Strengthening access to and confidence in COVID-19 vaccines among equity-deserving populations across Canada: An exploratory qualitative study (preprint)

Introduction: There is a need to reflect on the COVID-19 vaccine distribution across Canada and the extent to which they considered equity-deserving populations. This paper examined and compared strategies implemented by six Canadian provinces to increase access and promote the uptake of COVID-19 vaccines among selected priority populations. We also explored the factors that impacted the implementation of these strategies. Methods: In six provinces (Alberta, British Columbia, Manitoba, Nova Scotia, Ontario, and Quebec), we conducted an environmental scan of provincial rollout documents and media sources reporting vaccine distribution among selected priority populations:First Nations, Inuit, and Metis; Black communities; essential workers; people experiencing homelessness; and people with disabilities. We subsequently interviewed 39 key informants to validate the environmental scan results, identify additional strategies to increase COVID-19 vaccine uptake, and uncover perceptions of the facilitators and challenges that influenced the strategies implementation. Results: Through the environmental scans and key informant interviews, we identified that provincial health authorities employed a panoply of strategies to overcome geographic, financial, and attitudinal barriers to COVID-19 vaccines experienced by the priority populations. Most provinces implemented walk-in, mobile, and pop-up vaccination clinics, mobilized public and private health workforce, and designed multilingual communication materials. Facilitators in implementing COVID-19 vaccination strategies included fostering inter-governmental cooperation, harmonizing communication efforts, leveraging existing relationships and networks, and ensuring representation and leadership of community partners. Challenges to implementing COVID-19 vaccination strategies included uncoordinated communication efforts, inadequate distribution of vaccines to areas with the greatest need, mistrust in the government and healthcare system, vaccine hesitancy, and lack of cultural competence by vaccine providers. Conclusions: This study highlights the divide between well-intentioned strategies and interventions and the reality of on-the-ground implementation. The findings offer valuable insights and can inform the implementation of strategies to distribute vaccines equitably in future large-scale vaccination efforts in Canada and globally.

Inactivation of the Niemann Pick C1 cholesterol transporter 1 (NPC1) restricts SARS-CoV-2 infection (preprint)

The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) and is involved in cholesterol mobilization. Loss-of-function mutations of the NPC1 gene lead to accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway. Because the angiotensin-converting enzyme 2 (ACE2) and type 2 serine transmembrane protease (TMPRSS2) of the SARS-CoV-2 Spike (S) protein also localize to lipid rafts, we sought to investigate the hypothesis that NPC1 inactivation would generate an intrinsically unfavorable barrier to SARS-CoV-2 entry. In this study, we demonstrate that NPC1 pharmacological inactivation or CRISP/R-Cas mediated ablation of NPC1 dramatically reduced SARS-CoV-2 infectivity. More specifically, our findings demonstrate that pharmacological inactivation of NPC1 results in massive accumulation of ACE2 in the autophagosomal/lysosomal compartment. A >40-fold decrease in virus titer indicates that this effectively prevents VSV-Spike-GFP infection by impeding virus binding and entry. A similarly marked decrease in viral infectivity is observed in cells that had NPC1 expression genetically abrogated. These observations were further confirmed in a de novo SARS-CoV-2 infection paradigm, where cells were infected with the naturally pathogenic SARS-CoV-2. Overall, this work offers strong evidence that NPC1 function is essential for successful SARS-CoV-2 infection, thus implicating NPC1 as a potential therapeutic target in COVID-19 management.

Pandemic modelling for regions implementing an elimination strategy (preprint)

During the COVID-19 pandemic, some countries, such as Australia, China, Iceland, New Zealand, Thailand and Vietnam, successfully implemented an elimination strategy. Until June 2021, Atlantic Canada and Canada's territories had also experienced prolonged periods with few SARS-CoV-2 community cases. Such regions had a need for epidemiological models that could assess the risk of SARS-CoV-2 outbreaks, but most existing frameworks are applicable to regions where SARS-CoV-2 is spreading in the community, and so it was necessary to adapt existing frameworks to meet this need. We distinguish between infections that are travel-related and those that occur in the community, and find that in Newfoundland and Labrador (NL), Nova Scotia, and Prince Edward Island the mean percentage of daily cases that were travel-related was 80% or greater (July 1, 2020 -- May 31, 2021). We show that by December 24, 2021, the daily probability of an Omicron variant community outbreak establishing in NL was near one, and nearly twice as high as the previous high, which occurred in September 2021 when the Delta variant was dominant. We evaluate how vaccination and new variants might affect hypothetical future outbreaks in Mt. Pearl, NL. Our modelling framework can be used to evaluate alternative plans to relax public health restrictions when high levels of vaccination are achieved in regions that have implemented an elimination strategy.

