COVID-19 vaccine: Canadian Immunization Guide

For health professionals

Last partial content update (see Table of updates): March 22, 2023

This chapter was updated based on the following statement from the National Advisory Committee on Immunization (NACI):

• March 3, 2023: Guidance on an additional COVID-19 booster dose in the spring of 2023 for individuals at high risk of severe illness due to COVID-19

Additionally, the following content was added:

• Information on a Health Canada-authorized Moderna Spikevax Original & Omicron BA.1 (bivalent) booster dose for individuals 6 years of age and older. Previously, a booster dose had been authorized only for individuals 18 years of age and older.

On this page

• Key information
• Epidemiology
• Preparations authorized for use in Canada
• Immunogenicity, efficacy and effectiveness
• Recommendations for use
  • Children
  • Adolescents
  • Adults
  • Schedule
    • Table 1. Immunization schedule for a primary series, by COVID-19 vaccine
    • Table 2. Immunization schedule and minimum intervals for a primary series for moderately to severely immunocompromised individuals, by COVID-19 vaccine
  • Booster doses
    • Table 3. Summary table of mRNA COVID-19 booster doses by age group
• Vaccination of specific populations
  • Pregnancy and breastfeeding
    • Table 4: Pregnancy registry information by vaccine product
  • Individuals previously infected with SARS-CoV-2
    • Table 5. Suggested intervals between previous SARS-CoV-2 infection and COVID-19 vaccination
  • Persons with an autoimmune condition
  • Immunocompromised persons
  • Travellers
  • Persons new to Canada
• Serologic testing
• Administration practices
  • Dose and route of administration
    • Table 6. Dosing for Moderna Spikevax vaccines
  • Interchangeability of vaccines
  • Concurrent administration with other vaccines
  • Pre-vaccination counselling
  • Post-vaccination counselling
• Storage requirements
• Safety and adverse events
  • Very common and common adverse events
  • Uncommon, rare and very rare adverse events
  • Guidance on reporting adverse events following immunization (AEFI)
  • Contraindications and precautions
    • Table 7. Vaccine products and potential allergens
• Other considerations
  • Drug interactions
  • Tuberculin skin testing (TST) and interferon gamma release assay (IGRA)
  • Blood products, human immunoglobulin and timing of immunization
• Chapter revision process
• Acknowledgments
• Selected references

Key information (refer to text and tables for details)

What

• 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 due to living or occupational settings and some populations are at increased risk of severe outcomes due to biological factors and/or social factors.
• The following elements are recommended to guide ethical decision-making as outlined in NACI's Guidance on the Prioritization of Key Populations for COVID-19 Immunization:
  • Efforts should continually be made to increase access to immunization services to reduce health equalities without further stigmatization or discrimination, and to engage systematically marginalized populations and racialized populations in immunization program planning.
  • Jurisdictions should continue to 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 continue to be made to improve knowledge about the benefits of vaccines in general and of COVID-19 vaccines as each becomes available, address misinformation, and communicate transparently about COVID-19 allocation decisions.
• Two vaccine manufacturers have messenger ribonucleic acid (mRNA) vaccines authorized for use in Canada, based on the original strain, for the primary series in individuals 6 months of age and older (Pfizer-BioNTech Comirnaty and Moderna Spikevax).
• There are two Moderna Spikevax bivalent COVID-19 vaccines authorized for use as a booster dose: Original & Omicron BA.1 (authorized for use in individuals 6 years of age and older) and Original & Omicron BA.4/5 (authorized for use in adults 18 years of age and older).
• There are two Pfizer-BioNTech Comirnaty bivalent COVID-19 vaccines authorized for use as a booster dose: Original & Omicron BA.1 (authorized for use in individuals 12 years of age and older) and Original & Omicron BA.4/5 (authorized for use in individuals 5 years of age and older). Only the BA.4/5 formulation is available for distribution in Canada.
• The Novavax Nuvaxovid COVID-19 vaccine is the first protein subunit COVID-19 vaccine authorized in Canada. Novavax Nuvaxovid is authorized for use in individuals 12 years of age and older as a primary series and as a booster dose in those 18 years of age and older.
• The Medicago Covifenz COVID-19 vaccine was the first virus-like particle (VLP) COVID-19 vaccine authorized in Canada. Medicago Covifenz is authorized for use in adults 18-64 years of age as a primary series but was not marketed.
• There are two viral vector (non-replicating) vaccines authorized for use in Canada for individuals 18 years of age and older (AstraZeneca Vaxzevria COVID-19 vaccine and Janssen Jcovden COVID-19 vaccine) as a primary series. Janssen Jcovden is also authorized as a booster dose.
• For all vaccines, some solicited adverse events are 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 may include: pain, redness and swelling at the injection site, axillary (or groin) swelling or tenderness, fatigue, headache, muscle pain, chills, joint pain, and fever.
• Very rare adverse events following immunization have been reported. Refer to Safety and adverse events for more information.

Who

• A complete series with an mRNA COVID-19 vaccine is recommended for children in the authorized age groups without contraindications to the vaccine, with a dosing interval of at least 8 weeks between the first and second dose. Refer to Recommendations for use, Children for more information.
• A complete primary series, preferentially with an mRNA COVID-19 vaccine, should be offered to individuals 12 years of age and older without contraindications to the vaccine. Refer to Recommendations for use, Adolescents and Adults for more information.
• For recommendations for individuals 6 months of age and older who are moderately to severely immunocompromised, refer to Vaccination of specific populations, Immunocompromised persons.
• A first booster dose of mRNA COVID-19 vaccine should be offered to adults 18 years of age and older and select adolescents 12 to 17 years of age as well as select children 5 to 11 years of age. A first booster of mRNA COVID-19 vaccine may also be offered to all other children and adolescents 5 to 17 years of age. An additional booster dose is recommended for select populations. Refer to Recommendations for use, Booster doses for more information.
• It is recommended that mRNA COVID-19 vaccines should be offered to individuals 6 months of age and older with previous SARS-CoV-2 infection without contraindications to the vaccine. Refer to Individuals previously infected with SARS-CoV-2 for more information, including recommended intervals.
• It is recommended that an authorized protein subunit COVID-19 vaccine (Novavax Nuvaxovid) may be offered to individuals in the authorized age group without contraindications to the vaccine who are not able or willing to receive an mRNA COVID-19 vaccine.
• An authorized viral vector COVID-19 vaccine may be offered to individuals 18 years of age and over, without contraindications to the vaccine, when all other authorized COVID-19 vaccines are contraindicated.

How

• Currently, for immunocompetent individuals, the Pfizer-BioNTech Comirnaty COVID-19 vaccine [original] is administered as a 2-dose primary series for those 5 years of age and over and as a 3-dose primary series for those 6 months to less than 5 years of age; Moderna Spikevax [original] is administered as a 2-dose primary series for those 6 months of age and over; Novavax Nuvaxovid is administered as 2-dose primary series for those 12 years of age and over; and Janssen Jcovden is a one dose primary series for those 18 years of age and over. For those who are moderately to severely immunocompromised an additional dose is recommended to be added to the primary series (refer to Table 2).
• Bivalent mRNA COVID-19 vaccines are currently authorized only as booster doses. Refer to Recommendations for use, Booster doses for more information.
• Prior to providing a COVID-19 vaccine informed consent should include discussion about frequently occurring minor adverse events and the risks and symptoms of potential rare severe adverse events.
• Serologic testing is not recommended before or after receipt of a COVID-19 vaccine to assess susceptibility to SARS-CoV-2 or immune response to the vaccine.
• For individuals 6 months of age and older, COVID-19 vaccines may be given concurrently with (i.e., same day), or at any time before or after, non-COVID-19 vaccines (including live and non-live vaccines).
• Individuals should continue to follow recommended public health measures for prevention and control of SARS-CoV-2 infection and transmission.

Why

• The COVID-19 pandemic has caused significant morbidity and mortality, as well as social and economic disruption in Canada and worldwide.
• COVID-19 vaccines have been shown to be very effective at preventing severe disease, including hospitalization and death due to COVID-19.

Epidemiology

Disease description

Infectious agent

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

Transmission

Current evidence suggests that SARS-CoV-2 is spread through respiratory droplets and aerosols created when an infected person breathes, coughs, sneezes, sings, shouts, or talks. A person may be infectious for up to 3 days before showing symptoms and most people are considered no longer infectious 10 days from onset of symptoms (or first detection of infection if asymptomatic).

More information on the transmission of SARS-CoV-2 can be found on the Public Health Agency of Canada (PHAC) webpages for COVID-19: Main modes of transmission.

Variants of concern

Genetic mutations in the SARS-CoV-2 virus have led to the designation of variants of concern (VOCs) and these variants are more transmissible than the original strain. Mutations in VOCs may also affect the severity of disease and the level of protection offered by vaccines.

More information on the VOCs reported in Canada is available in the COVID-19 epidemiology update. The COVID-19 Weekly Epidemiological Update by the World Health Organization (WHO) provides a summary on the global distribution and emerging evidence on VOC and variants of interest (VOI). Differences between VOC and VOI are available from SARS-CoV-2 variants: National definitions, classifications and public health actions.

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 biological factors (e.g., advanced age, pre-existing medical conditions, pregnancy) and social factors (e.g., socioeconomic status, belonging to a racialized population) that may intersect. Exposure and risk factors for 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 characterized by increased rates of infection and disease, severe illness, hospitalizations, and/or deaths.

There is a spectrum of COVID-19 disease severity, ranging from asymptomatic to mild, moderate, severe and critical disease. Severe disease more often occurs in those with increasing age and those with underlying medical conditions, with the risk increasing with the number of underlying conditions. A list of underlying medical conditions associated with more severe COVID-19 disease can be found in COVID-19 signs, symptoms and severity of disease: A clinician guide.

There is limited evidence on clinical risk factors for severe COVID-19 disease in pediatric populations. Children at increased risk for severe outcomes may include children who are obese, children who are medically fragile/ have medical complexities, children with more than one comorbidity, children with neurological disorders, and children with immune dysregulation associated with Down syndrome (Trisomy 21) and other immunocompromising conditions.

Adolescents 12 to 17 years of age who may be at higher risk of severe illness due to COVID-19 include those with one or more of the following underlying medical conditions (based on expert opinion and evolving evidence):

• Cancer: active treatment
• Chronic kidney disease
• Chronic lung diseases, including uncontrolled asthma
• Cystic fibrosis
• Neurodevelopmental and other chronic neurological conditions including epilepsy and cerebrovascular disease
• Diabetes (type 1 & 2)
• Down syndrome (Trisomy 21)
• Congenital heart disease or other chronic heart diseases, including pulmonary hypertension
• Chronic liver disease
• Obesity (body mass index [BMI] ≥30)
• Pregnancy
• Sickle cell disease or thalassemia
• Substance use disorders
• Immunocompromised state, including primary immune deficiency, solid organ or haematopoietic stem cell transplant, HIV infection, or immunosuppressive therapy
• Medically fragile/having medically complex needs.

Spectrum of clinical illness

The median incubation period (the time from exposure to symptom onset) for non-variant SARS-CoV-2 has been estimated to be 5 to 6 days, with most individuals (97.5%) developing symptoms within 11.5 days of exposure. The incubation period ranges from 1 to 14 days.

Clinical presentation and symptoms of COVID-19 vary in frequency and severity, from asymptomatic to severe and fatal disease. 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.

While most children and adolescents with COVID-19 have mild or no symptoms, some do experience severe disease. However, children and adolescents report fewer severe outcomes of COVID-19 (i.e., hospitalizations due to COVID-19, ICU admission, and deaths) compared to older age groups.

Children, adolescents and adults with SARS-CoV-2 infection are also at risk of multisystem inflammatory syndrome (MIS), a rare but serious condition that can occur several weeks following SARS-CoV-2 infection.

Post-COVID condition or post-acute COVID syndrome (PCC) occurs in people with a history of probable or confirmed SARS-CoV-2 infection who experience symptoms more than 12 weeks after infection.

Disease incidence

Global

Updated international data on COVID-19 cases and deaths are available.

Weekly epidemiological updates highlighting key global, regional and country-level data on COVID-19 cases and deaths are available from WHO.

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.

Preparations authorized for use in Canada

When referring to COVID-19 vaccines throughout this chapter, only those currently authorized by Health Canada for use in Canada are included. Refer to Vaccination of specific populations, Persons new to Canada for information regarding non-Health Canada authorized vaccines.

mRNA vaccines

• Comirnaty^TM (tozinameran, BNT162b2), Original, (formulations of 30 mcg, 10 mcg or 3 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus), BioNTech Manufacturing GmbH
  • Authorized as a primary series in those 12 years of age and older (30 mcg), children 5 to 11 years of age (10 mcg), and children 6 months of age to less than 5 years of age (3 mcg)
  • Authorized as a booster dose in children 5 to 11 years of age (10 mcg) and those 16 years of age and older (30 mcg)
• Comirnaty^® Original & Omicron BA.4/BA.5, (Bivalent), BioNTech Manufacturing GmbH
  • Authorized as a booster dose only, in those 5 to 11 years of age (total 10 mcg of mRNA, with 5 mcg of mRNA encoding for the original SARS-CoV-2 virus and 5 mcg encoding for the Omicron BA.4/5 variant) and 12 years of age and older (total 30 mcg of mRNA, with 15 mcg of mRNA encoding for the original SARS-CoV-2 virus and 15 mcg encoding for the Omicron BA.4/5 variant)
• Comirnaty® Original & Omicron BA.1, (Bivalent, total 30 mcg of mRNA, with 15 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 15 mcg encoding for the spike protein of the Omicron BA.1 variant), BioNTech Manufacturing GmbH
  • Authorized as a booster dose only, in those 12 years of age and older (30 mcg)
  • This formulation of Comirnaty was not distributed in Canada, so recommendations only refer to the BA.4/5 formulation throughout the rest of the chapter.
• Spikevax^TM (elasomeran, mRNA-1273), Original, (formulations of 100 mcg, 50 mcg or 25 mcg of mRNA of mRNA encoding for the spike protein of the original SARS-CoV-2 virus), Moderna TX Inc.
  • Authorized as a primary series for use in those 12 years of age and older (100 mcg), children 6 to 11 years of age (50 mcg) and children 6 months to 5 years of age (25 mcg)
  • Authorized as a booster dose in those 12 years of age and older (50 mcg)
• Spikevax Bivalent^TM (elasomeran/imelasomeran) Original/Omicron BA. 4/BA.5 (Bivalent, total 50 mcg of mRNA, with 25 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 25 mcg encoding for the spike protein of the Omicron BA.4/5 variant), Moderna TX Inc.
  • Authorized as a booster dose only, in those 18 years of age and older (50 mcg)
• Spikevax Bivalent^TM (elasomeran/imelasomeran) Original/Omicron BA.1 (Bivalent, total 50 mcg of mRNA, with 25 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 25 mcg encoding for the spike protein of the Omicron BA.1 variant), Moderna TX Inc.
  • Authorized as a booster dose only, in those 12 years of age and older (50 mcg) and in children 6 to 11 years of age (25 mcg)

COVID-19 vaccines that use 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.

Protein subunit vaccine

• Nuvaxovid^TM (SARS-CoV-2 recombinant spike protein of the original strain) with Matrix-M adjuvant, Novavax
  • Authorized for use as a primary series in those 12 years of age and older and a booster dose in those 18 years of age and older (5 mcg of recombinant protein)
  • NACI guidance on the use of Novavax Nuvaxovid in those 12-17 years of age and as a booster dose in those 18 years of age and older is forthcoming.

Novavax Nuvaxovid consists of a purified full-length SARS-CoV-2 recombinant spike protein nanoparticle administered as a co-formulation with the adjuvant Matrix-M. Matrix-M is a novel saponin-based adjuvant that facilitates activation of the cells of the innate immune system, which enhances the magnitude of the spike protein-specific immune response. Matrix-M has been used in Novavax Nuvaxovid clinical trials and in pre-licensure studies targeting other pathogens, but has not previously been used in any licensed vaccine.

Virus-like particle (VLP) vaccine

• Covifenz® (SARS-CoV-2 recombinant spike protein of the original strain, plant-based virus-like particle to which ASO3 adjuvant is added by the immunizer), Medicago Inc.
  • Authorized for use as a primary series in adults 18-64 years of age (3.75 mcg of virus-like particles)
  • Note that Covifenz was never marketed.

The Medicago Covifenz COVID-19 vaccine is an adjuvanted vaccine consisting of recombinant SARS-CoV-2 spike glycoproteins stabilized in the prefusion conformation that are produced by transient expression in Nicotiana benthamiana plants and become membrane imbedded in self-assembled enveloped VLPs. The vaccine also contains Adjuvant System 03 (AS03), produced by GlaxoSmithKline, that was used as the adjuvant in three influenza vaccines: Prepandrix (H5N1), Pandemrix (H1N1pdm09) and Arepanrix (H1N1pdm09).

