Genomic Surveillance of a Canadian Airport Wastewater Samples Allows Early Detection of Emerging SARS-CoV-2 Lineages (preprint)

The SARS-CoV-2 pandemic has shown that wastewater (WW) surveillance is an effective means of tracking the emergence of viral lineages in communities, arriving by many routes including via transportation hubs. In Ontario, numerous municipal WWTPs participate in WW surveillance of infectious disease targets such as SARS-CoV-2 by qPCR and whole genome sequencing (WGS). The Greater Toronto Airports Authority (GTAA), operator of Toronto Pearson International Airport (Toronto Pearson), has been participating in WW surveillance since January 2022. As a major international airport in Canada and the largest national hub, this airport is an ideal location for tracking globally emerging SARS-CoV-2 variants of concern (VOCs). In this study, WW collected from Toronto Pearson’s two terminals and pooled aircraft sewage was processed for WGS using a tiled-amplicon approach targeting the SARS-CoV-2 virus. Data generated was analyzed to monitor trends SARS-CoV-2 lineage frequencies. Initial detections of emerging lineages were compared between Toronto Pearson WW samples, municipal WW samples collected from the surrounding regions, and Ontario clinical data as published by Public Health Ontario. Results enabled the early detection of VOCs and individual mutations emerging in Ontario. On average, emergence of novel lineages at the airport ahead of clinical detections was 1–4 weeks, and up to 16 weeks. This project illustrates the efficacy of WW surveillance at transitory transportation hubs and sets an example that could be applied to other viruses as part of a pandemic preparedness strategy and to provide monitoring on a mass scale.

Learning novel SARS-CoV-2 lineages from wastewater sequencing data (preprint)

Background:Wastewater surveillance of SARS-CoV-2 has emerged as a critical tool for tracking the spread of COVID-19.In addition to estimating the relative case numbers using quantitative PCR, SARS-CoV-2 genomic RNA can be extracted from wastewater and sequenced.There are many existing techniques for using the sequenced RNA to determine the relative abundance of known lineages in a sample.However, it is very challenging to predict novel lineages from wastewater data due to its mixed composition and unreliable genomic coverage.Results:In this work, we present a novel technique based on non-negative matrix factorization which is able to extract novel lineage definitions by analyzing data from across different samples.We test the method both on synthetic and real wastewater sequencing data.We show that the technique is able to determine major lineages such as Omicron and Delta as well as sub-lineages such as BA.5.2.1.Conclusions:We provide a method for determining emerging lineages in wastewater without the need for genomic data from clinical samples. This could be used for routine monitoring of SARS-CoV-2 as well as other emerging viral pathogens in wastewater. Additionally, it may be used to derive more sequences for viruses with fewer complete genomes.

Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data (preprint)

Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic "novel" lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances, and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1% frequency, results were more reliable above a 5% threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of noise or bias in wastewater sequencing data and to appreciate the commonalities and differences across methods.

Principles of diagnostic stewardship: A practical guide from the Society for Healthcare Epidemiology of America Diagnostic Stewardship Task Force.

We provide an overview of diagnostic stewardship with key concepts that include the diagnostic pathway and the multiple points where interventions can be implemented, strategies for interventions, the importance of multidisciplinary collaboration, and key microbiologic diagnostic tests that should be considered for diagnostic stewardship. The document focuses on microbiologic laboratory testing for adult and pediatric patients and is intended for a target audience of healthcare workers involved in diagnostic stewardship interventions and all workers affected by any step of the diagnostic pathway (ie, ordering, collecting, processing, reporting, and interpreting results of a diagnostic test). This document was developed by the Society for Healthcare Epidemiology of America Diagnostic Stewardship Taskforce.

