Archived 4: Recommendations on the use of COVID-19 vaccines [2021-03-01]

Notice to reader

This is an archived version.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

Publication date: March 1, 2021

Table of updates
Preamble
Summary
Introduction
Methods
Epidemiology
Vaccines
- Preparations of COVID-19 vaccines authorized for use in Canada
  - Table 1: COVID-19 vaccines authorized for use in Canada
- Efficacy and effectiveness
- Immunogenicity
- Vaccine administration
  - Table 2: Recommended immunization schedule, by COVID-19 vaccine
- Serological testing
- Storage requirements
- Simultaneous administration with other vaccines
- Vaccine safety and adverse events following immunization (AEFI)
- Contraindications and precautions
  - Table 3: Ingredients of authorized COVID-19 vaccines that have been associated with allergic reactions in other products
- Drug interactions
- Blood products, human immunoglobulin and timing of immunization
Recommendations
Management options for COVID-19 vaccines authorized for use in Canada
- Table 4: Management options for types of COVID-19 vaccines authorized for use in Canada
Management options for COVID-19 immunizations program roll-out in the context of limited vaccine supply
- Table 5: International strategies and recommendations for COVID-19 immunization program roll-out in the context of limited vaccine supply
- Table 6: Management Options Table for mRNA COVID-19 immunization program roll-out in the context of limited mRNA vaccine supply
Research priorities
Surveillance issues
- Table 7: Strength of NACI recommendations
List of abbreviations
Acknowledgments
Appendix A: Evidence summary for Pfizer-BioNTech COVID-19 vaccine
- Table 8: Pfizer-BioNTech vaccine efficacy against the first occurrence of symptomatic COVID-19 disease after dose 1
Appendix B: Evidence summary for Moderna COVID-19 vaccine
- Table 9: Moderna vaccine efficacy against the first occurrence of symptomatic COVID-19 disease after dose 1
Appendix C: Evidence summary for AstraZeneca COVID-19 vaccine
- Table 10: Estimates of vaccine efficacy against the first occurrence of confirmed COVID-19 beginning ≥15 days after Dose 2 in all participants, by dosing interval
- Table 11: Estimates of vaccine efficacy against the first occurrence of confirmed COVID-19 beginning ≥15 days after Dose 2, by dosing interval and age group
- Table 12: Estimates of vaccine efficacy against the first occurrence of confirmed COVID-19 beginning after Dose 1
- Table 13: Estimates of vaccine efficacy against the hospitalization, by dosing interval
- Table 14: Estimates of vaccine efficacy against asymptomatic infection, by dosing interval
Appendix D: Frequency of solicited adverse events following immunization for COVID-19 vaccines
- Table 15: Frequency of solicited local adverse events in authorized populations
- Table 16: Frequency of solicited systemic adverse events in authorized populations
Appendix E: Application of the EEFA framework - Ethical analysis of options for the delivery of a second dose of COVID-19 vaccine in the context of a limited vaccine supply
References

Table of updates

This evergreen document will be updated as COVID-19 vaccines are authorized for use in Canada, and as evidence on these vaccines and COVID-19 evolves. This table summarizes the latest changes to this current version. Please refer to the Table of updates for a full list of updates to previous versions.
Section	Update	Date
Vaccines	All sub-sections under Vaccines have been updated to include evidence or information from the product monograph related to the AstraZeneca COVID-19 vaccine. This includes: Table 1. COVID-19 vaccines authorized for use in Canada Dose, Route of administration, and Schedule Efficacy and Immunogenicity Storage requirements Vaccine safety and adverse events following immunization	2021-03-01
Vaccines	Table 1. COVID-19 vaccines authorized for use in Canada has been updated to reflect the change in the Pfizer BioNTech COVID-19 product monograph stating one multi-dose vial contains 6 doses.	2021-03-01
Contraindications and Precautions	Tromethamine as an ingredient in the Moderna COVID-19 vaccine that has been associated with allergic reactions in other products has been added to Table 3. Clarification on the management of allergies and allergic reactions has been added, in consultation with NACI's Vaccine Safety Working Group.	2021-03-01
Contraindications and Precautions	Potential allergens for AstraZeneca COVID-19 vaccine have been added to Table 3.	2021-03-01
Drug Interactions	Guidance on the use of tuberculin skin tests and interferon gamma release assays before or after administration of COVID-19 vaccine has been added.	2021-03-01
Recommendations	Recommendations on COVID-19 vaccine now include use of the AstraZeneca COVID-19 vaccine, and the rationales have been updated with evidence from AstraZeneca COVID-19 vaccine clinical trials.	2021-03-01
Recommendations	A management options table for the use of different types of COVID-19 vaccines authorized for use in Canada has been added.	2021-03-01
Appendix C	Evidence on the efficacy, immunogenicity, and safety of the AstraZeneca COVID-19 vaccine has been added in a new appendix.	2021-03-01
Appendix D	Frequency of Solicited Adverse Events Following Immunization for COVID-19 vaccines has been updated to include information on the AstraZeneca COVID-19 vaccine.	2021-03-01

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.

This document is being disseminated 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 vaccines. Manufacturer(s) have sought approval of the vaccines 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

The following highlights key, current information for immunization providers on COVID-19 vaccine. The evidence on COVID-19 disease and vaccines is evolving. Evidence from clinical trial data is limited due to limitations in the size and duration of follow-up of trial populations; however, studies are ongoing. NACI will continue to monitor the data and update its recommendations as needed. Please refer to the remainder of the Statement for details.

What

Disease

Novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Anyone can be infected with SARS-CoV-2. However, some populations are at increased risk of exposure to the virus (e.g., due to living or work settings), and some populations are at increased risk of severe disease and death due to biological (e.g., advanced age, pre-existing medical conditions) and social (e.g., low socioeconomic status, belonging to a racialized population) factors that may intersect. Risk factors for exposure and severe disease may overlap, further increasing risk. Any combination of these factors, as well as varying access to health care services, has the potential for disproportionate consequences for specific populations.

Currently authorized vaccines (Pfizer BioNTech COVID-19, Moderna COVID-19, AstraZeneca COVID-19 vaccine)

mRNA vaccines are authorized for use in Canada for individuals 16 years of age and older. (Pfizer-BioNTech COVID-19 vaccine) or 18 years of age and older (Moderna COVID-19 vaccine).
A non-replicating viral vector vaccine is authorized for use in Canada for individuals 18 years of age and older (AstraZeneca COVID-19 vaccine). NACI does not recommend the use of this vaccine in individuals 65 years of age and older due to limited information on the efficacy of this vaccine in this age group at this time.
In clinical trials, all COVID-19 vaccines are efficacious in the short-term against symptomatic, confirmed COVID-19 disease; trials are ongoing. mRNA COVID-19 vaccines have demonstrated high efficacy (approximately 94%). The AstraZeneca COVID-19 vaccine has demonstrated an average efficacy of approximately 62% in those 18-64 years of age.
Protection offered by the first dose of mRNA vaccines is lower than the efficacy achieved after the second dose. The protection offered by the first dose of the viral vector vaccine is comparable to the efficacy observed after the second dose, with protection lasting until the second dose is administered (up to 12 weeks later).
There is currently insufficient evidence on the duration of protection and on the efficacy of these vaccines in preventing death, hospitalization, asymptomatic infection and reducing transmission of SARS-CoV-2, although studies are ongoing.
No serious safety concerns related to the vaccines have been identified to date in clinical trials; however, studies are ongoing. For all vaccines, some solicited adverse events were reported to be very common (defined as 10% or more) among vaccine recipients. However, they are mild or moderate and transient, resolving within a few days. These include: pain at the injection site, fatigue, headache, muscle pain, chills, joint pain, and fever. In clinical trials of mRNA vaccines, some adverse events, including fever, are more frequent after the second dose; this was not the case with the AstraZeneca COVID-19 vaccine.
There is currently minimal evidence to inform on differences in vaccine efficacy or safety between those with and those without prior evidence of SARS-CoV-2 infection at the time of vaccination.

