HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Pulmonary rehabilitation online: current status and availability in 2022

BackgroundPulmonary rehabilitation (PR) is a core component of COPD treatment. An alternative to traditional face-to-face PR is online PR, also known as tele-rehabilitation. Despite lack of delivery standardisation there has been recent progression towards an online platform with myCOPD (NICE, 2022)1. The British Thoracic Society advising face-to-face PR suspension and COVID-19 restrictions may have encouraged services to develop tele-rehabilitation.MethodsA questionnaire survey of PR services in England explored the availability and practice of tele-rehabilitation in England. Additional aims were the investigation of recent development of tele-rehabilitation including changes following the COVID-19 pandemic, and potential barriers to and predictors of success for tele-rehabilitation delivery. The questionnaire used closed and open-ended questions and free text-boxes. Data was collected between 30th March 2022 and 19th April 2022.Results61 responses (33%) were received. 11 PR services (18%) stated that they had used a form of tele-rehabilitation prior to the COVID-19 pandemic and 59 (97%) services described using a form of tele-rehabilitation during COVID-19 restrictions. Common remote methods during COVID-19 restrictions included telephone (27%), videoconferencing with patients in groups (23%) and individual patient videoconferencing (21%).15 (25%) PR services strongly agreed, and 23 (38%) agreed, that inability to use tele-rehabilitation due to unfamiliarity with digital equipment or lack of access to the internet prevented many service users from using remote PR. 31 (51%) PR services strongly agreed, and 14 (23%) agreed, that face-to-face PR was preferred by users.31 (51%) PR services disagreed, and 13 (21%) strongly disagreed that tele-rehabilitation would be too costly whilst 7 (11%) strongly agreed, and 45 (74%) agreed that tele-rehabilitation would be beneficial to users.ConclusionTele-rehabilitation became widespread following COVID-19 restrictions, most commonly through telephone and videoconferencing. Most service users were thought to be unable to access tele-rehabilitation due to inability to access the internet and prefer face-to-face PR. Most services reported that cost was not an obstacle to tele-rehabilitation and would be beneficial to users.ReferencesNICE. (2022). Recommendations ;myCOPD for managing chronic obstructive pulmonary disease. [online] Available at: <https://www.nice.org.uk/guidance/MTG68/chapter/1-Recommendations> [Accessed 30 June 2022].

Hypothesis-Agnostic Network-Based Analysis of Real-World Data Suggests Ondansetron is Associated with Lower COVID-19 Any Cause Mortality.

BACKGROUND: The COVID-19 pandemic generated a massive amount of clinical data, which potentially hold yet undiscovered answers related to COVID-19 morbidity, mortality, long-term effects, and therapeutic solutions. OBJECTIVES: The objectives of this study were (1) to identify novel predictors of COVID-19 any cause mortality by employing artificial intelligence analytics on real-world data through a hypothesis-agnostic approach and (2) to determine if these effects are maintained after adjusting for potential confounders and to what degree they are moderated by other variables. METHODS: A Bayesian statistics-based artificial intelligence data analytics tool (bAIcis®) within the Interrogative Biology® platform was used for Bayesian network learning and hypothesis generation to analyze 16,277 PCR+ patients from a database of 279,281 inpatients and outpatients tested for SARS-CoV-2 infection by antigen, antibody, or PCR methods during the first pandemic year in Central Florida. This approach generated Bayesian networks that enabled unbiased identification of significant predictors of any cause mortality for specific COVID-19 patient populations. These findings were further analyzed by logistic regression, regression by least absolute shrinkage and selection operator, and bootstrapping. RESULTS: We found that in the COVID-19 PCR+ patient cohort, early use of the antiemetic agent ondansetron was associated with decreased any cause mortality 30 days post-PCR+ testing in mechanically ventilated patients. CONCLUSIONS: The results demonstrate how a real-world COVID-19-focused data analysis using artificial intelligence can generate unexpected yet valid insights that could possibly support clinical decision making and minimize the future loss of lives and resources.