Viral vector (non-replicating) vaccines

• Vaxzevria^™ (ChAdOx1-S recombinant), AstraZeneca Canada Inc.
  • Authorized for use in those 18 years of age and older (5 x 10¹⁰ viral particles)
  • Vaxzevria is no longer available in Canada
• Jcovden COVID-19 vaccine (Ad26.COV2.S), Janssen Inc.
  • Authorized for use in those 18 years of age and older as a primary series and as a booster (5 x 10¹⁰ virus particles)

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 of the adenovirus so that it does not cause disease. 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 Vaxzevria vaccine uses a modified chimpanzee adenovirus vector (ChAd) and the Janssen Jcovden vaccine uses a modified human adenovirus serotype 26 vector (Ad26).

Note that Health Canada authorized 2 manufacturers to produce the ChAdOx1-S recombinant viral vector vaccine: AstraZeneca and Serum Institute of India (SII). Authorization by interim order for the SII product marketed as COVISHIELD has expired and therefore it is no longer authorized for use in Canada.

Anti-SARS-CoV-2 monoclonal antibodies authorized for pre-exposure prophylaxis of COVID-19

• EVUSHELD^™ (tixagevimab and cilgavimab), AstraZeneca Canada Inc.
  • Authorized for use in those 12 years of age and older weighing at least 40 kg (300 mcg of tixagevimab and 300 mcg of cilgavimab administered in sequence)

Tixagevimab and cilgavimab are two recombinant human monoclonal antibodies with amino acid substitutions to extend antibody half-life and thus duration of protection, as well as minimize the potential risk of antibody-dependent enhancement of disease. In addition to authorization for pre-exposure prophylaxis, Evusheld has also been authorized to treat mild to moderate COVID-19.

For complete prescribing information for any of the Preparations authorized for use in Canada, consult the product leaflet or information contained within Health Canada's authorized product monographs available through the Drug Product Database.

Immunogenicity, efficacy and effectiveness

Immunogenicity

All COVID-19 vaccines induce humoral immune responses, including binding and neutralizing antibody responses. As well, all authorized COVID-19 vaccines have been shown to produce cellular immune responses in adult populations. The immune responses may vary depending on the product used, number of doses, interval between the doses, and the age and underlying medical conditions of the vaccine recipient. No immunological correlate of protection has been determined for SARS-CoV-2, and therefore the implications of differences in immune responses post-COVID-19 vaccination on protection against infection and severe disease, as well as on duration of protection, is uncertain.

Efficacy and effectiveness

Efficacy and effectiveness of COVID-19 vaccines tends to be lowest against infection, somewhat higher against symptomatic disease and highest against severe disease. Vaccine effectiveness varies by variant. Clinical trials for original COVID-19 vaccines were conducted mostly when the original or Alpha VOC strains were circulating and prior to the emergence of Omicron. Compared to the original SARS-CoV-2 strain and earlier variants, COVID-19 vaccines have substantially lower vaccine effectiveness for Omicron sublineages when assessed against infection/symptomatic disease and also somewhat lower vaccine effectiveness against severe disease.

Vaccine effectiveness decreases over time since vaccination. Vaccine efficacy as determined by clinical trials was generally assessed within a few months of vaccination. Subsequent effectiveness studies have demonstrated waning over time, particularly against infection and symptomatic disease, and to a lesser extent against severe disease as well. Booster doses are intended to increase protection, particularly against severe disease, that may have decreased over time.

Similar to factors that impact the immune response, vaccine effectiveness may be affected by the vaccine product received, the interval between doses, and the age and health status of the recipient. Vaccine effectiveness of bivalent Omicron-containing mRNA COVID-19 vaccines has yet to be established.

Vaccine effectiveness against transmission is also measured in some studies. To the extent that COVID-19 vaccines protect against infection, they also prevent transmission as those who are not infected cannot spread infection to others. In addition, vaccination may offer additional protection against transmission even if infection is not prevented (i.e., shorter duration of symptomatic illness). This has been demonstrated particularly with a booster dose, although the duration of this protection against transmission remains uncertain.

To the extent that vaccines prevent infection, they also prevent PCC. In addition, compared to those who are unvaccinated, those vaccinated with two or more doses of COVID-19 vaccines have been shown to be less likely to develop PCC if they do become infected compared to those who are unvaccinated.

Efficacy of the primary series against symptomatic COVID-19 disease

In clinical trials, the original mRNA COVID-19 vaccines have been shown to be highly efficacious in the short term against confirmed symptomatic COVID-19 disease. There is similar efficacy in adults with 1 or more comorbidities, as well as in children (5 to 11 years), adolescents (12 to 17 years)and adults (18 years of age and older). There is some evidence of waning of immunogenicity and effectiveness over time that varies by age and vaccine interval. The original mRNA vaccines are efficacious in individuals aged 12 years and over with or without evidence of prior SARS-CoV-2 infection. Efficacy estimates for the Pfizer-BioNTech Comirnaty original (10 mcg) vaccine and for the Moderna Spikevax original (50 mcg) vaccine in children aged 5 to 11 and 6 to 11 years, respectively, with evidence of prior SARS-CoV-2 infection are not currently known.

Vaccine efficacy was assessed among children aged 6 months to 4 to 5 years following one and two doses of Moderna Spikevax (25 mcg) mRNA COVID-19 vaccine and three doses of Pfizer/BioNTech Comirnaty (3 mcg) mRNA COVID-19 vaccine, during a time when Omicron was the predominant variant of SARS-CoV-2. For Moderna Spikevax, efficacy against confirmed symptomatic infection starting 14 days after dose 2 among participants without evidence of prior SARS-CoV-2 infection was estimated at 50.6% among study participants aged 6 to 23 months with a median follow-up of 68 days and 36.8% among participants aged 2 to 5 years with a median follow-up of 72 days. For Pfizer Comirnaty, among children without prior infection, vaccine efficacy about 2 months following the third dose was estimated at 75.8% among children 6 to 23 months of age and 71.8% among children 2 through 4 years of age.

Clinical trial data available to date have shown that Novavax Nuvaxovid COVID-19 vaccine is highly efficacious (approximately 90%) in preventing confirmed symptomatic COVID-19 disease in the short term during a time period when the Alpha VOC predominated. However, efficacy was lower against the Beta variant in a study from South Africa (48.6%). No efficacy or effectiveness data are available against Omicron.

Clinical trial data available to date have shown that Medicago Covifenz is efficacious (approximately 71%) in preventing confirmed symptomatic COVID-19 disease in the short-term starting at one to two weeks after receiving the full 2-dose series, in populations where the Delta and Gamma VOC were predominantly in circulation. No efficacy or effectiveness data are available for Medicago Covifenz against the Omicron variant.

The AstraZeneca Vaxzevria COVID-19 vaccine has shown moderate short-term efficacy (approximately 62%) against symptomatic COVID-19 disease in adults 18 to 64 years of age, with increased efficacy as the interval between doses increases. The Janssen Jcovden COVID-19 vaccine demonstrated moderate efficacy against symptomatic confirmed moderate to severe COVID-19 infection from 14 days and 28 days post-vaccination of approximately 66% and 67% respectively in the primary analysis, prior to the emergence of SARS-CoV-2 variants. Estimates in the final analysis inclusive of variants, against moderate to severe COVID-19 at least 14 days after vaccination with a median follow-up of 4 months was approximately 56%.

Studies about the duration of protection provided by COVID-19 vaccination are ongoing. Decreased protection against infection/symptomatic disease over time has been noted to occur with mRNA vaccines, the protein subunit vaccine and the viral vector vaccines. Studies of vaccine efficacy against symptomatic disease after vaccination with the primary series suggest that protection with Moderna Spikevax original may be more durable than with Pfizer-BioNTech Comirnaty original vaccine. Shorter intervals between the first and second dose of a 2-dose COVID-19 vaccine series result in lower initial titres that may result in protection that decreases sooner. Observational studies show a reduction in vaccine effectiveness against infection/symptomatic disease in immunocompromised adults when compared to the general population with a 2-dose vaccine series.

Efficacy and effectiveness of the primary series against severe disease

The clinical trials of the authorized and available COVID-19 vaccines assessed efficacy against severe COVID-19 disease, but not all provided sufficient data to be able to assess the efficacy against hospitalizations or deaths.

Real world evidence suggests moderate to high vaccine effectiveness at preventing severe illness, such as hospitalization and death, which is sustained out to at least 6 months in most populations ages 12 years and older. There is some decline noted in older adults (such as those 80 years of age and over) and residents in long term care homes in overall effectiveness over time, although protection against severe outcomes appears to be more durable than protection against infection. Effectiveness estimates suggest the Pfizer-BioNTech Comirnaty (10 mcg) original vaccine in children 5 to 11 years of age for the primary series is similarly effective against severe disease due to Omicron as it is in older populations. Vaccine effectiveness against severe disease is unknown for Moderna Spikevax original (50 mcg) vaccine in children 6 to 11 years of age, Novavax Nuvaxovid and Medicago Covifenz. There were no deaths or cases of severe COVID-19 among trial participants 6 months to 5 years of age for the Moderna Spikevax original (25 mcg) vaccine. Therefore, efficacy against outcomes of severe COVID-19 could not be estimated. Similarly, efficacy against severe disease was not evaluated for Pfizer-BioNTech original (3 mcg) for children 6 months to 4 years of age due to very few events, including no deaths in the clinical trial.

An ad-hoc analysis examined vaccine efficacy by moderate and by moderate or severe COVID-19 for Medicago Covifenz. The estimate of efficacy against moderate or severe COVID-19 at least 7 days after dose 2 was 78.1% in the per-protocol analysis.

Effectiveness of the primary series against hospitalization due to MIS-C

Real world evidence suggests the Pfizer-BioNTech Comirnaty COVID-19 original vaccine has high vaccine effectiveness at preventing hospitalization due to MIS-C among adolescents 12 to 18 years of age. Effectiveness estimates against hospitalization due to MIS-C for the Pfizer-BioNTech Comirnaty (10 mcg) original vaccine in children aged 5 to 11, or for the Moderna Spikevax original (50 mcg) vaccine in children aged 6 to 11 years are not currently known. There were no cases of MIS-C among trial participants 6 months to 5 years of age for the Moderna Spikevax original (25 mcg) vaccine; however, one case of MIS-C was reported in a placebo recipient after the data cut-off. In the Pfizer-BioNTech Comirnaty study for children 6 months to 4 years of age, there were no cases of MIS-C identified. Therefore, efficacy against MIS-C was not able to be evaluated in either of these studies of young children.

There are no results specific to other COVID-19 vaccines yet, however studies are ongoing.

Efficacy and effectiveness of the primary series against asymptomatic infection

Clinical trials for currently authorized COVID-19 vaccines were primarily designed to evaluate efficacy against symptomatic illness and conducted prior to the emergence of Omicron. While data on efficacy against asymptomatic infection remain limited, effectiveness studies have generally found that effectiveness against infection is somewhat lower than against symptomatic disease.

Vaccine effectiveness of booster doses

Booster doses improve the immune response and vaccine effectiveness that has decreased over time. A booster dose achieved very high vaccine effectiveness (generally >90%) against the Delta variant for infection/symptomatic disease and severe disease. Against Omicron, a booster dose increased protection compared to pre-booster levels, however after a booster dose, protection against infection/symptomatic disease was approximately 60% (ranging from approximately 40 to 80%) and decreased over time. Protection against severe Omicron disease after a booster dose was higher at around 90%, and generally remained above 70% for approximately 6 months post booster dose. Subsequent booster doses raise protection again, but waning continues to occur, particularly against infection/symptomatic disease.

While there are currently no efficacy or effectiveness data for the bivalent booster products, there is some clinical immunogenicity data, particularly for Moderna Spikevax BA.1. With the Moderna Spikevax Bivalent BA.1 (50 mcg) vaccine, the neutralizing antibody titre against Omicron BA.1 was 1.75 times higher than with the original Moderna Spikevax vaccine, and the immune response against the original strain was similar between the original and bivalent Moderna Spikevax BA.1 products. There is very little clinical data for Pfizer-BioNTech Comirnaty BA.4/5 Bivalent (30 mcg) and Moderna Spikevax BA.4/5 (50 mcg) vaccines, although studies are ongoing.

There is currently no data comparing the immune response between different bivalent booster vaccines targeting BA.1 versus BA.4/5, nor any immunogenicity data directly comparing the immune response of Moderna (50 mcg) and Pfizer-BioNTech (30 mcg) bivalent booster products.

Recommendations for use

Children

Recommendations for children 6 months to 4 years of age

It is recommended that children 6 months to 4 years of age may be offered a primary series of an mRNA COVID-19 vaccine if they have no contraindications to the vaccine.

For children who are not moderately to severely immunocompromised a primary series of Moderna Spikevax (25 mcg) consists of two doses for those 6 months to 5 years of age while a primary series of Pfizer-BioNTech Comirnaty (3 mcg) consists of three doses for those 6 months to 4 years of age, using an interval of at least 8 weeks between each dose for both products.

If readily available (i.e., easily available at the time of vaccination without delay or vaccine wastage), the same mRNA COVID-19 vaccine product should be offered for the subsequent dose in a vaccine series started with a specific mRNA COVID-19 vaccine.

If two different products are administered (i.e., a mixed schedule with at least one Moderna Spikevax and one Pfizer-BioNTech Comirnaty dose), it is recommended that the 3-dose schedule be used. Either product can be used to complete the remaining dose of the 3-dose mixed schedule.

There are currently no recommendations for booster doses in those 6 months to 4 years of age and no product is authorized as a booster dose for this age group.

Recommendations for children 6 months to 4 years of age who are moderately to severely immunocompromised

It is recommended that children 6 months to 4 years of age who are moderately to severely immunocompromised and do not have contraindications may be offered a primary series that consists of an additional dose of an mRNA COVID-19 vaccine compared to the age-based schedules noted above for non-immunocompromised children. Therefore, a primary series for children who are moderately to severely immunocompromised consists of three doses of the Moderna Spikevax (25 mcg) vaccine for those 6 months to 5 years of age or four doses of the Pfizer-BioNTech Comirnaty (3 mcg) for those 6 months to 4 years of age, using an interval of 4 to 8 weeks between each dose for both products.

Because there are fewer doses in the schedule and may be more acceptable and feasible, the Moderna Spikevax (25 mcg) is the recommended product for those who are moderately to severely immunocompromised, however, four doses of the Pfizer-BioNTech Comirnaty (3mcg) vaccine may be offered if the Moderna Spikevax (25 mcg) is not readily available.

If readily available (i.e., easily available at the time of vaccination without delay or vaccine wastage), the same mRNA COVID-19 vaccine product should be offered for the subsequent dose in a vaccine series started with a specific mRNA COVID-19 vaccine.

For mixed schedules consisting of at least one dose of Moderna Spikevax (25 mcg) and one dose of Pfizer-BioNTech Comirnaty (3 mcg), four doses given 4 to 8 weeks apart are recommended for those who are moderately to severely immunocompromised. Either mRNA product can be used to complete the remaining doses of the four-dose mixed schedule.

Recommendations for children 5 to 11 years of age

It is recommended that children who are 5 to 11 years of age should be offered a primary series of an mRNA COVID-19 vaccine if they have no contraindications to the vaccine.

For children 5 to 11 years of age who are not moderately to severely immunocompromised a primary series of an mRNA vaccine consists of 2-doses, with a dosing interval of at least 8 weeks between the first and second dose.

For children 5 to 11 years of age, the use of Pfizer-BioNTech Comirnaty original (10 mcg) COVID-19 vaccine is preferred to Moderna Spikevax original to start or continue the primary vaccine series, due to a potentially lower risk of myocarditis/pericarditis with the Pfizer-BioNTech product. However, Moderna Spikevax original (25 mcg at 5 years of age or 50 mcg from 6 to 11 years of age) vaccine may be offered as an alternative.

Children who have received Pfizer-BioNTech original (3 mcg) starting at 4 years of age and then turn 5 years of age prior to completing their primary series, should be offered three doses in the primary series, however any doses of Pfizer-BioNTech vaccine given at 5 years of age should be 10 mcg. Doses less than 10 mcg at 5 years of age are considered invalid and should be repeated. See PHAC's resource: Quick reference guide on the use of COVID-19 vaccines: Managing vaccine administration errors or deviations for additional guidance.

Children who have received Moderna Spikevax original (25 mcg) for a previous dose at 5 years of age and turn 6 years of age prior to completing their primary series should be offered Moderna Spikevax original (50 mcg) to complete their 2-dose primary series. If the primary series was completed with Moderna Spikevax original (25 mcg) or with Pfizer-BioNTech Comirnaty original (10 mcg), the dose should be considered valid and the primary series complete.