Impact of Healthcare System and Patient Factors on Telemedicine Adoption (preprint)

Background: Telemedicine has become one of the standards in healthcare delivery, particularly since onset of the COVID pandemic. However, healthcare disparities in telemedicine care delivery among historically disadvantaged groups remains unclear with most studies demonstrating its persistence. We aim to evaluate patient and healthcare system factors in telemedicine utilization in a large, diverse population. Methods: Retrospective study of patient visits across Kaiser Permanente Southern California between January 1, 2019, and June 30, 2021. Patient factors included age, gender, ethnicity, median household income, primary spoken/written language, marital status, and registration on kp.org. Healthcare factors included type of visit, provider age, gender, specialty, number of years in practice and primary language. Rates of utilization compared between office and virtual visits, prior to and after March 2020, with an interrupted time series and slope analysis. Results: There were 177,171,288 visits during the study period. There was a decrease in patient visits after March 2020 (lockdown), driven by a sharp decline in office visits. Within three months of lockdown, total visits increased until the end of study, at 2.8 million/month, compared to 2.5 million/month prior to lockdown, driven by office visits that approached pre-lockdown and high telemedicine visits. In a multivariate regression analysis, there were no significant differences in patient age, race, gender, income, marital status, language, and kp.org registration in telemedicine utilization. Providers with 6-10 years in practice, aged < 30 utilized the most telemedicine (p=.01). General surgery, medical specialties, OBGYN, pediatrics and psychiatry utilized more telemedicine compared to primary care, but podiatry and surgical specialties utilized less (p < 0.01). Conclusions: Our study of over 177 million patient visits in an integrated healthcare system of a large, diverse population shows sustained high utilization of telemedicine after the pandemic lockdown, with an increase of office visits, and overall increase of total patient visits. No significant healthcare disparities across various populations were found in telemedicine utilization, contrary to most current literature demonstrates. Results of this study may prompt more investigation to the role of telemedicine in various populations.

A General Computational Framework for COVID-19 Modelling with Applications to Testing Varied Interventions in Education Environments

We construct a spatially-compartmental, individual-based model of the spread of SARS-CoV-2 in indoor spaces. The model can be used to predict the infection rates in a variety of locations when various non-pharmaceutical interventions (NPIs) are introduced. Tasked by the Welsh Government, we apply the model to secondary schools and to Further and Higher Education environments. Specifically, we consider student populations mixing in a classroom and in halls of residence. We focus on assessing the potential efficacy of Lateral Flow Devices (LFDs) when used in broad-based screens for asymptomatic infection or in 'test-to-release’scenarios in which individuals who have been exposed to infection are released from isolation after a negative LFD result. LFDs are also compared to other NPIs;we find that, although LFD testing can be used to mitigate the spread of SARS-CoV-2, it is more effective to invest in personal protective equipment, e.g., masks, and in increasing ventilation quality. In addition, we provide an open-access and user-friendly online applet that simulates the model, complete with user tutorials to encourage the use of the model to aid educational policy decisions as input infection data becomes available.

Antibacterial use in the age of SARS-CoV-2.

BACKGROUND: Balancing the use of antibacterial therapy against selection for resistance in this pandemic era has introduced both questions and guidelines. In this project, we explored how prescription of empirical antibacterial therapy differs between those with and without SARS-CoV-2 infection. METHODS: Multivariable logistic regression was used to determine whether COVID-19 status and other factors play a role in the prescription of antibacterial therapy in an inpatient setting at a large referral academic medical centre. Further analysis was conducted to determine whether these factors differ between those testing positive and negative for SARS-CoV-2. RESULTS: Of 405 patients in the cohort, 175 received antibacterial therapy and 296 tested positive for SARS-CoV-2. A positive SARS-CoV-2 test carried an OR of 0.3 (95% CI: 0.19, 0.49) for receiving antibacterial treatment in the first 48 h after admission (P < 0.0001) adjusting for age and procalcitonin results. Patients were 1% and 3% less likely to receive antibacterials for every year increase in age in the overall group and among those testing negative for SARS-CoV-2, respectively. Younger age was found to impact use of antibacterial therapy in both the overall analysis as well as the SARS-CoV-2 negative subgroup (P = 0.03 and P = 0.01). High procalcitonin values were found to be associated with increased antibacterial therapy use in both the overall and stratified analyses. CONCLUSIONS: Antibacterial therapy prescription differs by COVID-19 disease status, and procalcitonin results are most highly associated with antibacterial use across strata.

Acute psychosis associated with recent SARS-CoV-2 infection: A case report.

