Impact of population mixing between vaccinated and unvaccinated subpopulations on infectious disease dynamics: implications for SARS-CoV-2 transmission.

BACKGROUND: The speed of vaccine development has been a singular achievement during the COVID-19 pandemic, although uptake has not been universal. Vaccine opponents often frame their opposition in terms of the rights of the unvaccinated. We sought to explore the impact of mixing of vaccinated and unvaccinated populations on risk of SARS-CoV-2 infection among vaccinated people. METHODS: We constructed a simple susceptible-infectious-recovered compartmental model of a respiratory infectious disease with 2 connected subpopulations: people who were vaccinated and those who were unvaccinated. We simulated a spectrum of patterns of mixing between vaccinated and unvaccinated groups that ranged from random mixing to complete like-with-like mixing (complete assortativity), in which people have contact exclusively with others with the same vaccination status. We evaluated the dynamics of an epidemic within each subgroup and in the population as a whole. RESULTS: We found that the risk of infection was markedly higher among unvaccinated people than among vaccinated people under all mixing assumptions. The contact-adjusted contribution of unvaccinated people to infection risk was disproportionate, with unvaccinated people contributing to infections among those who were vaccinated at a rate higher than would have been expected based on contact numbers alone. We found that as like-with-like mixing increased, attack rates among vaccinated people decreased from 15% to 10% (and increased from 62% to 79% among unvaccinated people), but the contact-adjusted contribution to risk among vaccinated people derived from contact with unvaccinated people increased. INTERPRETATION: Although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to people who are unvaccinated, their choices affect risk of viral infection among those who are vaccinated in a manner that is disproportionate to the portion of unvaccinated people in the population.

Impact of immune evasion, waning and boosting on dynamics of population mixing between a vaccinated majority and unvaccinated minority.

BACKGROUND: We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid. METHODS: We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, "hybrid" effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon. RESULTS: Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3-4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of "hybrid immunity", frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people. INTERPRETATION: Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people.

Relative pandemic severity in Canada and four peer nations during the SARS-CoV-2 pandemic.

Background: National responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been highly variable. We sought to explore the effectiveness of the Canadian pandemic response up to May 2022 relative to responses in four peer countries with similar political, economic and health systems, and with close historical and cultural ties to Canada. Methods: We used reported age-specific mortality data to generate estimates of pandemic mortality standardized to the Canadian population. Age-specific case fatality, hospitalization, and intensive care admission probabilities for the Canadian province of Ontario were applied to estimated deaths, to calculate hospitalizations and intensive care admissions averted by the Canadian response. Health impacts were valued in both monetary terms, and in terms of lost quality-adjusted life years. Results: We estimated that the Canadian pandemic response averted 94,492, 64,306 and 13,641 deaths relative to the responses of the United States, United Kingdom and France, respectively, and more than 480,000 hospitalizations relative to the United States. The United States pandemic response, if applied to Canada, would have resulted in more than $40 billion in economic losses due to healthcare expenditures and lost quality-adjusted life years. In contrast, an Australian pandemic response applied to Canada would have averted over 28,000 additional deaths and averted nearly $9 billion in costs. Conclusion: Canada outperformed several peer countries that aimed for mitigation rather than elimination of SARS-CoV-2 in the first two years of the pandemic, with substantial numbers of lives saved and economic costs averted. However, a comparison with Australia demonstrated that an elimination focus would have saved Canada tens of thousands of lives as well as substantial economic costs.

Vaccine effectiveness against hospitalization among adolescent and pediatric SARS-CoV-2 cases between May 2021 and January 2022 in Ontario, Canada: A retrospective cohort study.

