Specimen sharing for epidemic preparedness: Building a virtual biorepository system from local governance to global partnerships.

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and managed specimens, as a 'global public good' model based on principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics. The purpose of our initial research is to lay the basis of the collaboration, management and principles of equitable sharing focused on low- and middle-income country partners. Here we report on surveys and interviews undertaken with biorepository-interested parties to better understand needs and barriers for specimen access and share examples from the ZIKAlliance partnership on the governance and operations of locally organized biorepositories.

Limitations introduced by a low participation rate of SARS-CoV-2 seroprevalence data.

BACKGROUND: There has been a large influx of COVID-19 seroprevalence studies, but comparability between the seroprevalence estimates has been an issue because of heterogeneities in testing platforms and study methodology. One potential source of heterogeneity is the response or participation rate. METHODS: We conducted a review of participation rates (PR) in SARS-CoV-2 seroprevalence studies collected by SeroTracker and examined their effect on the validity of study conclusions. PR was calculated as the count of participants for whom the investigators had collected a valid sample, divided by the number of people invited to participate in the study. A multivariable beta generalized linear model with logit link was fitted to determine if the PR of international household and community-based seroprevalence studies was associated with the factors of interest, from 1 December 2019 to 10 March 2021. RESULTS: We identified 90 papers based on screening and were able to calculate the PR for 35 out of 90 papers (39%), with a median PR of 70% and an interquartile range of 40.92; 61% of the studies did not report PR. CONCLUSIONS: Many SARS-CoV-2 seroprevalence studies do not report PR. It is unclear what the median PR rate would be had a larger portion not had limitations in reporting. Low participation rates indicate limited representativeness of results. Non-probabilistic sampling frames were associated with higher participation rates but may be less representative. Standardized definitions of participation rate and data reporting necessary for the PR calculations are essential for understanding the representativeness of seroprevalence estimates in the population of interest.

Serology Assays Used in SARS-CoV-2 Seroprevalence Surveys Worldwide: A Systematic Review and Meta-Analysis of Assay Features, Testing Algorithms, and Performance.

Background: Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. Methods: We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between 1 January 2020, and 19 November 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. Results: Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [−0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. Conclusions: The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays.

Perceived Workload Using Separate (Filtering Facepiece Respirator and Face Shield) and Powered Air-Purifying Respirator and Integrated Lightweight Protective Air-Purifying Respirator: Protocol for an International Multisite Human Factors Randomized Crossover Feasibility Study.

BACKGROUND: The design of personal protective equipment (PPE) may affect well-being and clinical work. PPE as an integrated item may improve usability and increase adherence by healthcare professionals. Human factors design and safety may reduce occupational-acquired diseases. As an integrated PPE, a lightweight protective air-purifying respirator (L-PAPR) could be used during health procedures where healthcare professionals are exposed to airborne pathogens. The human factors affecting the implementation of alternative PPE such as L-PAPR have not been thoroughly studied. The population of interest is health care professionals, the intervention is the performance by PPE during tasks across the three PPE types 1.) N95 respirators and face shields, 2.)traditional powered air-purifying respirator(PAPR), and 3.) L-PAPR. The outcomes are user error, communications, safety, and end-user preferences. OBJECTIVE: This study will assess whether the L-PAPR improves health care professionals' comfort in terms of perceived workload and physical and psychological burden during direct patient care when compared with the traditional PAPR or N95 and face shield. This study also aims to evaluate human factors during the comparison of the use of L-PAPR with a combination of N95 respirators plus face shields or the traditional PAPRs. METHODS: This is an interventional randomized crossover quality improvement feasibility study consisting of a 3-site simulation phase with 10 participants per site and subsequent field testing in 2 sites with 30 participants at each site. The 3 types of respiratory PPE will be compared across medical tasks and while donning and doffing. We will evaluate the user's perceived workload, usability, usage errors, and heart rate. We will conduct semistructured interviews to identify barriers and enablers to implementation across each PPE type over a single continuous wear episode and observe interpersonal communications across conditions and PPE types. RESULTS: We expect the research may highlight communication challenges and differences in usability and convenience across PPE types along with error frequency during PPE use across PPE types, tasks, and time. CONCLUSIONS: The design of PPE may affect overall well-being and hinder or facilitate clinical work. Combining 2 pieces of PPE into a single integrated item may improve usability and reduce occupational-acquired diseases. The human factors affecting the implementation of an alternative PPE such as L-PAPR or PAPR have not been thoroughly studied. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/36549.

Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting.

INTRODUCTION: This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling-a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals. METHODS AND ANALYSIS: In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests. ETHICS AND DISSEMINATION: This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions-and ultimately to assist with keeping congregate settings open that are essential for our social fabric. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (#NCT05145803).

Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report.

The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.

Detection of SARS-CoV-2 in exhaled air using non-invasive embedded strips in masks.

BACKGROUND: SARS-CoV-2 emerged in 2019 and resulted in a pandemic causing millions of infections worldwide. Gold-standard for SARS-CoV-2 detection uses quantitative RT-qPCR on respiratory secretions to detect viral RNA (vRNA). Acquiring these samples is invasive, can be painful for those with xerostomia and other health conditions, and sample quality can vary greatly. Frequently only symptomatic individuals are tested even though asymptomatic individuals can have comparable viral loads and efficiently transmit virus. METHODS: We utilized a non-invasive approach to detect SARS-CoV-2 in individuals, using polyvinyl alcohol (PVA) strips embedded in KN95 masks. PVA strips were tested for SARS-CoV-2 vRNA via qRT-PCR and infectious virus. RESULTS: We show efficient recovery of vRNA and infectious virus from virus-spiked PVA with detection limits comparable to nasal swab samples. In infected individuals, we detect both human and SARS-CoV-2 RNA on PVA strips, however, these levels are not correlated with length of time mask was worn, number of times coughed or sneezed, or level of virus in nasal swab samples. We successfully cultured and deep-sequenced PVA-associated virus. CONCLUSIONS: These results demonstrate the feasibility of using PVA-embedded masks as a non-invasive platform for detecting SARS-CoV-2 in exhaled air in COVID-positive individuals regardless of symptom status.

Harmonization of Multiple SARS-CoV-2 Reference Materials Using the WHO IS (NIBSC 20/136): Results and Implications.

Background: There is an urgent need for harmonization between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology platforms and assays prior to defining appropriate correlates of protection and as well inform the development of new rapid diagnostic tests that can be used for serosurveillance as new variants of concern (VOC) emerge. We compared multiple SARS-CoV-2 serology reference materials to the WHO International Standard (WHO IS) to determine their utility as secondary standards, using an international network of laboratories with high-throughput quantitative serology assays. This enabled the comparison of quantitative results between multiple serology platforms. Methods: Between April and December 2020, 13 well-characterized and validated SARS-CoV-2 serology reference materials were recruited from six different providers to qualify as secondary standards to the WHO IS. All the samples were tested in parallel with the National Institute for Biological Standards and Control (NIBSC) 20/136 and parallel-line assays were used to calculate the relevant potency and binding antibody units. Results: All the samples saw varying levels of concordance between diagnostic methods at specific antigen-antibody combinations. Seven of the 12 candidate materials had high concordance for the spike-immunoglobulin G (IgG) analyte [percent coefficient of variation (%CV) between 5 and 44%]. Conclusion: Despite some concordance between laboratories, qualification of secondary materials to the WHO IS using arbitrary international units or binding antibody units per milliliter (BAU/ml) does not provide any benefit to the reference materials overall, due to the lack of consistent agreeable international unit (IU) or BAU/ml conversions between laboratories. Secondary standards should be qualified to well-characterized reference materials, such as the WHO IS, using serology assays that are similar to the ones used for the original characterization of the WHO IS.

COVID-19 Serology Control Panel Using the Dried-Tube Specimen Method.

