Local and systemic responses to SARS-CoV-2 infection in children and adults.

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children

Confronting structural violence in sex work: lessons from a community-led HIV prevention project in Mysore, India

Evidence from community-led HIV prevention projects suggests that structural interventions may result in reduced rates of HIV and STIs. However, the complex relationship between empowerment and confronting stigma, discrimination and physical abuse necessitates further investigation into the impact that such interventions have on the personal risks for sex workers. This article aims to describe the lived experiences of members from a sex worker’s collective in Mysore, India and the ways in which they have confronted structural violence with various social actors and institutions. The collection of narratives highlights experiences of violence and the development and implementation of strategies that have altered the social, physical, and emotional environment for sex workers. Building an enabling environment has been key to reducing the personal risks inherent to sex work for this community, emphasizing the importance of community-led structural interventions for sex workers in India

Exploring trajectories of drug use, violence, and suicidality among marginalized women : avenues of intervention and the therapeutic potential of psychedelics

Background: Women who are marginalized due to social and/or economic disadvantage, including street-involved women, sex workers, and women who use drugs, experience numerous health and social inequities that disproportionately elevate risk of violence and suicidality. However, research and intervention programs to prevent violence and address systemic drivers of suicidality have been largely absent for this population and the socio-structural determinants remain poorly understood and under investigated. This dissertation therefore sought to explore trajectories of drug use, violence and suicidality among marginalized sex workers and aimed to identify avenues of intervention with a special focus on the therapeutic utility of psychedelics. Methods: This dissertation drew on data collected from AESHA (An Evaluation of Sex Workers’ Health Access), a community-based open prospective cohort of women sex workers across Metro Vancouver, Canada. Bivariate and multivariable logistic regression analyses using generalized estimating equations were employed to examine associations between various intersecting socio-structural factors and suicidality. Cox regression analyses were used to examine the impact of individual and socio-structural factors on incidence of crystal methamphetamine injection and suicidality, and assessed the independent effect of naturalistic psychedelic use on suicidality. Results: This dissertation identified that sex workers experience elevated risk and rates of suicidality influenced by dynamic, interrelated socio-structural factors. Experiences of interpersonal violence, homelessness, trauma/mental illness and physical/sexual childhood abuse were among the strongest determinants shaping drug use trajectories and risk of suicidality. Importantly, the study findings demonstrated that increased social cohesion had an independent protective effect on suicidality, as did psychedelic use, which was associated with a 60% reduced hazard of suicidality. Conclusion: Socio-structural factors play a critical role in potentiating and mitigating risk of suicide. Strengthening social cohesion among sex workers may be an important protective strategy, and this dissertation provides some of the first empirical evidence of the potential benefits of psychedelic use for preventing suicidality. The collective findings of this dissertation offer critical insights into how integrated, trauma-informed, community-led structural interventions may mitigate risk of suicide, and underscore the need to advance research on the therapeutic utility of psychedelics alongside broader interventions that facilitate social cohesion and connectedness.Graduate and Postdoctoral StudiesGraduat

Preventing sexually transmitted and blood borne infections (STBBIs) among sex workers: a critical review of the evidence on determinants and interventions in high-income countries

Background: Across diverse regions globally, sex workers continue to face a disproportionate burden of HIV and other sexually transmitted and blood borne infections (STBBIs). Evidence suggests that behavioural and biomedical interventions are only moderately successful in reducing STBBIs at the population level, leading to calls for increased structural and community-led interventions. Given that structural approaches to mitigating STBBI risk beyond HIV among sex workers in high-income settings remain poorly understood, this critical review aimed to provide a comprehensive synthesis of the global research and literature on determinants of HIV and other STBBIs and promising intervention practices for sex workers of all genders in high-income countries. Methods: We searched for publications over the last decade (January 2005–March 2016) among sex workers (cis women, cis men, and trans individuals). Data obtained from quantitative peer-reviewed studies were triangulated with publicly available reports and qualitative/ethnographic research where quantitative evidence was limited. Results: Research demonstrates consistent evidence of the direct and indirect impacts of structural factors (e.g., violence, stigma, criminalization, poor working conditions) on increasing risk for STBBIs among sex workers, further compounded by individual and interpersonal factors (e.g., mental health, substance use, unprotected sex). Sub-optimal access to health and STBBI prevention services remains concerning. Full decriminalization of sex work has been shown to have the largest potential to avert new infections in sex work, through reducing workplace violence and increasing access to safer workspaces. Promising practices and strategies that should be scaled-up and evaluated to prevent STBBIs are highlighted. Conclusions: The high burden of STBBIs among sex workers across high-income settings is of major concern. This review uniquely contributes to our understanding of multilevel factors that potentiate and mitigate STBBI risk for sex workers of all genders. Research suggests that multipronged structural and community-led approaches are paramount to addressing STBBI burden, and are necessary to realizing health and human rights for sex workers. Given the heterogeneity of sex worker populations, and distinct vulnerabilities faced by cis men and trans sex workers, further research utilizing mixed-methods should be implemented to delineate the intersections of risk and ameliorate critical health inequalities.Graduate and Postdoctoral StudiesMedicine, Faculty ofNon UBCMedicine, Department ofPopulation and Public Health (SPPH), School ofReviewedFacult

Safety considerations in the evolving legal landscape of psychedelic-assisted psychotherapy