BACKGROUND: Vaccines against SARS-CoV-2 have been shown to reduce risk of infection as well as severe disease among those with breakthrough infection in adults. The latter effect is particularly important as immune evasion by Omicron variants appears to have made vaccines less effective at preventing infection. Therefore, we aimed to quantify the protection conferred by mRNA vaccination against hospitalization due to SARS-CoV-2 in adolescent and pediatric populations. METHODS: We retrospectively created a cohort of reported SARS-CoV-2 case records from Ontario's Public Health Case and Contact Management Solution among those aged 4 to 17 linked to vaccination records from the COVaxON database on January 19, 2022. We used multivariable logistic regression to estimate the association between vaccination and hospitalization among SARS-CoV-2 cases prior to and during the emergence of Omicron. RESULTS: We included 62 hospitalized and 27,674 non-hospitalized SARS-CoV-2 cases, with disease onset from May 28, 2021 to December 4, 2021 (Pre-Omicron) and from December 23, 2021 to January 9, 2022 (Omicron). Among adolescents, two mRNA vaccine doses were associated with an 85% (aOR = 0.15; 95% CI: [0.04, 0.53]; p<0.01) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. Among children, one mRNA vaccine dose was associated with a 79% (aOR = 0.21; 95% CI: [0.03, 0.77]; p<0.05) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. The calculation of E-values, which quantifies how strong an unmeasured confounder would need to be to nullify our findings, suggest that these effects are unlikely to be explained by unmeasured confounding. CONCLUSIONS: Despite immune evasion by SARS-CoV-2 variants, vaccination continues to be associated with a lower likelihood of hospitalization among adolescent and pediatric Omicron (B.1.1.529) SARS-CoV-2 cases, even when the vaccines do not prevent infection. Continued efforts are needed to increase vaccine uptake among adolescent and pediatric populations.

Interventions to Improve Uptake of Direct-Acting Antivirals for Hepatitis C Virus in Priority Populations: A Systematic Review.

Background & Objective: Access to Hepatitis C (HCV) care remains suboptimal. This systematic review sought to identify existing interventions designed to improve direct-acting antiviral (DAA) uptake among HCV infected women, people who inject drugs (PWID), men who have sex with men (MSM), and Indigenous peoples. Methods: Studies published in high- and middle-income countries were retrieved from eight electronic databases and gray literature (e.g., articles, research reports, theses, abstracts) were screened by two independent reviewers. Identified interventions were summarized using textual narrative synthesis. Results: After screening 3,139 records, 39 studies were included (11 controlled comparative studies; 36 from high-income countries). Three groups of interventions were identified: interventions involving patients; providers; or the healthcare system. Interventions directed to patients included care co-ordination, accelerated DAA initiation, and patient education. Interventions involving providers included provider education, telemedicine, multidisciplinary teams, and general practitioner-led care. System-based interventions comprised DAA universal access policies and offering HCV services in four settings (primary care, secondary care, tertiary care, and community settings). Most studies (30/39) described complex interventions, i.e., those with two or more strategies combined. Most interventions (37/39) were tailored to, or studied among, PWID. Only one study described an intervention that was aimed at women. Conclusions: Combining multiple interventions is a common approach for supporting DAA initiation. Three main research gaps were identified, specifically, a lack of: (1) controlled trials estimating the individual or combined effects of interventions on DAA uptake; (2) studies in middle-income countries; and (3) interventions tailored to women, MSM, and Indigenous people.

Potential interventions to support HCV treatment uptake among HIV co-infected people in Canada: Perceptions of patients and health care providers.

BACKGROUND: Increasing direct-acting antiviral (DAA) treatment uptake is key to eliminating HCV infection as a public health threat in Canada. People living with human immunodeficiency virus (HIV) and hepatitis C (HCV) co-infection face barriers to HCV treatment initiation. We sought to identify interventions that could support HCV treatment initiation based on patient and HCV care provider perspectives. METHODS: Eleven people living with HIV with a history of HCV infection and 12 HCV care providers were recruited for this qualitative descriptive study. Participants created ranked-ordered lists of potential interventions during nominal groups (n = 4) and individual interviews (n = 6). Following the nominal group technique, transcripts and intervention lists underwent thematic analysis and ranking scores were merged to create consolidated and prioritized lists from patient and provider perspectives. RESULTS: Patient participants identified a total of eight interventions. The highest-ranked interventions were multidisciplinary clinics, HCV awareness campaigns and patient education, nurse- or pharmacist-led care, peer involvement, and more and better-prepared health professionals. Provider participants identified 11 interventions. The highest-ranked were mobile outreach, DAA initiation at pharmacies, a simplified process of DAA prescription, integration of primary and specialist care, and patient-centred approaches. CONCLUSION: Participants proposed alternatives to hospital-based specialist HCV care, which require increasing capacity for nurses, pharmacists, primary care providers, and peers to have more direct roles in HCV treatment provision. They also identified the need for structural changes and educational initiatives. In addition to optimizing HCV care, these interventions might result in broader benefits for the health of HIV-HCV co-infected people.