Insulin requirements of covid-19 patients with diabetes on steroid treatment in a South London hospital

Aim: Steroid use has been widespread during the covid- 19 pandemic. We reviewed total daily dose of insulin (TDDI) in our cohort and compared it with standard practice guidelines issued by the JBDS in 2020. Methods: We audited TDDI in patients with type 1 or 2 diabetes admitted with covid-19 pneumonitis, requiring steroids, between December 2020 and February 2021. Those on mechanical ventilation were excluded. Dose was considered sufficient if CBG ≤ 13mM within 10 hours of steroid administration. Age, gender, ethnicity, HbA1c, TDDI, weight, eGFR, type and dose of steroids and oral hypoglycaemic agents were recorded. For ease of comparison, steroids used were converted to dose equivalent of dexamethasone, using standard steroid conversion charts. We compared TDDI of our cohort to JBDS guidelines which suggest using 0.3-0.5 units kg-1 day-1. We used RStudio for statistical analysis and used linear regression modelling to analyse our data. Results: 67 patients were identified, 47(70%) were on dexamethasone (0.5-200mg day-1), 10(15%) on prednisolone (10-40mg day-1) and 10(15%) on methylprednisolone (40-750mg day-1). CBG readings ranged from 5.9mM to 24.2mM. Mean TDDI was 0.48 units kg-1 day-1 (0.05-1.43 units kg-1 day-1). There were no differences in TDDI across age, gender, renal function, ethnic group or by use of other medication. Mean TDDI was 0.4 units kg-1 day-1 for those on ≤10mg of dexamethasone day-1 (or equivalent) and 0.74 units kg-1 day-1 ( ± 0.11, p = 0.003) for those on >10mg dexamethasone day-1 (or equivalent). Conclusion: Insulin requirement in individuals with diabetes admitted with covid-19 and needing high dose steroids (>10mg dexamethasone day-1 (or equivalent)) was significantly higher than the standard JBDS recommendation.

GIANT CELL ARTERITIS PATIENT PATHWAY: A MULTIDISCIPLINARY APPROACH TO SERVICE IMPROVEMENT IN THE TIME OF COVID-19

Background/Aims The RNHRD is a tertiary rheumatology centre offering a fast-track GCA assessment service. A 2018 departmental audit highlighted areas of good practice including timely assessment of cases but demonstrated irregularities in follow up processes. COVID-19 dramatically changed the way we could deliver our GCA service. Additionally, we saw increases in referrals, confirmed diagnoses and complex disease in our local population during the pandemic. This prompted us to undertake a service improvement project. Our main aims were to optimise follow up in line with national guidelines, enhance patient safety and improve the patient experience. Methods We undertook a service review, starting by mapping the patients' journey. Guidelines were reviewed and stakeholders consulted. We identified several areas for improvement including;consultant-led risk stratification of patients, formalised follow up pathways and closer collaborative working with relevant departments. Additionally, we sought to streamline our processes to accommodate the increased COVID-19 workload. Results A risk stratified follow up pathway was created. Patients are stratified at initial review, by consultants, into low and high-risk pathways. Follow up intervals have been standardised in line with BSR guidance. Follow up patients are reviewed in a dedicated clinic;medical and nursing clinics run supervised by a vasculitis specialist. Patients transfer between different clinics, dependent on clinical stability. Patient information provided has been standardised, with increased emphasis on flare management and steroid side effects. In collaboration with patients this is being incorporated into a 'GCA patient passport', offering a consistent information resource for patients and clinicians. The nurse-led patient advice line is used frequently by GCA patients. All GCA queries are now directed to the on-call registrar, to ensure same day responses. Temporal artery ultrasound is well utilised and completed efficiently;82% of scans between September 2019 and September 2021 occurred within 48 hours of referral. Via close working with vascular ultrasound, we have been able to create dedicated daily ultrasound capacity. Collaborative working with our Ophthalmology department has increased;communication channels between departments have been agreed, and education sessions have been provided. Processes for new GCA patients were streamlined, for example moving location of reviews. This ensured ongoing timely review of new GCA patients despite increased referral numbers. Conclusion COVID-19 had a significant impact on service delivery but provided a catalyst to develop our service. By engaging with stakeholders across disciplines, and reacting to patient feedback, we have been able to institute effective and meaningful change. This process is iterative and we plan further assessment of outcomes including co-morbidities and complications. Further formal patient surveys and development of a GCA expert patient group are underway and will inform further service Development.