Who

NACI makes the following recommendations:

A complete vaccine series with a currently authorized COVID-19 vaccine should be offered to:

Individuals in the authorized age group without contraindications to the vaccine. In the context of limited vaccine supply, initial doses of mRNA COVID-19 vaccines should be prioritized for the key populations outlined in NACI's Guidance on the Prioritization of Initial Doses of COVID-19 Vaccine(s).
- Due to suggested superior efficacy, mRNA COVID-19 vaccine is preferentially recommended for individuals in the authorized age group without contraindications, especially in those at highest risk of severe illness and death and highest risk of exposure to COVID-19 who are prioritized for early COVID-19 vaccination.
- In the context of limited vaccine supply, AstraZeneca COVID-19 vaccine may be offered to individuals 18-64 years without contraindications if:
  - The advantages of earlier vaccination outweigh the limitations of vaccinating with a less efficacious vaccine;
  - The ease of transport, storage and handling of this vaccine facilitates access to vaccination which may otherwise be challenging; and
  - Informed consent includes discussion about current vaccine options and the timing of future vaccine options.

A complete vaccine series with a currently authorized COVID-19 vaccine may be offered to:

Individuals in the authorized age group without contraindications to the vaccine who have had previously polymerase chain reaction (PCR) SARS-CoV-2 infection. In the context of limited vaccine supply, initial doses may be prioritized for those who have not had previously PCR-confirmed SARS-CoV-2 infection. Testing for previous SARS-CoV-2 infection is not needed prior to COVID-19 vaccination.

For some specific populations who were either excluded from, or were represented by small numbers of participants in clinical trials, NACI recommends that a complete vaccine series with a currently authorized COVID-19 vaccine may be offered, if a risk assessment deems that the benefits of vaccination outweigh the potential risks for the individual (e.g., where the risk of severe outcomes of COVID-19 and/or risk of exposure to SARS-CoV-2 is high) or for the fetus/infant (in the case of pregnancy/breastfeeding) and if informed consent includes discussion about the insufficient evidence in these populations:

Immunosuppressed due to disease or treatment
Individuals with an autoimmune condition
Pregnant or breastfeeding
Adolescents 12 to 15 years of age (Only Pfizer-BioNTech COVID-19 vaccine may be offered)

These recommendations may change as more evidence on safety and/or effectiveness in these populations becomes available.

NACI also recommends that:

All individuals should continue to practice recommended public health measures for prevention and control of SARS-CoV-2 infection and transmission regardless of vaccination with COVID-19 vaccine, at this time, due to insufficient evidence on the duration of protection and effectiveness of COVID-19 vaccines in preventing asymptomatic infection and reducing transmission of SARS-CoV-2.
Routine immunization programs and immunization with other vaccines recommended by NACI should continue during the COVID-19 pandemic with mitigation of risks of COVID-19 transmission during the immunization process as outlined in the Interim guidance on continuity of immunization programs during the COVID-19 pandemic.
Clinical trials assessing COVID-19 vaccines should continue to be encouraged to include individuals with potential vulnerabilities to disease related to biological (e.g., pre-existing medical conditions, frailty, pregnancy and breastfeeding, immunocompromised), and social (e.g., residence in long term care facilities or crowded/remote locations, belonging to a racialized population, occupation) factors to ensure that vaccine options are informed by robust safety, immunogenicity, and efficacy data as outlined in NACI's guidance on Research Priorities for COVID-19 Vaccines to Support Public Health Decisions. Furthermore, NACI recommends the continuation of clinical trials and ongoing follow-up of participants for as long as it is ethically feasible to determine the level of immunity needed to prevent disease, duration of protection, efficacy in different sub-populations, and medium- and long-term safety.
In addition to ongoing vaccine pharmacovigilance activities in Canada with Phase 4 clinical trials and post-marketing studies, additional research and surveillance of COVID-19 vaccination, particularly in populations not currently included in clinical trials (e.g., pregnant, breastfeeding, immunosuppressed, seniors living in congregate care settings, children and adolescents) is recommended.

NACI continues to recommend the following elements to guide ethical decision-making, as outlined in NACI's guidance on Key Populations for Early COVID-19 Immunization:

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 ensure close and rapid monitoring of safety, coverage and effectiveness of the vaccines in different key populations, as well as effective and efficient immunization of populations in hardly reached, remote and isolated communities.
Efforts should be made to improve knowledge about the benefits of vaccines in general and of COVID-19 vaccines specifically once available, address misinformation, and communicate transparently about COVID-19 vaccine allocation decisions.

How

Currently authorized COVID-19 vaccines are administered intramuscularly in a two-dose schedule.
Attempts should be made to complete the vaccine series with the same vaccine product.
Serologic testing is not needed before or after receipt of a COVID-19 vaccine to assess susceptibility to SARS-CoV-2 or immune response to the vaccine.
COVID-19 vaccines should not be given simultaneously with other live or inactivated vaccines at this time, unless other vaccines are required for post-exposure prophylaxis.
COVID-19 vaccines should not be given simultaneously with monoclonal antibodies or convalescent plasma.

Why

The COVID-19 pandemic has caused significant morbidity and mortality, as well as social and economic disruption in Canada and worldwide.
The authorized COVID-19 vaccines that are recommended for use by NACI in this Statement have been shown to be safe, as well as efficacious against symptomatic laboratory-confirmed COVID-19 disease.

Introduction

The goal of Canada's pandemic response is to minimize serious illness and death while minimizing societal disruption as a result of the COVID-19 pandemic. Safe and effective COVID-19 vaccines could help achieve this goal. Clinical trials of numerous candidate COVID-19 vaccines are currently underway.

This guidance document will provide recommendations on the use of authorized COVID-19 vaccines as they are approved for use in Canada, and as evidence on authorized vaccines evolves.

COVID-19 vaccines currently authorized for use in Canada:

The Pfizer-BioNTech COVID-19 vaccine was authorized for use in Canada on December 9, 2020.
The Moderna COVID-19 vaccine was authorized for use in Canada on December 23, 2020.
The AstraZeneca COVID-19 vaccine was authorized for use in Canada on February 26, 2021.

The evidence on COVID-19 and COVID-19 vaccines has been rapidly evolving. To date, NACI has published the following evidence-informed guidance:

Research priorities for COVID-19 vaccines to support public health decisions to inform clinical trials of candidate COVID-19 vaccines to protect against infection, serious illness, and deaths caused by SARS-CoV-2.
Preliminary guidance on key populations for early COVID-19 immunization 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.
Guidance on the prioritization of initial doses of COVID-19 vaccine(s) for the efficient and equitable prioritization of initial doses of COVID-19 vaccines to assist with the planning for allocation of the first COVID-19 immunization programs.
Guidance on the prioritization of key populations for COVID-19 vaccination to provide guidance for the equitable, ethical, and efficient allocation of authorized COVID-19 vaccines in the context of staggered arrival of vaccine supply that will necessitate offering vaccines to some populations earlier than others.
Recommendations on the use of COVID-19 vaccine initially published on December 12, 2020 and updated iteratively as new evidence becomes available and the authorization of additional COVID-19 vaccines.

Guidance objective

The objective of this advisory committee statement is to provide guidance on the effective and equitable use of COVID-19 vaccines authorized for use in Canada in the context of staggered authorization of these vaccines. This evergreen document will be updated as COVID-19 vaccines are authorized for use in Canada, and as evidence on these vaccines evolves. In this guidance document, the evidence and rationale for recommendations as well as current knowledge gaps (e.g. due to the size and short-term follow up in ongoing clinical trials) will be summarized. Clinical trial details on vaccine characteristics for specific COVID-19 vaccines will be included in appendices.

Methods

Details of NACI's recommendation development process can be found elsewhere.^{Footnote 1}^{Footnote 2}

In brief, the broad stages in the preparation of this NACI advisory committee statement included:

Knowledge synthesis
Synthesis of the body of evidence of benefits and harms, considering the quality of the synthesized evidence and magnitude and certainty of effects observed across the studies
Translation of evidence into recommendations

In order to develop comprehensive, appropriate immunization program recommendations, NACI considers a number of factors. In addition to critically appraising evidence on burden of disease and vaccine characteristics such as safety, efficacy, immunogenicity and effectiveness, NACI uses a published, peer-reviewed framework and evidence-informed tools to ensure that issues related to ethics, equity, feasibility, and acceptability (EEFA) are systematically assessed and integrated into its guidance^{Footnote 2}. The NACI Secretariat applied this framework 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.

