Archived: Preliminary guidance on key populations for early COVID-19 immunization [2020-11-03]

Notice to reader

This is an archived version. Please refer to current COVID-19 vaccine pages:

Preamble
Summary of content included in this NACI statement
Introduction
Methods
Vaccine(s)
Ethics, equity, feasibility and acceptability considerations
Recommendations
Research priorities
List of abbreviations
Acknowledgments
Appendix A: Algorithm outlining the process for applying the EEFA framework
Appendix B: Core ethical dimensions filter applied to COVID-19
Appendix C: Ethical procedural considerations filter applied to COVID-19
Appendix D: Equity matrix applied to COVID-19 with evidence to date
Appendix E: Feasibility matrix applied to COVID-19
Appendix F: Acceptability matrix applied to COVID-19
References

Preamble

The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.

In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence-based recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels.

The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI Statements will require in-depth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidence-informed tools to identify distinct issues that could impact decision-making for recommendation development, only distinct issues identified as being specific to the vaccine or vaccine-preventable disease will be included.

This statement contains NACI’s independent advice and recommendations, which are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

Summary of information contained in this NACI Statement

The objective of this advisory committee statement is to provide preliminary guidance for public health program level decision-making to plan for the efficient, effective, and equitable allocation of a novel coronavirus disease 2019 (COVID-19) vaccine once it is authorized for use in Canada when limited initial vaccine supply will necessitate the prioritization of immunization in some populations earlier than others. These recommendations aim to achieve Canada's pandemic response goal: "To minimize serious illness and overall deaths while minimizing societal disruption as a result of the COVID-19 pandemic." Due to anticipated constraints in supply, these National Advisory Committee on Immunization (NACI) recommendations apply to provincial/territorial publicly-funded immunization programs only and not for individuals wishing to prevent COVID-19 with vaccines not included in such programs.

The recommendations are informed by evidence available at the time of NACI deliberations, including the results of a rapid review of risk factors for severe COVID-19,^{Footnote 1} an expert stakeholder survey on the relative importance of pandemic immunization strategies,^{Footnote 2} and the systematic assessment of ethics, equity, feasibility and acceptability (EEFA) considerations with the peer-reviewed EEFA Framework.^{Footnote 3} NACI will continue to carefully monitor the evidence related to COVID-19 and COVID-19 vaccine(s) and will update recommendations as evidence evolves.

Recommendations for public health program level decision-making

Given arrival of vaccine supply is expected to be staggered over several months, NACI recommends that key populations in whom vaccine is deemed safe and effective based on clinical evidence available at the time of vaccine availability should be prioritized for COVID-19 immunization. These groups are not mutually exclusive and may overlap. A sequential approach cannot be determined until vaccine characteristics, results of clinical trials and the number of available doses are known. Key populations may change as the evidence base for COVID-19 (e.g., epidemiology, transmission dynamics) and vaccine characteristics (e.g., immunogenicity, safety, efficacy, effectiveness in preventing severe illness and interruption of transmission in different populations), as well as information on vaccine supply, evolves.

Sequencing of populations and sub-prioritization within these populations will be based on:

A population-based risk-benefit analysis taking into consideration risk of exposure, risk of transmission to others, risk of severe illness and death, and the safety and effectiveness of vaccine(s) in key populations
Vaccine supply (number of available vaccine types, number and timing of available doses, number of doses required)
COVID-19 epidemic conditions when the vaccine(s) become(s) available

Key populations include:

Those at high risk of severe illness and death from COVID-19

Advanced age
Other high-risk conditions (to be defined as the evidence base evolves)

Those most likely to transmit COVID-19 to those at high risk of severe illness and death from COVID-19 and workers essential to maintaining the COVID-19 response

Healthcare workers, personal care workers, and caregivers providing care in long-term care facilities, or other congregate care facilities for seniors
Other workers most essential in managing the COVID-19 response or providing frontline care for COVID-19 patients
Household contacts of those at high-risk of severe illness and death from COVID-19

Those contributing to the maintenance of other essential services for the functioning of society

To be defined, prioritized and informed by federal/provincial/territorial (FPT) discussions
Examples: those who cannot work virtually and have differential exposure to COVID-19 (e.g., police, firefighters, grocery store staff)

Those whose living or working conditions put them at elevated risk of infection and where infection could have disproportionate consequences, including Indigenous communities

To be defined based on COVID-19 epidemiology and previous pandemic experience
Examples: settings where physical distancing and other infection prevention and control measures are challenging, access to healthcare infrastructure is reduced, and infection could have disproportionate consequences

Other considerations for public health program level decision-making

Efforts should be made to increase access to immunization services to reduce health inequities without further stigmatization or discrimination, and to engage systemically marginalized populations and racialized populations in immunization program planning.
Jurisdictions should begin planning for the implementation of a COVID-19 immunization program, including close and rapid monitoring of safety, effectiveness, and coverage of the vaccine(s) in different key populations, as well as effective and efficient immunization of populations in remote and isolated communities.
Efforts should be made to improve knowledge about the benefits of vaccines in general and of COVID-19 vaccine(s) specifically once available, address misinformation about immunization, and communicate transparently about COVID-19 vaccine allocation decisions.

Figure 1 summarizes NACI's interim recommendations on key populations for early COVID-19 immunization for public health program level decision-making.