The dried-tube specimen (DTS) procedure was used to develop the COVID-19 serology control panel (CSCP). The DTS offers the benefit of shipping materials without a cold chain, allowing for greater access without deterioration of material integrity. Samples in the panel were sourced from COVID-19 convalescent persons from March to May 2020. The immunoglobulin subtypes (total Ig, IgM, and IgG) and their respective reactivity to severe acute respiratory syndrome coronavirus 2 nucleocapsid, spike, and receptor-binding domain antigens of the samples were delineated and compared with the WHO International Standard to elucidate the exact binding antibody units of each CSCP sample and ensure the CSCP provides adequate reactivity for different types of serological test platforms. We distribute the CSCP as a kit with five coded tubes to laboratories around the world to be used to compare test kits for external quality assurance, for harmonizing laboratory testing, and for use as training materials for laboratory workers.

Consumers' Food Safety Risk Communication on Social Media Following the Suan Tang Zi Accident: An Extended Protection Motivation Theory Perspective.

There are many hidden safety hazards in homemade food due to an absence of food preparation and storage knowledge, and this has led to many food safety incidents. The purpose of this study was to explore the influencing factors of consumers' food risk communication behavior on social media in northeast China, using the protection motivation theory. We integrate the Suan Tang Zi food poisoning accident and the protection motivation theory to develop a conceptual model to predict food safety risk communication on social media. We conducted a questionnaire which adapted measures from the existing Likert scales. A total of 789 respondents from northeast China participated in this study. We tested our hypotheses using a structural equation model. Results show that perceived severity, perceived vulnerability and self-efficacy have a significant influence on consumer protection motivation. Response efficacies have a positive impact on consumer protection motivation, but response barriers have a negative impact on consumer protection motivation. Additionally, information need and protection motivation of consumers have a significant impact on food safety risk communication on social media. Overall, the protection motivation theory accounted for 71% of the variance in food safety risk communication on social media. Practical implications and suggestions are proposed for the related stakeholders, as well as consumers, to encourage the public to participate in the food risk communication in this study. The research findings presented the social media as a kind of food risk communication channel contributes to consumers acquire accurate information on food quickly, in turn, reduce the probability of food poisoning in daily life. Protection motivation theory may provide some insights into how we can increase the rate of food safety risk communication on social media.

Correction to: Use of medical face masks versus particulate respirators as a component of personal protective equipment for health care workers in the context of the COVID-19 pandemic.

An amendment to this paper has been published and can be accessed via the original article.

Use of medical face masks versus particulate respirators as a component of personal protective equipment for health care workers in the context of the COVID-19 pandemic.

Currently available evidence supports that the predominant route of human-to-human transmission of the SARS-CoV-2 is through respiratory droplets and/or contact routes. The report by the World Health Organization (WHO) Joint Mission on Coronavirus Disease 2019 (COVID-19) in China supports person-to-person droplet and fomite transmission during close unprotected contact with the vast majority of the investigated infection clusters occurring within families, with a household secondary attack rate varying between 3 and 10%, a finding that is not consistent with airborne transmission. The reproduction number (R0) for the SARS-CoV-2 is estimated to be between 2.2-2.7, compatible with other respiratory viruses associated with a droplet/contact mode of transmission and very different than an airborne virus like measles with a R0 widely cited to be between 12 and 18. Based on the scientific evidence accumulated to date, our view is that SARS-CoV-2 is not spread by the airborne route  to  any significant extent and the use of particulate respirators offers no advantage over medical masks as a component of personal protective equipment for the routine care of patients with COVID-19 in the health care setting. Moreover, prolonged use of particulate respirators may result in unintended harms. In conjunction with appropriate hand hygiene, personal protective equipment (PPE) used by health care workers caring for patients with COVID-19 must be used with attention to detail and precision of execution to prevent lapses in adherence and active failures in the donning and doffing of the PPE.

Household Materials Selection for Homemade Cloth Face Coverings and Their Filtration Efficiency Enhancement with Triboelectric Charging.