Public Health Communication: Consistency, Accuracy, and Community Engagement during the COVID-19 Pandemic (preprint)

Objectives: Communication is central to the implementation and efficacy of public health measures. This paper explores public health messaging in Canada during the COVID-19 pandemic, assessing its potential to encourage or undermine public trust and adherence. Methods This study analyzed data from two primary sources. The first is government press briefings, associated press releases, and public health directives from January 2020 to October 2021 in Nova Scotia, Ontario, and Alberta. The second data source is 34 semi-structured key-informant interviews with public health actors across Canada. A directed qualitative content analysis approach was employed to analyze press briefing transcripts. Team-based coding and thematic analysis were conducted to analyze interview transcripts. Results Three main themes emerged from the data: inconsistency, lack of clarity, and need for engaged communication practice. Ambiguous and inconsistent language practices across and within jurisdictions were common. Clear language that combines scientific evidence with an appeal to social and emotional factors was lacking, specifically in relation to nuanced matters. Communication practices revealed a disconnect between local communities and jurisdictional communicators who often lacked sensitivity and understanding of local concerns and values. Conclusion Effective communication must be consistent, clear, and community-driven. Increased federal leadership surrounding public health communication, further jurisdictional collaboration, improved communication training, established engagement infrastructure, and increased diversity of decision-makers and communicators are suggested to improve the effectiveness of communication practices by instilling public trust and thus adherence with public health measures.

Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C.

OBJECTIVE: To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. METHODS: In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. RESULTS: 33 subjects aged 7-64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. CONCLUSIONS: NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. CLINICALTRIALS. GOV IDENTIFIER: NCT03759639.

Evaluation of an emergency safe supply drug and managed alcohol program in COVID-19 isolation hotel shelters for people experiencing homelessness (preprint)

Background: During a COVID-19 outbreak in the congregate shelter system in Halifax, Nova Scotia, Canada, a multidisciplinary health care team provided an emergency safe supply of pharmaceutical-grade medications and beverage-grade alcohol to facilitate isolation in COVID-19 hotel shelters for residents who are dependent on these substances. We aimed to evaluate (a) substances and dosages provided, and (b) effectiveness and safety of the program. Methods: We retrospectively reviewed medical records of all COVID-19 isolation hotel shelter residents during May 2021. We extracted data on medication and alcohol dosages provided each day. The primary outcome was residents prematurely leaving isolation against public health orders. Adverse events included (a) overdose; (b) intoxication; and (c) diversion, selling, or sharing of medications or alcohol. Results: Over 25 days, 77 isolation hotel residents were assessed (mean age 42 +/- 14 years; 24% women). Sixty-two (81%) residents were provided medications, alcohol, or cigarettes. Seventeen residents (22%) received opioid agonist treatment medications (methadone, buprenorphine, or slow-release oral morphine) and 27 (35%) received hydromorphone tablets. Thirty-one (40%) residents received stimulant tablets with methylphenidate (27; 35%), dextroamphetamine (8; 10%), or lisdexamfetamine (2; 3%). Six residents (8%) received benzodiazepines. Forty-two (55%) residents received alcohol, including 41 (53%) with strong beer, three (3%) with wine, and one (1%) with hard liquor. Over 14 days in isolation, mean daily dosages increased of hydromorphone (45 +/- 32 to 57 +/- 42mg), methylphenidate (51 +/- 28 to 77 +/- 37mg), dextroamphetamine (33 +/- 16 to 46 +/- 13mg), and alcohol (12.3 +/- 7.6 to 13.0 +/- 6.9 standard drinks). Six residents (8%) left isolation prematurely, but four of those residents returned. Over 1,059 person-days in isolation, there were zero overdoses. Documented concerns regarding intoxication occurred six times (0.005 events/person-day) and medication diversion or sharing three times (0.003 events/person-day). Conclusions: An emergency safe supply and managed alcohol program, paired with housing, was associated with low rates of adverse events and high rates of successful completion of the 14-day isolation period in COVID-19 isolation hotel shelters. This supports the effectiveness and safety of emergency safe supply prescribing and managed alcohol in this setting.