Pfizer-BioNTech Comirnaty original (10 mcg) and Pfizer-BioNTech Comirnaty BA.4/5 Bivalent (10 mcg) are authorized as a booster dose in those 5 to 11 years of age. Moderna Spikevax bivalent BA.1 (25 mcg) is authorized as a booster dose in those 6 to 11 years of age. A bivalent booster dose is preferred, and should be given ≥ 6 months after completion of a primary COVID-19 vaccine series or previous SARS-CoV-2 infection. It should be offered to children 5 to 11 years of age with an underlying medical condition that places them at high risk of severe illness due to COVID-19, and may also be offered to all other children in this age group.

Only one booster dose after the primary series for children 5 to 11 years of age is recommended. However, at the provider’s discretion, a bivalent booster dose (as per recommended interval) could be offered to children considered at high risk of severe COVID-19 who have previously received a booster dose with the original Pfizer-BioNTech Comirnaty mRNA vaccine.

Refer to Booster doses for additional information on booster doses for children 5 to 11 years of age.

Recommendations for children 5 to 11 years of age who are moderately to severely immunocompromised

It is recommended that children 5 to 11 years of age who are moderately to severely immunocompromised and do not have contraindications should be offered a primary series of three doses of an mRNA COVID-19 vaccine authorized for their age, using an interval of 4 to 8 weeks between each dose.

Indirect data from adult populations (≥18 years of age) on original mRNA COVID-19 vaccines suggest Moderna Spikevax original (100 mcg) may result in higher vaccine effectiveness after a 2-dose primary series compared to Pfizer-BioNTech Comirnaty original (30 mcg) and is associated with a higher seroconversion rate among adult immunocompromised patients. Given this potential benefit, administration of the Moderna Spikevax original (25 mcg at 5 years of age or 50 mcg at 6 to 11 years of age) vaccine as a 3-dose primary series may be considered for children 5 to 11 years of age who are moderately to severely immunocompromised.

Pfizer-BioNTech Comirnaty original (10 mcg) and Pfizer-BioNTech Comirnaty BA.4/5 Bivalent (10 mcg) are authorized as a booster dose in those 5 to 11 years of age. Moderna Spikevax bivalent BA.1 (25 mcg) is authorized as a booster dose in those 6 to 11 years of age. A bivalent booster dose is preferred, and is recommended to be given ≥6 months after completion of a 3-dose primary COVID-19 vaccine series, or previous SARS-CoV-2 infection, to children 5 to 11 years of age who are moderately to severely immunocompromised.

Only one booster dose after the primary series for children 5 to 11 years of age is recommended. However, at the provider’s discretion, a bivalent booster dose (as per recommended interval) could be offered to children considered at high risk of severe COVID-19 who have previously received a booster dose with the original Pfizer-BioNTech Comirnaty mRNA vaccine.

Refer to Booster doses for additional information on booster doses for children 5 to 11 years of age.

Considerations

The risk of myocarditis or pericarditis with the Moderna Spikevax original vaccine (50 mcg) in children 6 to 11 years of age is unknown, given the limited use in this age group. However, in adolescents and young adults 12 years of age and older, the rare risk of myocarditis or pericarditis was higher with Moderna Spikevax original (100 mcg) than with Pfizer-BioNTech Comirnaty original (30 mcg) with a primary series. In younger children, vaccine safety surveillance data suggests the risk of myocarditis and/or pericarditis is lower than that of adolescents or young adults. Among children 5 to 11 years of age following vaccination with Pfizer-BioNTech Comirnaty original (10 mcg), very rare cases of myocarditis/pericarditis were most often reported following the second dose and among males. Therefore, Pfizer-BioNTech Comirnaty original is the preferred product for the primary series in children 5 to 11 years of age.

Adolescents

Recommendations for adolescents 12 to 17 years of age

It is recommended that a complete primary series consisting of two doses of an mRNA COVID-19 vaccine should be offered to adolescents 12 to 17 years of age who do not have contraindications to the vaccine.

• The use of Pfizer-BioNTech Comirnaty original (30 mcg) is preferred to Moderna Spikevax original (100 mcg) to start or continue the mRNA primary vaccine series due to a lower risk of myocarditis/pericarditis with the Pfizer-BioNTech product.
• For those who are not moderately to severely immunocompromised, the second dose of the 2-dose primary series of mRNA vaccine should be provided 8 weeks after the first dose.

Eleven year olds who receive the 10 mcg Pfizer-BioNTech Comirnaty original or 50 mcg Moderna Spikevax original for their first dose and who have turned 12 years of age by the time the second dose is due should receive the 30 mcg Pfizer-BioNTech Comirnaty original that is authorized for individuals aged 12 years and older to complete their primary series. The 100 mcg dose of Moderna Spikevax original is also authorized for those 12 years of age and older but Pfizer-BioNTech Comirnaty original is preferred for adolescents due to a lower risk of myocarditis/pericarditis. If the second dose of 10 mcg Pfizer-BioNTech Comirnaty original is given at 12 years of age, the dose is considered invalid. See PHAC's resource: Quick reference guide on the use of COVID-19 vaccines: Managing vaccine administration errors or deviations for additional guidance. If the second dose is 50 mcg Moderna Spikevax original, the dose should still be considered valid and the series complete.

A bivalent booster dose should be offered to 12 to 17 year olds who are at increased risk of severe illness for COVID-19 and may be offered to other 12 to 17 year olds, with an interval of 6 months from the last dose of the primary series or COVID-19 infection, although shorter intervals down to 3 months may be recommended in some circumstances. Pfizer-BioNTech Comirnaty bivalent BA.4/5 (30 mcg) and Moderna Spikevax bivalent BA.1 (50 mcg) are authorized booster doses for this age group. Moderna Spikevax bivalent BA.4/5 (50 mcg) may also be used off label. Refer to Booster doses for additional information on booster doses for adolescents 12 to 17 years of age.

Recommendations for adolescents 12 to 17 years of age who are moderately to severely immunocompromised

For moderately to severely immunocompromised adolescents 12 to 17 years of age without contraindications, it is recommended that a primary series of three doses of an mRNA vaccine should be offered with an interval of 4 to 8 weeks between doses.

Pfizer-BioNTech Comirnaty bivalent BA.4/5 (30 mcg) and Moderna Spikevax bivalent BA.1 (50 mcg) are authorized booster doses for this age group. Moderna Spikevax bivalent BA.4/5 (50 mcg) may also be used off label. Booster doses should be offered to 12 to 17 year olds who are moderately to severely immunocompromised with an interval of 6 months from the last dose of the primary series or COVID-19 infection, although shorter intervals down to 3 months may be recommended in some circumstances. Refer to Booster doses for information on booster doses for adolescents 12 to 17 years of age who are moderately to severely immunocompromised.

Considerations

The known risks of COVID-19 illness (including complications like myocarditis/pericarditis) outweigh the potential harms of having an adverse reaction following mRNA vaccination. The risk of myocarditis or pericarditis following mRNA vaccination is rare, relatively mild, and resolves quickly in most individuals. The use of the Pfizer-BioNTech Comirnaty original vaccine is preferred to the Moderna Spikevax original vaccine in individuals 12 to 17 years of age because of a lower reported rate of myocarditis/pericarditis following the Pfizer-BioNTech Comirnaty original (30 mcg) compared to the Moderna Spikevax original (100 mcg) vaccine. Additionally, a longer interval between doses is associated with higher vaccine effectiveness and potentially lower risk of myocarditis/pericarditis.

Adults

Recommendations for adults 18 years of age and older

It is recommended that a complete primary series, preferentially with an mRNA COVID-19 vaccine, should be offered to individuals in the authorized age group without contraindications to the vaccine.

• For those who are not moderately to severely immunocompromised, the second dose of the 2-dose primary series of mRNA vaccine should be provided 8 weeks after the first dose.

There is a preferential recommendation for the use of mRNA COVID-19 vaccines in all authorized age groups due to greater effectiveness of mRNA vaccines and the rare risk of certain serious adverse events with viral vector vaccines, such as vaccine-induced immune thrombotic thrombocytopenia (VITT).

The known risks of COVID-19 illness (including complications like myocarditis/pericarditis) outweigh the potential harms of having an adverse reaction following mRNA vaccination, including the rare risk of myocarditis or pericarditis which despite hospitalization, is relatively mild and resolves quickly in most individuals.

For individuals aged 18 to 29 years receiving an mRNA COVID-19 vaccine primary series:

• The use of Pfizer-BioNTech Comirnaty original (30 mcg) is preferred to Moderna Spikevax original (100 mcg) to start or continue the mRNA primary vaccine series because of a lower reported rate of myocarditis/pericarditis following Pfizer-BioNTech Comirnaty original (30 mcg) compared to Moderna Spikevax original (100 mcg) for the mRNA primary vaccine series.

For adults aged 30 years or older receiving an mRNA COVID-19 vaccine primary series:

• Either of the mRNA COVID-19 vaccines (Moderna Spikevax original [100 mcg] or Pfizer-BioNTech Comirnaty original [30 mcg]) should be used to start or continue the primary series given that this age group has a lower risk of vaccine-associated myocarditis/pericarditis.

It is recommended that a primary series of an authorized protein subunit COVID-19 vaccine (Novavax Nuvaxovid) may be offered to individuals in the authorized age group without contraindications to the vaccine who are not able or willing to receive an mRNA COVID-19 vaccine. A viral vector COVID-19 vaccine may be offered to individuals in the authorized age group without contraindications to the vaccine only when all other authorized COVID-19 vaccines are contraindicated.

At least one booster dose should be offered to all adults 18 years of age and over. Regardless of past booster doses, recommendations in fall 2022 indicated that adults 65 years of age and over, as well as individuals 12 to 64 years of age who are at increased risk of severe illness from COVID-19 should be offered a COVID-19 booster dose, and all others 12 to 64 years of age may be offered a booster dose. An interval of 6 months from the last dose of the primary series or the last booster dose is recommended, although shorter intervals down to 3 months may be recommended in some circumstances.

The protein subunit COVID-19 vaccine (Novavax Nuvaxovid) is authorized by Health Canada as a booster. Novavax Nuvaxovid may be offered to as a booster to those who are not able or willing to receive an mRNA vaccine. Refer to Booster doses for information regarding booster doses for adults 18 years of age and older.

Recommendations for adults 18 years of age and older who are moderately to severely immunocompromised

For moderately to severely immunocompromised adults 18 years of age and over, a primary series of three doses, preferentially with an mRNA vaccine, should be offered with intervals of 4 to 8 weeks between doses. For these individuals who have previously received a 1- or 2-dose COVID-19 vaccine series (with a homologous or heterologous schedule using mRNA or viral vector vaccines) and have not received an additional dose, it is recommended that an additional dose with an mRNA COVID-19 vaccine (original) should be offered.

There is heterogeneity among those who are moderately to severely immunocompromised, and risks from COVID-19, as well as the likelihood of a reduced response to vaccines, will vary depending on age and the immunocompromising condition. Some immunocompromised individuals have a diminished immune response to the vaccines. Moderna Spikevax original (100 mcg) induces somewhat higher antibody levels compared to Pfizer-BioNTech Comirnaty original (30 mcg) and protection (against infection and severe disease) from a primary series with Moderna Spikevax original (100 mcg) may be more durable than Pfizer-BioNTech Comirnaty original (30 mcg).

Booster doses should be offered to all adults 18 years of age and over who are moderately to severely immunocompromised. Regardless of past booster doses, based on a fall 2022 recommendation, adults 65 years of age and over, as well as individuals 12 to 64 years of age who are moderately to severely immunocompromised should be offered a COVID-19 booster dose. An interval of 6 months from the last dose of the primary series or the last booster dose is recommended, although shorter intervals down to 3 months may be recommended in some circumstances. Refer to Booster doses for information on booster doses.

Schedule

For individuals 12 years of age and older, when the first dose in a COVID-19 vaccine series is an mRNA vaccine, the same mRNA vaccine product should be offered for the subsequent dose if readily available. When the same mRNA vaccine product is not readily available, or is unknown, another mRNA COVID-19 vaccine product recommended in that age group can be considered interchangeable and should be offered to complete the series.

Table 1 provides the immunization schedule and minimum, authorized and optimal interval by product and age for those who are not moderately to severely immunocompromised. Doses administered at less than the minimum interval are considered invalid. See PHAC's resource: Quick reference guide on the use of COVID-19 vaccines: Managing vaccine administration errors or deviations for additional guidance.

For mixed COVID-19 vaccine schedules, the minimum interval between doses should be based on the minimum interval of the product used for the first dose.

Optimal intervals between doses of 8 weeks (or at least 8 weeks) are longer than the authorized intervals as longer intervals are likely to result in a more robust and potentially more durable immune response and potentially higher vaccine effectiveness. Data from adults also suggests an extended interval may be associated with a reduced risk of myocarditis/pericarditis following a second dose of an mRNA COVID-19 vaccine.

Table 2 provides the immunization schedule and minimum interval by product and age for those who are moderately to severely immunocompromised. For these individuals, providers should aim to administer each dose of the 3-dose series (or four doses for Pfizer-BioNTech Comirnaty [3 mcg]) for moderately to severely immunocompromised children 6 months to 4 years of age) 4 to 8 weeks apart from each other. An interval longer than 4 weeks between each dose is likely to result in a more robust and potentially more durable immune response and potentially higher vaccine effectiveness and may be associated with lower risk of myocarditis/pericarditis. However, if a longer interval between doses is being considered, then the need for earlier protection due to risk of exposure (including local transmission of SARS-CoV-2) and risk of severe disease (e.g., underlying high-risk medical condition) should be taken into account. Some moderately to severely immunocompromised individuals may still be susceptible after the initial first or second doses in the primary series, so their period of susceptibility until receipt of the additional dose will also increase if the interval between doses is increased. Some of these individuals will also remain susceptible after a third dose of COVID-19 vaccine.

Refer to Table 5 for suggested intervals between previous SARS-CoV-2 infection and COVID-19 vaccination.

Table 1. Immunization schedule for a primary series, by COVID-19 vaccine for those who are not moderately to severely immunocompromised
(see Table 2 for those who are moderately to severely immunocompromised)

Vaccine product	Immunization scheduleTable 1 Footnote a	Authorized age indication	Minimum interval	Authorized interval	Optimal intervalTable 1 Footnote b
Pfizer-BioNTech Comirnaty original (30 mcg)	2-dose schedule	12 years of age and older	19 daysTable 1 Footnote c	21 days	8 weeks
Pfizer-BioNTech Comirnaty original (10 mcg, pediatric formulation)	2-dose schedule	5 to 11 years of age	19 days	21 days	At least 8 weeks
Pfizer-BioNTech Comirnaty original (3 mcg, pediatric formulation)	3-dose schedule	6 months to 4 years of age	19 daysTable 1 Footnote c	First 2 doses, 21 days apart, 3rd dose at least 8 weeks after 2nd dose	At least 8 weeks between each dose
Moderna Spikevax original (100 mcg)	2-dose schedule	12 years of age and older	21 daysTable 1 Footnote d	28 days	8 weeks
Moderna Spikevax original (50 mcg)	2-dose schedule	6 to 11 years of age	21 daysTable 1 Footnote d	28 days	At least 8 weeks
Moderna Spikevax original (25 mcg)	2-dose schedule	6 months to 5 years of age	28 daysTable 1 Footnote e	28 days	At least 8 weeks
Novavax Nuvaxovid	2-dose schedule	12 years of age and older	21 daysTable 1 Footnote f	21 days	8 weeks
Medicago Covifenz	2-dose schedule	18 to 64 years of age	21 daysTable 1 Footnote g	21 days	8 weeks
AstraZeneca Vaxzevria	2-dose schedule	18 years of age and older	28 days	4 to 12 weeks	At least 8 weeks
Janssen Jcovden	1-dose schedule	18 years of age and older	N/A	N/A	N/A
Table 1 Footnote a It is recommended that for moderately to severely immunocompromised individuals, a primary series consists of three doses, preferentially with an mRNA COVID-19 vaccine, noting that for children 6 months to 4 years of age who are moderately to severely immunocompromised and vaccinated with Pfizer-BioNTech Comirnaty (3 mcg), a primary series consists of four doses. Refer to Table 2 for additional information on schedules and intervals for those who are moderately to severely immunocompromised. Return Table 1 to footnote a referrer Table 1 Footnote b There is evidence that longer intervals between the first and second doses of COVID-19 vaccines are likely to result in more robust and potentially more durable immune response and potentially higher vaccine effectiveness and a lower risk of myocarditis/pericarditis. Balancing this potential enhanced protection from a longer interval with simultaneously minimizing the time at risk of infection due to having protection from only 1 dose, for all COVID-19 vaccines in those who are not moderately to severely immunocompromised, an 8-week (or at least 8 week) interval is recommended. Return Table 1 to footnote b referrer Table 1 Footnote c The basis for this minimum interval is that the per-protocol design for the Pfizer-BioNTech Comirnaty COVID-19 vaccine clinical trial was 19 to 23 days. Return Table 1 to footnote c referrer Table 1 Footnote d The basis for this minimum interval is that the majority of participants in the Moderna Spikevax COVID-19 vaccine clinical trials received the second dose 21 to 42 days after the first, as per the pre-defined window. Return Table 1 to footnote d referrer Table 1 Footnote e The participants in the clinical trial received the second dose a minimum of 28 days after the first dose. Return Table 1 to footnote e referrer Table 1 Footnote f The basis for this minimum interval is that the majority of participants in the Novavax Nuvaxovid clinical trial received the second dose 21+7 days after the first, as per the pre-defined window. Return Table 1 to footnote f referrer Table 1 Footnote g The minimum interval follows from the clinical trial protocol. Return Table 1 to footnote g referrer

Moderately to severely immunocompromised individuals

The recommended interval between doses in the primary series for those who are moderately to severely immunocompromised is 4 to 8 weeks.