A comprehensive genome report for COVID-19 patients: GENCOV Study Canada

Background: Severe acute respiratory syndrome coronavirus (SARSCoV- 2) is a novel virus that causes Coronavirus Disease 2019 (COVID- 19). High-throughput sequencing technologies such as whole genome sequencing (WGS) and sequencing of viral genome DNA are being implemented to identify and report on genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. Genome sequencing has been useful for clinical diagnostic purposes, and can reveal other useful information such as disease risk factors that might lead to disease prevention or patient management strategies. UsingWGS and bioinformatics software tools, we describe a novel pipeline for the analysis of medically relevant genetic results and other findings identified in COVID-19 positive individuals, and the generation of a genome report that can effectively communicate these results to patients and their physicians. Study design: Enrollment will include up to 1500 patients with a positive COVID-19 nasopharyngeal swab. Blood samples will be collected at baseline, 1 month, 6 months, and 1 year after diagnosis. Antibody isotype (IgG, IgA, and IgM), titers, and viral neutralization will be analyzed. DNA will be isolated from blood lymphocytes and host genomes will be sequenced. Whole genomes will be assessed using ACMG criteria for the interpretation of pathogenic sequence variation using in-house and third-party software tools, and publicly available disease and control databases. Comprehensive gene panels will be implemented to allow for patients to receive clinically significant findings, including risk factor and carrier status, from multiple categories of potential genetic conditions including blood and immunology, endocrine, metabolic/mitochondrial, musculoskeletal, hearing loss, neurology, cardiology, ophthalmology, renal, skin, and gastrointestinal disorders. Common disease risk will be assessed using polygenic risk scores calculated for 6 diseases (atrial fibrillation, coronary artery disease, type 2 diabetes, prostate cancer, colorectal cancer, breast cancer). Pharmacogenomic gene variants that alter metabolizer phenotype and drug response in individuals will be reported, in addition to patient HLA-type. The genomic predictions fromABO and Rh blood types will be summarized and reported. Largescale continental ancestry estimation will be performed using publicly available reference populations. Finally, using viral genome DNA sequencing, the SARS-CoV-2 viral lineage will be identified and reported. An appointment with the study genetic counsellor will be scheduled to discuss results identified in the genome report and manage appropriate clinical referrals if necessary. Serology results will be reported. Regression models will examine associations between antibody response (titer, antigen target, viral neutralization ability), physiological response (biochemical, hematological and clinical characteristics), patient outcomes, viral lineage and genomic results. Significance: This study will link clinically relevant genomic results, in addition to other biological and serological characteristics, to potential factors that contribute to variability in SARS-CoV-2 outcomes. Results will be shared with family physicians for clinical follow up. This study will establish an efficient workflow using highthroughput genomic sequencing technology coupled with emerging bioinformatics platforms for the generation of comprehensive genome reports to aid in COVID-19 patient management and follow-up.

Arrhythmia patterns in patients with COVID-19 infection during and post hospitalization detected via a patch-based mobile cardiac telemetry system