COVID-19 – An Opportunity to Improve Access to Primary Care Through Organizational Innovations? (preprint)

Background: COVID-19 catalyzed a rapid and substantial reorganization of primary care, accelerating the spread of existing strategies and fostering a proliferation of innovations. Access to primary care is an essential component of a health care system, particularly during a pandemic. We describe organizational innovations aiming to improve access to primary care and related contextual changes, during the first year of the COVID-19 pandemic in two Canadian provinces, Quebec and Nova Scotia. Methods: We conducted a multiple case studies, based on 63 semi-structured interviews (n=33 in Quebec, n=30 in Nova Scotia) conducted between October 2020 and May 2021 and a review of related internal documents from both jurisdictions. We recruited a diverse range of provincial and regional stakeholders (e.g., policymakers, decision-makers, family physicians, nurses) involved in reorganizing primary care during COVID-19 using purposeful sampling (e.g., based on role, region). Interviews were transcribed verbatim and thematic analysis was conducted in NVivo12. Emerging results were discussed by team members to identify salient themes and organized into logic models. Results: We identified and analyzed six organizational innovations. Four of these - centralized public online booking systems, centralized access centers for unattached patients, and interim primary care clinics for unattached patients and community connector to health and social services for older adults – pre-dated COVID-19 but were accelerated by the pandemic context. The remaining two innovations were created to specifically address pandemic-related needs: COVID-19 hotlines and COVID dedicated primary healthcare clinics. Innovation spread and proliferation was influenced by several factors such as a strengthened sense of community amongst providers, decreased patient demand at the beginning of the first wave, renewed policy and provider interest in population-wide access (versus attachment of patients only), suspended performance targets (e.g., continuity ≥80%) in Quebec, in modality of care delivery, modified fee codes, and greater regional flexibility to implement tailored innovations. Conclusion: COVID-19 accelerated the uptake and creation of organizational innovations to potentially improve access to primary healthcare, removing, at least temporarily, certain longstanding barriers. Many stakeholders believed this reorganization would have positive impacts on access to primary care after COVID-19. Further studies should analyze the effectiveness and sustainability of innovations adapted, developed, and implemented during the COVID-19 pandemic.

“COVID Affected Us All:” The Birth and Postnatal Health Experiences of Resettled Syrian Refugee Women During COVID-19 in Canada (preprint)

Background: Prior to COVID-19, postnatal resettled refugee women in Canada reported barriers to healthcare and low levels of social support, contributing to maternal health morbidities. The COVID-19 pandemic appears to be further exacerbating health inequities for marginalized populations—yet the experiences of resettled refugee women are not fully known. Aim: To understand Syrian refugee women’s experiences accessing postnatal healthcare services and supports during the COVID-19 pandemic. Methods: In-depth interviews were conducted with eight resettled Syrian refugee women living in Nova Scotia (Canada) who were postnatal between March and August 2020. Data analysis was informed by constructivist grounded theory. Findings: Three themes emerged: “the impacts of COVID-19 on postnatal healthcare;” “loss of informal support;” and “grief and anxiety.” Women experienced difficult healthcare interactions, including socially and physically isolated deliveries, challenges accessing in-person interpreters, and cancelled or unavailable in-home services (e.g., public health nurse and doula visits). Increased childcare responsibilities and limited informal supports due to pandemic restrictions left women feeling overwhelmed and exhausted. Stay-at-home orders resulted in some women reporting feelings of isolation and loss, as they were unable to share in person postnatal moments with friends and family, ultimately impacting their mental wellness. Conclusions: COVID-19 and associated public health restrictions had significant impacts on postnatal Syrian refugee women. Data presented in this study demonstrated the ways in which the pandemic environment and related restrictions amplified pre-existing barriers to care and postnatal health inequalities for resettled refugee women—particularly a lack of postnatal informal supports and systemic barriers to care.