For this advisory committee statement, NACI used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to develop population-focused recommendations. Further information on this framework can be found in the GRADE handbook.

NACI reviewed and approved the key policy questions used to guide recommendation development on November 25, 2020 and rated the outcomes for their importance for decision-making. The Canadian Immunization Committee (CIC) provided feedback on the key policy questions to ensure alignment with program needs. Important ethical considerations relating to the key policy questions were presented on November 26, 2020, December 15, 2020 and January 26, 2021 to the PHAC Public Health Ethics Consultative Group, who provided an assessment of ethical considerations that are relevant to the development of recommendations. Knowledge synthesis and quality appraisal were performed by the NACI Secretariat for unpublished clinical trial evidence and were informed by NACI's rating of the outcomes. Unpublished data from Phase 1, 2, and 3 clinical trials were presented to the High Consequence Infectious Disease Working Group and NACI for discussion. Proposed recommendations were then presented and approved at emergency NACI meetings. The description of relevant considerations, rationale for specific decisions, and knowledge gaps are described in the text.

Key Dates:

Pfizer-BioNTech COVID-19 vaccine was discussed on December 4, 2020 and related recommendations were approved on December 7, 2020.
The Moderna COVID-19 vaccine was discussed on December 14, 2020 and related recommendations were approved on December 17, 2020.
The AstraZeneca COVID-19 vaccine was discussed on January 19, 28 and February 24, 2021 and related recommendations were approved on February 24, 2021.
Considerations regarding an extended interval between authorized vaccine doses in the context of limited vaccine supplies, and clarifications to recommendations for populations who were either excluded from or were represented by small numbers of participants in clinical trials were discussed on January 7, 2021 and were approved on January 8, 2021.

Epidemiology

Information on COVID-19 is continually evolving. The following section will describe the current basis of knowledge, with an emphasis on the best available Canadian data where possible. To access the most recent updates to specific elements, please refer to the links below.

Disease description

Infectious agent

COVID-19 is caused by the SARS-CoV-2, which was first recognized in Wuhan, China in December 2019.

Transmission

Current evidence suggests that COVID-19 is spread through respiratory droplets and aerosols created when an infected person coughs, sneezes, sings, shouts, or talks. A person may be infectious for up to three days before showing symptoms. More information on the transmission of COVID-19 can be found on the PHAC webpages for COVID-19: Main modes of transmission and COVID-19 signs, symptoms and severity of disease: A clinician guide.

Risk factors

Anyone can be infected with SARS-CoV-2. However, some populations are at increased risk of exposure to the virus (e.g., due to living or occupational settings), and some populations are at increased risk of severe disease and outcomes (e.g., hospitalization and death) due to various biological (e.g. advanced age, pre-existing medical conditions) and social (e.g., socioeconomic status, belonging to a racialized population) factors that may intersect. Exposure and risk of severe disease factors may overlap, further increasing risk. Any combination of these factors, as well as varying access to health care services, has the potential for disproportionate consequences for specific populations characterized by increased rates of infection and disease, severe illness, hospitalizations, and/or deaths.

Please see NACI's Advisory Committee Statement on Key Populations for Early COVID-19 Immunization and the Equity Matrix^{Footnote 3} for a summary of inequities associated with COVID-19, potential reasons for and intersections between these inequities, and suggested interventions to reduce inequities and improve access to vaccines.

More information on the risk factors associated with COVID-19 can be found on PHAC webpages for People who are at high risk for severe illness from COVID-19 and Vulnerable populations and COVID-19.

Spectrum of clinical illness

The median incubation period for COVID-19 has been estimated to be 5 to 6 days from exposure to symptom onset, with most individuals (97.5%) developing symptoms within 11.5 days of exposure.

Clinical presentation and symptoms of COVID-19 vary in frequency and severity. To date, there is no list of symptoms that has been validated to have high specificity or sensitivity for COVID-19.

More information on the spectrum of clinical illness is available on the PHAC webpage for COVID-19 signs, symptoms and severity of disease: A clinician guide.

Disease incidence

Global

Updated international data on COVID-19 cases and deaths is available at: Interactive data visualizations of COVID-19.

Weekly epidemiological updates highlighting key global, regional and country-level data on COVID-19 cases and deaths are available from the World Health Organization (WHO) at: Coronavirus disease (COVID-19) Weekly Epidemiological Update and Weekly Operational Update.

National

Updated national, provincial and territorial-level data on COVID-19 cases and deaths in Canada over time is available from the PHAC webpage on Coronavirus disease (COVID-19): Outbreak update.

Vaccines

The following section summarizes information about COVID-19 vaccines authorized for use in Canada. More detailed vaccine-specific information is included in Appendices A through D. The current landscape of all candidate COVID-19 vaccines in clinical evaluation can be found on the WHO webpage Draft landscape of COVID-19 candidate vaccines. Under the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19, Health Canada can make regulatory decisions for COVID-19 vaccines that have completed Phase 3 clinical trials for authorized use in Canada.

Most vaccine candidates in development that may become authorized for use in Canada use various technologies to deliver SARS-CoV-2 spike protein to vaccine recipients. This protein is expressed on the surface of the SARS-CoV-2 virus and is a major target for binding and neutralizing antibodies as well as cell-mediated immune responses.

mRNA vaccines

COVID-19 vaccines that use messenger RNA (mRNA) platforms contain modified nucleotides that code for the SARS-CoV-2 spike protein. A lipid nanoparticle formulation delivers the mRNA into the recipient's cells. Once inside the cytoplasm of a cell, the mRNA provides instructions to the cell's protein production machinery to produce the trans-membrane spike protein antigen that becomes anchored on the cell's external surface. The mRNA does not enter the nucleus of the cell and does not interact with, or alter, human DNA. The immune system is engaged by both the transmembrane spike protein and immune receptors carrying spike antigens to induce humoral and cellular immune responses. The mRNA, lipid nanoparticle, and spike protein are degraded or excreted within days to weeks from time of immunization. mRNA vaccines are not live vaccines and cannot cause infection in the host.

Non-replicating viral vector vaccines

COVID-19 vaccines based on viral vector platforms use a modified virus to carry genes that encode SARS-CoV-2 spike proteins into the host cells. The vector virus is a type of adenovirus that has been modified to carry COVID-19 genes and to prevent replication. These modifications are intended to prevent the viral vector from causing disease. (i.e., they are non-replicating). Once inside the cell, the SARS-CoV-2 spike protein genes are transcribed into mRNA in the nucleus and translated into proteins in the cytosol of the cell. The AstraZeneca vaccine uses a modified chimpanzee adenovirus vector (ChAd).