Table 2. Immunization schedule and minimum intervals for a primary series for moderately to severely immunocompromised individuals, by COVID-19 vaccine

Vaccine product	Immunization scheduleTable 2 Footnote a	Minimum interval between the initial doses of a primary seriesTable 2 Footnote b	Minimum interval between the previous dose and the additional dose in the primary seriesTable 2 Footnote b
Pfizer-BioNTech Comirnaty original (3 mcg, pediatric formulation)Table 2 Footnote c	4-dose schedule	19 daysTable 2 Footnote d	28 days
Pfizer-BioNTech Comirnaty original (30 mcg) (10 mcg, pediatric formulation)Table 2 Footnote e	3-dose schedule	19 daysTable 2 Footnote d	28 days
Moderna Spikevax original (100 mcg) (50 mcg)Table 2 Footnote f	3-dose schedule	21 daysTable 2 Footnote g	28 days
Moderna Spikevax original (25 mcg)Table 2 Footnote c	3-dose schedule	28 daysTable 2 Footnote h	28 days
Novavax NuvaxovidTable 2 Footnote i	2-3 dose schedule	21 days	28 days
Medicago CovifenzTable 2 Footnote i	2-3 dose schedule	21 days	28 days
AstraZeneca Vaxzevria	2-dose scheduleTable 2 Footnote j +1 mRNA	28 days	28 days
Janssen Jcovden	1-dose scheduleTable 2 Footnote j +1 mRNA	N/A	28 days
Table 2 Footnote a It is recommended that for moderately to severely immunocompromised individuals, a primary series consists of three doses, preferentially with an mRNA COVID-19 vaccine, noting that for children 6 months to 4 years of age who are moderately to severely immunocompromised and vaccinated with Pfizer-BioNTech Comirnaty (3 mcg), a primary series consists of four doses. Table 2 Return to footnote a referrer Table 2 Footnote b For immunocompromised individuals, providers should aim to provide each dose of the primary series 4 to 8 weeks apart from each other. An interval longer than 4 weeks between each dose is likely to result in a more robust and durable immune response, potentially higher vaccine effectiveness and a lower risk of myocarditis/pericarditis. However, if a longer interval is being considered, risk factors for exposure and risk of severe disease should also be taken into account. Table 2 Return to footnote b referrer Table 2 Footnote c For children 6 months to 4 years of age who are moderately to severely immunocompromised and vaccinated with Pfizer-BioNTech Comirnaty (3 mcg), a primary series consists of 4 doses, using an interval of 4 to 8 weeks between each dose. For children 6 months to 4 years of age who are moderately to severely immunocompromised, Moderna Spikevax original (25 mcg) is the recommended product because it has one fewer dose than Pfizer-BioNTech original (3 mcg) and so may be more acceptable and feasible for this group. Table 2 Return to footnote c referrer Table 2 Footnote d The basis for this minimum interval is that the per-protocol design for the Pfizer-BioNTech Comirnaty original COVID-19 vaccine clinical trial was 19 to 23 days. Table 2 Return to footnote d referrer Table 2 Footnote e The 30 mcg dose of Pfizer-BioNTech Comirnaty original COVID-19 vaccine is authorized for those 12 years of age and older. The 10 mcg dose of Pfizer-BioNTech Comirnaty original COVID-19 vaccine is authorized for those 5 to 11 years of age. Table 2 Return to footnote e referrer Table 2 Footnote f The 100 mcg dose of Moderna Spikevax original COVID-19 vaccine is authorized for those 12 years of age and older. The 50 mcg dose of Moderna Spikevax original COVID-19 vaccine is authorized for those 6 to 11 years of age. Table 2 Return to footnote f referrer Table 2 Footnote g The basis for this minimum interval is that the majority of participants in the Moderna Spikevax original COVID-19 vaccine clinical trials received the second dose 21 to 42 days after the first, as per the pre-defined window. Table 2 Return to footnote g referrer Table 2 Footnote h The participants in the clinical trial received the second dose a minimum of 28 days after the first dose. Table 2 Return to footnote h referrer Table 2 Footnote i mRNA COVID-19 vaccines are preferred and are authorized for a 3-dose primary series in moderately to severely immunocompromised individuals, while Novavax Nuvaxovid and Medicago Covifenz are not currently authorized as a 3-dose primary series in these populations. Based on clinical discretion, a protein subunit or virus-like particle vaccine may be offered as a 3-dose primary series for moderately to severely immunocompromised individuals in the authorized age group who are not able or willing to receive an mRNA COVID-19 vaccine. Table 2 Return to footnote i referrer Table 2 Footnote j An initial or additional dose of a viral vector vaccine should only be considered for those in the authorized age group when all other authorized COVID-19 vaccines are contraindicated. Table 2 Return to footnote j referrer

Booster doses

All doses of COVID-19 vaccines after the primary series are described as booster doses. Note that for moderately to severely immunocompromised individuals, the primary series includes one additional dose that is not referred to as a booster dose.

Evidence suggests that protection against infection decreases with time from receipt of the last dose of vaccine. Booster doses provides additional protection, including and especially against severe disease. However, the duration of protection is currently unknown, and the absolute benefit of additional booster doses will depend on the residual protection from the previous booster dose and on the level of circulating disease in the community. See Table 3 for a summary of COVID-19 booster doses by age group.

An mRNA COVID-19 vaccine dose is preferred for the booster dose. Recipients of a viral vector vaccine series completed with only viral vector vaccines (AstraZeneca or Janssen Jcovden COVID-19 vaccine) should receive booster doses with an mRNA vaccine.

Bivalent vaccines are the preferred vaccine for booster doses among individuals in the authorized age groups, as, in addition to containing mRNA that encodes the spike protein of the original strain, they contain mRNA that encodes the spike protein of strains of the Omicron VOC, which is the most antigenically-distinct variant from the original SARS-CoV-2 strain.

Bivalent vaccines that encode for the BA.1 and BA.4/5 sublineages of Omicron are now available. Either type of vaccine can be used for the booster dose in authorized age groups.

Refer to Administration practices, Pre-vaccination counselling and Safety and adverse events for further information.

Timing of booster doses

The additional protection from a booster dose may be affected by the interval between doses. A longer time between doses may result in a better response after any subsequent dose, as this allows time for the immune response to mature in breadth and strength. A longer interval may, however, also increase the chance of a period with waning (lower) protection while awaiting a next dose.

COVID-19 booster doses may be offered at an interval of 6 months after a previous COVID-19 vaccine dose or SARS-CoV-2 infection (see Table 5), regardless of the product offered. However, a shorter interval of at least 3 months may be warranted in the context of heightened epidemiologic risk, evolving SARS-COV-2 epidemiology, as well as operational considerations for the efficient deployment of the vaccine program.

Table 3. Summary table of COVID-19 booster doses by age group

Population by age	Recommendation	Rationale
Adults ≥ 65 years of ageTable 3 Footnote aTable 3 Footnote b	Regardless of previous booster doses, a booster dose since the start of fall 2022 should be offered. Bivalent Omicron-containing mRNA vaccines are preferred.Table 3 Footnote c	Data to date indicate that bivalent Omicron-containing mRNA COVID-19 vaccines have a similar safety profile to original mRNA COVID-19 vaccines. Post-market safety surveillance data to date indicate that the risk of myocarditis following a booster dose is lower compared to that following the second dose in the primary series, and current data do not show a product-specific difference in the risks of myocarditis and/or pericarditis after a booster dose of an mRNA COVID-19 vaccine. Adults can receive a booster dose with any available bivalent Omicron-containing mRNA COVID-19 vaccine.
Adults 18 to 64 years of age who are at increased risk of severe illness from COVID-19 (including those who are immunocompromised and who received a 3-dose primary series)Table 3 Footnote b	Regardless of previous booster doses, a booster dose since the start of fall 2022 should be offered. Bivalent Omicron-containing mRNA vaccines are preferred.Table 3 Footnote cTable 3 Footnote d
All other adults 18 to 64 years of ageTable 3 Footnote aTable 3 Footnote b	At least one booster dose should be offered since the primary series. If a booster dose was received before the start of fall 2022, another booster dose may be offered since the start of fall 2022, with at least a 6-month interval since the previous dose (which could be shortened to at least 3 months in some circumstances).
Adolescents 12 to 17 years of age who are at increased risk of severe illness from COVID-19 (including those who are immunocompromised and who received a 3-dose primary series)	Regardless of previous booster doses, a booster dose since the start of fall 2022 should be offered. A bivalent Omicron-containing mRNA vaccine is preferred.Table 3 Footnote d	Moderna Spikevax Bivalent BA.1 (50 mcg) COVID-19 vaccine is authorized, however Moderna Spikevax bivalent BA.4/5 (50 mcg) COVID-19 vaccine may be used off-label.
All other adolescents 12 to 17 years of age	A booster dose since the start of fall 2022 may be offered. A bivalent Omicron-containing mRNA vaccine is preferred.Table 3 Footnote d
Children 5 to 11 years of age with an underlying medical condition that places them at high risk of severe illness due to COVID-19 (including those that are immunocompromised and who received an additional -dose in the primary series)	A booster dose should be offered. A bivalent Omicron-containing mRNA vaccine is preferred.Table 3 Footnote d	Moderna Spikevax bivalent BA.1 (25 mcg) COVID-19 vaccine is authorized in individuals 6 to 11 years of age, however Moderna Spikevax bivalent BA.4/5 (25 mcg) COVID-19 vaccine may be used off-label. Children 5 to 11 years of age who already received a booster dose with an original COVID-19 mRNA vaccine are not recommended to receive a bivalent Omicron-containing booster. However, at the provider's discretion, a bivalent booster dose could be offered to children considered at high risk of severe COVID-19 who have previously received a booster dose with the original Pfizer-BioNTech Comirnaty mRNA vaccine. There should be at least a 6-month interval since the previous dose (which could be shortened to at least 3 months in some circumstances).
For all other children 5 to 11 years of age	A booster may be offered. A bivalent Omicron-containing mRNA vaccine is preferred.Table 3 Footnote d	Moderna Spikevax bivalent BA.1 (25 mcg) COVID-19 vaccine is authorized in individuals 6 to 11 years of age, however Moderna Spikevax bivalent BA.4/5 (25 mcg) COVID-19 vaccine may be used off-label.
Table 3 Footnote a For booster doses for adults 18 years of age and older who are not able or willing to receive an mRNA COVID-19 vaccine, a protein subunit COVID-19 vaccine (Novavax Nuvaxovid) may be offered to adults without contraindications to the vaccine. Janssen Jcovden COVID-19 vaccine may be offered as a first booster to individuals 18 years of age and older without contraindications to the vaccine only when all other COVID-19 vaccines are contraindicated. Medicago Covifenz was not authorized for use as a booster dose. Table 3 Return to footnote a referrer Table 3 Footnote b Starting in the spring of 2023, NACI recommends that an additional booster dose may be offered as per the recommended interval to the following individuals who are at increased risk of severe illness from COVID-19: Adults 80 years of age and older Adult residents of long-term care homes and other congregate living settings for seniors or those with complex medical care needs Adults 18 years of age and older who are moderately to severely immunocompromised (due to an underlying condition or treatment) Adults 65 to 79 years of age, particularly if they do not have a known prior history of SARS-CoV-2 infection. Table 3 Return to footnote b referrer Table 3 Footnote c For individuals in authorized age groups who are not able or willing to receive a bivalent Omicron-containing mRNA COVID-19 vaccine, an original mRNA COVID-19 vaccine may be offered. Table 3 Return to footnote c referrer Table 3 Footnote d Pfizer-BioNTech Comirnaty bivalent BA.4/5 is authorized in individuals ≥ 5 years of age. Moderna Spikevax bivalent BA.1 is authorized in individuals ≥ 6 years of age. Moderna Spikevax bivalent BA.4/5 (50 mcg) vaccine is authorized in individuals ≥ 18 years of age. Table 3 Return to footnote d referrer

Vaccination of specific populations

Pregnancy and breastfeeding

Compared to non-pregnant persons, SARS-CoV-2 infection in pregnancy is associated with increased risk of hospitalization and admission to an intensive care unit (ICU). SARS-CoV-2 infection during pregnancy is also associated with an increased risk in the neonate of preterm birth, low birth weight and admission to a neonatal intensive care unit (NICU).

Recommendations

It is recommended that a complete vaccine series with an mRNA COVID-19 vaccine should be offered to individuals in the authorized age group who are pregnant or breastfeeding. An mRNA vaccine is preferred due to reassuring published data on the safety of these vaccines in pregnancy.

It is recommended that an authorized protein subunit COVID-19 vaccine (Novavax Nuvaxovid) or virus-like particle COVID-19 vaccine (Medicago Covifenz) may be offered to individuals in the authorized age group without contraindications to the vaccine who are not able or willing to receive an mRNA COVID-19 vaccine. Safety and efficacy data in individuals who are pregnant or breastfeeding following vaccination with a protein subunit COVID-19 vaccine or a virus-like particle COVID-19 vaccine are not available.

A viral vector COVID-19 vaccine may be offered to individuals in the authorized age group who are pregnant or breastfeeding when all other authorized COVID-19 vaccines are contraindicated.

For booster doses, persons who are pregnant or breastfeeding are included among those for whom they are recommended. A recommended booster dose should be offered at any stage of pregnancy (i.e., in any trimester), regardless of the number of booster doses previously received. COVID-19 vaccine booster doses may be offered at an interval of 6 months since previous COVID-19 vaccine dose or SARS-CoV-2 infection. However, a shorter interval of at least 3 months may be warranted to optimize protection for the pregnant person in the context of heightened epidemiological risk (including increased risk of severe outcomes in pregnant people).

An individual may receive all doses for which they are eligible during the course of a pregnancy.

Considerations

Pregnant or breastfeeding individuals were excluded from the mRNA and viral vector COVID-19 vaccine clinical trials. However, analysis of data collected through international COVID-19 immunization registries to date have not revealed any maternal or neonatal safety signals. Most real-world evidence is for mRNA vaccination.

Those who are trying to become pregnant do not need to avoid pregnancy after vaccination with an mRNA vaccine.

No safety signals have been detected with mRNA vaccination during breastfeeding and individuals should continue to breastfeed after vaccination. People who are breastfeeding experience the same rates of side effects as do those who are not breastfeeding, and studies have not found any impacts of mRNA COVID-19 vaccination on the infant/child being fed human milk or on milk production or excretion.

Evidence suggests that COVID-19 mRNA vaccination during pregnancy results in comparable antibody titres to those generated in non-pregnant women. Maternal IgG humoral response to mRNA COVID-19 vaccines transfers across the placenta to the fetus, leading to a significant and potentially protective antibody titre in the neonatal bloodstream 1 week after the second dose. Infants of people who received a 2-dose primary series during pregnancy had a lower risk of hospitalization with COVID-19 (including Omicron) in the first 6 months of life compared to infants born to individuals who were unvaccinated. Observational studies consistently show that both anti-spike IgG and IgA are present in breastmilk for at least 6 weeks after maternal vaccination with mRNA vaccines.

The safety and efficacy of Novavax Nuvaxovid and Medicago Covifenz have not been established in individuals who are pregnant or breastfeeding. Informed consent should include discussion that there is currently limited evidence on the use of the Novavax Nuvaxovid and Medicago Covifenz vaccines in individuals who are pregnant or breastfeeding, while there is evidence on the safety profile and effectiveness of mRNA COVID-19 vaccines in these populations based on real world use with large numbers of individuals.