Effects of Various Policy Options on COVID-19 Cases in Nova Scotia including Vaccination Rollout Schedule: A Modelling Study (preprint)

BackgroundThe COVID-19 pandemic presents a significant challenge to minimize mortality and hospitalizations due to this disease. Vaccinations have begun to roll-out; however, restriction policies required during and after the rollout remain uncertain. A susceptible-exposed-infected-recovered (SEIR) model was developed for Nova Scotia, and it accounted for the provinces policy interventions, demographics, and vaccine rollout schedule. MethodsA modified SEIR model was developed to simulate the spread and outcomes from COVID-19 in Nova Scotia under different policy options. The model incorporated the age distribution and co-morbidity of the province. A system dynamics model was developed in Vensim. Several scenarios were run to determine the effects of various policy options and loosening of restrictions during and after the vaccine roll-out period. ResultsWhen restrictions policy include moderate closure of businesses, restricting travel to Atlantic Canada, and the mandating of masks and physical distancing, the number of cumulative infections after 110 days was less than 120. However, if national travel was opened by July 5 2021 and there were no restrictions by September 2021, the number of active infections will peak at 6,114 by February 16 2022, and there will be a peak of 104 hospitalizations on February 16 2022. Immediate opening of travel and all restrictions on March 15, 2021 will result in 71,731 active infections by June 4 2021. DiscussionModerate restrictions will be required even after the population is fully vaccinated in order to avoid a large number of infections and hospitalizations because herd immunity is not reached due to children under 12 not being vaccinated, the efficacy of the vaccine, and the portion of the population that will choose not to be vaccinated.

Older Age and Frailty Are Associated With Higher Mortality but Lower Intensive Care Unit Admission Among Adults Admitted to Canadian Hospitals With COVID-19: A Report From the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance Network (preprint)

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020. Methods: Adult patients with laboratory-confirmed COVID-19 admitted to eleven sites in Ontario, Quebec, Alberta and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Age, sex, demographics, housing, exposure characteristics, Clinical Frailty Scale, comorbidities, and outcomes including length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were conducted. Descriptive analyses and multivariable logistic regressions were conducted. Findings: Among 2011 patients, mean age was 71·0 (range 19-105) years. 45·7% were women and 74·0% were white. 21·5% were admitted from Assisted Living facilities, 8·2% from long term care, and 2·1% from homeless shelters. The full spectrum of frailty was represented in both younger and older age groups. The majority (61·7% of adults <65 and 91·2% of those >=65) had at least one underlying comorbidity and 27·2% had obesity. Mortality was 14·3% among those not admitted to ICU, and 24·6% for those admitted to ICU. Older age and higher frailty were associated with reduced ICU admission but increased mortality. Obesity was independently associated with ICU admission but not with death. Associations between underlying comorbidities and adverse outcomes were attenuated but persisted when adjusting for frailty.Interpretation: Frailty and age were independent predictors of lower ICU use and higher mortality; when accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened.Funding Statement: Funding was provided by the Public Health Agency of Canada and the Canadian Institutes of Health Research.Declaration of Interests: MKA reports grant funding from the Public Health Association of Canada, CIHR, Canadian Frailty Network, Sanofi Pasteur and GSK group of companies, and payments from Pfizer, Sanofi Pasteur and Seqirus outside the submitted work. AM reports payments from GSK, Seqirus and Sanofi Pasteur, outside the submitted work. JEM reports payments from RestorBio, Sanofi, GSK, Merck and Medicago outside of the submitted work. TFH reports grants from Pfizer and GSK. ML reports payments from Sanofi, Medicago, Sequirus, and Pfizer outside the submitted work. SAM reports grants and payments from Pfizer, GSK, Merck, Novartis and Sanofi, outside the submitted work. JG, JJL, GB, LV, ME, DM-C, AA, KW, ST, SS, AMc and KK report no conflicts of interest.Ethics Approval Statement: The protocol for active COVID-19 surveillance has been approved by each local site’s Research Ethics Board.