Background: Coronavirus infection (COVID-19) is the cause of the current world-wide pandemic. Cardiovascular complications occur in 20-30% of patients with COVID-19 infection including myocardial injury and arrhythmias. Current understanding of specific arrhythmia type and frequency is limited. In response to COVID-19 pandemic and overwhelmed hospital critical care and telemetry recourses, patch-based cardiac monitoring system received emergency Food and Drug Administration (FDA) approval for inpatient monitoring. A patch-based cardiac telemetry system has been shown to be useful for patient management during the COVID-19 pandemic and provides detailed analysis of cardiac rhythms. Purpose: To analyze arrhythmia type and frequency in patients with COVID-19 infection, identifying arrhythmia patterns over time during hospitalization and after discharge. Methods: A prospective cohort study during the COVID-19 pandemic was performed. We included patients hospitalized with COVID-19 infection who had a patch-based mobile telemetry device placed for cardiac monitoring. A quantitative analysis including type, frequency and duration of detected arrhythmias was performed at the end of the monitoring period. Results: A total of 103 patients hospitalized with COVID-19 diagnosis underwent monitoring. Quantitative reports for 59 patients were available for analysis, among those 59% were males, median age 65 (IQR 56-76) yrs. Mean wear time was 6.8±5.0 days. Arrhythmias were detected in 72.9% of patients. Majority of arrhythmias were SVT (59.3% of patients) and AF (22.0%). Episodes of AF duration >30 min were detected in 12 patients. New onset AF was noted in 15.0% of patients and was significantly associated with age (OR 1.4 for 5 yrs difference;95% CI 1.01-2.05). Brady arrhythmias (2nd degree, 3rd degree AV bock, pause≥3 seconds) were seen in 18.7% of patients. Arrhythmias were consistently detected throughout the monitoring period in 52.9%-89.5% of patients daily (Figure 1). In 9 patients who were discharged with continued patch monitoring, 3 patients (33.3%) had arrhythmic events during their outpatient monitoring period. Conclusion: A majority of patients hospitalized with COVID-19 infection had arrhythmias detected by patch cardiac monitor. Arrhythmias were observed throughout hospitalization with a consistent daily frequency. Patients continued to exhibit cardiac arrhythmias after hospital discharge of a type similar to that seen during hospitalization. New onset AF often occurred and was associated with older age. Inpatient application of a patch cardiac telemetry with continued monitoring as outpatient is feasible and effective in detecting occult arrhythmias in patients with COVID-19 infection. (Figure Presented).

Excess giant cell arteritis cases are associated with peaks in COVID-19 prevalence

Background: Immediately following the first wave of the COVID-19 pandemic, the number of giant cell arteritis (GCA) diagnoses noticeably increased at the Royal National Hospital for Rheumatic Diseases in Bath, UK. Furthermore, there was an increase in the proportion of patients with visual complications [1]. The finding supports the viral hypothesis of GCA aetiopathogenesis as previously described [2]. This not only has ramifications for understanding the underlying disease mechanisms in GCA but also has implications for the provision of local GCA services which may have already be affected by the pandemic. Objectives: The objective of the study was to estimate the incidence of giant cell arteritis during the COVID-19 pandemic years of 2020 -2021 and compare it to 2019 data. Given that there have now been two distinct peaks of COVID-19 as reflected by hospital admissions of COVID-19-positive patients this has allowed us to investigate if there is a temporal relationship between the prevalence of COVID-19 and the incidence of GCA. Methods: The incidence of GCA was calculated by assessing emailed referrals to the GCA service and the hospital electronic medical records to identity positive cases from 2019 to the current date. Local COVID-19 prevalence was estimated by measuring the number of hospital beds taken up by COVID-19 positive patients, available publicly in a UK Government COVID-19 dataset [3]. Results: There were 61 (95% Poisson distribution confidence interval [CI] 47 -78) probable or definite GCA diagnoses made in 2020 compared to 28 (CI 19 -40) in 2019 (Figure 1). This is an excess of 33 cases in 2020, or an increase in 118%. Given that 41% of the hospital's catchment population is over 50, this equates to an annual incidence rate of 13.7 per 100,000 in 2019 and 29.8 per 100,000 in 2020. This compares to a previously estimated regional incidence rate of 21.6 per 100,000 for the South West of the UK [4]. A peak in COVID-19-positive inpatients was seen on 10th April 2020 with a corresponding peak of GCA diagnoses on 29th May 2020, giving a lag period of approximately 6 weeks between these peaks (Figure 1). Conclusion: The incidence of GCA in Bath was significantly increased in 2020 compared to 2019. This may be the result of the widespread infection of the local population with the COVID-19 virus as a precipitating factor. Possible mechanisms include, but are not limited to, endothelial disruption by the virus, immune system priming towards T helper cell type 1 (Th1) cellular immunity and/or activation of the monocyte-macrophage system. More work is currently underway to assess the causal relationship between the two diseases. There was a lag period of 6 weeks between the peak during the first wave of the pandemic and the rise in GCA cases. We shall be closely monitoring the number of referrals that follow the current wave of the pandemic.