**Figure 1: Summary of the preliminary NACI recommendations on key populations for early COVID-19 immunization**

Abbreviations: LTC (long-term care), FPT (federal, provincial and territorial), IPC (infection prevention and control)

Introduction

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is ongoing. It was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. The pandemic has caused significant morbidity and mortality, as well as social and economic disruption worldwide.

The goal of Canada's pandemic response is to minimize serious illness and overall deaths while minimizing societal disruption as a result of the COVID-19 pandemic.

Clinical trials of candidate COVID-19 vaccines are currently underway. The National Advisory Committee on Immunization (NACI) has developed guidance on the research priorities for these clinical trials to support public health decisions.^{Footnote 4} Initial supplies of prospective COVID-19 vaccines are not expected to be sufficient to meet the demand for immunization. Therefore, recommendations are needed on key populations for early immunization.

Guidance objective

The objective of this advisory committee statement is to provide preliminary guidance to plan for the efficient, effective, and equitable allocation of an eventual COVID-19 vaccine when limited initial vaccine supply will necessitate the immunization of some populations earlier than others.

In order to support this objective, the advisory committee statement will:

Summarize the current COVID-19 vaccine landscape;
Present the results of a rapid review on risk factors for severe COVID-19;^{Footnote 1}
Present the results of an expert stakeholder survey ranking the relative importance of COVID-19 pandemic immunization strategies for different pandemic scenarios;^{Footnote 2}
Apply the evidence-informed tools (Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, Acceptability Matrix) of NACI's Ethics, Equity, Feasibility and Acceptability (EEFA) Framework,^{Footnote 3} and finally;
Present key populations prioritized for early COVID-19 immunization to best achieve Canada's pandemic response public health goal when initial vaccine supply is limited, based on the above.

NACI acknowledges that at the time of the development of this statement many uncertainties remain about COVID-19, potential COVID-19 vaccine(s), and therapeutics for COVID-19, as well as what the epidemiology and vaccine supply will be at the time of initial COVID-19 vaccine availability. This guidance is based on the evidence available at the time of NACI deliberations, along with expert and stakeholder opinion. NACI will provide further guidance when additional information on vaccine-specific characteristics (e.g., efficacy, immunogenicity, safety, effectiveness to prevent severe disease or interrupt transmission) in different populations (e.g., age groups, those with underlying medical conditions) becomes available. NACI will continue to monitor the evidence as it evolves.

Methods

This advisory committee statement will aim to address the following policy question:

Assuming constrained early supply for COVID-19 vaccine(s) in Canada, which populations should be prioritized for early doses of vaccine?

To develop these recommendations over the summer of 2020, NACI reviewed available epidemiological summaries from national analyses of federal/provincial/territorial (FPT) surveillance data reported to the Public Health Agency of Canada (PHAC);^{Footnote 5} summaries of the COVID-19 vaccine product landscape from clinical trial registry data; and the Vaccine Annex of the Canadian Pandemic Influenza Preparedness: Planning Guidance for the Health Sector.^{Footnote 6} In addition:

The NACI Secretariat conducted an environmental scan of international guidance on prioritization of key populations for initial COVID-19 immunization.
The NACI Secretariat conducted a national survey of expert stakeholders between July 22 and August 14, 2020 to establish a comprehensive perspective on the relative importance of pandemic immunization strategies under four different pandemic scenarios at the time of initial COVID-19 vaccine availability. Full methodological details and results can be found in the preprint.^{Footnote 2}
The Alberta Research Centre for Health Evidence (ARCHE) was commissioned to conduct a rapid review of risk factors for severe COVID-19 (literature search carried out on June 15, 2020). Full methodological details and results can be found in the preprint.^{Footnote 1} An updated evidence synthesis will be carried out at a later date.
The NACI Secretariat applied NACI's EEFA Framework^{Footnote 3} with accompanying evidence-informed tools (Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, Acceptability Matrix) to systematically consider these programmatic factors for the development of clear, comprehensive, appropriate recommendations for timely, transparent decision-making. For details on the development and application of NACI's EEFA Framework and evidence-informed tools (including the Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, and Acceptability Matrix), please see A framework for the systematic consideration of ethics, equity, feasibility, and acceptability in vaccine program recommendations .

As per the published process for the application of this Framework (see Appendix A), experts and stakeholder groups (e.g., Public Health Ethics Consultative Group, First Nations and Inuit Health Branch [FNIHB], Indigenous Services Canada, and other NACI liaison and ex-officio organisations ) were consulted. The following FPT committees were consulted during the development of this statement: Canadian Immunization Committee (CIC), the Pan-Canadian Public Health Network's Special Advisory Committee on COVID-19 (SAC), and SAC's Technical Advisory Committee. The Sex and Gender Based Analysis Plus (SGBA+) network with the Social Determinants of Health Division at PHAC also reviewed this guidance. The CIC, FNIHB, and PHAC's vaccine supply manager discussed the feasibility of proposed immunization strategies and validated the Feasibility Matrix. Emerging acceptability data related to COVID-19 vaccines were sought and included in the Acceptability Matrix. See Section IV for further details.

Available evidence was presented to the NACI High Consequence Infectious Disease Working Group (HCID WG) on July 24, 2020, and to NACI on August 13, 2020. NACI deliberated on the cumulative evidence and proposed recommendations on August 20, 2020, provided feedback through to September 1, 2020, and approved the revised recommendations on September 16, 2020.