The PUPPY Study – Protocol for a Longitudinal Mixed Methods Study Exploring Problems Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year (preprint)

Background The COVID-19 pandemic significantly disrupted primary care in Canada, with many walk-in clinics and family practices initially closing or being perceived as inaccessible, pharmacies remaining open with restrictions on patient interactions, rapid uptake of virtual care, and reduced referrals for lab tests, diagnostics, and specialist care. The PUPPY Study (Problems Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year) seeks to understand the impact of COVID-19 across the quadruple aim of primary care, with particular focus on the impacts on patients without attachment to a regular provider and those with chronic health conditions. Objective The PUPPY Study objective is to understand the impact of COVID-19 across the quadruple aim of primary care. Methods The PUPPY study builds on an existing research program exploring patients’ access and attachment to primary care, pivoted to adapt to the emerging COVID-19 context. We will undertake a longitudinal mixed methods study to understand critical gaps in primary care access and coordination, comparing data pre- and post-pandemic in three Canadian provinces (Quebec, Ontario, and Nova Scotia). Multiple data sources will be used including: a policy review; qualitative interviews with primary care policymakers, providers (i.e., family physicians, nurse practitioners, and pharmacists), and patients (N=120); and medication prescribing and healthcare billings. The findings will inform the strengthening of primary care during and beyond the COVID-19 pandemic. Results Funding was provided by the Canadian Institutes of Health Research COVID-19 Rapid Funding Opportunity Grant. Ethical approval to conduct this study was granted in Ontario (Queens Health Sciences & Affiliated Teaching Hospitals Research Ethics Board, file number 6028052; Western University Health Sciences Research Ethics Board, project 116591; University of Toronto Health Sciences Research Ethics Board, protocol number 40335), Québec (Centre intégré universitaire de santé et de services sociaux de l’Estrie, project number 2020-3446) and Nova Scotia (Nova Scotia Health Research Ethics Board, file number 1024979). Conclusions This is the first study of its kind exploring the impacts of COVID-19 on primary care systems, with particular focus on the issues of patient’s attachment and access to primary care. Through a multi-stakeholder, cross-jurisdictional approach, the PUPPY Study will generate findings and implications for future policy and practice.

Health Service Experiences and Preferences of Frail Home Care Clients and Their Family and Friend Caregivers During the COVID-19 Pandemic (preprint)

Objective: The COVID-19 pandemic has brought about a major upheaval in the lives of older adults and their family/friend caregivers, including those utilizing home care services. In this article, we focus on results from a qualitative component added to a pragmatic randomized controlled trial that focuses on the experiences of our study participants during COVID-19. A total of 29 participants responded to the COVID-19 related questions focused on their health services experiences and preferences from March-June 2020 including 10 home care clients and 19 family/friend caregivers in the provinces of Ontario and Nova Scotia, Canada. ResultsMany participants were affected drastically by the elimination or reduction of access to services, highlighting the vulnerability of home care clients and their caregivers during COVID-19. This took an emotional toll on home care clients and increased the need for family/friend caregiver support. While many participants expressed reduced desire to utilize residential long-term care homes, some caregivers found that passive remote monitoring technology was particularly useful within the COVID-19 context. Our results provide important insights into the ways the older adults and their caregivers have been affected during the COVID-19 context and how to better support them in the future.

Implementing Essential Coaching for Every Mother during COVID-19: A Pilot Pre-Post Intervention Study (preprint)

ObjectivesThe primary objective was to evaluate the preliminary impact of Essential Coaching for Every Mother on self-efficacy, social support, postpartum anxiety and postpartum depression. The second objective was to explore the acceptability of the Essential Coaching for Every Mother program provided during the COVID-19 pandemic. MethodsA prospective pre-post study was conducted with first time mothers in Nova Scotia, Canada between July 15th and September 19th, 2020. Participants completed a self-report survey at enrolment (after birth) and six-weeks postpartum. Variety of standardized measures were used and qualitative feedback on the program was also collected. Paired t-tests were carried out to determine changes from baseline to follow-up on psychosocial outcomes and qualitative feedback was analysed through thematic analysis. ResultsA total of 88 women enrolled. Self-efficacy increased between baseline (B) and follow-up (F) (B:33.33; F:37.11, p=0.000) while anxiety (STAI) declined (B:38.49; F:34.79; p=0.004). No other significant changes were found. In terms of acceptability, 89% of participants felt that the number of messages were just right, 84.5% felt the messages contained all the information they needed relative to caring for a newborn and 98.8% indicated they would recommend this program to other new mothers. ConclusionEssential Coaching for Every Mother may play a role increasing maternal self-efficacy and decreasing anxiety, although future work with a control group is important to delineate the true effects of the program. Overall, mothers were satisfied with the Essential Coaching for Every Mother program and would recommend it for other mothers, during COVID-19 and beyond.