Preparations of COVID-19 vaccines authorized for use in Canada

Table 1: COVID-19 vaccines authorized for use in Canada
Product Brand Name	Pfizer-BioNTech COVID-19 Vaccine	Moderna COVID-19 Vaccine	AstraZeneca COVID-19 Vaccine
Type of vaccine	mRNA	mRNA	Non-replicating viral vector (ChAd)
Date of authorization in Canada	December 9, 2020	December 23, 2020	February 26, 2021
Authorized ages for use	16 years of age and older	18 years of age and older	18 years of age and older
Dose	0.3 mL (30 mcg of mRNA)^{Footnote 1}	0.5 mL (100 mcg of mRNA)	0.5 mL (5 x 10¹⁰ viral particles)
Schedule^{Footnote 2}	2 Doses, 3 weeks apart	2 Doses, 4 weeks apart	2 Doses, 4 to 12 weeks apart
Route of administration	IM	IM	IM
Nature of the antigen	Transmembrane prefusion spike protein	Transmembrane prefusion spike protein	Transmembrane spike protein
Adjuvant (if present)	None	None	None
Primary storage requirements pre-puncture	-80°C to -60°C^{Footnote 3}	-25°C to -15°C^{Footnote 3}^{Footnote 4}	+2ºC to +8ºC
Storage requirements pre-puncture^{Footnote 3}	120 hours (5 days) at +2°C to +8°C and/or 2 hours up to +25°C	30 days at +2°C to +8°C and/or 12 hours at +8°C to +25°C	+2ºC to +8ºC
Diluent	Yes	No	No
Usage limit post-puncture	6 hours at +2°C to +25°C^{Footnote 5}	6 hours at +2°C to +25°C	6 hours at room temperature (up to +30ºC) or 48 hours at +2ºC to +8ºC
Formats available	Multi-dose vial (6 doses)^{Footnote 1}, preservative-free	Multi-dose vial (10 doses), preservative-free	Multi-dose vial (8-and 10-dose presentations), preservative-free
Footnotes Footnote 1 After dilution, one vial contains 6 doses of 0.3 mL each. However, vial labels and cartons may state that after dilution, a vial contains 5 doses of 0.3 mL. Information in the product monograph supersedes the number of doses stated on vial labels and cartons. Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6^th dose from a single vial. Refer to the product monograph available through Health Canada's Drug Product Database for choice of diluent, dilution instructions and type of syringes which can be used to extract 6 doses from a single vial. Return to footnote 1 referrer Footnote 2 Authorized schedule. For NACI recommendations on intervals between doses refer to Table 2 for details Return to footnote 2 referrer Footnote 3 Protected from light during storage Return to footnote 3 referrer Footnote 4 Do not store on dry ice or below -40ºC Return to footnote 4 referrer Footnote 5 After dilution, vaccine must be used within 6 hours Return to footnote 5 referrer Abbreviations: ChAd: Chimpanzee adenovirus IM: Intramuscular mRNA: Messenger ribonucleic acid

Efficacy and effectiveness

Due to the availability of only short-term clinical trial data, the duration of COVID-19 vaccine efficacy, and vaccine effectiveness, are currently unknown. However, studies are ongoing.

The following section highlights key efficacy data for authorized COVID-19 vaccines (Pfizer-BioNTech COVID-19 vaccine, Moderna COVID-19 vaccine) and viral vector based COVID-19 vaccine (AstraZeneca COVID-19 vaccine) only. For additional details regarding trial design, including study population, length of follow-up, and efficacy for the authorized vaccines, refer to the evidence summary in Appendix A (for the Pfizer-BioNTech COVID-19 vaccine), Appendix B (for the Moderna COVID-19 vaccine), and Appendix C (for the AstraZeneca COVID-19 vaccine).

Efficacy against symptomatic COVID-19 disease

The currently authorized mRNA COVID-19 vaccines have been shown to be highly efficacious in the short term against confirmed symptomatic COVID-19 disease (presence of one or more symptoms plus laboratory confirmation of SARS-CoV-2 infection) from one to two weeks after receiving the full two-dose series. The authorized mRNA vaccines are similarly efficacious in adults with one or more comorbidities, as well as in younger adults and older adults. However, evidence in adults of a much more advanced age (e.g., 85 years and older) and in long-term care facilities is limited. In clinical trials, the currently authorized viral vector vaccine has shown moderate short-term efficacy against symptomatic COVID-19 disease (presence of at least one pre-defined COVID-19 symptom plus laboratory confirmation of SARS-CoV-2 infection) in adults 18-64 years of age at least two weeks after receiving the full series of two standard doses of the vaccine. At present, there are insufficient data in adults ≥65 years of age to conclude the vaccine is efficacious in this age group. The vaccine is similarly efficacious in adults ≥18 years of age with and without pre-defined comorbidities (presence of one or more mild to moderate and controlled cardiovascular disease, respiratory disease, diabetes or obesity).

The clinical trial data demonstrates that the authorized mRNA COVID-19 vaccines are efficacious over the short-term in individuals with or without evidence of prior SARS-CoV-2 infection. However, participants with laboratory-confirmed SARS-CoV-2 infection prior to enrollment were excluded from the trials and the number of trial participants with evidence of previous infection (as defined by trial protocol) who had confirmed symptomatic COVID-19 disease during the trials were small; therefore, the efficacy in this population and how it compares to those without evidence of previous infection is unknown at this time.

The first dose of the authorized COVID-19 vaccines has been shown to offer at least short-term protection against confirmed COVID-19 disease. The highest efficacy is seen after the second dose is administered. There is currently no available evidence on medium- and long-term efficacy of the authorized COVID-19 vaccines, however trials are ongoing and this Statement will be updated as evidence emerges.

Efficacy against severe disease

There are limited data to be able to assess the efficacy of the authorized COVID-19 vaccines against hospitalizations or deaths specifically, but studies are ongoing and further evidence is expected.

The authorized COVID-19 vaccines appear to be efficacious against severe COVID-19 outcomes (defined as laboratory-confirmed COVID-19 with one of the following additional features: clinical signs at rest that are indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; or death). However, the follow-up time for this outcome was short in trials of both mRNA vaccines and the number of severe cases that have been observed to date in one of the vaccine trials (Pfizer-BioNTech COVID-19 vaccine) is small. At the present time, there are insufficient data to estimate the efficacy of the viral vector vaccine against severe COVID-19 disease.

Efficacy against asymptomatic infection and transmission

Preliminary data from the ongoing Moderna COVID-19 vaccine trial showed a lower prevalence of SARS-CoV-2 positivity by PCR in asymptomatic participants at one particular time point (before Dose 2), and therefore viral shedding, in the group that received the vaccine compared to the placebo group. However, the current data is insufficient to draw conclusions. Exploratory analyses for the viral vector vaccine have not demonstrated efficacy against confirmed SARS-CoV-2 asymptomatic infection, however the number of asymptomatic infections was small. Studies are ongoing for these vaccines.

Efficacy against variants of concern

Data about the efficacy of authorized mRNA COVID-19 vaccines (Pfizer-BioNTech COVID-19 vaccine, Moderna COVID-19 vaccine) and viral vector-based COVID-19 vaccine (AstraZeneca COVID-19 vaccine) against VOC is evolving. NACI will continue to monitor the evidence and update recommendations as needed.

Immunogenicity

No immunological correlate of protection has been determined for SARS-COV-2; therefore, all immunological evidence in support of vaccine efficacy is indirect and cannot directly be used to estimate efficacy.

There are several key knowledge gaps that affect the understanding of immune responses to COVID-19 vaccine:

Which type of immune responses are important for protection from infection, severe disease, or transmission
The durability of immune responses and how they may change over time
How immune responses to natural infection compare to responses elicited from a vaccine
How immune responses differ across populations (e.g., in immunocompromised, children) or by SARS-CoV-2 serostatus (i.e., past COVID-19 infection)
How immune responses differ based on previous infection with non-SARS-CoV-2 coronaviruses

Due to limitations in the number of participants and duration of follow up from COVID-19 clinical trial data, long-term evidence on immunogenicity is unknown. However, studies are ongoing.

The following section highlights key immunogenicity data for the authorized mRNA COVID-19 vaccines (Pfizer-BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine) and viral vector based COVID-19 vaccine (AstraZeneca COVID-19 vaccine) only. For additional details regarding trial design, including study population and length of follow-up, and immunogenicity for these authorized vaccines refer to the evidence summaries in Appendix A (for the Pfizer-BioNTech COVID-19 vaccine), Appendix B (for the Moderna COVID-19 vaccine), and Appendix C (for the AstraZeneca COVID-19 vaccine).

Humoral immune responses

All authorized COVID-19 vaccines induce humoral immune responses, including binding and neutralizing antibody responses. Humoral responses peaked after the second dose of mRNA vaccine, and after the second dose of AstraZeneca COVID-19 vaccine in participants who were not previously infected. Some vaccines induce higher immune responses in younger populations, see Appendix A, Appendix B, and Appendix C for details.

Viral vector-based vaccines may induce anti-vector immune responses, which may impact future vaccine efficacy and effectiveness and may vary by age, dose, and interval between doses.