Developing Human Papillomavirus Education Material for HPV-Positive Oropharyngeal Cancer Patients with an Interprofessional Health Care Team and Patient Representatives

Purpose: The incidence of human papillomavirus (HPV)-related head and neck cancer now exceeds the incidence of HPV-related cervical cancer in Canada. A study conducted at our institution identified that patients were not provided with sufficient information regarding HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPSCC). It was also recognized that patients and their partner felt guilt and stigma about the HPV diagnosis, which had a negative impact on their intimacy. The aim of this project was to create an educational tool to address the concerns of patients and their families with HPV-OPSCC through collaboration of an interprofessional health care team and patient representatives. Methods: As part of the needs assessment, an environmental scan of patient education tools and a literature review on current evidence and management of HPV-OPSCC was conducted, resulting in pamphlets, articles and websites from various cancer centres in North America. Our institutional study was used to identify the patients’ needs including: more information on the cause of HPV, consequences to their health, and future implications to the health of their partner(s). Three virtual meetings with the development team were conducted to identify the key messages and resources suggested to be included in the educational tool. The principles of lay language and clear design was adhered to in order to ensure the educational tool was acceptable and understandable for patients and their families. Feedback was elicited from stakeholders of the Head and Neck Site Group and the Patient and Family Education Committee. Results: Discussing an HPV diagnosis on top of cancer treatment options can be overwhelming for the patient on their first visit. Furthermore, family members may not be able to accompany the patient to their appointment due to current restrictions of the COVID-19 pandemic, thereby removing an aspect of support and opportunity for family members to ask questions. This educational tool provides patients and their loved ones answers to common questions regarding HPV-OPSCC, explains how this diagnosis affects their treatment outcomes, and helps patients and family navigate the available resources and supportive services within the cancer centre and on the internet. Challenges identified throughout the project include recruiting patient representatives who felt comfortable sharing their experience, as well as obtaining feedback from a large and diverse team of busy health care professionals. Conclusions: This tool will be in the form of a printed document and will be found on the cancer centre website. Not only was the development of this tool driven by patient need, but patient engagement was prioritized with two patient representatives on the development team to collaborate on the content and design of the education tool. An evaluation of the educational tool will be conducted and may consist of tracking the number of times the educational tool was accessed and administering a survey during the patient's next appointment to determine satisfaction.

All in the family: A comparative look at coronaviruses

Coronaviruses, members of the order Nidovirales, the largest and most complex of the positive-stranded RNA viruses, have been recognized as important causes of disease in veterinary medicine for nearly a century. In contrast, in human medicine, especially until the recent SARS-CoV-2 pandemic, they were unimportant viruses associated with the common cold. This is a brief comparative review of the biology of coronaviral infections emphasizing the commonalities among the various members of the family and considering how the veterinary experience with coronaviruses can inform the response to SARS-CoV-2. Coronaviruses are perhaps best viewed as mutation machines whose genetic sequences can readily change through genetic drift, recombination, and deletions from a large genome. However, to be of clinical concern, variants must have the perfect set of amino acids in the S protein receptor binding domain and in their replication-mediating nonstructural proteins. Extensive experience with veterinary coronaviral vaccines suggests that optimal clinical immunity is a tandem of mucosal and systemic responses induced by a combination of mucosal and parenteral vaccines.