The COVID-19 pandemic is currently causing a severe disruption and shortage in the global supply chain of necessary personal protective equipment (e.g., N95 respirators). The U.S. CDC has recommended use of household cloth by the general public to make cloth face coverings as a method of source control. We evaluated the filtration properties of natural and synthetic materials using a modified procedure for N95 respirator approval. Common fabrics of cotton, polyester, nylon, and silk had filtration efficiency of 5-25%, polypropylene spunbond had filtration efficiency 6-10%, and paper-based products had filtration efficiency of 10-20%. An advantage of polypropylene spunbond is that it can be simply triboelectrically charged to enhance the filtration efficiency (from 6 to >10%) without any increase in pressure (stable overnight and in humid environments). Using the filtration quality factor, fabric microstructure, and charging ability, we are able to provide an assessment of suggested fabric materials for homemade facial coverings.

Low-pass Whole-genome Sequencing of Circulating Cell-free DNA Demonstrates Dynamic Changes in Genomic Copy Number in a Squamous Lung Cancer Clinical Cohort.

PURPOSE: We developed a method to monitor copy number variations (CNV) in plasma cell-free DNA (cfDNA) from patients with metastatic squamous non-small cell lung cancer (NSCLC). We aimed to explore the association between tumor-derived cfDNA and clinical outcomes, and sought CNVs that may suggest potential resistance mechanisms. EXPERIMENTAL DESIGN: Sensitivity and specificity of low-pass whole-genome sequencing (LP-WGS) were first determined using cell line DNA and cfDNA. LP-WGS was performed on baseline and longitudinal cfDNA of 152 patients with squamous NSCLC treated with chemotherapy, or in combination with pictilisib, a pan-PI3K inhibitor. cfDNA tumor fraction and detected CNVs were analyzed in association with clinical outcomes. RESULTS: LP-WGS successfully detected CNVs in cfDNA with tumor fraction ≥10%, which represented approximately 30% of the first-line NSCLC patients in this study. The most frequent CNVs were gains in chromosome 3q, which harbors the PIK3CA and SOX2 oncogenes. The CNV landscape in cfDNA with a high tumor fraction generally matched that of corresponding tumor tissue. Tumor fraction in cfDNA was dynamic during treatment, and increases in tumor fraction and corresponding CNVs could be detected before radiographic progression in 7 of 12 patients. Recurrent CNVs, such as MYC amplification, were enriched in cfDNA from posttreatment samples compared with the baseline, suggesting a potential resistance mechanism to pictilisib. CONCLUSIONS: LP-WGS offers an unbiased and high-throughput way to investigate CNVs and tumor fraction in cfDNA of patients with cancer. It may also be valuable for monitoring treatment response, detecting disease progression early, and identifying emergent clones associated with therapeutic resistance.

Innovative and New Approaches to Laboratory Diagnosis of Zika and Dengue: A Meeting Report.

Epidemics of dengue, Zika, and other arboviral diseases are increasing in frequency and severity. Current efforts to rapidly identify and manage these epidemics are limited by the short diagnostic window in acute infection, the extensive serologic cross-reactivity among flaviviruses, and the lack of point-of-care diagnostic tools to detect these viral species in primary care settings. The Partnership for Dengue Control organized a workshop to review the current landscape of Flavivirus diagnostic tools, identified current gaps, and developed strategies to accelerate the adoption of promising novel technologies into national programs. The rate-limiting step to bringing new diagnostic tools to the market is access to reference materials and well-characterized clinical samples to facilitate performance evaluation. We suggest the creation of an international laboratory-response consortium for flaviviruses with a decentralized biobank of well-characterized samples to facilitate assay validation. Access to proficiency panels are needed to ensure quality control, in additional to in-country capacity building.

A postmenopausal woman with sciatica from broad ligament leiomyoma: a case report.