Further information on NACI's process and procedures can be found elsewhere.^{Footnote 7}

Vaccine(s)

Current COVID-19 vaccine landscape

Global efforts are underway to develop a COVID-19 vaccine and work is progressing at an unprecedented pace. The Government of Canada is reviewing regulatory pathways to help expedite access to safe and effective vaccine for Canadians.

As of August 5, 2020, there are over 130 candidate COVID-19 vaccines at different stages of development by academia and industry. Many candidates have shown promise to enter into human clinical trials, 15 Phase 1 clinical trials have been registered, 23 Phase 2 clinical trials have been registered, and five Phase 3 clinical trials are underway or planned to start. Phase 3 clinical trials have been started in the United Kingdom (UK), the United States (US), Brazil, and the United Arab Emirates with results expected in late 2020 or in early 2021 (e.g., University of Oxford/AstraZeneca, Moderna, Sinopharm, Sinovac). More than one vaccine developer plans to start clinical trials in Canada. As of September 4, 2020, one vaccine developer has already begun Phase 1 clinical trials and several others are expected to advance to that stage in the coming months.

The current landscape of candidate COVID-19 vaccines in clinical evaluation can be found at: Draft landscape of COVID-19 candidate vaccines

Summary of vaccine clinical development

Most of the trials in Phase 1 of clinical development are assessing the safety of vaccines in healthy adults 18 to 49 years of age without underlying health conditions. Due to the high burden of COVID-19 in older adult populations, some Phase 1 studies have expanded age ranges to include older adult populations. In later stages of clinical development (Phases 2 and 3), some vulnerable and at-risk populations (including people who are HIV+ and adults over 65 years of age) are included in study recruitment. Both established and experimental vaccine technologies, including nucleic acid (mRNA and DNA), vectored (viral and bacterial vectors), subunit (protein and glycan), particles (nanoparticles and virus-like-particles), inactivated virus vaccines, and prophylactic immune products (antibodies and sera) are being explored. Vaccine candidates are administered via different routes of administration, including intramuscular, intradermal (and electroporation), oral, and subcutaneous. Schedules of candidate vaccines range between one and three doses.

Canadian vaccine access

The unprecedented nature of this pandemic and vaccine development efforts has led to a highly competitive global landscape of vaccine access. As of October 27^th, 2020, seven suppliers of promising vaccine candidates have committed to supply Canada with vaccine to cover a portion of or the entire Canadian population. It is still to be determined if these vaccines will be safe, efficacious, authorized in Canada, and be recommended by NACI.

Ethics, equity, feasibility and acceptability considerations

The EEFA Framework^{Footnote 3} facilitates the systematic consideration of factors critical for comprehensive immunization program decision-making and successful implementation of recommendations. The use of the EEFA Framework empowers the committee to review and balance all of the available evidence and transparently summarize their rationale for appropriate, timely recommendations. The evidence informed tools associated with the framework (Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, Acceptability Matrix; see Appendices B-F) ensure that issues related to EEFA of expert committee guidance are adequately integrated. NACI followed the process outlined in the algorithm for applying the EEFA Framework (Appendix A) to this guidance.

Ethics considerations

NACI used the Public health ethics framework: A guide for use in response to the COVID-19 pandemic in Canada^{Footnote 8} to support ethics deliberation and decision-making. NACI's Ethics Integrated Filters for core ethical dimensions (respect for persons and communities, beneficence and non-maleficence, justice, trust) and procedural ethical dimensions (accountability, inclusiveness, responsibility, responsiveness, transparency) were applied to this guidance document, and are summarized in Appendices B and C. An in-depth ethics analysis was conducted to analyse and weigh relative considerations and assess options for prioritization of COVID-19 immunization in the face of an uncertain pandemic vaccine supply.

NACI upheld the following core ethical principles:

1. Respect for persons and communities

In order to respect the right to exercise informed choice, NACI has reviewed the evidence to date and summarized it for stakeholders throughout this guidance document. The values and preferences of persons and communities have been considered through the national expert stakeholder survey ranking the relative importance of pandemic immunization strategies,^{Footnote 2} as well as evidence available to date on the acceptability of COVID-19 vaccines in various populations in Canada (summarized in Section IV.4). Extensive consultations were conducted in the development of this guidance (summarized in Section II).

2. Beneficence and non-maleficence

NACI considered evidence for minimizing the risk of harm and maximizing benefits for all potential key populations in their deliberations. As information about vaccine characteristics (including safety and efficacy in different populations) becomes available, the principles of proportionality (measures should be proportionate to the level of risk and benefits gained), effectiveness (reasonable likelihood that the action will achieve the goals and will be feasible), and precaution (take prudent action in the face of scientific uncertainty) will be applied. NACI has previously recommended that individuals with potential biological, social, and occupational vulnerabilities to COVID-19 be included in vaccine clinical trial groups4. However, in the absence of direct data in populations at high risk of severe illness and death due to COVID-19 (e.g., due to age or underlying medical conditions), NACI will consider the principles of proportionality, effectiveness, and precaution, and conduct an in-depth ethics analysis before making specific recommendations. Immunization strategies aimed at protecting healthcare capacity and other services essential for the functioning of society uphold the principle of reciprocity, as they aim to minimize the disproportionate burden faced by those taking on additional risks to protect the public. The public also benefits from the ongoing work of those who provide these services and could potentially benefit from reduced transmission from frontline workers, which aligns with the principle of beneficence.