Variability in instructions for performance of nasopharyngeal swabs across Canada in the era of COVID-19 – what type of swab is actually being performed? (preprint)

Background The primary method of surveillance for the presence of SARS-CoV-2 is with nasopharyngeal swabs. Given the significant demand for nasopharyngeal swabs, a large number of previously untrained and unfamiliar staff are now performing this test. It was noted that there was significant heterogeneity in instructions for performing nasopharyngeal swabs in Canada, in contrast to the guidance provided by the Centers for Disease Control and Prevention (CDC), and the Pan American Health Organization (PAHO). The objective of this study was to review the instructions provided across Canada and contrast them to those of the CDC and PAHO.Methods A standard series of steps for nasopharyngeal swab performance was outlined based on the CDC, PAHO, and New England Journal of Medicine instructions. A comprehensive search was performed in August 2020 to identify nasopharyngeal swab guidelines provided by public health in the provinces and territories of Canada. Regional health authority guidance was also collected. Instructions provided were contrasted against the standardized steps.Results Instructions were identified for all provinces and territories, and for 81 regional health authorities. From the provincial and territorial guidelines, 10/13 (77%) cleared the nasal passages before swab insertion, 11/13 (85%) tilted the patient’s head back slightly, 12/13 (92%) inserted the swab parallel to the palate, but only 3/13 (23%) inserted the swab to at least a depth of the distance between the patient’s nose and ear. A clear majority (81%) of regional health authority guidelines followed their respective provincial guidelines.For depth of insertion, Quebec provided a pictogram but no distance or technique for estimation. Six provinces and territories - Northwest Territories, Nunavut, Ontario, Saskatchewan, Prince Edward Island and Alberta - recommended 4 cm or one-half the distance from nostrils to ear. British Columbia and Manitoba recommended a 7 cm depth of insertion. Nova Scotia recommended one-half to two-thirds the distance from nose to ear. Lastly, Newfoundland, New Brunswick and the Yukon recommended an insertion from nose to the external ear canal.Conclusion There is significant heterogeneity in guidance for nasopharyngeal swab performance across Canada. The instructions provided by the majority of provinces and territories in Canada would not be effective in reaching the nasopharynx.

Look before diving into pooling of SARS-CoV-2 samples on high throughput analyzers (preprint)

Given the unprecedented demand for SARS-CoV-2 testing during the COVID-19 pandemic, the benefits of specimen pooling have recently been explored. As previous studies were limited to mathematical modeling or testing on low throughput PCR instruments, this study aimed to assess pooling on high throughput analyzers. To assess the impact of pooling, SARS-CoV-2 dilutions were performed at varying pool depths (i.e. 1:2, 1:4, and 1:8) into test-negative nasopharyngeal or oropharynx/anterior nares swabs matrix. Testing was evaluated on the automated Roche Cobas 6800 system, or the Roche MagNApure LC 2.0 or MagNAPure 96 instruments paired with a laboratory-developed test using a 96-well PCR format. The frequency of detection in specimens with low viral loads was evaluated using archived specimens collected throughout the first pandemic wave. The proportion of detectable results per pool depths was used to estimate the potential impact. In addition, workflow at the analytical stage, and pre-and post-stages of testing were also considered. The current study estimated that pool depths of 1:2, 1:4, and 1:8 would have allowed the detection of 98.3%, 96.0%, and 92.6% of positive SARS-CoV-2 results identified in the first wave of the pandemic in Nova Scotia. Overall, this study demonstrated that pooling on high throughput instrumentation can dramatically increase the overall testing capacity to meet increased demands, with little compromising to sensitivity at low pool depths. However, the human resources required at the pre-analytical stage of testing is a particular challenging to achieve.