Pregnant persons vaccinated with an mRNA COVID-19 vaccine during pregnancy experience the same rates of expected local and systemic adverse events as non-pregnant persons. Vaccination during pregnancy does not increase risk for miscarriage, stillbirth, low birth weight, preterm birth, NICU admission, or other adverse pregnancy/birth outcomes.

COVID-19 vaccines may be administered concurrently with (i.e., same day), or at any time before or after other vaccines recommended during pregnancy or while breastfeeding. Refer to Administration practices, Pre-vaccination counselling and Safety and adverse events for further information.

Vaccine recipients and health care providers are encouraged to enroll patients who have received a COVID-19 vaccine during pregnancy in COVID-19 vaccine pregnancy registries (see Table 4).

There is a Canadian COVID-19 Vaccine Registry for Pregnant and Lactating Individuals, hosted at the University of British Columbia and supported by the COVID-19 Immunity Task Force (CITF) to assess the safety and effectiveness of COVID-19 vaccines.

Table 4: Pregnancy registry information by vaccine product

Vaccine product	Registry information
Pfizer-BioNTech Comirnaty COVID-19 vaccine	Pfizer does not have a pregnancy exposure registry. Individuals who are vaccinated with the Pfizer COVID-19 vaccine during pregnancy are encouraged to enroll into the Canadian COVID-19 Vaccine Registry for Pregnant and Lactating Individuals described above.
Moderna Spikevax COVID-19 vaccines	There is a pregnancy exposure registry that monitors pregnancy outcomes in persons exposed to the Moderna COVID-19 vaccine during pregnancy. Individuals who are vaccinated with the Moderna COVID-19 vaccine during pregnancy are encouraged to enroll in the registry by calling 1-866-MODERNA (1-866-663-3762).
AstraZeneca Vaxzevria COVID-19 vaccine	There is a pregnancy exposure registry that monitors pregnancy outcomes in persons exposed to AstraZeneca COVID-19 vaccine during pregnancy. Individuals who are vaccinated with AstraZeneca COVID-19 vaccine during pregnancy are encouraged to enroll in the registry by visiting C-VIPER: COVID-19 Vaccines International Pregnancy Exposure Registry or calling 1-800-616-3791.
Janssen Jcovden COVID-19 vaccine	There is a pregnancy exposure registry that monitors pregnancy outcomes in persons exposed to Janssen Jcovden COVID-19 vaccine during pregnancy. Individuals who are vaccinated with Janssen Jcovden COVID-19 vaccine during pregnancy are encouraged to enroll in the registry by visiting C-VIPER: COVID-19 Vaccines International Pregnancy Exposure Registry.
Novavax Nuvaxovid COVID-19 vaccine	There is a pregnancy exposure registry that monitors pregnancy outcomes in persons exposed to NUVAXOVID during pregnancy. Individuals who are vaccinated with NUVAXOVID during pregnancy are encouraged to enroll in the registry by visiting C-VIPER: COVID-19 Vaccines International Pregnancy Exposure Registry

Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional general information.

Individuals previously infected with SARS-CoV-2

The immune response due to prior infection may vary due to factors such as the severity of infection, age, presence of comorbidities, the SARS-CoV-2 variant causing the infection, time since the infection and vaccination history. People with both SARS-CoV-2 infection and COVID-19 vaccination are said to have “hybrid immunity” and have the highest vaccine effectiveness compared to either infection or vaccination alone.

Recommendations

COVID-19 vaccines, with a preference for mRNA vaccines, should or may be offered to individuals 6 months of age and older with previous SARS-CoV-2 infection without contraindications to the vaccine based on the recommendation for their age and other risk factors (see Recommendations for use section).

It is recommended that an authorized protein subunit COVID-19 vaccine (Novavax Nuvaxovid) or virus-like particle COVID-19 vaccine (Medicago Covifenz) may be offered to individuals in the authorized age group without contraindications to the vaccine who are not able or willing to receive an mRNA COVID-19 vaccine. Safety and efficacy data in individuals previously infected with SARS-CoV-2 following vaccination with a protein subunit COVID-19 vaccine or a virus-like particle COVID-19 vaccine are not available.

Recommendations for booster doses also apply to individuals with previous SARS-CoV-2 infection. Refer to Table 5 for suggested intervals between previous infection and COVID-19 vaccination. Refer to Booster doses for information regarding booster doses for individuals 5 years of age and older.

Table 5. Suggested intervals between previous SARS-CoV-2 infection^{Table 5 Footnote a} and COVID-19 vaccination

SARS-CoV-2 infectionTable 5 Footnote a timing relative to COVID-19 vaccination	Population	Suggested interval between SARS-CoV-2 infectionTable 5 Footnote a and vaccination (clinical discretion is advised)Table 5 Footnote bTable 5 Footnote c
Infection prior to completion or initiationTable 5 Footnote c of primary vaccination series	Individuals 6 months of age and older who are not considered moderately to severely immunocompromised and with no history of MIS-C or MIS-A	Receive the vaccine 8 weeks after symptom onset or positive test (if asymptomatic)Table 5 Footnote b
	Individuals 6 months of age and older who are moderately to severely immunocompromised and with no history of MIS-C or MIS-A	Receive the vaccine dose 4 to 8 weeks after symptom onset or positive test (if asymptomatic)Table 5 Footnote b
	Individuals 6 months of age and older with a history of MIS-C or MIS-A (regardless of immunocompromised status)	Receive the vaccine dose when clinical recovery has been achieved or ≥90 days since diagnosis of MIS-C or MIS-A, whichever is longer
Infection after primary seriesTable 5 Footnote d but before a booster dose, or after a booster dose but before a next booster dose	Individuals 5 years of age and older currently eligible for a booster dose	6 months since infection unless a shorter interval of 3 to <6 months is warranted in the context of heightened epidemiological riskTable 5 Footnote b
Table 5 Footnote a Previous infection can be defined in different ways based on jurisdictional policies and access to testing. The following suggestion can be considered to define previous infection with SARS-CoV-2: Confirmed by a molecular (e.g., PCR) or Health Canada-approved antigen detection-based test; or Symptomatic disease compatible with COVID-19 AND household exposure to a confirmed COVID-19 case. Table 5 Return to footnote a referrer Table 5 Footnote b These suggested intervals are based on immunological principles and expert opinion, and may change as evidence on COVID-19, VOCs, and COVID-19 vaccines emerge. When considering whether or not to administer vaccine doses following the suggested intervals outlined in this table, biological and social risk factors for exposure (e.g., local epidemiology, circulating VOCs, living settings) and severe disease should also be taken into account. These intervals are a guide and clinical discretion is advised. Table 5 Return to footnote b referrer Table 5 Footnote c For individuals who have not had any previous doses, they may receive their first dose after acute symptoms of COVID-19 have resolved and they are no longer infectious, or they may follow these suggested intervals. Individual benefit/risk assessment and clinical discretion are advised as per footnote "b". Waiting until at least the infected person is no longer infectious is intended to minimize the risk of transmission of COVID-19 at an immunization venue and to enable monitoring for COVID-19 vaccine adverse events without potential confounding from symptoms of COVID-19. Table 5 Return to footnote c referrer Table 5 Footnote d The primary series is outlined in Recommendations for use. Note that for moderately to severely immunocompromised individuals who were immunized with a primary series that includes one additional dose, a booster dose would be subsequent to that additional dose. Table 5 Return to footnote d referrer

Considerations

Testing for previous SARS-CoV-2 infection is not needed prior to COVID-19 vaccination.

A longer interval between infection and vaccination may result in a better immune response from the infection as this allows time for this response to mature in breadth and strength, and for circulating antibodies from the infection to decrease, thus avoiding immune interference when the vaccine is administered.

Current evidence suggests protection is more robust and longer lasting with vaccination in previously infected individuals compared to immunity from SARS-CoV-2 infection alone.

COVID-19 vaccination in individuals previously infected with SARS-CoV-2 has a good safety profile and is well tolerated. Limited evidence suggests reactogenicity may be slightly increased in individuals previously infected with SARS-CoV-2 compared to those with no history of previous infection, however this evidence is limited to the primary series and variants prior to Omicron.

The safety and efficacy of Novavax Nuvaxovid and Medicago Covifenz have not been established in individuals previously infected with SARS-CoV-2. Informed consent should include discussion that there is currently limited evidence on the use of the Novavax Nuvaxovid and Medicago Covifenz vaccines in individuals previously infected with SARS-CoV-2, while there is evidence on the safety profile and effectiveness of mRNA COVID-19 vaccines in this population based on real world use with large numbers of individuals.

Persons with an autoimmune condition

Recommendations

It is recommended that people with autoimmune disease be vaccinated against COVID-19, with a preference for mRNA vaccines, based on their age and recommendations for people with underlying medical conditions. If their condition or medications make them moderately to severely immunocompromised, they should follow the recommended schedule for this group (see Recommendations for use section).

It is recommended that an authorized protein subunit COVID-19 vaccine (Novavax Nuvaxovid) or virus-like particle COVID-19 vaccine (Medicago Covifenz) may be offered to individuals in the authorized age group without contraindications to the vaccine who are not able or willing to receive an mRNA COVID-19 vaccine. Safety and efficacy data in persons with an autoimmune condition following vaccination with a protein subunit COVID-19 vaccine or a virus-like particle COVID-19 vaccine are not available.

A viral vector COVID-19 vaccine may be offered to individuals in the authorized age group with an autoimmune condition only when all other authorized COVID-19 vaccines are contraindicated. Safety data in these populations following vaccination with a viral vector vaccine are not available.

Considerations

Although participants with autoimmune conditions who were not immunosuppressed were not excluded from trials, they constitute a very small proportion of trial participants and represent a very narrow range of autoimmune conditions. However, real-world evidence (mostly with mRNA vaccination) has become available.

Observational studies in individuals with autoimmune conditions indicate that the frequency and severity of adverse events in this population is comparable to that of individuals without autoimmune conditions and what was reported in clinical trials. The onset of new autoimmune disease or disease exacerbation following vaccination with mRNA COVID-19 vaccines was rare or comparable to the background incidence of these events in the general population.

The safety and efficacy of Novavax Nuvaxovid and Medicago Covifenz have not been established in individuals who have an autoimmune condition. Informed consent should include discussion that there is currently limited evidence on the use of the Novavax Nuvaxovid and Medicago Covifenz vaccines in persons with an autoimmune condition, while there is evidence on the safety profile and effectiveness of mRNA COVID-19 vaccines in this population based on real world use with large numbers of individuals.

Refer to Immunization of persons with chronic diseases in Part 3 for additional general information on autoimmune conditions.

Immunocompromised persons

Recommendations

It is recommended that children 6 months to 4 years of age who are moderately to severely immunocompromised and do not have contraindications to the vaccine may be offered a primary series that includes an additional dose of an mRNA COVID-19 vaccine.

• With regard to the product offered for children 6 months to 4 years of age who are moderately to severely immunocompromised, a primary series consisting of three doses of the Moderna Spikevax original (25 mcg) vaccine should be offered, using an interval of 4 to 8 weeks between each dose, as this product requires one fewer dose than the Pfizer-BioNTech original (3 mcg) product and may therefore be more acceptable and feasible for this group.
• If the Moderna Spikevax original (25 mcg) COVID-19 vaccine is not readily available, Pfizer-BioNTech Comirnaty original (3mcg) COVID-19 vaccine may be offered with a primary series consisting of four doses, using an interval of 4 to 8 weeks between each dose.

It is recommended that individuals 5 years of age and older who are moderately to severely immunocompromised should be immunized with a primary series of three doses of an original mRNA COVID-19 vaccine authorized for their age, using an interval of 4 to 8 weeks between each dose.

For those individuals who have previously received a 1- or 2-dose primary series with a COVID-19 vaccine (or a homologous or heterologous schedule using an mRNA or viral vector vaccine as per authorized age groups) and have not received an additional dose, it is recommended that an additional dose of an mRNA COVID-19 vaccine (original) should be offered 4 to 8 weeks after the second dose.

Indirect data from adult populations (≥18 years of age) suggest Moderna Spikevax original (100 mcg) may result in higher vaccine effectiveness after a 2-dose primary series compared to Pfizer-BioNTech Comirnaty original (30 mcg) and is associated with a higher seroconversion rate among adult immunocompromised patients. While Pfizer-BioNTech original is generally preferred for the primary series in those 5 to 29 years of age due to the lower risk of myocarditis/pericarditis, given the potential benefit in the immune response, for some moderately to severely immunocompromised individuals 5 to 29 years of age administration of Moderna Spikevax original as a 3-dose primary series may be considered (based on clinical judgement) (25 mcg at 5 years of age; 50 mcg at 6 to 11 years of age; and 100 mcg for those 12 years of age and over).

mRNA COVID-19 vaccines are preferred in moderately to severely immunocompromised individuals. Based on clinical discretion, a protein subunit COVID-19 vaccine (Novavax Nuvaxovid) or virus-like particle COVID-19 vaccine (Medicago Covifenz) may be offered to moderately to severely immunocompromised individuals in the authorized age group without contraindications to the vaccine who are not able or willing to receive an mRNA COVID-19 vaccine. However, neither the protein subunit COVID-19 vaccine (Novavax Nuvaxovid) nor the virus-like particle COVID-19 vaccine (Medicago Covifenz) is currently authorized as a 3-dose primary series in these populations and safety and efficacy data in immunocompromised persons following vaccination with a protein subunit COVID-19 vaccine or a virus-like particle COVID-19 vaccine are not available.

A viral vector COVID-19 vaccine may be offered to individuals in the authorized age group who are immunosuppressed due to disease or treatment only when all other authorized COVID-19 vaccines are contraindicated.

Note that for moderately to severely immunocompromised individuals who were immunized with a primary series that includes one additional dose, all booster doses would be subsequent to that additional dose.

Refer to Booster doses for information regarding booster doses for moderately to severely immunocompromised adults 5 years of age and older.

Considerations

Immunocompromised individuals, including those receiving immunosuppressive therapy, are at increased risk for prolonged infection and serious complications from SARS-CoV-2 infection. Numerous studies have shown that immunogenicity is substantially decreased in some immunocompromised individuals when compared to healthy vaccine recipients, although evidence is limited to studies in adolescent and adult populations. Observational studies in adults with complete 1 or 2 dose series, show lower vaccine effectiveness against SARS-CoV-2 infection and COVID-19 disease in immunocompromised adults when compared to the general population.

The minimum interval between the initial doses of the primary series and the additional dose should be 28 days but can up to 8 weeks. An interval longer than the minimum 28 days between doses is likely to result in a better immune response. However, moderately to severely immunocompromised individuals (after the initial 1- or 2- doses of the primary series) may still be susceptible during this time before the next dose is administered. If a longer interval between doses is being considered, then the need for earlier protection due to risk of exposure (including local transmission of SARS-CoV-2, circulation of VOC) and risk of severe disease (e.g., underlying high risk medical condition) should be taken into account.

A vaccine series should ideally be completed at least 2 weeks before initiation of immunosuppressive therapies where possible.

Moderately to severely immunocompromised includes individuals with the following conditions:

• Immunocompromised due to solid tumour or hematologic malignancies or treatments for these conditions
• Solid-organ transplant and taking immunosuppressive therapy
• Hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy)
• Immunocompromise due to chimeric antigen receptor (CAR) T cell therapy targeting lymphocytes
• Moderate to severe primary immunodeficiency with associated humoral and/or cell-mediated immunodeficiency or immune dysregulation
• HIV with AIDS-defining illness or TB diagnosis in last 12 months before starting vaccine series, or severe immune compromise with CD4<200 cells/uL or CD4%<15%, or without HIV viral suppression
• Recent treatment with the following categories of immunosuppressive therapies: anti-B cell therapies (monoclonal antibodies targeting CD19, CD20 and CD22), high-dose systemic corticosteroids, alkylating agents, antimetabolites, or tumor-necrosis factor (TNF) inhibitors and other biologic agents that are significantly immunosuppressive
• Chronic kidney disease on dialysis

A range of factors can impact the relative degree of immunocompromise and response to COVID-19 vaccines, and clinical and public health judgement should be applied. Jurisdictions may modify the list based on population considerations.

Refer to Immunization of Immunocompromised Persons in Part 3 for a suggested definition of high dose steroids and for guidance on vaccination with COVID-19 vaccines for individuals pre- and post-hematopoietic stem cell transplantation (HSCT) and for chimeric antigen receptor (CAR) T cell therapy recipients.

The safety and efficacy of Novavax Nuvaxovid and Medicago Covifenz have not been established in individuals who are immunocompromised due to disease or treatment. Informed consent for use of either vaccine in these populations should include discussion that there is currently limited evidence on the use of Novavax Nuvaxovid and Medicago Covifenz in these populations, while there is evidence on the safety profile and effectiveness of mRNA COVID-19 vaccines in these populations based on real world use with large numbers of individuals.