3. Justice

Treating people and groups with equal concern and respect entails setting and applying prioritization criteria fairly, considering the needs of those most at risk of exposure or of severe disease, and weighing risks of furthering inequities, stigmatization, and discrimination. NACI reviewed special considerations for vulnerability of those most at risk through its application of the Equity Matrix (Appendix D), a rapid review of risk factors for severe COVID-19,^{Footnote 1} as well as a review of disease epidemiology in Canada.^{Footnote 5} NACI also considered evidence concerning other factors, such as systemic marginalization of groups with differential disease severity and differential access to healthcare, as well as the demonstrated potential for reduced exposure among healthcare workers with increased training in and access to personal protective equipment (PPE) and other infection prevention and control (IPC) measures.^{Footnote 9}^{Footnote 10} In the face of uncertainties about the disease and vaccine with resulting challenges in program planning for an eventual COVID-19 vaccine, and in consultation with jurisdictions and vaccine supply experts, NACI considered the principle of distributive justice with the application of the Feasibility Matrix (Appendix E). The systematic assessment of all of these factors informed NACI's recommendations for the fair and equitable allocation of limited COVID-19 vaccine supply.

4. Trust

Reliability and integrity of guidance must be maintained for trust in this and other immunization programs. Expedited regulatory reviews of COVID-19 vaccines and evolving evidence about the disease may have an impact on the trust of the public in this immunization program and their perception of risks associated with these vaccines. NACI followed its established methodology, standard operating procedures (SOP), and conflict of interest guidelines^{Footnote 7} in the context of this expedited review to ensure a robust analysis of evidence and to maintain stakeholder trust. This guidance is based on the best, current evidence available for all groups at risk of COVID-19, with transparency about knowns and unknowns, as well as certainty of evidence. NACI will monitor the evidence with revision of guidance as necessary. To maintain trust among stakeholders, NACI has upheld ethical procedural considerations (accountability, inclusiveness, responsibility, responsiveness, and transparency) with the tools and procedures as summarized in Appendix C.

NACI acknowledges the risk that there could be a perception of conflict of interest, and a resulting loss of trust, when expert groups of healthcare professionals are making recommendations on the prioritization of immunization strategies involving health care workers and personnel. NACI also acknowledges that trust may be eroded if healthcare professionals are not included in a priority group for earlier immunization with a novel vaccine. To maintain trust, reliability, integrity, and a mutually fair relationship with individuals and communities, NACI applied the Ethics Integrated Filters described above (Appendices B and C), made recommendations based on the evidence transparently summarized in this document, and considered a wide range of stakeholder views (including patient and community advocates) through an expert stakeholder survey,^{Footnote 2} as well as the views of the general public through public opinion research^{Footnote 11} when developing this guidance.

Equity considerations

NACI reviewed the epidemiology of COVID-19 in Canada^{Footnote 5} and the results of the rapid review of risk factors for severe COVID-191 (summarized in Section IV.2.1) to identify distinct inequities associated with COVID-19, potential reasons for these inequities, and suggested interventions to reduce inequities and improve access to vaccine when it becomes available. The results of this analysis are summarized in the Equity Matrix (Appendix D).

Factors contributing to severe COVID-19: results of a rapid review of risk factors

A rapid review was conducted by ARCHE to examine the magnitude of association between factors that may contribute to health inequity (summarized by the acronym "P²ROGRESS And Other Factors" in NACI's Equity Matrix, Appendix D) and severe COVID-19. The HCID WG decided on the primary outcomes, settings, and populations of interest and the protocol was registered in PROSPERO (CRD42020198001). Full details of the rapid review methodology and findings can be found in the preprint.^{Footnote 1}

Literature searches were conducted on June 15, 2020 in the following bibliographic databases: Medline, Epistimonikos COVID-19 in LOVE Platform, and McMaster COVID-19 Evidence Alerts. The following inclusion criteria were used: studies from the Organisation for Economic Co-operation and Development (OECD) countries, published (vs. preprints), and using multivariate analysis to report on the independent contribution of each risk factor while accounting for confounders such as age, sex, race/ethnicity, socioeconomic status, and comorbidities. Populations included a general/community sample, people with confirmed COVID-19, and people hospitalized with COVID-19 (studies were excluded if all patients were in the intensive care unit (ICU) or were in a treatment study). Outcomes of interest included hospitalization and length of stay, severe disease (as defined by study authors) and mortality. The risk of bias/quality of each study was assessed, accounting for the extent of adjustment, follow-up duration/extent of censorship for length of stay and mortality, and inappropriate or large exclusions from the study and/or analysis.

No meta-analysis was conducted. For each risk factor and outcome, findings were assessed across studies in terms of the estimated magnitude of associations (i.e., "not important/not large" [e.g., odds ratio (OR) <1.7], moderate [OR ≥1.7 to 1.99], important/large [OR ≥2.0], very large [OR ≥5.0], and the review team's confidence in the magnitude of association based on the number, size and consistency between studies and the risk of bias. Varying confidence in the associations is referred to using the terms "uncertain" (no/very low), "may" (low/some), and "probably" (moderate).