Cellular immune responses

All authorized COVID-19 vaccines have been shown to produce cellular immune responses. Cellular immune responses increased after the second dose of mRNA COVID-19 vaccine, while responses for AstraZeneca COVID-19 vaccine were maintained or decreased after the second dose. Refer to Appendix A, Appendix B, and Appendix C for details.

Vaccine administration

For additional vaccine product-specific information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database. Refer to Vaccine Administration Practices in the Canadian Immunization Guide (CIG), Part 1 - Key Immunization Information for additional general information.

As for the routine administration of all vaccines, COVID-19 vaccines should be administered in settings capable of managing anaphylaxis. Refer to Anaphylaxis and other Acute Reactions Following Vaccination in the CIG, Part 2 — Vaccine Safety for information on the management of anaphylaxis post-vaccination.

Dose, route of administration, and schedule

Dose

Pfizer-BioNTech COVID-19 vaccine

Each dose is 0.3 mL after dilution, containing 30 mcg of SARS-CoV-2 spike protein mRNA.

The dose for the Pfizer-BioNTech COVID-19 vaccine (0.3 mL) is unique compared to that of most routine vaccinations. Special precaution should be taken to ensure the correct dose is taken from the multi-dose vial.

Moderna COVID-19 vaccine

Each dose is 0.5 mL, containing 100 mcg of SARS-CoV-2 spike protein mRNA.

No dilution is required.

AstraZeneca COVID-19 vaccine

Each dose is 0.5 mL, containing 5 x 10¹⁰ particles of SARS-CoV-2 spike protein.

No dilution is required.

Route of administration

COVID-19 vaccines are given as an intramuscular (IM) injection into the deltoid muscle.

Refer to Vaccine Administration Practices in the CIG, Part 1 — Key Immunization Information for additional information.

Schedule

Refer to Table 2 for a summary of immunization schedules for authorized COVID-19 vaccines.

Table 2: Recommended immunization schedule, by COVID-19 vaccine
Vaccine product (manufacturer)	Immunization schedule	Minimum interval	Authorized interval	Alternate interval
Pfizer-BioNTech COVID-19 (Pfizer-BioNTech)	2-dose schedule	19 days	21 days	3 to 6 weeks^{Footnote a}
Moderna COVID-19 (Moderna)	2-dose schedule	21 days	28 days	4 to 6 weeks^{Footnote a}
AztraZeneca COVID-19 (AstraZeneca)	2-dose schedule	28 days	4 to 12 weeks	12 weeks^{Footnote b}
Footnotes Footnote a While efforts should be made to vaccinate according to the recommended schedules, some jurisdictions considering vaccine delivery logistics, current epidemiological status and projections, and healthcare system capacity may maximize the number of individuals benefiting from a first dose of mRNA vaccine by delaying the second dose, until further supplies of the vaccine become available, preferably within 6 weeks of receipt of the first dose Return to footnote a referrer Footnote b A 12-week interval is preferred for the AstraZeneca COVID-19 vaccine based on vaccine principles, feasibility considerations for pandemic supply management, and available ad hoc analyses of clinical trial interval data from the manufacturer Return to footnote b referrer

Refer to Timing of Vaccine Administration in the CIG, Part 1 — Key Immunization Information for additional general information.

The authorized COVID-19 vaccines are efficacious against symptomatic laboratory-confirmed COVID-19 disease when provided as a two-dose schedule.

The majority of participants in the Pfizer-BioNTech COVID-19 vaccine clinical trial received the second dose 21 to 27 days apart. The per-protocol design was 19 to 23 days. An alternate interval of 28 days may be more feasible to implement. This interval is consistent with the minimum interval required for many other routine immunizations and the authorized interval for the Moderna COVID-19 vaccine. The majority of participants in the Moderna COVID-19 vaccine clinical trial received the second dose 21 to 42 days after the first, as per the pre-defined window. A harmonized approach to the scheduling of COVID-19 vaccines 28 days apart could prevent erroneous administration of other vaccine doses at less than the recommended minimal interval.

For AstraZeneca COVID-19 vaccine, a secondary analysis of vaccine efficacy by interval between doses demonstrated a potential for higher efficacy with increasing duration between doses. Given the potential for higher efficacy, the longer interval within the range AstraZeneca COVID-19 vaccine is authorized for (i.e., 12 weeks) is preferred. Refer to Appendix C for details on these analyses.

Delay in receipt of dose 2 in a mRNA COVID-19 vaccine series

Currently, no data on a maximum interval between doses or on medium- or long-term efficacy of COVID-19 vaccines are available and peak humoral response occurs after second dose.

In general, interruption of a vaccine series resulting in a greater than recommended interval between doses does not require restarting the series as delays between doses do not result in a reduction in final antibody concentrations for most multi-dose (prime-boost) products. For many other multi-dose vaccines provided in adulthood using other vaccine technologies, the greatest proportion of short-term protection is achieved with the first dose with additional doses primarily intended to extend protection over the longer term. However, the follow-up time in COVID-19 vaccine clinical trials is short, the duration of protection after one or both is unknown, and mRNA vaccines represent a new vaccine technology. If administration of the second dose of a COVID-19 vaccine is delayed, the second dose should be provided as soon as possible.

Although not specified in the Phase 3 study protocol, a post-hoc analysis of the Pfizer-BioNTech clinical trial data suggests a vaccine efficacy of 52% (95% confidence interval [CI], 29.5 to 68.4%) between the first and second dose. This estimate of vaccine efficacy is likely an underestimate of the short-term efficacy as cases occurring immediately after dose 1 were included. It is presumed that there would be minimal efficacy in the first 14 days following dose 1, because the immune response usually requires 7 to 14 days to develop and because recipients who are already infected and incubating the virus upon vaccination are unlikely to be protected. A further post-hoc estimate of vaccine efficacy calculated from 14 days after dose 1 until dose 2 (a period of one week for the majority of study participants) was 92.3% (95% CI: 69 to 98%)^{Footnote 4}^{Footnote 5}. However, these estimates of vaccine efficacy are based on short periods of follow-up and therefore cannot predict the duration of protection offered by one dose of the vaccine.

An exploratory analysis of data from the Phase 3 Moderna clinical trial also suggests there may be protection against symptomatic COVID-19 disease starting as soon as 12 or 14 days after the first dose. An interim analysis in a small, non-random subgroup of study participants who had only received one dose of vaccine at the time of analysis (n=996 in the vaccine arm and n=1,079 in the placebo arm) was used to calculate an estimated vaccine efficacy of 80.2% (95% CI 55.2 to 92.5%) between the first and second dose. This estimate of vaccine efficacy is likely an underestimate as cases occurring immediately after dose one were included. Vaccine efficacy calculated in the same small subgroup of study participants from 14 days after dose 1 (was 92.1% (95% CI, 68.8 to 99.1%)^{Footnote 6}. These estimates of vaccine efficacy after one dose should be interpreted with caution, given the short period of follow-up (median 28 days). In addition, the calculations after dose 1 are based on a small subset of the larger randomized cohort of study participants resulting in efficacy estimates with reduced precision, as indicated by the relatively wide confidence intervals.

Humoral responses for both mRNA COVID-19 vaccines peak one to two weeks after a second dose, and then decline but remain detectable over the period of assessment in the clinical trials (either 4 weeks in the Pfizer-BioNTech trial or 3 months in the Moderna trial). However, as a correlate of protection is not known, these humoral responses cannot be interpreted as corresponding with vaccine efficacy or effectiveness.

Efforts should be made to vaccinate with the second dose of COVID-19 vaccine following the schedules outlined in Table 2. If, due to logistical jurisdictions do not complete the two-dose COVID-19 vaccine series within these recommended schedules, they may refer to the Management options section of this statement for a summary of evidence and decision points for COVID-19 immunization program roll-out in the context of limited vaccine supply, as well as Appendix E for an ethics analysis using NACI's Core Ethical Dimensions Filter of the EEFA Framework ^{Footnote 2}.