Barriers and facilitators related to HCV treatment uptake among HIV coinfected populations in Canada: Patient and treatment provider perceptions.

BACKGROUND: Direct-acting antiviral (DAA) uptake is challenging across HIV-hepatitis C (HCV) coinfected populations. This study sought to identify barriers and facilitators related to DAA uptake in priority populations in Canada. METHODS: This qualitative descriptive study included 11 people living with HIV with a history of HCV and 15 HCV care providers. Participants were part of either nominal groups (n = 4) or individual interviews (n = 6) in which they identified and ranked barriers and facilitators to DAA uptake. Consolidated lists of barriers and facilitators were identified thematically. RESULTS: Patient participants highly ranked the following barriers: competing priorities and needs (ie, social instability and mental health), delays in care, lack of adherence, and polypharmacy. Provider participant top barriers were the following: competing priorities and needs (ie, social chaos), delays in care (eg, systemic barriers, difficulties engaging patients, lack of trained HCV providers), and HCV-related stigma. Patient participants identified having a strong network of health care providers, family, and friends, possessing intrinsic motivation, and DAAs being a simple and tolerable oral treatment as important facilitators. Provider participant top-ranked facilitators were having resources to identify hard-to-reach populations (eg, patient navigation, outreach), holistic care and addiction management, provider HCV education, and a strong network of interprofessional collaboration. CONCLUSION: The barriers to DAA initiation addressed by patients and providers overlapped, with some nuances. Multidisciplinary care fostering a strong supportive network and intrinsically motivated patients along with HCV education emerged as key facilitators. This study provides insights for developing potential strategies to improve DAA uptake among HIV-HCV coinfected people in Canada.

Patient and provider perceived barriers and facilitators to direct acting antiviral hepatitis C treatment among priority populations in high income countries: A knowledge synthesis.

BACKGROUND: Direct acting antivirals (DAAs) have increased cure rates for hepatitis C virus (HCV) infection; however, there are several obstacles to the uptake of DAAs in populations where substance use contributes to HCV risk. This synthesis aimed to identify the patient and provider perceived barriers and facilitators to DAA treatment initiation in key patient subgroups-people who inject drugs (PWID), men who have sex with men (MSM), and Indigenous people. METHODS: We systematically searched seven databases and conducted a gray literature search for studies that qualitatively explored patient and provider perceived barriers and facilitators to DAA treatment in our populations of interest. Selected studies were published after 2013 when second generation DAAs became available. The titles, abstracts, and subsequently full texts were screened by two independent reviewers and critically appraised. Barriers and facilitators to DAA treatment uptake were then extracted and thematically synthesized. RESULTS: 2144 titles and abstracts were identified and screened; 29 full texts were subsequently reviewed. Twelve qualitative studies were finally included. Among providers, perceived barriers to DAA treatment uptake included lack of resources and lack of provider knowledge on HCV while facilitators to treatment provision included simplicity of DAA regimens and professional identity as a doctor to advocate for patients. Among patients, perceived barriers to treatment uptake included current drug use, concerns about side effects of DAAs, stigma, gaps in community care, competing social responsibilities and mental health issues while facilitators included having a trustworthy provider and access to multidisciplinary HCV care. CONCLUSION: Despite simplicity of DAAs, many structural barriers to optimal HCV care continue to be experienced by patients and providers. In highlighting nuanced patient and provider perceived barriers and facilitators, this review underscores the need to involve participatory methods in the design and evaluation of interventions to best improve access to care.