A total of 34 published studies were included, although three from the UK had overlapping populations and another UK study is likely to overlap but the degree of overlap is unknown. Studies were conducted in the US (n=17), Italy (n=9), the UK (n=7 using 5 populations), and across multiple countries (n=1). Sample sizes ranged from 44 to 418,794 (median 596) and mean age in most studies was 54 to 71 years. The majority of studies (n=19; 56%) were rated low risk of bias.

None of the associations had a high level of certainty of evidence. There was low or moderate certainty of evidence for large/important associations (OR or risk ratio [RR]) with increased risk of hospitalization in people having confirmed COVID-19 for the following risk factors: obesity class III (body mass index [BMI] ≥40 kg/m²), heart failure, diabetes, chronic kidney disease, dementia, age (particularly over 70 years vs. 45 years or younger), male sex, Black race/ethnicity (vs. non-Hispanic white), homelessness, and low income (<25^th vs. >50^th percentile). Evidence that age over 70 years may be associated with important increases in the rate of severe disease was considered to be of moderate certainty. Risk factors that have large/important and very large important associations with hospitalization and mortality are presented in Table 1.

**Table 1**: Risk factors identified through a rapid review that have large/important (++) or very large/important (+++) associations with severe COVID-19 outcomes and the corresponding level of confidence in the association
Risk factor	Outcome of interest	Magnitude of risk^{Footnote 1} (confidence in association)^{Footnote 2}
Age
>80 vs. ≤ 45 years	Hospitalization	+++ (low)
>80 vs. ≤ 45 years	Mortality	+++ (low)
>70 vs. ≤ 45 years	Hospitalization	+++ (moderate)
>70 vs. ≤ 45 years	Mortality	+++ (moderate)
>60 vs. ≤ 45 years	Hospitalization	++/+++ (moderate/low)
>60 vs. ≤ 45 years	Mortality	++/+++ (moderate/low)
50-64 vs. ≤ 45 years	Hospitalization	++ (moderate)
50-64 vs. ≤ 45 years	Mortality	++ (moderate)
45-54 vs. ≤ 45 years	Hospitalization	++ (moderate)
45-54 vs. ≤ 45 years	Mortality	++ (low)
Pre-existing conditions
Obesity (BMI ≥40)	Hospitalization	++ (low)
Heart failure	Hospitalization	++ (low)
Diabetes	Hospitalization	++ (low)
Liver disease	Mortality	++ (low)
Chronic kidney disease	Hospitalization	++ (low)
Alzheimer disease or dementia	Hospitalization	++ (low)
Sex
Male vs. female	Hospitalization	++ (moderate)
Race/ethnicity
Black vs. non-Hispanic white	Hospitalization	++ (low)
Asian (Bangladeshi) vs. British white	Mortality	++ (low)
Place of residence
Homeless vs. has a home	Hospitalization	++ (low)
Socioeconomic status
Income ≤25^th vs. >50^th or 75^th percentile	Hospitalization	++ (low)
Table 1 - footnotes Footnote 1 Magnitude of associations are shown as large/important (++; OR or RR ≥2.00) or very large important association (+++; OR or RR ≥5.00). Return to footnote 1 referrer Footnote 2 A formal assessment of the quality/confidence of the evidence was not performed but was informed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Confidence in the magnitude of the associations was determined by considering primarily study limitations (risk of bias), consistency in findings across studies, and precision (sample size). Low confidence indicates that there may be an association and moderate means that the evidence indicates that there probably is an association. Return to footnote 2 referrer

For mortality, important associations with increased risk may exist for liver disease, Bangladeshi ethnicity (vs. British white), and age particularly if over 70 years (vs. <45 years). The data were somewhat inconsistent for sex, with most studies showing moderate certainty of no important effect. One study directly compared subgroups of older adults, showing that compared to those aged 65-69 years, there may be no important increased risk of mortality among hospitalized adults aged 70-79 years, but risk may increase about 2-fold for those 80 years and older. Studies treating age on a continuum or across small increments consistently found that risks for hospitalization and mortality increased with increasing age (e.g., approximately 2-6% and 5-10% relative increase in risk per year).

Moderate association with low level of confidence may exist for increased risk of hospitalization with obesity (BMI ≥30 or 40 kg/m²); severe disease with heart failure; mortality with hematological malignancy; and hospitalization with social deprivation (lowest vs. highest quintile).

There was moderate certainty evidence for no important increase in risk of hospitalization with chronic respiratory conditions, cardiovascular disease (i.e., coronary artery disease, hypertension, hyperlipidaemia) apart from heart failure, non-specific cancer, Asian race/ethnicity other than Bangladeshi (vs. non-Hispanic white), and current or former smoking. Additionally, there was moderate certainty evidence for no important increase in severe disease (as defined by each study) with chronic respiratory conditions, chronic kidney disease, nonspecific cancer, and Black race/ethnicity (vs. non-Hispanic white) and no important increase in risk of mortality with obesity (BMI ≥30 kg/m²), chronic respiratory conditions, diabetes, chronic kidney disease, nonspecific cancer, male sex, Black or Asian race/ethnicity (vs. non-Hispanic white), and social deprivation (lowest vs. highest quintile).

In the rapid review, data for immunocompromised patients (specifically rheumatic disease and HIV) were limited by small studies and no conclusions could be drawn about the magnitude and certainty of the associations. Further, no studies on pregnancy met the publication date and eligibility criteria.