Follow-up of vaccine effectiveness in individuals for whom the second dose is delayed or who have otherwise missed their second dose (e.g., missed a follow-up immunization appointment) will be important to inform future recommendations and ensure completion of the vaccine series as soon as possible. NACI will continue to monitor the evidence and update recommendations as needed.

Booster doses and re-immunization

There is currently no evidence on the need for booster doses of COVID-19 vaccine after the vaccine series is complete. Given the emergence of variants of concern against which vaccine effectiveness may be decreased, additional vaccine doses may be necessary. NACI will continue to monitor the evidence and update recommendations as needed.

Interchangeability

NACI recommends that the vaccine series be completed with the same COVID-19 vaccine product.

Currently, no data exist on the interchangeability of COVID-19 vaccines. However, the spike proteins encoded by either of the authorized mRNA vaccines have the same sequence and are stabilized in the same manner to remain in the pre-fusion conformation, though other vaccine components like the lipid nanoparticle and the mRNA sequence may be different. The spike protein encoded by the authorized viral vector vaccine is not stabilized in any specific conformation. Vaccines of different types (e.g., mRNA, viral vector) should be considered different vaccines and should not be used in the same series.

If the vaccine product used for a previously received dose is not known, or not available, attempts should be made to complete the vaccine series with a similar type of COVID-19 vaccine (e.g., mRNA vaccine and mRNA vaccine). It is not recommended that vaccines of different types (e.g., mRNA vaccine and viral vector vaccine) be used in the same series. In the context of limited COVID-19 vaccine supply and the absence of evidence on interchangeability of COVID-19 vaccines, the previous dose may be counted, and the series need not be restarted.

At this time, it is not recommended that vaccines of different types (e.g., mRNA vaccine and viral vector vaccine) be used in the same series. Active surveillance of effectiveness and safety of a mixed schedule will be important and these recommendations may change as further evidence becomes available. Accurate recording of vaccines received will be critical. NACI will continue to monitor the evidence and update recommendations as needed.

Refer to Principles of Vaccine Interchangeability in the CIG, Part 1 — Key Immunization Information for additional general information.

Post-vaccination counseling

NACI recommends that prophylactic oral analgesics or antipyretics (e.g., acetaminophen or ibuprofen) should not be routinely used before or at the time of vaccination, but their use is not a contraindication to vaccination. Oral analgesics or antipyretics may be considered for the management of adverse events (e.g., pain or fever, respectively), if they occur after vaccination.

Analgesics and antipyretics were used in clinical trials of COVID-19 vaccine for the management of pain and/or fever after vaccination. There is currently no evidence on the benefit from administration of oral analgesics for the prevention of immunization injection pain or systemic reactions. All vaccine recipients should be instructed to seek medical care if they develop signs or symptoms of an allergic reaction after their observation period ends and they have left the immunization clinic/venue.

All vaccine recipients who develop symptoms compatible with COVID-19 should be tested for SARS-CoV-2 to document breakthrough illness, particularly in the context of the emergence of variants of concern.

Refer to Vaccine Administration Practices in the CIG, Part 1 — Key Immunization Information for additional information on pre- and post-vaccination counseling.

Serological testing

Serologic testing is not needed before or after immunization with COVID-19 vaccine.

Storage requirements

Pfizer-BioNTech COVID-19 vaccine

Frozen vials prior to use

The Pfizer-BioNTech COVID-19 vaccine must be stored at ultra-low temperatures of -80°C to -60°C and protected from light, in the original packaging, until ready to use.

Refer to the re-icing guidelines (available at Pfizer-BioNTech COVID-19 Vaccine) for instructions regarding the use of the manufacturer's original thermal container for temporary storage.

Thawed, unpunctured vials (prior to dilution)

The Pfizer-BioNTech COVID-19 vaccine may be thawed and stored at +2°C to +8°C for up to 120 hours (5 days) or at room temperature (up to +25°C) for no more than 2 hours. During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. Thawed vials can be handled in room light conditions.

Do not refreeze thawed vials.

Thawed, punctured vials (after dilution)

The Pfizer-BioNTech COVID-19 vaccine must be stored between +2°C to +25°C and used within 6 hours from the time of dilution. During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. After dilution, the vaccine vials can be handled in room light conditions.

Moderna COVID-19 vaccine

Frozen vials prior to use

The Moderna COVID-19 vaccine should be stored at temperatures of -25ºC to - 15ºC and protected from light in the original packaging. Do not store on dry ice or below -40ºC.

Thawed, unpunctured vials

If not punctured, the Moderna COVID-19 vaccine can be thawed and stored at +2°C to +8°C for up to 30 days, or at +8°C to +25°C for up to 12 hours.

Do not refreeze thawed vials.

Thawed, punctured vials

The Moderna COVID-19 vaccine can be stored between +2°C to below +25°C but must be discarded after 6 hours from the time of first puncture. During storage, vials should be protected from light.

AstraZeneca COVID-19 vaccine

Unopened multidose vial

The AstraZeneca vaccine can be stored between +2ºC to +8ºC and protected from light in the original packaging. Do not freeze.

Opened multidose vial

After first opening, chemical and physical in-use stability has been demonstrated from the time of vial puncture to administration for no more than 6 hours at room temperature (up to +30ºC) or 48 hours in a refrigerator (+2ºC to +8ºC).

After the first puncture, the vial can be re-refrigerated, but the cumulative storage time at room temperature must not exceed 6 hours, and the total cumulative storage time must not exceed 48 hours. After this time, the vial must be discarded.

For more information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database. Refer to Storage and Handling of Immunizing Agents in the CIG, Part 1 — Key Immunization Information for additional general information.

Simultaneous administration with other vaccines

NACI recommends that COVID-19 vaccines should not be given simultaneously with other vaccines (live or inactivated).

Currently, no data exist on the simultaneous administration of COVID-19 vaccine with other vaccines. In the absence of evidence, attempts should be made to avoid simultaneous administration to maximize benefits of COVID-19 vaccination while minimizing any risks of harm, including the potential for immune interference or the erroneous attribution of an adverse event following immunization (AEFI) to a particular vaccine. However, if a COVID-19 vaccine is inadvertently administered at the same time as another vaccine, neither dose should be repeated.

In the absence of evidence, it would be prudent to wait for a period of at least 28 days after each vaccine dose of an mRNA or viral vector COVID-19 vaccine before the administration of another vaccine (except in the case where another vaccine is required for post-exposure prophylaxis) due to the elicitation of an inflammatory cytokine response. It would be prudent to wait for a period of at least 14 days after the administration of another vaccine before administrating a COVID-19 vaccine to prevent erroneous attribution of an AEFI to a particular vaccine.

Refer to Timing of Vaccine Administration in the CIG, Part 1 — Key Immunization Information for additional general information on simultaneous administration of other vaccines in general.

Vaccine safety and adverse events following immunization (AEFI)

Due to limitations in the number of participants and duration of follow-up from COVID-19 clinical trials, medium- and long-term evidence on vaccine safety is limited. Clinical trials of the authorized COVID-19 vaccines excluded individuals with a history of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine. However, studies are ongoing.

The following section highlights key safety and AEFI data for the authorized COVID-19 vaccines. For additional details regarding trial design, including study population and length of follow-up, and safety for the COVID-19 vaccines authorized for use in Canada, refer to the evidence summaries in Appendix A (for the Pfizer-BioNTech COVID-19 vaccine), Appendix B (for the Moderna COVID-19 vaccine) and Appendix C (for the AstraZeneca COVID-19 vaccine). Refer to Appendix D for a summary of the frequency of AEFI for the different COVID-19 vaccine products.

Refer to Part 2 - Vaccine Safety in the CIG for definitions of AEFIs and additional general information.

Very common and common adverse events

Common adverse events are defined as those that occur in 1% to less than 10% of vaccine recipients; very common adverse events occur in 10% or more of vaccine recipients. Please see Appendix D for a summary of adverse events identified in clinical trials of authorized COVID-19 vaccines.