Evidence indicates that humoral immune responses increase in some individuals after a third dose of mRNA COVID-19 vaccine is administered as part of an extended primary series to adults with immunocompromising conditions, although the degree of increase varies between studies and according to the type of immunocompromising condition or treatment. As for additional booster doses (beyond the first booster dose), studies reviewed by the WHO in 2022 showed some short-term benefit of an additional booster of mRNA vaccine in health workers, individuals over 60 years of age or with immunocompromising conditions.

Studies assessing additional doses in immunocompromised individuals have primarily used mRNA vaccines, for both the initial primary series doses and additional dose, and are limited to studies in adult populations. Moderna Spikevax vaccines may produce a greater immune response in this population. Investigations are ongoing.

In observational studies and clinical trials, humoral and cellular immune responses were similar between fully vaccinated people living with HIV on antiretroviral therapy and those who were HIV-negative.

Based on observational studies, the frequency and severity of AEFIs with an mRNA COVID-19 vaccine in certain immunocompromised populations were comparable to those of non-immunosuppressed individuals. No worsening of underlying disease was reported after immunization.

Refer to Immunization of Immunocompromised Persons in Part 3 for definitions and additional general information.

Travellers

Travellers should receive a complete series of COVID-19 vaccine and optimally should receive a booster dose, if they are eligible, at least 2 weeks prior to departure. Two weeks or more may be required to meet entry requirements for other countries. Travellers should verify the travel requirements in place at their destination(s) and for their return to Canada. For more information, refer to the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement on COVID-19 and International Travel.

Persons new to Canada

Based on a recommendation by PHAC to provinces and territories, people who are planning to live, work or study in Canada who have had only a complete or incomplete primary series of non-Health Canada authorized vaccines, should be offered an additional dose of an mRNA vaccine, unless they have already received 3 doses of a COVID-19 vaccine. They should receive booster doses when eligible.

Serologic testing

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

Administration practices

Dose and route of administration

Dose

Pfizer-BioNTech Comirnaty COVID-19 original vaccine (30 mcg)

This formulation has a grey cap and a grey label border and is authorized for use in individuals 12 years of age and older.

No dilution is required.

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

The dose for the Pfizer-BioNTech Comirnaty 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.

Pfizer-BioNTech Comirnaty COVID-19 original vaccine (10 mcg, pediatric formulation)

This formulation has an orange vial cap and orange label border and is authorized for use in children 5 to 11 years of age.

Dilute with 1.3 mL 0.9% Sodium Chloride Injection, USP prior to use.

Each dose is 0.2 mL after dilution, containing 10 mcg of SARS-CoV-2 spike protein mRNA.

The dose for the Pfizer-BioNTech Comirnaty COVID-19 vaccine pediatric formulation (0.2 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.

Pfizer-BioNTech Comirnaty COVID-19 vaccine (3 mcg, pediatric formulation)

This formulation has a maroon vial cap and maroon label border and is authorized for use in children 6 months to 4 years of age.

Dilute with 2.2 mL 0.9% Sodium Chloride Injection, USP prior to use.

Each dose is 0.2 mL after dilution, containing 3 mcg of SARS-CoV-2 spike protein mRNA.

The dose for the Pfizer-BioNTech Comirnaty COVID-19 vaccine pediatric formulation (0.2 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.

Pfizer-BioNTech Comirnaty Original & Omicron BA.4/BA.5 COVID-19 vaccine (Bivalent)

There are two formulations of Pfizer-BioNTech Comirnaty bivalent BA.4/5 vaccine authorized for use.

• Vials with a gray cap and gray label border containing 30 mcg of mRNA (15 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 15 mcg of mRNA encoding for the spike protein of the Omicron BA.4/BA.5 variant). This vaccine authorized for use in individuals 12 years of age and older. Each dose is 0.3 mL. No dilution is required.
• Vials with an orange cap and an orange label border containing 10 mcg of mRNA (5 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 5 mcg of mRNA encoding for the spike protein of the Omicron BA.4/BA.5 variant). This vaccine authorized for use in individuals 5 to 11 years of age. Each dose is 0.2 mL after dilution with 1.3 mL sterile 0.9% Sodium Chloride Injection, USP prior to use.

Moderna Spikevax original COVID-19 vaccine

There are two formulations of Moderna Spikevax original authorized for use in individuals 6 months of age and older.

• Vials with a red cap and light blue label border containing 0.20 mg/mL in a 5mL multidose vial
• Vials with a royal blue cap and a purple label border containing 0.10 mg/mL in a 2.5mL multidose vial

No dilution is required.

The volume (mL) required for primary series and booster dosing will be different depending on which presentation of the vaccine is being administered. Careful attention should be paid to the vial and carton label, vial cap colour, label border colour and corresponding dose volumes. See Table 6 for primary series and booster doses of Moderna Spikevax by product and age.

Moderna Spikevax Bivalent (Original & Omicron BA.1) COVID-19 vaccine

This formulation has a royal blue vial cap and a green label border and is authorized for use as a booster dose in individuals 6 years of age and older.

For individuals 6 to 11 years of age, the booster dose is 0.25 mL containing 25 mcg of mRNA (12.5 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 12.5 mcg of mRNA encoding for the spike protein of the Omicron BA.1 variant).

For individuals 12 years of age and older, the booster dose is 0.5 mL containing 50 mcg of mRNA (25 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 25 mcg of mRNA encoding for the spike protein of the Omicron BA.1 variant).

No dilution is required.

Vials contain 0.10 mg/mL in a 2.5 mL multidose vial.

Careful attention should be paid to the vial and carton label, vial cap colour and label border colour. See Table 6 for booster doses of Moderna Spikevax by product and age.

Moderna Spikevax Bivalent (Original & Omicron BA.4/5) COVID-19 vaccine

This formulation has a royal blue vial cap and a grey label border and is authorized for use as a booster dose in individuals 18 years of age and older.

Each booster dose is 0.5 mL, containing 50 mcg of mRNA (25 mcg of mRNA encoding for the spike protein of the original SARS-CoV-2 virus and 25 mcg of mRNA encoding for the spike protein of the Omicron BA.4/5 variant).

No dilution is required.

Vials contain 0.10 mg/mL in a 2.5 mL multidose vial.

Careful attention should be paid to the vial and carton label, vial cap colour and label border colour. See Table 6 for booster doses of Moderna Spikevax by product and age.

Table 6. Dosing for Moderna Spikevax vaccines

Presentation	Cap/label colour	Age	Vaccination	Dose	Dose volume
Original 0.2 mg/mL Multidose vial (5 mL)	Red cap/light blue label border	12+ years	primary series	100 mcgTable 6 Footnote a	0.5 mL
		12+ years	boosterTable 6 Footnote bTable 6 Footnote c	50 mcg	0.25 mL
		6 to 11 years	primary series	50 mcg	0.25 mL
Original 0.1 mg/mL Multidose vial (2.5 mL)	Royal blue cap/purple label border	12+ years	boosterTable 6 Footnote c	50 mcgTable 6 Footnote c	0.5 mL
		6 to 11 years	primary series	50 mcg	0.5 mL
		6 months to 5 years	primary series	25 mcgTable 6 Footnote d	0.25 mL
Bivalent (Original & Omicron BA.1) 0.1 mg/mL Multidose vial (2.5 mL)	Royal blue cap/green label border	12+ years	booster	50 mcg	0.5 mL
		6 to 11 years	booster	25 mcg	0.25 mL
Bivalent (Original & Omicron BA.4/5) 0.1 mg/mL Multidose vial (2.5 mL)	Royal blue cap/grey label border	18+ years	booster	50 mcg	0.5 mL
Table 6 Footnote a The 0.10 mg/mL presentation is not intended for preparation of the 100 mcg dose. Table 6 Return to footnote a referrer Table 6 Footnote b Moderna Spikevax COVID-19 vaccine (original) is authorized as a booster dose for individuals 12 years of age and older. Table 6 Return to footnote b referrer Table 6 Footnote c Bivalent products are preferred as booster doses for those in the authorized age groups. Table 6 Return to footnote c referrer Table 6 Footnote d The 0.20 mg/mL presentation is not intended for preparation of the 25 mcg dose. Table 6 Return to footnote d referrer

Refer to Booster doses for additional information.

Novavax Nuvaxovid COVID-19 vaccine

Each dose is 0.5 mL, containing 5 mcg SARS-CoV-2 recombinant original strain spike protein. Vials contain 5 mcg/0.5 mL in a 5.0 mL multidose vial.

The product comes premixed with the Matrix-M adjuvant. No dilution or reconstitution is required.

Medicago Covifenz COVID-19 vaccine

The product is supplied as the antigen in the larger vial and ASO3 adjuvant emulsion in the smaller vial. They must be mixed 1:1 before use by adding the adjuvant into the vial with antigen.

After mixing with the adjuvant, each dose is 0.5 mL, containing 3.75 mcg of viral-like particles of SARS-CoV-2 original strain spike protein. After mixing there is 5.0 mL in the multidose vial.

AstraZeneca Vaxzevria COVID-19 vaccine

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

No dilution is required.

Janssen Jcovden COVID-19 vaccine

Each dose is 0.5 mL, containing 5 x 10¹⁰ viral particles of SARS-CoV-2 original strain spike protein. The vial contains 3.1 mL in a multidose vial.

No dilution is required.

Route of administration

COVID-19 vaccines are given as an intramuscular (IM) injection. The deltoid muscle of the arm is the preferred injection site in adolescents and adults, unless the muscle mass is not adequate or vaccination in that site is not possible, in which case the anterolateral thigh can be used.

Refer to Vaccine Administration Practices in Part 1 for additional general information, including recommended routes of administration for children.

If an error in vaccine administration occurs, refer to Managing COVID-19 vaccine administration errors or deviations for guidance.

Interchangeability of vaccines

Regardless of which product is offered, the previous dose should be counted, and the series need not be restarted.

mRNA COVID-19 vaccines

If readily available (i.e., easily available at the time of vaccination without delay or vaccine wastage), the same mRNA COVID-19 vaccine product should be offered for the subsequent dose in a vaccine series started with an mRNA COVID-19 vaccine. However, when the same mRNA COVID-19 vaccine product is not readily available, or is unknown, another mRNA COVID-19 vaccine product recommended for use in that age group can be considered interchangeable and should be offered to complete the vaccine series.

There are currently no data on the use of bivalent Omicron-containing mRNA COVID-19 vaccines as part of a primary series. A primary series with an original mRNA vaccine is recommended in all authorized age groups. If a bivalent vaccine is inadvertently used in the primary series, it is considered valid as long as a valid dosage was used. Refer to Managing COVID-19 vaccine administration errors or deviations for guidance. Bivalent Omicron-containing mRNA vaccines are the preferred booster products for the authorized age groups; however, original strain mRNA vaccines used as a booster dose are considered valid.

Novavax Nuvaxovid COVID-19 vaccine

Novavax Nuvaxovid may be used to start or complete a primary series, or used as a booster dose in a mixed prime-boost series, for individuals for whom mRNA COVID-19 vaccine is contraindicated, inaccessible, or has been refused.

Informed consent should include a discussion of the benefits and risks given the limited data available on mixed schedules with Novavax Nuvaxovid. There is currently no data on the use of Novavax Nuvaxovid in a mixed series with Moderna Spikevax original (100 mcg) or Janssen Jcovden COVID-19 vaccines.

Medicago Covifenz COVID-19 vaccine

Medicago Covifenz has not been evaluated in a heterologous (mixed) primary series.

Mixed schedules using Medicago Covifenz specifically and other COVID-19 vaccines, have not been studied.

AstraZeneca Vaxzevria COVID-19 vaccine

While an mRNA COVID-19 vaccine or Novavax Nuvaxovid COVID-19 vaccine product may be offered for the subsequent dose in a primary vaccine series started with an AstraZeneca Vaxzevria COVID-19 vaccine, an mRNA COVID-19 product is preferred as a subsequent dose.

Mixed COVID-19 vaccine schedules

For mixed COVID-19 vaccine schedules, the minimum interval between doses should be based on the minimum interval of the product used for the first dose. When using mixed schedules, the suggested optimal interval between doses is 8 weeks (or at least 8 weeks) based on considerations found in Table 2.

Evidence indicates that mixed COVID-19 viral vector and mRNA vaccine schedules with dosing intervals between 4 and 12 weeks have acceptable safety profiles that may be associated with increased short-term systemic reactogenicity, which is potentially increased with shorter intervals between vaccines.

Limited evidence suggests that a mixed schedule in which Novavax Nuvaxovid is administered following a partial or complete primary series of AstraZeneca Vaxzevria or Pfizer-BioNTech Comirnaty original COVID-19 vaccines may not be as immunogenic as continuing with Pfizer-BioNTech Comirnaty original or Moderna Spikevax original vaccines – despite it having an acceptable safety profile and immunogenicity.

Concurrent administration with other vaccines

For individuals 6 months of age and older, COVID-19 vaccines may be given concurrently (i.e., same day), or at any time before or after, non-COVID-19 vaccines (including live and non-live vaccines).

It is recommended that COVID-19 vaccines may be concurrently administered with other vaccines among all vaccine eligible populations (i.e., individuals 6 months of age and older) based on the following observations: 1) no safety signal has emerged from ongoing post-market safety surveillance for mRNA COVID-19 vaccine products in children 6 months to 5 years of age; and 2) there is no evidence of safety concerns for concurrent administration based on data from adult populations. In addition, concurrent administration will reduce barriers to the provision of routine childhood immunizations and seasonal influenza immunization.

If more than one type of vaccine is administered at a single visit, they should be administered at different injection sites using separate injection equipment. Preferably this is in different limbs, however if the same limb must be used, the injection sites should be separated by at least 2.5 cm (1 inch).

Informed consent should include a discussion of the benefits and risks given the limited data available on administration of COVID-19 vaccines at the same time as, or shortly before or after, other vaccines.

Data are currently more limited on the reactogenicity of COVID-19 vaccines with concurrent administration of other vaccines. No specific safety concerns have been identified to date, but studies and surveillance activities to assess the safety and immunogenicity of concurrent administration of COVID-19 vaccines with other vaccines are ongoing.

Refer to Timing of Vaccine Administration in Part 1 for additional general information on concurrent administration of other vaccines.

Pre-vaccination counselling

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. There is currently no evidence of benefit from administration of oral analgesics for the prevention of immunization injection pain or systemic reactions.

Prior to providing a COVID-19 vaccine, informed consent should include discussion about frequently occurring minor adverse events and the risks and symptoms of potential rare severe adverse events.

Anyone receiving any viral vector COVID-19 vaccine (AstraZeneca Vaxzevria or Janssen Jcovden) should be informed of adverse events that may occur following vaccination with viral vector vaccines: Guillain-Barré syndrome (GBS), thrombosis with thrombocytopenia syndrome (TTS) including vaccine-induced immune thrombotic thrombocytopenia (VITT), capillary leak syndrome (CLS), venous thromboembolism (VTE), immune thrombocytopenia (ITP), Bell’s palsy and anaphylaxis, and be advised to seek medical attention if they develop signs or symptoms suggestive of these conditions.

Anyone receiving any mRNA COVID-19 vaccine (Pfizer-BioNTech Comirnaty original or bivalent, or Moderna Spikevax original or bivalent) should be informed of the risks associated with mRNA COVID-19 vaccines: myocarditis/pericarditis, Bell's palsy and anaphylaxis, and be advised to seek medical attention if they develop signs or symptoms suggestive of these conditions.

Refer to Safety and adverse events for further information.

Post-vaccination counselling

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 vaccines for the management of pain and/or fever after vaccination.

All vaccine recipients should be instructed to seek medical care if they develop signs or symptoms of a serious adverse event or an allergic reaction following vaccination.

Refer to Vaccine Administration Practices in Part 1 for additional information on pre- and post-vaccination counseling.

Storage requirements

For information on storage, handling and transport of frozen and thawed vaccine vials, refer to the Overview of key features of COVID-19 vaccines authorized in Canada.

For additional 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 Part 1 for additional general information.

Safety and adverse events

Evidence on vaccine safety is available from COVID-19 clinical trials and ongoing international COVID-19 vaccine safety monitoring. The clinical trials solicited adverse events for defined lengths of time following a vaccine dose, as well as collecting unsolicited and serious events.

For reported side effects following COVID-19 vaccination in Canada, refer to the PHAC AEFI report.

Refer to Vaccine Safety and Pharmacovigilance and Adverse Events Following Immunization (AEFI) in Part 2 for additional information on vaccine safety and for definitions of AEFIs, and reporting of AEFI to public health.

For individuals who develop AEFIs following COVID-19 vaccination, refer to the Contraindications and precautions section for advice on future vaccinations.

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.