Generalization of findings from other countries to Canada should be made with caution, as high-risk groups may differ by population. Furthermore, because of differences in methodology, the list of important risk factors identified in this rapid review may differ from other sources. Updated evidence syntheses will inform future NACI decisions.

Feasibility considerations

NACI recognizes that there are a number of challenges to the feasible implementation of a COVID-19 immunization program due, in part, to the uncertainties around vaccine characteristics (e.g., indications, adverse events) and supply, as well as the novel nature of the disease and vaccine(s). Issues around the vaccine and the immunization program with respect to resources (e.g., vaccine and immunization supplies including storage and dissemination of new vaccine technologies in different vaccine delivery venues; human resources for administration of vaccine, communication, training, data entry, screening for COVID-19, operational planning, etc.) as well as integration with existing programs (e.g., registries, surveillance, adverse event following immunization (AEFI) reporting) abound. Close and rapid monitoring of safety, effectiveness, and coverage of the vaccine(s) in potentially different key populations will be critical.

To assist jurisdictions with the planning of a potential COVID-19 immunization program, jurisdictions may refer to the Feasibility Matrix (Appendix E), summarizing potential issues with implementing a COVID-19 immunization program. These issues apply to immunization in any population. Jurisdictions may also wish to refer to the Interim guidance on continuity of immunization programs during the COVID-19 pandemic^{Footnote 12} to minimize disruption to existing immunization programs.

The feasibility of immunizing different populations will vary with the size of the population to be immunized, vaccine characteristics in the population, and vaccine supply, among other considerations. Sub-prioritization or sequencing within key populations may be necessary, either initially and/or gradually.

In some Indigenous communities, crowded multi-generational living makes segregation of at-risk groups challenging, and precarious supply chain, infrastructure, and health systems are vulnerable to critical disruption. In these cases, there may be value in implementing multiple strategies concurrently and completely immunizing entire communities where relatively small quantities of vaccine are needed to achieve the pandemic response goal.

Acceptability considerations

In alignment with the ethical principle of respect for persons and communities, the values and preferences of a range of stakeholders, including experts, patient/community advocates, and the general public were considered. Factors influencing acceptability of a COVID-19 vaccine are summarized using the Acceptability Matrix (Appendix E).

Results of an expert stakeholder survey on COVID-19 immunization strategies

A PHAC-led survey was conducted to establish a preliminary expert stakeholder perspective on the relative importance of pandemic immunization strategies for different COVID-19 pandemic scenarios at the time of initial COVID-19 vaccine availability. These pandemic scenarios are visualized along a hypothetical pandemic curve in Figure 2. Scenario 4 was further delineated in the survey into two sub-scenarios where the vaccine or previous infection provides or does not provide long-term protection against COVID-19. Full methodology and results of the survey can be found in the preprint.^{Footnote 2}

The survey was comprised of five questions that asked the respondent to rank, in order of importance with a rank of "1" being the most important, four COVID-19 pandemic immunization strategies (proposed by PHAC staff with input from the HCID WG) plus an optional respondent-specified strategy for each pandemic scenario. The respondents were asked to assume that the COVID-19 vaccine is in limited supply for each scenario and that the COVID-19 vaccine is safe and efficacious for all populations for the purposes of the survey.

**Figure 2: Pandemic scenarios at the time of initial COVID-19 vaccine availability plotted along a hypothetical pandemic curve**

Expert stakeholders were identified through consultations within PHAC and with the HCID WG. These stakeholders included members of clinical and public health expert groups involved with PHAC, members of provincial and territorial committees and representatives from national Indigenous groups, patient and community advocacy representatives and experts from the CanCOVID network, executives of Canadian health professional associations, and representatives of other federal government departments. An invitation to complete the survey, which was provided as a Word document in English and French, was sent by email to stakeholders in a format that facilitated shared review and discussion within their respective organisations. Members of expert groups (e.g., NACI) each provided individual expert responses, whereas organisational or provincial/territorial representatives each provided a single response on behalf of their organisation or jurisdiction.

The survey was conducted between July 22 and August 14, 2020. Survey results were analyzed using descriptive statistics across all respondents to identify overall trends and by stakeholder group to assess for any differences in prioritization among stakeholder groups. Trends in the rankings for each pandemic scenario were assessed by descriptive analysis in two ways: taking the average (mean, median, and mode) ranking and comparing the percentage of each ranking contributing to the total for COVID-19 pandemic immunization strategies for different pandemic scenarios at the time of initial COVID-19 vaccine availability.

Of 156 stakeholders contacted, 74 surveys were completed for a participation rate of 47.4%. A total of 22 (29.7%) respondents were members of clinical or public health expert groups involved with PHAC, 19 (25.7%) were patient or community advocacy representatives or experts from the CanCOVID network, 16 (21.6%) were executives of Canadian health professional associations, nine (12.2%) were members of provincial and territorial committees or national Indigenous groups, and eight (10.8%) were representatives of federal government departments.

For all pandemic scenarios, both descriptive analysis approaches showed that stakeholders generally ranked the strategies in the following order from most to least important:

Protect those who are most vulnerable to severe illness and death from COVID-19
Protect healthcare capacity
Minimize transmission of COVID-19
Protect critical infrastructure

In subgroup analysis by stakeholder group, the trends were less clear due to smaller sample sizes, but the strategy to protect those who are most vulnerable to severe illness and death from COVID-19 remained the most important in all groups and scenarios.