The COVID-19 pandemic has created overwhelming circumstances not only in the medical field, but in other walks of life. SARS-CoV-2, the causative virus of COVID-19 [1], primarily affects the respiratory system leading to respiratory illnesses of varying severity ranging from mild flu-like symptoms to acute respiratory distress syndrome [2]. However, the clinical manifestations of COVID-19 are not limited to the respiratory system [3]. There is a growing body of literature showing the incidence of a varying clinical spectrum of neuropsychiatric manifestations in a significant proportion of COVID-19 patients [4]. With the variability in neuropsychiatric presentation of COVID- 19, multiple mechanisms have been proposed to explain the pathophysiology of these presentations [5]. In this case report, we present a 20-year-old female with no significant respiratory symptoms or previous history of psychotic episodes who manifested with acute psychosis as a significant complication of COVID-19.

Evaluation of cycle threshold values at deisolation.

The decision to discontinue isolation in hospitalized patients with persistently positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) molecular testing is nuanced. Improvement in clinical status should be evaluated with expert consultation when considering whether discontinuation of isolation is appropriate. The cycle threshold value may serve as a useful adjunct to this decision-making process.

Just-In-Time Tools for Training Non-Critical Care Providers. Troubleshooting Problems in the Ventilated Patient.

Due to the limited number of critical care providers in the United States, even well-staffed hospitals are at risk of exhausting both physical and human resources during the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One potential response to this problem is redeployment of non-critical care providers to increase the supply of available clinicians. To support efforts to increase capacity as part of surge preparation for the coronavirus disease (COVID-19) outbreak, we created an online educational resource for non-intensivist providers to learn basic critical care content. Among those materials, we created a series of one-page learning guides for the management of common problems encountered in the intensive care unit (ICU). These guides were meant to be used as just-in-time tools to guide problem-solving during the provision of ICU care. This article presents five guides related to managing complications that can arise in patients receiving invasive mechanical ventilation.

Just-In-Time Tools for Training Non-Critical Care Providers. Basics of Respiratory Failure.

Due to the limited number of critical care providers in the United States, even well-staffed hospitals are at risk of exhausting both physical and human resources during the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One potential response to this problem is redeployment of non-critical care providers to increase the supply of available clinicians. To support efforts to increase capacity as part of surge preparation for the coronavirus disease (COVID-19) outbreak, we created an online educational resource for nonintensivist providers to learn basic critical care content. Among those materials, we created a series of one-page learning guides for the management of common problems encountered in the intensive care unit (ICU). These guides were meant to be used as just-in-time tools to guide problem-solving during the provision of ICU care. This article presents five guides related to the evaluation and management of patients with hypoxemic respiratory failure and the basics of invasive mechanical ventilation.

Utility of repeat testing for COVID-19: Laboratory stewardship when the stakes are high.

As the coronavirus disease 2019 (COVID-19) continues to circulate, testing strategies are of the utmost importance. Given national shortages of testing supplies, personal protective equipment, and other hospital resources, diagnostic stewardship is necessary to aid in resource management. We report the low utility of serial testing in a low-prevalence setting.

Non-Woven Materials for Cloth-Based Face Mask Inserts: Relationship Between Material Properties and Sub-Micron Aerosol Filtration (preprint)

Current guidance by leading public health agencies recommends wearing a 3-layer cloth-based face mask with a middle non-woven material insert to reduce the transmission of infectious respiratory viruses like SARS-CoV-2. In this work we explore the material characteristics for a range of readily available non-woven materials and their sub-micron particle filtration efficiency (PFE), with the aim of providing evidence-based guidelines for selecting appropriate materials as inserts in cloth-based masks. We observed a wide range of ideal PFE for the tested non-woven materials, with polypropylene, Swiffer and Rayon/polyester blend providing the highest PFE and breathability. Our results suggest that materials comprising loose 3D fibrous webs (e.g. flannel, Swiffer and gauze) exhibited enhanced filtration efficiency compared to compressed counterparts. Common modifications to fabrics, such as water-resistant treatment and a sewn seam were also investigated. Overall, we demonstrate that adding an appropriate non-woven material as an insert filter can significantly improve the performance of cloth-based masks, and there exist suitable cellulose-based alternatives to polypropylene.