Local

Local adverse events were usually mild or moderate and resolved within a few days of vaccination in all age groups (6 months and older). Pain at the injection site was very common. Redness and swelling were common or very common after administration of any authorized COVID-19 vaccine. Compared to adolescents and young adults, children aged 5 to 11 years or 6 to 11 years (Pfizer-BioNTech Comirnaty original or Moderna Spikevax original, respectively) had similar frequencies of pain at the injection site, however children 5 to 11 years of age that received Pfizer-BioNTech Comirnaty original had higher frequencies of swelling and redness. Localized axillary (or groin) swelling and tenderness (lymphadenopathy) was a solicited adverse event in the Moderna Spikevax original COVID-19 vaccine clinical trial and was very common after administration of that vaccine.

Systemic

Systemic adverse events were usually mild or moderate and resolved within a few days of vaccination in all age groups (6 months and older). Fatigue, headache, muscle pain, chills, and joint pain were all either common or very common after the administration of any authorized COVID-19 vaccine. Relative to adolescents and young adults, systemic adverse events in children aged 5 to 11 years of age were comparable or less frequent for some events (such as fever and chills). However, fever was more frequently reported following dose 2 for the Moderna Spikevax original COVID-19 vaccine among children aged 6-11 years compared to adolescents.

For the Moderna Spikevax original (25mcg pediatric dose) and the Pfizer-BioNTech Comirnaty original (3mcg pediatric dose) vaccines, clinical trial and post-market safety data show that both vaccines are well tolerated. Systemic reactions were more frequently reported after COVID-19 vaccination among children aged 6 months to 2 years than those aged 3 to 5 years. The most frequent reactions reported for children aged 6 months to 2 years included irritability or crying, sleepiness, and loss of appetite. These reactions are common after childhood vaccination.

Adverse events following the second dose of COVID-19 vaccine in individuals previously infected with SARS-CoV-2

COVID-19 vaccination in individuals previously infected with SARS-CoV-2 has a good safety profile and is well tolerated. Limited evidence suggests reactogenicity may be slightly increased in individuals previously infected with SARS-CoV-2 compared to those with no history of previous infection; however, this evidence is limited to the primary series and infection with variants prior to Omicron.

Adverse events following bivalent Omicron- containing mRNA COVID-19 vaccines

Available clinical trial data show that Moderna Spikevax Bivalent BA.1 (50 mcg) administered as a second booster dose to individuals ≥18 years of age had a similar reactogenicity profile to that of Moderna Spikevax original (50 mcg) given as a second booster dose. Post licensure surveillance is ongoing.

There are no clinical safety data currently available for Pfizer-BioNTech Comirnaty Original & Omicron BA.4/5 (30 mcg) bivalent vaccine specifically; however, indirect data (clinical and post-market safety data) suggest that this vaccine will likely be well tolerated with a similar safety profile to Comirnaty original (30 mcg) and Comirnaty BA.1 Bivalent (30 mcg) vaccines, when used as a booster dose.

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 sample sizes; therefore, ongoing pharmacovigilance is essential.

Lymphadenopathy

Lymphadenopathy was an unsolicited event that was uncommonly reported after administration of the Pfizer-BioNTech Comirnaty original (both 10 mcg and 30 mcg formulations), AstraZeneca Vaxzevria and Janssen Jcovden COVID-19 vaccines in clinical trials. As noted above, lymphadenopathy was a solicited adverse event in the clinical trials for Moderna Spikevax original and was very commonly reported.

Myocarditis or pericarditis following vaccination with an mRNA COVID-19 vaccine

Rare cases of myocarditis (inflammation of the heart muscle) and/or pericarditis (inflammation of the lining around the heart) have been reported following vaccination with COVID-19 mRNA vaccines.

Cases following mRNA COVID-19 vaccination are consistently reported to have occurred:

• More often after the second dose
• Usually within a week after vaccination
• More often in those 12 to 29 years of age
• More often in males

Analyses of primary series surveillance data in Canada, US and European Nordic countries suggests a higher rate of myocarditis/pericarditis cases reported after vaccination with Moderna Spikevax original (100 mcg) compared to Pfizer-BioNTech Comirnaty original (30 mcg) vaccine especially among 12 to 29 year old males following a second dose of vaccine.

Myocarditis unrelated to exposure to COVID-19 disease or COVID-19 vaccines is typically less common in younger children 5 to 11 years of age. Safety surveillance data from the US suggests that the risk of myocarditis or pericarditis may be lower in children aged 5 to 11 years following Pfizer-BioNTech original (10 mcg) vaccination compared to adolescents and young adults (who receive a 30 mcg Pfizer-BioNTech original dose). Among children 5 to 11 years of age following vaccination with Pfizer-BioNTech Comirnaty original (10 mcg), very rare cases were most often reported following dose 2 and among males. The risk of myocarditis or pericarditis with Moderna Spikevax original (50 mcg) in children 6 to 11 years of age is unknown. Post-market safety surveillance is ongoing.

Available post-market vaccine safety data from V-safe, Vaccine Safety Datalink (VSD) and Vaccine Adverse Event Reporting System (VAERS) in the US as of September 2022 show that the Moderna Spikevax (25 mcg) and Pfizer-BioNTech Comirnaty (3 mcg) mRNA COVID-19 vaccines are well tolerated among children aged 6 months to 5 years. No safety signals (including myocarditis) have been identified after administration of about 1.5 million vaccine doses.

While long-term follow-up is ongoing, available data indicate that the majority of individuals who reported myocarditis/pericarditis after mRNA COVID-19 vaccination, though requiring hospitalization, have responded well to conservative therapy and tend to recover quickly.

Healthcare providers should consider myocarditis/pericarditis in their evaluation if the patient presents with clinically compatible symptoms (e.g., chest pain, shortness of breath, palpitations) after an mRNA COVID-19 vaccine regardless of timing from vaccination to symptoms onset. Investigations include electrocardiogram, serum troponins and echocardiogram. Frequent abnormal electrocardiogram findings and elevated troponin levels have been noted with myocarditis/pericarditis following mRNA vaccine.

Consultation with a cardiologist, infectious disease specialist, internal medicine specialist and/or rheumatologist may be advisable to assist in this evaluation, particularly to investigate the many potential causes of myocarditis and pericarditis. Investigations may include diagnostic testing for acute COVID-19 infection (e.g., PCR testing), prior SARS-CoV-2 infection and consideration of other potential infectious or non-infectious etiologies including auto-immune conditions.

Refer to the Contraindications and precautions section for advice on re-vaccination of individuals who developed myocarditis/pericarditis after a COVID-19 vaccine.

Myocarditis/pericarditis following vaccination with other COVID-19 vaccines

Cases of myocarditis/pericarditis have been reported following the administration of Novavax Nuvaxovid including two teenage males who had myocarditis shortly after receiving a second dose of vaccine. In both individuals, clinical course was mild with complete resolution and no sequelae. The information currently available is insufficient to determine a causal relationship with the vaccine. Post-market safety surveillance is required to determine whether this is an adverse event of interest associated with Novavax Nuvaxovid.

Venous thromboembolism (VTE)

Venous thromboembolism (VTE) has been observed rarely following vaccination with the Janssen Jcovden COVID-19 Vaccine. In individuals with a pre-existing increased risk for thromboembolism, the possible increased risk of VTE with vaccine use should be considered. See the Contraindications and precautions section if considering the use of Janssen Jcovden in an individual with a history of VTE.

Guillain-Barré syndrome (GBS) following vaccination with viral vector COVID-19 vaccines

Guillain-Barré syndrome (GBS) is a rare but potentially serious immune-mediated neurologic disorder that results in numbness, muscle weakness and/or paralysis in severe cases, as well as pain, often in the back or legs. Most people fully recover from GBS but some have residual deficits or symptoms and rarely, fatal cases can occur. To date, no increased risk of GBS has been identified following vaccination with the mRNA COVID-19 vaccines (Pfizer-BioNTech Comirnaty original and Moderna Spikevax original). Investigations have identified an increased risk of GBS following vaccination with the viral vector COVID-19 vaccines (AstraZeneca Vaxzevria and Janssen Jcovden).

The risk of GBS recurrence after COVID-19 vaccination amongst those with a past history of GBS appears to be low. Two cases have been described in the literature: 1 following Pfizer-BioNTech Comirnaty original (30 mcg) vaccine and 1 following a viral vector vaccine (product unknown). A causal association between these recurrences and COVID-19 vaccination has not been established. Both cases were recovering at the time of reporting.

Symptoms of GBS may include:

• weakness or tingling sensations, especially in the upper or lower limbs, that worsens and spreads to other parts of the body
• coordination problems and unsteadiness
• difficulty walking
• weakness in the limbs, chest or face
• pain that can be severe, particularly at night
• difficulty with bladder control and bowel function
• double vision or difficulty moving eyes
• difficulty with facial movements, including swallowing, speaking, or chewing

Individuals should seek medical attention if they develop symptoms of GBS following vaccination. Healthcare providers should consider GBS in their evaluation if the patient presents with clinically compatible symptoms and exclude other potential causes.

See the Contraindications and precautions section regarding individuals who developed GBS after COVID-19 vaccination for advice on re-vaccination.

Bell's palsy

Very rare cases of Bell's palsy (typically temporary weakness or paralysis on one side of the face) have been reported following vaccination with Janssen Jcovden COVID-19 vaccine and COVID-19 mRNA vaccines (Pfizer-BioNTech Comirnaty original or Moderna Spikevax original) among individuals aged 12 years and older. Symptoms of Bell’s palsy appear suddenly and generally start to improve after a few weeks. The exact cause is unknown. It's believed to be the result of swelling and inflammation of the nerve that controls muscles on the face.

Symptoms of Bell's palsy may include:

• uncoordinated movement of the muscles that control facial expressions, such as smiling, squinting, blinking or closing the eyelid
• loss of feeling in the face
• headache
• tearing from the eye
• drooling
• lost sense of taste on the front two-thirds of the tongue
• hypersensitivity to sound in the one ear
• inability to close an eye on one side of the face

Individuals should seek medical attention if they develop symptoms of Bell's palsy following receipt of COVID-19 vaccines. Healthcare providers should consider Bell's palsy in their evaluation if the patient presents with clinically compatible symptoms after a COVID-19 vaccine. Investigations should exclude other potential causes of facial paralysis.

Multisystem inflammatory syndrome in children or in adults (MIS-C or MIS-A) following vaccination with an mRNA COVID-19 vaccine

During the manufacturer-led clinical trials for mRNA COVID-19 vaccines, no cases of MIS-C were reported among children or adolescents. However, any rare or very rare AE that occurs at a frequency less often than 1 in 10,000 would likely not be detected due to the limitations of the trial size.

Very rare cases of MIS-C or MIS-A have been reported following vaccination with COVID-19 mRNA vaccines in Canada and internationally among individuals aged 12 years and older. In October 2021, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (EMA-PRAC) issued a statement that there is currently insufficient evidence regarding a possible link between mRNA COVID-19 vaccines and very rare cases of MIS-C or MIS-A.

Severe immediate allergic reactions (e.g., anaphylaxis) following vaccination with COVID-19 vaccines

Anaphylaxis is a very 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.

Very rare cases of severe immediate allergic reactions (e.g., anaphylaxis) have been reported following vaccination with mRNA COVID-19 vaccines. Individuals tend to recover quickly with appropriate treatment and there have been no fatalities nor long-term morbidity observed with any of these severe immediate allergic reactions in Canada. Most of the reported cases have occurred within 30 minutes of vaccination.

Studies have shown that individuals with a severe immediate allergic reaction after a previous dose of mRNA vaccine can be re-vaccinated with the same vaccine or another mRNA COVID-19 vaccine following an appropriate medical assessment. In these studies, re-vaccination was safe and well tolerated with predominantly no, or mild, reactions after re-vaccination when provided in a controlled environment. Available evidence also suggests that most of the reported severe immediate allergic reactions following mRNA COVID-19 vaccines are likely not Immunoglobulin E (IgE)-mediated and therefore have a low risk of recurrence following future vaccine doses. Refer to Precautions below for additional information.

Refer to Anaphylaxis and other Acute Reactions Following Vaccination in Part 2 for information on the management of anaphylaxis post-vaccination.

Refer to the Contraindications and precautions section for advice on re-vaccination of individuals who had an anaphylactic reaction after vaccination and for vaccination advice for those allergic to components of the COVID-19 vaccines.

Thrombosis with thrombocytopenia syndrome (TTS) following vaccination with viral vector COVID-19 vaccines

Very rare cases of serious blood clots or thrombosis (at unusual sites such as cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial thrombosis) associated with thrombocytopenia have been reported following vaccination with viral vector COVID-19 vaccines. The terminology for this syndrome has been evolving. The Canadian Adverse Events Following Immunization Surveillance System (CAEFISS) uses the Brighton Collaboration case definition for TTS to detect and evaluate reported cases. In Canada, TTS cases that test positive for a biomarker, anti-PF4 (antibodies to platelet factor 4-polyanion complexes), represent a subset of events and are being referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT).

The exact mechanism by which the viral vector COVID-19 vaccines trigger this syndrome is still under investigation. Viral vector vaccines appear to trigger a presentation similar to spontaneous heparin-induced thrombosis (HIT)/autoimmune heparin-induced thrombosis, where antibodies to platelet factor 4 (PF4)-polyanion complexes induce platelet activation, which causes thrombosis and thrombocytopenia. Clots related to VITT can be very aggressive and challenging to treat. Please refer to Thrombosis Canada guidance for clinical management of VITT. They cannot be managed the same way as clots related to oral contraceptives, immobility, or long-haul flights, and have an entirely different biologic pathophysiology.

Cases of TTS usually occur between 4 and 28 days after receipt of a viral vector COVID-19 vaccine, and patients should be monitored for symptoms up to 42 days. The rate of TTS after the first dose is estimated to be between 1 per 26,000 and 1 per 100,000 doses of AstraZeneca Vaxzevria COVID-19 vaccine administered and 1 per 300,000 doses of Janssen Jcovden COVID-19 vaccine administered. The frequency of TTS following a second dose of AstraZeneca Vaxzevria vaccine appears to be lower at about 1 per 520,000 doses administered. After the first dose, there was a higher reported incidence rate of TTS in the younger adults compared to the older adults. The reported incidence was also higher in women compared to men in some age groups. The case fatality rate ranges between 20 and 50%. Many cases have been reported to have serious long-term morbidity, including neurologic injury.

Anyone receiving a viral vector COVID-19 vaccine should be informed of the adverse event of TTS and advised to seek immediate medical attention if they develop symptoms following vaccination.

Symptoms of TTS may include:

• shortness of breath
• chest pain
• leg swelling or pain
• persistent abdominal pain
• sudden onset of severe headaches
• persistent or worsening headaches
• blurred vision
• confusion or seizures
• skin bruising (other than at the site of vaccination) or petechiae

Healthcare professionals should be aware of TTS including how to diagnose and treat the condition (see guidance from Thrombosis Canada). People who developed TTS after a viral vector vaccine should not receive additional viral vector vaccines. Refer to the Contraindications and precautions section.

Capillary leak syndrome (CLS) following vaccination with viral vector COVID-19 vaccines

Very rare cases of CLS have been reported following immunization with the viral vector COVID-19 vaccines (AstraZeneca Vaxzevria and Janssen Jcovden). CLS is a very rare, serious condition that causes fluid leakage from small blood vessels (capillaries), resulting in swelling mainly in the arms and legs, low blood pressure, thickening of the blood and low blood levels of albumin (an important blood protein). Symptoms are often associated with feeling faint (due to low blood pressure).

The frequency of CLS has been estimated at less than 1 per million doses of viral vector vaccines administered. Some of those affected had a history of CLS. People with a history of CLS should not be offered viral vector vaccines. Refer to the Contraindications and precautions section.

Immune thrombocytopenia (ITP) following vaccination with viral vector COVID-19 vaccines

Cases of immune thrombocytopenia with very low platelet levels (<20,000 per uL) have been reported very rarely after vaccination with Janssen Jcovden and AstraZeneca Vaxzevria COVID-19 vaccines, usually within the first four weeks after vaccination. This included cases with bleeding and cases with fatal outcome. Some of these cases occurred in individuals with a history of immune thrombocytopenia (ITP). If an individual has a history of ITP, the risks of developing low platelet levels should be considered before vaccination, and platelet monitoring is recommended after vaccination.

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. Refer to Reporting AEFI in Canada for additional information on the completion and submission of AEFI reports.

At the international level, the Brighton Collaboration has developed a list of Adverse Events of Special Interest (AESI). AESI are pre-specified medically significant events that have the potential to be causally associated with a vaccine product. Refer to Brighton Collaboration: COVID-19 resources and tools for the list of AESIs and for case definitions of specific AEFIs.