Results of surveys of the general Canadian public on COVID-19 immunization

Canada's COVID-19 Snapshot Monitoring Study (COSMO Canada) is a longitudinal study led by Impact Canada in collaboration with the Public Opinion Research Team within the Privy Council Office that began in April 2020 and continued through September 2020 in eight waves.^{Footnote 11} This online survey leverages a tool developed by the WHO to monitor knowledge, risk perceptions, and behaviour related to COVID-19, is adapted wave-to-wave in consultation with an external academic advisory committee, and collects data from a representative sample of approximately 2000 Canadians. NACI considered the most up-to-date results of this survey (up to wave 7, conducted between August 13 and 17, 2020)^{Footnote 13}^{Footnote 14} and populated the Acceptability Matrix (Appendix F) to inform its guidance.

NACI acknowledges that survey data on intent to receive a vaccine can fluctuate, especially in the context of uncertainty about possible COVID-19 vaccines. NACI will continue to monitor data from the remaining wave of the COSMO study, as well as another study assessing acceptability of COVID-19 and other vaccines among Canadians, planned in the coming months.

Which immunization strategies do Canadians prioritize if COVID-19 vaccine supply is limited?

Wave 7 of the COSMO Canada survey asked respondents to prioritize the same immunization strategies that expert stakeholders were asked to rank in order of importance in the context of limited initial COVID-19 vaccine supply (see Section IV.4.1). A majority of these respondents prioritized protecting those most vulnerable (51%), followed by protecting healthcare capacity (28%), minimizing the spread (15%), and protecting critical infrastructure (5%).^{Footnote 14} The opinions of respondents from the general public on priority immunization strategies are consistent with those of expert stakeholders surveyed.

Which populations do Canadians prioritize to receive COVID-19 vaccine if supply is limited?

Three-quarters of COSMO Canada respondents (76% in wave 6 and 78% in wave 7) agree that specific groups should be first to get a safe and effective COVID-19 vaccine in the context of limited initial supplies.^{Footnote 13}^{Footnote 14} In response to an open ended question in wave 6 asking which group should get the vaccine first, the most commonly identified populations for priority immunization included those with underlying medical conditions (57%), the elderly (53%), healthcare workers (22%), and frontline/essential workers^{Footnote a} (18%). Although endorsed less frequently, respondents also identified children (9%), long-term care/nursing homes (3%), and hospitalized/ill individuals (2%), as other populations that should receive the vaccine first should there be a shortage.^{Footnote 13} When asked to rank a pre-determined list of groups to be prioritized to receive a COVID-19 vaccine before others in wave 7 of the survey, the most commonly identified group for priority immunization was healthcare workers (40%), followed by individuals with high risk medical conditions (19%), frontline workers (16%), seniors (12%), long-term care/nursing homes (10%), and children (2%).^{Footnote 14}

The majority of respondents (87%) to an Angus Reid Institute online survey about COVID-19 in July 2020 of a representative sample of 1,519 Canadian adults agreed that "it is vital that people with chronic health conditions, such as asthma or diabetes, get vaccinated".^{Footnote 15}

Does a high level of acceptability for a COVID-19 vaccine exist?

Almost two-thirds of COSMO Canada respondents (61%) in August 2020 were willing to get an effective recommended COVID-19 vaccine.^{Footnote 14} This has decreased from 71% in April. While willingness to get an effective recommended vaccine has decreased among all age groups surveyed, older Canadian respondents (aged 55 years of age and older) are significantly more willing to get immunized than younger Canadian respondents (72% in >54 year olds vs. 57% in 35-54 year olds and 51% in 18-34 year olds; p<0.05). Respondents 35 years and older with a "serious, long-term illness" are somewhat more willing to get an effective recommended vaccine compared to those without (68% vs 62%). This was not observed in younger individuals 18 to 34 years old with a "serious, long-term illness" compared to those without (43% vs. 57%). Non-visible minorities are more willing than visible minorities or Indigenous respondents to get an effective recommended vaccine (63% vs. 53% vs. 43%, respectively; p<0.05). About half of workers in frontline occupations such as grocery and gas station staff (51% vs. 63% for non-frontline workers; p<0.05) and healthcare providers (55% vs. 62% for non-healthcare workers; p>0.05) would get an effective recommended vaccine. Willingness to receive an effective COVID-19 vaccine does not seem to be significantly influenced by socioeconomic status or sex.^{Footnote 14}

The findings from the COSMO Canada study are similar to results from other Canadian surveys. The Canadian Perspectives Survey Series 3 (CPSS3) in June 2020 (survey sample is representative of the Canadian population living in the ten provinces) found that approximately three-quarters of Canadians were either very likely (57.5%) or somewhat likely (19.0%) to get a COVID-19 vaccine when it becomes available.^{Footnote 16} The largest differences in intent to get a COVID-19 vaccine were observed across age groups and education levels. Significantly more Canadians 65 years and older reported being very likely to get a COVID-19 vaccine than those aged 15-64 (70% vs. 52-58%; p<0.05). Respondents with a university degree higher than a bachelor's degree were significantly more likely to report being very likely to get a COVID-19 vaccine (73% vs. 53% of those with a trades or university certificate below a bachelor's degree; p<0.05). The Angus Reid Institute online survey in July 2020 found that 46% of respondents would get a coronavirus vaccine as soon as one became available, but 32% would wait a while first.^{Footnote 15}

What factors affect acceptability of immunization with a COVID-19 vaccine?

