CoV-2 pandemic there has been swift development and clinical trial assessment of candidate vaccines, with subsequent deployment as part of mass vaccination campaigns. However, the SARS-CoV-2 virus has demonstrated the ability to mutate and develop variants, which can modify epidemiological properties and potentially also the effectiveness of vaccines.

The widespread deployment of highly effective vaccines may rapidly exert selection pressure on the SARS-CoV-2 virus directed towards mutations that escape the vaccine induced immune response. This is particularly concerning whilst infection is widespread. By developing and analysing a mathematical model of two population groupings with differing vulnerability and contact rates, we explore the impact of the deployment of vaccine amongst the population on R, cases, disease abundance and vaccine escape pressure.

The results from this model illustrate two insights (i) vaccination aimed at reducing prevalence could be more effective at reducing disease than directly vaccinating the vulnerable; (ii) the highest risk for vaccine escape can occur at intermediate levels of vaccination. This work demonstrates a key principle that the careful targeting of vaccines towards particular population groups could reduce disease as much as possible whilst limiting the risk of vaccine escape.


title: Impact of booster COVID-19 vaccine for Moroccan adults: A discrete age-structured model approach

abstract: Public health control strategies, such as lockdown, seem to be effective in reducing the spread of the pandemic, but are ineffective as a whole since lockdown is responsible of global economic crisis and badly lived by the majority of children and adults who have developed mental health disorders and familial problems as well. Thus, the development of a vaccine against COVID-19 is needed to control this disease. We have developed a discrete age-structured model and followed the Moroccan vaccination program to assess the impact of booster vaccination targeting Moroccan adults against COVID-19. Using the derived model, we estimated some relevant model parameters related to COVID-19 using collected cumulative mortality and reported Moroccan data. A control reproduction number Rc, which determines the necessary level of vaccine uptake that lead to COVID-19 eradication is determined. Furthermore, a herd immunity threshold above which the population can be protected from COVID-19 infection is derived. Analyzing the model, sufficient and necessary conditions for the eradication of the disease are obtained as well. Next, we perform numerical simulations to study the impact of several uptake levels of the potential vaccine on the persistence and the extinction of COVID-19 pandemic. Our results show that the COVID-19 is expected to last past 2021 in the absence of a vaccination program. Moreover, a vaccination of the adult population at rate 0.6% per day needs at least 67% of vaccine efficacy and 90% of immunogenicity rate to eradicate the disease. Using Sinopharm vaccine, the herd immunity can be achieved when about half of Moroccan adult population is immunized against the COVID-19. However, using Oxford-Astrazeneca vaccine, less than 60% of adult population must be immunized against the disease to achieve the herd immunity. Finally, if vaccine efficacy is about 80% and the immunogenicity is about 50% then vaccinating adults at rate of 0.6% per day could protect roughly 22% of children from COVID-19 infection.


title: An integrated analysis of contact tracing and genomics to assess the efficacy of travel restrictions on SARS-CoV-2 introduction and transmission in England from June to September, 2020

abstract:
BackgroundMitigation of SARS-CoV-2 transmission from international travel is a priority. Travellers from countries with travel restrictions (closed travel-corridors) were required to quarantine for 14 days over Summer 2020 in England. We describe the genomic epidemiology of travel-related cases in England and evaluate the effectiveness of this travel policy.

MethodsBetween 27/05/2020 and 13/09/2020, probable travel-related SARS-CoV-2 cases and their contacts were identified and combined with UK SARS-CoV-2 sequencing data. The epidemiology and demographics of cases was identified, and the number of contacts per case modelled using negative binomial regression to estimate the effect of travel restriction, and any variation by age, sex and calendar date. Unique travel-related SARS-CoV-2 genomes in the COG-UK dataset were identified to estimate the effect travel restrictions on cluster size generated from these. The Polecat Clustering Tool was used to identify a travel-related SARS-CoV-2 cluster of infection.

Findings4,207 travel-related SARS-CoV-2 cases are identified. 51.2% (2155/4207) of cases reported travel to one of three countries; 21.0% (882) Greece, 16.3% (685) Croatia and 14.0% (589) Spain. Median number of contacts per case was 3 (IQR 1-5), and greatest for the 16-20 age-group (9.0, 95% C.I.=5.6-14.5), which saw the largest attenuation by travel restriction. Travel restriction was associated with a 40% (rate ratio=0.60, 95% C.I.=0.37-0.95) lower rate of contacts. 827/4207 (19.7%) of cases had high-quality SARS-CoV-2 genomes available. Fewer genomically-linked cases were observed for index cases related to countries with travel restrictions compared to cases from non-travel restriction countries (rate ratio=0.17, 95% C.I.=0.05-0.52). A large travel-related cluster dispersed across England is identified through genomics, confirmed with contact-tracing data.

InterpretationThis study demonstrates the efficacy of travel restriction policy in reducing the onward transmission of imported cases.

FundingWellcome Trust, Biotechnology and Biological Sciences Research Council, UK Research & Innovation, National Institute of Health Research, Wellcome Sanger Institute.

RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, medRxiv, bioRxiv, Web of Science and Scopus for the terms (COVID-19 OR SARS-COV-2) AND (imported or importation) AND (sequenc* OR genom* or WGS). We filtered the 55 articles identified through this search and rejected any that did not undertake SARS-CoV-2 sequencing as part of an epidemiological investigation for importation into a different country. The remaining 20 papers were reviewed in greater detail to understand the patterns of importation and the methods used in each case.

Added value of this studyThis is the first published study on importations of SARS-CoV-2 into England using genomics. Plessis et al., (2021) used a predictive model to infer the number of importations in to the UK from all SARS-CoV-2 genomes generated before 26th June 2020. The current study assesses the period 27/05/2020 to 13/09/2020 and presents findings of case-reported travel linked to genomic data. Two unpublished reports exist for Wales and Scotland, although only examine a comparatively small number of importations.

Implications of all the available evidenceThis large-scale study has a number of findings that are pertinent to public health and of global significance, not available from prior evidence to our knowledge. The study demonstrates travel restrictions, through the implementation of  travel-corridors, are effective in reducing the number of contacts per case based on observational data. Age has a significant effect on the number of contacts and this can be mitigated with travel restrictions. Analysis of divergent clusters indicates travel restrictions can reduce the number of onwards cases following a travel-associated case. Analysis of divergent clusters can allow for importations to be identified from genomics, as subsequently evidenced by cluster characteristics derived from contact tracing. The majority of importations of SARS-CoV-2 in England over Summer 2020 were from coastal European countries. The highest number of cases and onward contacts were from Greece, which was largely exempt from self-isolation requirements (bar some islands in September at the end of the study period). Systematic monitoring of imported SARS-CoV-2 cases would help refine implementation of travel restrictions. Finally, along with multiple studies, this study highlights the use of genomics to monitor and track importations of SARS-CoV-2 mutations of interest; this will be of particular use as the repertoire of clinically relevant SARS-CoV-2 variants expand over time and globally.