Local

Pain at the injection site is very common after administration of the currently authorized COVID-19 vaccine. More than 50% of recipients experienced injection site pain. Redness and swelling are common or very common after administration. Localized axillary swelling and tenderness was a solicited adverse event in the Moderna COVID-19 clinical trial and was very common after administration with that vaccine. Local adverse events are usually mild or moderate and resolve within a few days of vaccination. For the authorized mRNA COVID-19 vaccines, pain at the injection site was slightly more frequent in younger adults compared to older adults. For AstraZeneca COVID-19 vaccine, local reactions were milder and reported less frequently after the second vaccine dose in all age groups.

Systemic

Fatigue, headache, muscle pain, chills, and joint pain are all either common or very common after the administration of the currently authorized COVID-19 vaccines. Fever was very common after administration of the second dose of the mRNA COVID-19 vaccines and common after any dose of AstraZeneca COVID-19 vaccine. More than a quarter of vaccine recipients experienced headache, and/or fatigue after any dose. For the mRNA COVID-19 vaccines, systemic adverse events are usually mild or moderate intensity and resolve within a few days of vaccination. Systemic reactions are more frequent after the second vaccine dose and in younger adults. For AstraZeneca COVID-19 vaccine, systemic reactions are milder and reported less frequently after the second vaccine dose in all age groups.

Uncommon, rare, and very rare adverse events

Uncommon adverse events occur in 0.1% to less than 1% of vaccine recipients. Rare and very rare adverse events occur in 0.01% to less than 0.1% and less than 0.01% of vaccine recipients, respectively. The probability of detection of very rare adverse events in clinical trials is low given clinical trial population sizes; therefore, ongoing pharmacovigilance is essential.

mNRA COVID-19 vaccines

To date, the available data does not indicate that vaccination of SARS-CoV-2 naïve individuals with authorized COVID-19 vaccines will elicit enhanced or altered disease upon subsequent infection by SARS-CoV-2 (e.g., vaccine-enhanced disease); however, further study is needed.

Lymphadenopathy was not a solicited adverse event (unless indicated, see Appendix D) but was uncommonly reported after administration of the Pfizer-BioNTech and AstraZeneca COVID-19 vaccines.

No other solicited uncommon, rare, or very rare adverse events were reported among vaccinated participants in the clinical trials at this time.

Guidance on reporting adverse events following immunization (AEFI)

Vaccine providers are asked to report AEFIs through local public health departments and to follow AEFI reporting requirements that are specific to their province or territory. In general, any serious (defined as resulting in hospitalization, permanent disability or death) or unexpected adverse event that is temporally related to vaccination should be reported.

In addition to provincial or territorial reporting requirements, the Brighton Collaboration has developed a list of Adverse Events of Special Interest (AESI) that are of particular interest and should be reported. Refer to Brighton Collaboration: COVID-19 for the list with definitions.

There may be additional very rare AEFIs that have not been detected through clinical trials to date.

Refer to Adverse Events Following Immunization (AEFI) in the CIG, Part 2 — Vaccine Safety for additional information on definitions, reporting, investigating and managing, and causality assessments for AEFIs.

Refer to Reporting Adverse Events Following Immunization (AEFI) in Canada for additional information on the completion and submission of AEFI reports.

Contraindications and precautions

Rare anaphylactic reactions have been reported following immunization with mRNA COVID-19 vaccines; investigations are ongoing to identify the allergen(s) responsible and the recommendations will be updated as evidence becomes available.

Table 3 lists potential non-medicinal ingredients in authorized COVID-19 vaccines that have been associated with allergic reactions in other products. These reactions have occurred rarely, and ranged from mild cutaneous reactions to anaphylaxis. Anaphylaxis is typically a rare, severe, life-threatening allergic reaction typically with a rapid onset that involves multiple organ systems and can progress rapidly. Symptoms and signs of anaphylaxis may include, but are not limited to generalized urticaria; wheezing; swelling of the mouth, tongue, and throat; difficulty breathing; vomiting; diarrhea; hypotension; decreased level of consciousness; and shock. It is important to note that other, less serious reactions may mimic allergic reactions (e.g., vasovagal syncope) and vaccination is not contraindicated in these cases.

Table 3: Ingredients of authorized COVID-19 vaccines that have been associated with allergic reactions in other products
Vaccine product (manufacturer)	Potential allergen included in the vaccine or its container	Other products where the potential allergen may be found*
Pfizer-BioNTech COVID-19 (Pfizer-BioNTech)	polyethylene glycol (PEG)^{Footnote a}^{Footnote b}^{Footnote c}	Over the counter (e.g., cough syrup, laxatives), and prescription medications, medical bowel preparation products for colonoscopy, skin care products, dermal fillers, cosmetics, contact lens care solutions, products such as ultrasound gel^{Footnote d}.
Moderna COVID-19 (Moderna)	PEG ^{Footnote a}^{Footnote b}^{Footnote c}	Over the counter (e.g. cough syrup, laxatives), and prescription medications, medical bowel preparation products for colonoscopy, skin care products, dermal fillers, cosmetics, contact lens care solutions, products such as ultrasound gel^{Footnote d}.
Moderna COVID-19 (Moderna)	tromethamine^{Footnote e} (trometamol or Tris)	Component in contrast media, oral and parenteral medications.
AstraZeneca COVID-19 (AstraZeneca)	polysorbate 80^{Footnote c}	medical preparations (e.g., vitamin oils, tablets, and anticancer agents), cosmetics^{Footnote d}^{Footnote f}
Footnotes Note N.B. This is not a complete list of products. Footnote a Medications that contain PEG are described in Stone CA, et al., DOI:10.1016/j.jaip.2018.12.003 Return to footnote a referrer Footnote b A review of immediate type hypersensitivity reactions to PEG is available in Wenande et al, DOI: 10.1111/cea.12760 Return to footnote b referrer Footnote c There is a potential of cross-reactive hypersensitivity between PEG and polysorbates Return to footnote c referrer Footnote d PEG is an additive in some food and drinks but allergic reactions to PEG in food or drinks have not been documented. Return to footnote d referrer Footnote e One case report of anaphylaxis to tromethamine has been described (Lukawska et al, DOI: 10.1016/j.jaip.2018.08.035). Return to footnote e referrer Footnote f Case reports of anaphylaxis to polysorbate 80 have been described (Badiu et al, DOI: 10.1136/bcr.02.2012.5797, Palacios Castaño et al, DOI: 10.18176/jiaci.0109). Return to footnote f referrer

Contraindications

An authorized COVID-19 vaccine should not be offered routinely to individuals with a history of severe allergic reaction (e.g., anaphylaxis) after previous administration of a COVID-19 vaccine using a similar platform (mRNA or viral vector). If a risk assessment deems that the benefits outweigh the potential risks for the individual; and if informed consent is provided, an authorized COVID-19 vaccine using a different platform may be considered for re-immunization (i.e., individuals with anaphylaxis post mRNA vaccine may be offered a viral vector vaccine and individuals with anaphylaxis post viral vector vaccine may be offered a mRNA vaccine).

An authorized COVID-19 vaccine should not be routinely offered to individuals with a proven severe allergic reaction (e.g., anaphylaxis) to any component of the specific COVID-19 vaccine or its container.

For a comprehensive list of components in the vaccine and packaging, please consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database.

Precautions

If a risk assessment deems that the benefits outweigh the potential risks for the individual; and if informed consent is provided; vaccination may be considered in individuals with mild to moderate immediate allergic reactions (defined as limited in the scope of symptoms and involvement of organ systems or even localized to the site of administration) after a previous dose of authorized COVID-19 vaccines or any of its components. Assessment by a physician or nurse with expertise in immunization may be warranted prior to re-immunization. Most instances of anaphylaxis to a vaccine begin within 30 minutes after administration of the vaccine. Therefore, if vaccination is chosen, an extended period of observation post-vaccination of at least 30 minutes should be provided for the aforementioned individuals.

Individuals with proven severe allergic reaction (e.g., anaphylaxis) to injectable therapy not related to a component of authorized COVID-19 vaccines (e.g. intramuscular, intravenous, or subcutaneous vaccines or therapies) may be routinely vaccinated and do not need to be assessed. Most instances of anaphylaxis to a vaccine begin within 30 minutes after administration of the vaccine. Therefore, an extended period of observation post-vaccination of 30 minutes should be provided for the aforementioned individuals.