International drug policy is rapidly evolving in tandem with promising evidence for psychedelic-assisted psychotherapy (PAP) in treating a range of mental health conditions. Canada is among the countries increasingly expanding access to psychedelic substances for therapeutic purposes. The 8-year ban on medical exemptions through the Canadian Special Access Programme was recently reversed in January 2022 and the first exemptions for legal possession and personal use of psilocybin mushrooms were granted in 2020, nearly 50 years since their criminalization. In view of the evolving evidence base and regulatory landscape for PAP illustrated by recent shifts in Canadian and international drug policy, this piece seeks to clarify the special range of factors which ought to be considered to safely expand access to psychedelics. Streamlining access to safe and evidence-based compassionate use of PAP will provide a timely treatment option to those currently in need while encouraging further research and outcome surveillance to refine best practices.Medicine, Faculty ofMedicine, Department ofReviewedFacultyResearche

Psychedelic-Assisted Psychotherapy After COVID-19 : The Therapeutic Uses of Psilocybin and MDMA for Pandemic-Related Mental Health Problems

The COVID-19 pandemic stands to have impacts on mental health and well-being that will extend beyond its formal resolution. Before COVID-19, mental health disorders were already challenging global healthcare systems, directly accounting for 7.4% of the total burden of disease (1, 2). An estimated 1 billion people worldwide suffer from a mental health disorder, with the two most common disorders—depression and anxiety—costing the global economy US$1 trillion per year (3). Stigma and limited treatment options have amounted to substantial unmet need and violations in human rights for people with mental health disorders (1, 4, 5). Looking ahead, heightened post-pandemic demand for mental healthcare signifies an urgent need to bolster clinical capacity by integrating novel, cost-effective approaches into existing systems (6). Emergent literature globally describes the diverse impacts of COVID-19 on mental health (7, 8). For instance, available data among hospitalized COVID-19 patients in China revealed that approximately 96% suffered post-traumatic stress symptoms (9). Studies among intensive care unit (ICU) patients with previous coronaviruses infer high rates of posttraumatic stress disorder (PTSD), depression and anxiety (30-40%) persisting months after discharge (10), with similar rates observed in patients infected with COVID-19 (11). Highly exposed individuals such as frontline healthcare workers are susceptible to similarly negative outcomes due to prolonged occupational stress, elevating risk of PTSD and suicidality (12–14). Importantly, post-pandemic mental disorders are not limited to individuals directly exposed to COVID-19. Rather, research documents PTSD symptoms among individuals who have been indirectly exposed by witnessing (e.g., via the media) or being confronted with the threat of death or serious illness (e.g., worry/anticipation about the future) (7). COVID-19 has significantly altered lives in ways that exacerbate drivers of mental health problems, with widespread uncertainty, increased experiences of grief and loss, social isolation, economic and housing instability, and decreased access to critical services related to lockdowns (6, 15). Further, available data on the impacts of COVID-19 on substance use patterns indicate increased use of alcohol and other substances in response to stress and negative emotions (8, 16, 17). Social connections are crucial for people struggling with addiction and comorbidities such as depression, and increased social disconnection represents a key risk factor for adverse outcomes (e.g., relapse and overdose) (1, 6, 18). The societal and economic consequences are tremendous, with structurally vulnerable groups at greatest risk of harms. For example, North America has seen dramatic spikes in fatal overdoses attributable to socio-structural conditions worsened by COVID-19 (18, 19), disproportionately impacting racialized groups (20). The legacy of mental health problems that will be left behind by COVID-19 incites innovative solutions to address rising rates of PTSD, depression, anxiety, addictions, and social disconnection. As such, we would be remiss not to consider a novel approach with anti-depressive, anxiolytic, and antiaddictive potential that may also foster a sense of social and environmental connectedness, known as psychedelic-assisted psychotherapy (21–24).Arts, Faculty ofMedicine, Faculty ofNon UBCMedicine, Department ofPsychology, Department of (Okanagan)ReviewedFacultyResearcherGraduat

Prevalence and Correlates of Nonmedical Prescription Opioid Use Among a Cohort of Sex Workers in Vancouver, Canada

Background The nonmedical use of prescription opioids (POs) is a major public health concern, causing extensive morbidity and mortality in North America. Canada has the second highest consumption rate of POs globally and data indicate nonmedical PO use (NPOU) is growing among key populations and increasingly available in street-level drug markets. Despite accumulating evidence documenting the rise of NPOU, few studies have systematically examined NPOU in Canada among key vulnerable populations, such as sex workers. This study prospectively evaluated the prevalence and correlates of NPOU within a Vancouver cohort of sex workers over three-years follow-up. Methods Data were drawn from an open prospective cohort, AESHA (An Evaluation of Sex Workers Health Access) in Metro Vancouver, Canada (2010-2013). Women were recruited through outreach from outdoor street locations and indoor venues. Bivariate and multivariable logistic regression using Generalized Estimating Equations (GEE) were used to examine social and structural correlates of NPOU over 36 months. Results Of the 692 sex workers at baseline, close to one-fifth (n=130, 18.8%) reported NPOU (injection or non-injection) in the last six months. In multivariable GEE analyses, factors independently correlated with recent NPOU were: exchanging sex while high (AOR 3.26, 95%CI 2.29-4.64), police harassment/arrest (AOR 1.83, 95%CI 1.43-2.35), intimate partner injects drugs (AOR 1.66, 95%CI 1.11-2.49), and recent physical/sexual intimate partner violence (AOR 1.65, 95%CI 1.21-2.24). Conclusion Our results demonstrate that nearly one-fifth of sex workers in Metro Vancouver report NPOU. Factors independently statistically associated with NPOU included exchanging sex while high, police harassment/arrest, a drug injecting intimate partner and recent physical/sexual intimate partner violence. The high prevalence of NPOU use among sex workers underscores the need for further prevention and management strategies tailored to this key population. The correlates of NPOU uncovered here suggest that structural interventions may be further implemented to ameliorate this growing concern.Medicine, Faculty ofOther UBCMedicine, Department ofPopulation and Public Health (SPPH), School ofReviewedFacultyResearcherGraduat