Potential COVID-19 therapeutics from a rare disease: weaponizing lipid dysregulation to combat viral infectivity.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has resulted in the death of more than 328,000 persons worldwide in the first 5 months of 2020. Herculean efforts to rapidly design and produce vaccines and other antiviral interventions are ongoing. However, newly evolving viral mutations, the prospect of only temporary immunity, and a long path to regulatory approval pose significant challenges and call for a common, readily available, and inexpensive treatment. Strategic drug repurposing combined with rapid testing of established molecular targets could provide a pause in disease progression. SARS-CoV-2 shares extensive structural and functional conservation with SARS-CoV-1, including engagement of the same host cell receptor (angiotensin-converting enzyme 2) localized in cholesterol-rich microdomains. These lipid-enveloped viruses encounter the endosomal/lysosomal host compartment in a critical step of infection and maturation. Niemann-Pick type C (NP-C) disease is a rare monogenic neurodegenerative disease caused by deficient efflux of lipids from the late endosome/lysosome (LE/L). The NP-C disease-causing gene (NPC1) has been strongly associated with viral infection, both as a filovirus receptor (e.g., Ebola) and through LE/L lipid trafficking. This suggests that NPC1 inhibitors or NP-C disease mimetics could serve as anti-SARS-CoV-2 agents. Fortunately, there are such clinically approved molecules that elicit antiviral activity in preclinical studies, without causing NP-C disease. Inhibition of NPC1 may impair viral SARS-CoV-2 infectivity via several lipid-dependent mechanisms, which disturb the microenvironment optimum for viral infectivity. We suggest that known mechanistic information on NPC1 could be utilized to identify existing and future drugs to treat COVID-19.

The Coronavirus 2019 pandemic in Canada: the impact of public health interventions on the course of the outbreak in Alberta and other provinces (preprint)

Background: The SARS-CoV-2 disease 2019 (COVID-19) pandemic has spread across the world with varying impact on health systems and outcomes. We assessed how the type and timing of public- health interventions impacted the course of the outbreak in Alberta and other Canadian provinces. Methods: We used publicly-available data to summarize rates of laboratory data and mortality in relation to measures implemented to contain the outbreak and testing strategy. We estimated the transmission potential of SARS-CoV-2 before the state of emergency declaration for each province (R0) and at the study end date (Rt). Results: The first cases were confirmed in Ontario (January 25) and British Columbia (January 28). All provinces implemented the same health-policy measures between March 12 and March 30. Alberta had a higher percentage of the population tested (3.8%) and a lower mortality rate (3/100,000) than Ontario (2.6%; 11/100,000) or Quebec (3.1%; 31/100,000). British Columbia tested fewer people (1.7%) and had similar mortality as Alberta. Data on provincial testing strategies were insufficient to inform further analyses. Mortality rates increased with increasing rates of lab- confirmed cases in Ontario and Quebec, but not in Alberta. R0 was similar across all provinces, but varied widely from 2.6 (95% confidence intervals 1.9-3.4) to 6.4 (4.3-8.5), depending on the assumed time interval between onset of symptoms in a primary and a secondary case (serial interval). The outbreak is currently under control in Alberta, British Columbia and Nova Scotia (Rt <1). Interpretation: COVID-19-related health outcomes varied by province despite rapid implementation of similar health-policy interventions across Canada. Insufficient information about provincial testing strategies and a lack of primary data on serial interval are major limitations of existing data on the Canadian COVID-19 outbreak.

The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.

Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an "unfavorable" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.

The Lysosome: A Potential Therapeutic Juncture between the COVID-19 Pandemic and Niemann-Pick Type C Disease (preprint)

In the face of the newly emergent COVID-19 pandemic, researchers around the world are racing to identify efficacious drugs capable of preventing or treating its infection. They are doing that by testing already available and approved antimicrobials for their rapid repurposing against COVID-19. Using the data emerging on the comparable efficacy of various compounds having different mechanisms of action and indications, I suggest in this report, their potential mechanistic convergence. Specifically, I highlight the lysosome as a key possible therapeutic target for COVID-19, proposing one of the lysosomal storage disorders, Niemann-Pick type C disease (NPC), as a prototypical condition with inherent resistance or an “unfavorable” host cell environment for viral propagation. The included reasoning evolves from previously generated data in NPC, along with the emerging data on COVID-19. The aim of this report is to suggest that pharmacological induction of a “transient” NPC-like lysosomal dysfunction, could hold answers for targeting the ongoing COVID-19 pandemic.