The most reported reasons for unwillingness to get a COVID-19 vaccine in wave 7 of the COSMO Canada survey included insufficient research or testing of the vaccine (32%), concerns about vaccine safety or effectiveness (26%), and a lack of trust in the newness of the vaccine (13%).^{Footnote 14} The top two reasons selected by respondents to the CPSS3 survey who were hesitant to get a COVID-19 vaccine also related to concerns about safety (54% cited a lack of confidence in the safety of the vaccine and 52% were concerned about its risks and side effects; respondents could select more than one response).^{Footnote 16} Similarly, the majority of respondents to the Angus Reid Institute survey who would wait to get a COVID-19 vaccine reported that they are worried about side effects (76%), and 61% of respondents overall shared concerns about vaccine safety.^{Footnote 15}

Results from the Angus Reid Institute survey reveal that key factors for those willing to be immunized include trust in doctors (84% agree that "we should listen to doctors who recommend vaccines"), and a desire to protect their families (82% agree that they would "get a vaccine to protect my family").^{Footnote 15} Only 23% were concerned about getting infected with the coronavirus from a vaccine and only 23% believe a coronavirus vaccine will not be effective. Only a small minority (9%) agree that they will not have time to get a COVID-19 vaccine.

According to this poll, the majority of Canadians support mandatory immunization for healthcare workers (76%), extended care homes (76%), schools (63%), and workplaces such as offices and restaurants (52%).^{Footnote 15}

What factors affect acceptability of immunization in general?

Research conducted to validate NACI's Acceptability Matrix prior to the COVID-19 pandemic revealed multiple factors that affect the acceptability of immunization in general.^{Footnote 3} Consistent with what has been found in recent surveys on a potential COVID-19 vaccine, concern about vaccine safety is the main reason for reluctance to vaccinate among Canadians.^{Footnote 17} However, vaccine effectiveness has the largest influence on choice of vaccine between two provided options.^{Footnote 18} Likewise, among high risk groups, perceived safety and effectiveness of a vaccine are linked to increased vaccine acceptability.^{Footnote 17} Perceived risk of disease and a desire to protect oneself and others are also linked to increased vaccine acceptability, as are low cost of vaccine, low time required to be vaccinated, and access to vaccine or a vaccine provider.^{Footnote 17}^{Footnote 18}

In general, receiving a recommendation from, or being in contact with, a healthcare provider is linked to increased vaccine acceptability.^{Footnote 17} However, a lack of familiarity with a vaccine plays a role in reluctance by healthcare providers to recommend it.^{Footnote 17}^{Footnote 18} A recommendation by an expert committee is a notable factor for healthcare providers to recommend a vaccine.^{Footnote 18}

Recommendations

The following recommendations are meant to help plan for the efficient, effective, and equitable allocation of an eventual COVID-19 vaccine(s) when limited initial vaccine supply will necessitate recommendations for the immunization of certain groups earlier than others. These recommendations aim to achieve Canada's pandemic response goal: "To minimize serious illness and overall deaths while minimizing societal disruption as a result of the COVID-19 pandemic." Due to anticipated constraints in supply, these NACI recommendations apply to provincial/territorial publicly-funded immunization programs only and not for individuals wishing to prevent COVID-19 with vaccines not included in immunization programs.

The recommendations are informed by evidence available at the time of NACI deliberations summarized in this document, including the results of a rapid review of risk factors for severe COVID-19,^{Footnote 1} an expert stakeholder survey on the relative importance of pandemic immunization strategies,^{Footnote 2} and the systematic assessment of EEFA considerations with the peer-reviewed EEFA Framework.^{Footnote 3}

NACI has reviewed the available international guidance on priority groups for COVID-19 immunization at the time of deliberation. The key populations for early COVID-19 immunization identified by NACI have been similarly identified by other national immunization technical advisory groups^{Footnote 19}^{Footnote 20} and academic groups^{Footnote 21}^{Footnote 22} in their vaccine prioritization frameworks.

NACI will continue to carefully monitor the evidence related to COVID-19 and COVID-19 vaccine(s) and will update recommendations as evidence evolves.

Recommendations for public health program level decision-making

Due to anticipated challenges with sufficient supply to meet vaccine demand initially, NACI recommends that key populations in whom vaccine is deemed safe and effective based on evidence available at the time of vaccine availability should be prioritized for COVID-19 immunization. These groups are not mutually exclusive and may overlap. A sequential approach cannot be determined until vaccine characteristics, results of clinical trials, and the number of available doses are known. Key populations may change as the evidence base for COVID-19 and vaccine characteristics, as well as information on vaccine supply, evolves.

Sequencing of key populations and sub-prioritization within key populations will be based on:

A population-based risk-benefit analysis taking into consideration risk of exposure, risk of transmission to others, risk of severe illness and death, and the safety and effectiveness of vaccine(s) in key populations
Vaccine supply (number of available vaccine types, number and timing of available doses, number of doses required)
COVID-19 epidemic conditions when the vaccine(s) become(s) available