Individuals with a history of allergy not related to a component of authorized COVID-19 vaccines or other injectable therapy (e.g. foods, oral drugs, insect venom or environmental allergens) can receive COVID-19 vaccines without any special precautions. Individuals should be observed for a minimum of 15 minutes following vaccination.

In individuals with bleeding disorders, the condition should be managed prior to immunization to minimize the risk of bleeding. Individuals receiving long-term anticoagulation are not considered to be at higher risk of bleeding complications following immunization and may be safely immunized without discontinuation of their anticoagulation therapy.

Vaccination of individuals who may be currently infected with SARS-CoV-2 is not known to have a detrimental effect on the illness. However, vaccination should be deferred in symptomatic individuals with confirmed or suspected SARS-CoV-2 infection, or those with respiratory symptoms, in order to avoid attributing any complications resulting from SARS-CoV-2 infection to vaccine-related AEFI and to minimize the risk of COVID-19 transmission at an immunization clinic/venue. If any persons are identified with symptoms on arrival at the venue, they should be instructed to follow current local public health measures.

As a precautionary measure and in light of the need to be able to monitor for COVID-19 vaccine adverse events without potential confounding from symptoms of COVID-19 or other co-existing illnesses, it would be prudent to wait until all symptoms of an acute illness are completely resolved before vaccinating with an authorized COVID-19 vaccine.

Refer to Contraindications, Precautions and Concerns in the CIG, Part 2 - Vaccine Safety for additional general information.

Drug interactions

There have been no drug interactions studies performed to date.

For more information about potential interactions with products containing anti-SARS-CoV-2 antibodies, refer to section Blood products, human immunoglobulin and timing of immunization, in this Statement.

Tuberculin skin testing (TST) or interferon gamma release assay (IGRA)

There is a theoretical risk that mRNA or viral vector vaccines may temporarily affect cell-mediated immunity, resulting in false-negative TST or IGRA test results. If tuberculin skin testing or an IGRA test is required, it should be administered and read before immunization or delayed for at least 4 weeks after vaccination. Vaccination with COVID-19 vaccines may take place at any time after all steps of tuberculin skin testing have been completed.

In cases where an opportunity to perform the TST or IGRA test might be missed, the testing should not be delayed since these are theoretical considerations. However, re-testing (at least 4 weeks post immunization) of individuals with negative results for whom there is high suspicion of TB infection may be prudent in order to avoid missing cases due to potentially false-negative results.

Blood products, human immunoglobulin and timing of immunization

NACI recommends that COVID-19 vaccines should not be given simultaneously with monoclonal antibodies or convalescent plasma.

To date, there is insufficient evidence on the receipt of both a COVID-19 vaccine and anti-SARS-CoV-2 monoclonal antibodies or convalescent plasma for treatment or prevention. Therefore, timing of administration and potential interference between these two products are currently unknown. Administration of these products close together may result in decreased effectiveness of a COVID-19 vaccine and/or anti-SARS-CoV-2 monoclonal antibodies because the monoclonal antibodies have high affinity for the spike protein expressed by the vaccines, which could prevent the production of antibodies stimulated by the vaccine.

In the post-exposure setting, expert clinical opinion should be sought on a case-by-case basis when deciding whether anti-SARS-CoV-2 monoclonal antibodies would be appropriate to administer after receipt of COVID-19 vaccine, taking into consideration the risk of exposure and the risk of severe COVID-19 disease in the individual.

To date, there is also insufficient evidence on the receipt of both a COVID-19 vaccine and any monoclonal antibodies or convalescent plasma for treatment or prevention of non-COVID-19 disease. Therefore, timing of administration and potential interference between these two products are currently unknown and expert clinical opinion should be sought on a case-by-case basis.

Recommendations

Following the thorough review of available evidence summarized above, as well as the systematic assessment of ethics, equity, feasibility and acceptability considerations with the EEFA Framework^{Footnote 2} as summarized in NACI's Guidance on Key Populations for Early COVID-19 Immunization, NACI makes the following recommendations for public health program level decision-making for the effective and equitable use of COVID-19 vaccines authorized for use in Canada.

NACI will continue to carefully monitor the scientific developments related to COVID-19 and COVID-19 vaccines, as well as ongoing vaccine pharmacovigilance, and will update recommendations as evidence evolves.

Please note:

A strong recommendation applies to most populations/individuals and should be followed unless a clear and compelling rationale for an alternative approach is present.
A discretionary recommendation may be offered for some populations/individuals in some circumstances. Alternative approaches may be reasonable.

Please see Table 7 for a more detailed explanation of the strength of NACI recommendations.

Recommendations on authorized COVID-19 vaccines for public health program level decision-making

(i.e., Provinces/Territories making decisions for publicly funded immunization programs)

These recommendations apply only to COVID-19 vaccines currently authorized in Canada (Pfizer-BioNTech COVID-19 vaccine; Moderna COVID-19 vaccine; AstraZeneca COVID-19 vaccine). In considering these recommendations and for the purposes of publicly funded program implementation, provinces and territories may consider local programmatic factors (e.g., logistical and operational contexts, resources).

1. NACI recommends that a complete COVID-19 vaccine series should be offered to individuals in the authorized age group without contraindications to the vaccine. In the context of limited vaccine supply, initial doses of mRNA COVID-19 vaccine should be prioritized for the key populations outlined in NACI’s Guidance on the prioritization of key populations for COVID-19 immunization. (Strong NACI Recommendation)

Due to suggested superior efficacy, mRNA COVID-19 vaccine is preferentially recommended for individuals in the authorized age group without contraindications, especially in those at highest risk of severe illness and death and highest risk of exposure to COVID-19 who are prioritized for early COVID-19 immunization.
In the context of limited vaccine supply, AstraZeneca COVID-19 vaccine may be offered to individuals 18 to 64 years without contraindications if:
1. the advantages of earlier vaccination outweigh the limitations of vaccinating with a less efficacious vaccine;
2. the ease of transport, storage and handling of this vaccine facilitates access to vaccination which may otherwise be challenging; and
3. informed consent includes discussion about current vaccine options and the timing of future vaccine options

(Discretionary NACI Recommendation)

When considering which groups to offer the AstraZeneca COVID-19 vaccine to when an authorized mRNA COVID-19 vaccine is unavailable or inaccessible, the advantages of earlier immunization should outweigh the limitations of immunizing with a less efficacious vaccine. This assessment may vary between jurisdictions and groups and will depend on:

Local COVID-19 epidemic conditions (e.g., consider offering available AstraZeneca COVID-19 vaccine in regions of high epidemic transmission where immediate protection is needed to prevent symptomatic disease and preserve health system capacity; carefully considering the local transmission potential for viral variants of concern and anticipated effectiveness against them)
Local vaccine supply (e.g., consider how long a group will need to wait to be offered an mRNA vaccine, based on available and expected vaccine supply)
Risk of severe illness and death (e.g., consider offering available AstraZeneca COVID-19 vaccine to groups at lower risk of severe illness and death who will need to wait to receive mRNA vaccine while those at highest risk are offered a more efficacious vaccine)
Risk of exposure (e.g., consider offering the available AstraZeneca COVID-19 vaccine to groups at lower risk of exposure who will need to wait to receive mRNA vaccine while those at highest risk of exposure with minimal ability to physically distance are offered a more efficacious vaccine)
Logistical considerations (e.g., consider offering available AstraZeneca COVID-19 vaccine to those at lower risk of exposure or severe illness and death who would not otherwise get vaccinated due to personal barriers accessing mRNA vaccination sites despite jurisdictional efforts to increase access. Due to ease of transport, storage and handling of the AstraZeneca vaccine, a variety of alternate vaccination sites could increase convenience of vaccination and reduce vaccine hesitancy)

Refer to the Management options table for COVID-19 vaccines authorized for use in Canada for a summary of evidence and factors for jurisdictions to consider when implementing COVID-19 immunization programs.