BACKGROUND: Unilateral lower abdominal pain and/or sciatic nerve pain is a common presentation in the elderly population. The prevalence of broad ligament leiomyoma is <1 % with the prevalence declining after the menopause and it is rare for broad ligament leiomyomas to be clinically significant. Thus, we highlight a case of symptomatic broad ligament leiomyoma in a postmenopausal woman whose symptoms improved after definitive treatment. CASE PRESENTATION: A 62-year-old postmenopausal Macedonian woman was referred to our gynecological department with unexplained pain in her left leg and left iliac fossa region on walking. There was minimal relief with increasing analgesia use prescribed by the family physician. Investigations revealed an ipsilateral adnexal mass and subsequent treatment with laparoscopic broad ligament myomectomy helped to alleviate her symptoms. CONCLUSIONS: Our case highlights the importance of staying mindful of alternate diagnoses when presented with a common presentation of iliac fossa pain and pain in the leg. Although broad ligament leiomyomas are benign tumors, the uncommon symptomatic presentation led us to report and focus some attention on this type of tumor.

A resource for cell line authentication, annotation and quality control.

Cell line misidentification, contamination and poor annotation affect scientific reproducibility. Here we outline simple measures to detect or avoid cross-contamination, present a framework for cell line annotation linked to short tandem repeat and single nucleotide polymorphism profiles, and provide a catalogue of synonymous cell lines. This resource will enable our community to eradicate the use of misidentified lines and generate credible cell-based data.

Human biosample authentication using the high-throughput, cost-effective SNPtrace(TM) system.

Cell lines are the foundation for much of the fundamental research into the mechanisms underlying normal biologic processes and disease mechanisms. It is estimated that 15%-35% of human cell lines are misidentified or contaminated, resulting in a huge waste of resources and publication of false or misleading data. Here we evaluate a panel of 96 single-nucleotide polymorphism (SNP) assays utilizing Fluidigm microfluidics technology for authentication and sex determination of human cell lines. The SNPtrace Panel was tested on 907 human cell lines. Pairwise comparison of these data show the SNPtrace Panel discriminated among identical, related and unrelated pairs of samples with a high degree of confidence, equivalent to short tandem repeat (STR) profiling. We also compared annotated sex calls with those determined by the SNPtrace Panel, STR and Illumina SNP arrays, revealing a high number of male samples are identified as female due to loss of the Y chromosome. Finally we assessed the sensitivity of the SNPtrace Panel to detect intra-human cross-contamination, resulting in detection of as little as 2% contaminating cell population. In conclusion, this study has generated a database of SNP fingerprints for 907 cell lines used in biomedical research and provides a reliable, fast, and economic alternative to STR profiling which can be applied to any human cell line or tissue sample.

Diabetes and poor glycaemic control in rural patients with coronary artery disease.

BACKGROUND: The burden of cardiovascular disease is higher in rural populations. Existing data on rural cardiovascular health is mainly based on community surveys. Regional differences are not well addressed. This study aims to identify regional inequalities in cardiovascular risk factors (CVRFs) in Australian patients with suspected coronary artery disease. METHODS AND RESULTS: 538 subjects (72% male; mean age 63years) were recruited from a single cardiac catheter laboratory over a 24-month period. Subjects were stratified into Remoteness Areas (RAs) according to the Australian Standard Geographical Classification (RA1 corresponds to Major Cities, RA2 to Inner Regional Areas, RA3 to Outer Regional Areas). Body-mass index, blood pressure, hypertension, dyslipidaemia, diabetes and smoking history were recorded. A blood sample taken before the angiogram was analysed for lipids and fasting blood glucose (FBG). Distribution of the study population across RA1, RA2 and RA3 was 34.8%, 46.1% and 19.1%. Only FBG (p=0.019) and diagnosed diabetes (p=0.009) were significantly different i.e. higher in RA1. Of those without known diabetes, RA3 had the highest prevalence of dysglycaemia (p=0.023) with two-thirds having either pre-diabetes or undiagnosed diabetes. Logistic regression showed that age and RA3 were the only statistically significant predictors of elevated FBG. CONCLUSION: CAD patients from remote Australia had higher rates of pre-diabetes, undiagnosed diabetes and poorer glycaemic control. Analysis of the main CVRFs revealed a regional inequality in the recognition and management of diabetes alone. Attention to this gap in rural and urban healthcare is crucial to future cardiovascular health outcomes in Australia.