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

Refer to the PHAC weekly report for reported adverse events following COVID-19 vaccination in Canada.

Contraindications and precautions

Contraindications

Thrombosis with thrombocytopenia syndrome (TTS) following vaccination

Patients who have experienced venous and/or arterial thrombosis with thrombocytopenia following vaccination with a viral vector COVID-19 vaccine should not receive a subsequent dose of a viral vector COVID-19 vaccine. They may receive further doses of mRNA COVID-19 vaccines following consultation with their clinical team which may include a hematologist.

Capillary leak syndrome (CLS)

As a precautionary measure following the international cases that have been reported, individuals with a history of CLS (related or not to previous vaccination) should not receive viral vector COVID-19 vaccines.

Precautions

Hypersensitivity and allergies

Severe immediate allergic reaction (e.g., anaphylaxis) to a COVID-19 vaccine or a vaccine excipient

In individuals with a history of a severe, immediate (≤4 hours following vaccination) allergic reaction (e.g., anaphylaxis) after previous administration of an mRNA COVID-19 vaccine, re-vaccination may be offered with the same vaccine or the same mRNA platform if a risk assessment deems that the benefits outweigh the potential risks for the individual and if informed consent is provided. Consultation with an allergist or other appropriate physician should be sought prior to re-vaccination. If re-vaccinated, vaccine administration should be done in a controlled setting with expertise and equipment to manage anaphylaxis. Individuals should be observed for at least 30 minutes after re-vaccination. For example, a longer period of observation is warranted for individuals exhibiting any symptom suggestive of an evolving AEFI at the end of the 30-minute observation period.

For those with a previous history of allergy to an mRNA vaccine where consultation with an allergist or other appropriate physician precludes further vaccination with an mRNA vaccine, re-vaccination with Novavax Nuvaxovid or Medicago Covifenz may be preferred for individuals in the authorized age group without contraindications to the vaccine.

In individuals with a history of a severe, immediate (≤4 hours following vaccination) allergic reaction (e.g., anaphylaxis) after previous administration of a viral vector COVID-19 vaccine, re-vaccination may be offered with an mRNA platform if a risk assessment deems that the benefits outweigh the potential risks for the individual and if informed consent is provided. If re-vaccinated, individuals should be observed for an extended period of at least 30 minutes after re-vaccination.

Confirmed allergies to a component of a COVID-19 vaccine

Ingredients of authorized COVID-19 vaccines that have been associated with allergic reactions in other products are: polyethylene glycol (PEG) tromethamine (trometamol or Tris) and polysorbate 80. There is a potential of cross-reactive hypersensitivity between PEG and polysorbate. There are also trace amounts of PEG, kanamycin and carbenicillin in the Medicago Covifenz vaccine.

Table 7. Vaccine products and potential allergens

Vaccine product	Potential allergens
	Polyethylene glycol (PEG)	Tromethamine (trometamol or Tris)	Polysorbate 80	Others
Pfizer-BioNTech Comirnaty original (30 mcg, 12 years and older, gray vial cap and gray label border)	Yes	Yes	No	-
Pfizer-BioNTech Comirnaty original (10 mcg, 5 to 11 years of age, orange vial cap and orange label border)	Yes	Yes	No	-
Pfizer-BioNTech Comirnaty original (3mcg, 6 months to 4 years of age, maroon vial cap and maroon label border)	Yes	Yes	No	-
Pfizer-BioNTech Comirnaty Original & Omicron BA.4/5 (bivalent, 30 mcg, 12 years of age and older, gray vial cap and gray label border)	Yes	Yes	No	-
Pfizer-BioNTech Comirnaty Original & Omicron BA.4/5 (bivalent, 10 mcg, 5 to 11 years of age, orange vial cap and orange label border)	Yes	Yes	No	-
Moderna Spikevax original (0.20 mg/mL, red vial cap and light blue label border)	Yes	Yes	No	-
Moderna Spikevax original (0.10 mg/mL, royal blue cap and purple label border)	Yes	Yes	No	-
Moderna Spikevax Bivalent, Original & Omicron BA.4/5 (0.10mg/mL, royal blue cap and grey label border)	Yes	Yes	No	-
Moderna Spikevax Bivalent, Original & Omicron BA.1 (0.10 mg/mL, royal blue cap and green label border)	Yes	Yes	No	-
AstraZeneca Vaxzevria	No	No	Yes	-
Janssen Jcovden	No	No	Yes	-
Novavax Nuvaxovid	No	No	Yes	-
Medicago Covifenz	Trace amounts	No	Yes	Kanamycin and carbenicillin (trace)

In individuals with a confirmed severe, immediate (≤4 hours following exposure) allergy (e.g., anaphylaxis) to a component of a specific COVID-19 vaccine or its container (e.g., PEG), consultation with an allergist is recommended before receiving the specific COVID-19 vaccine. In individuals with a serious PEG allergy in whom mRNA vaccination is precluded based on a consultation with an allergist or other appropriate physician, vaccination with Novavax Nuvaxovid may be preferred for individuals in the authorized age group without contraindications to the vaccine. 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.

Mild to moderate immediate allergic reactions to a COVID-19 vaccine or a vaccine excipient

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) to a previous dose of mRNA COVID-19 vaccine or any of its components, re-vaccination may be offered with the same vaccine or the same platform (i.e., mRNA). 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 re-vaccination is chosen, an extended period of observation post-vaccination of at least 30 minutes should be provided for the aforementioned individuals.

Other allergies

The following individuals may be routinely vaccinated with COVID-19 vaccines with the following recommended observation periods.

30 minute post-vaccination observation period:

• Those with a proven severe allergic reaction (e.g., anaphylaxis) to injectable therapy not related to a component of the COVID-19 vaccines (e.g., other intramuscular, intravenous, or subcutaneous vaccines or therapies)
• Those with a suspected but unproven allergy to a vaccine component (e.g., PEG)

15 minute post-vaccination observation period:

• Those with a history of allergy not related to a component of the COVID-19 vaccines or other injectable therapy (e.g., foods, oral drugs, insect venom or environmental allergens)

Acute illness

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 individuals with confirmed or suspected SARS-CoV-2 infection, or those with respiratory symptoms, to minimize the risk of COVID-19 transmission at an immunization clinic/venue. If any person is identified with symptoms on arrival at the venue, they should not be immunized and should be instructed to seek medical and public health advice as appropriate and follow current local public health measures.

The recommended intervals between SARS-CoV-2 infection and COVID-19 vaccination are provided in Table 5.

Bleeding disorders

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.

Immune thrombocytopenia (ITP)

If an individual has a history of ITP, the risks of developing low platelet levels should be considered before vaccination with a viral vector vaccine, and platelet monitoring is recommended after vaccination.

Individuals should seek immediate medical attention if they develop symptoms such as unexplained bleeding, unexplained bruising, or small purplish spots beyond the site of vaccination.

Venous thromboembolism (VTE)

In individuals with a pre-existing increased risk for thromboembolism, the possible increased risk of VTE with the Janssen Jcovden COVID-19 vaccine should be considered. Along with the general preference for mRNA vaccines, mRNA vaccines would be a safer option for these individuals.

Individuals should seek immediate medical attention if they develop symptoms, such as shortness of breath, chest pain, leg pain, leg swelling, or persistent abdominal pain following vaccination.

Thrombosis with thrombocytopenia syndrome (TTS)

There is no evidence that individuals with previous cerebral venous sinus thrombosis (CVST) with thrombocytopenia not related to a viral vector or people with previous heparin-induced thrombocytopenia (HIT) not related to a viral vector vaccine are at increased risk of vaccine-induced immune thrombotic thrombocytopenia (VITT) compared to other individuals after receiving a viral vector vaccine. However, similar to other individuals, an mRNA vaccine is preferred. The Novavax Nuvaxovid or Medicago Covifenz may be used among individuals in the authorized age group without contraindications to the vaccine who are not able or willing to receive an mRNA vaccine.

Myocarditis and/or pericarditis following vaccination

As a precautionary measure until more information is available, further doses of mRNA COVID-19 vaccines should be deferred among individuals who have experienced myocarditis and/or pericarditis within 6 weeks following a previous dose of an mRNA COVID-19 vaccine in most circumstances. This includes any person who had an abnormal cardiac investigation including ECG, elevated troponins, echocardiogram or cardiac MRI after a dose of an mRNA COVID-19 vaccine.

Those with a history compatible with pericarditis and who either had no cardiac workup or had normal cardiac investigations, can receive the next dose once they are symptom-free and at least 90 days have elapsed since vaccination.

Some individuals 5 years of age and older with confirmed myocarditis and/or pericarditis after a dose of an mRNA COVID-19 vaccine may choose to receive another dose of vaccine after discussing the risk and benefit with their healthcare provider. If another dose of vaccine is offered, it should be with a Pfizer-BioNTech Comirnaty COVID-19 vaccine product (original for the primary series or bivalent for the booster dose, at the age-appropriate dose) due to the lower reported rate of myocarditis and/or pericarditis following the Pfizer-BioNTech Comirnaty original (30 mcg) vaccine compared to the Moderna Spikevax original (100 mcg) vaccine among individuals 12 years of age and older. Informed consent should include discussion about the unknown risk of recurrence of myocarditis and/or pericarditis following receipt of additional doses of Pfizer-BioNTech Comirnaty original or bivalent vaccines in individuals with a history of confirmed myocarditis and/or pericarditis after a previous dose of mRNA COVID-19 vaccine, as well as the need to seek immediate medical assessment and care should symptoms develop.

There have been case reports of myocarditis and/or pericarditis following the administration of Novavax Nuvaxovid. Information currently available is insufficient to determine a causal relationship with the vaccine.

Individuals who have a history of myocarditis unrelated to mRNA COVID-19 vaccination should consult their clinical team for individual considerations and recommendations. If the diagnosis is remote and they are no longer followed clinically for cardiac issues, they should receive the vaccine.

Guillain-Barré syndrome

Individuals with past history of GBS unrelated to COVID-19 vaccination should receive an mRNA COVID-19 vaccine. When mRNA COVID-19 vaccines are contraindicated, Novavax Nuvaxovid could be considered or individuals may receive a viral vector COVID-19 vaccine after weighing the risks and benefits in consultation with their health care provider.

Individuals who developed GBS after a previous dose of a COVID-19 vaccine may receive an mRNA COVID-19 vaccine, after consultation with their health care provider if it is determined that the benefits outweigh the risk and informed consent is provided.

Bell's palsy

Individuals should seek medical attention if they develop symptoms compatible with Bell's palsy following receipt of mRNA COVID-19 vaccines. Healthcare providers should consider Bell's palsy in their evaluation if the patient presents with clinically compatible symptoms after an mRNA COVID-19 vaccine. Investigations should exclude other potential causes of facial paralysis.

Multisystem inflammatory syndrome in children or adults (MIS-C or MIS-A)

For children or adults with a previous history of MIS-C or MIS-A, vaccination or re-vaccination should be postponed until clinical recovery has been achieved or until it has been ≥ 90 days since diagnosis, whichever is longer (see Table 5).

Other considerations

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 Blood products, human immunoglobulin and timing of immunization.

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

There is a theoretical risk that mRNA or viral vector vaccines could temporarily affect cell-mediated immunity, resulting in false-negative TST or IGRA test results. However, there is no direct evidence for this interaction. Therefore, in the absence of data and acknowledging the importance of both timely tuberculosis testing and immunization, vaccination with COVID-19 vaccines may take place at any time before, after or at the same visit as the TST or IGRA test. Repeat tuberculin skin testing or IGRA (at least 4 weeks post-COVID-19 immunization) of individuals with negative TST or IGRA results for whom there is high suspicion of latent tuberculosis infection may be considered in order to avoid missing persons with TB infection.

Blood products, human immunoglobulin and timing of immunization

It is recommended that COVID-19 vaccines should not be given concurrently with anti-SARS-CoV-2 monoclonal antibodies.

Administration of these products concurrently may result in decreased effectiveness of the COVID-19 vaccine and/or anti-SARS-CoV-2 monoclonal antibodies. Anti-SARS-CoV-2 monoclonal antibodies have high affinity for the spike protein expressed by COVID-19 vaccines, which could prevent the production of antibodies stimulated by the vaccine, or binding of vaccine antigen to the monoclonal antibody may neutralize the monoclonal antibody.

Pre-exposure prophylaxis for COVID-19 with anti-SARS-CoV-2 monoclonal antibodies

In some cases, anti-SARS-CoV-2 monoclonal antibodies may be given in addition to vaccination to some individuals with immunocompromising conditions, in consultation with clinical experts. Clinicians may consider the following factors when assessing the potential benefits or risks when recommending anti-SARS-CoV-2 monoclonal antibodies to their patients: the degree of immunocompromise, the presence of additional risk factors for severe COVID-19, the likelihood of not responding to COVID-19 vaccine, the risk of exposure to COVID-19 due to occupational or residential circumstances, as well as local circulation of variants with the potential for resistance to one or more of the anti-SARS-CoV-2 monoclonal antibodies, including some Omicron sublineages. Although anti-SARS-CoV-2 monoclonal antibodies could reduce humoral immune responses to a COVID-19 vaccine, cellular immune responses may not be impacted. Cellular immune responses to a COVID-19 vaccine are important for immunocompromised populations and, to sustain cellular immune responses, vaccination should be given to this group as recommended, whether or not their receive anti-SARS-CoV-2 monoclonal antibodies, noting the timing considerations below.

Implementation advice to inform decision-makers on the appropriate use of anti-SARS-CoV-2 monoclonal antibodies (e.g., patient prioritization) is available from the Canadian Agency for Drugs and Technologies in Health (CADTH), the Institut national d'excellence en santé et en services sociaux (INESSS ) and Ontario Health.

Up to date information on alerts including risk of treatment failure of specific anti-SARS-CoV-2 monoclonal antibodies as well as safety and recalls, is available from Health Canada.

Guidance on anti-SARS-CoV-2 monoclonal antibodies may change as additional evidence emerges.

Administration of anti-SARS-CoV-2 monoclonal antibodies following COVID-19 vaccines

To minimize interference, it is recommended that anti-SARS-CoV-2 monoclonal antibodies should be administered at least 2 weeks following COVID-19 vaccination.

Administration of COVID-19 vaccines following anti-SARS-CoV-2 monoclonal antibodies

There is no evidence on which to base a specific minimum interval for COVID-19 vaccination following anti-SARS-CoV-2 monoclonal antibodies administration. Timing should be assessed in consultation with clinical experts on a case-by-case basis.

Therapeutic management of COVID-19 with anti-SARS-CoV-2 monoclonal antibodies

Multiple products are authorized in Canada for therapeutic management of COVID-19. Expert clinical opinion should be sought on a case-by-case basis when deciding on the use of anti-SARS-CoV-2 monoclonal antibodies, as well as whether vaccination should be repeated if a therapeutic dose is given too close to vaccination.

Timing of administration of COVID-19 vaccines following administration of therapeutic or post-exposure anti-SARS-CoV-2 monoclonal antibodies should be assessed in consultation with clinical experts on a case-by-case basis.

For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database.

Chapter revision process

This chapter was updated to reflect guidance based on current evidence and the National Advisory Committee on Immunization’s (NACI’s) expert opinion since the last version of this chapter (March 7, 2023). Additional content changes may reflect changes to COVID-19 vaccine product monographs. Refer to the Table of Updates for additional information.

For supporting information on COVID-19 vaccine chapter updates, including additional references, refer to the Current and/or Previous summary of updates in the Canadian Immunization Guide published on the NACI webpage under COVID-19.

Acknowledgements

This chapter was prepared by SJ Ismail, K Young, MC Tunis, A Killikelly, R Stirling, O Baclic, J Zafack, MI Salvadori, N Forbes, L Coward, C Jensen, R Krishnan, NK Abraham, E Abrams, B Warshawsky, E Wong, J Montroy, R Pless, R Harrison, and S Deeks on behalf of NACI.

NACI gratefully acknowledges the contribution of: M Laplante, C Mauviel, K Ramotar, S Pierre, N Mohamed, E Tice.

Selected references

• Abraham N, Spruin S, Rossi T, Fireman B, Zafack J, Blaser C, et al. Myocarditis and/or Pericarditis Risk After mRNA COVID-19 Vaccination: A Canadian Head to Head Comparison of BNT162b2 and mRNA-1273 Vaccines. JVAC-D-21-03106, Available at SSRN: https://ssrn.com/abstract=3988612
• AstraZeneca Canada Inc. Product monograph - Evusheld^™. April 14, 2022.
• AstraZeneca Canada Inc. Product monograph - Vaxzevria^™. November 15, 2021.
• Brighton Collaboration. Interim case definition of Thrombosis with Thrombocytopenia Syndrome (TTS) [Internet]. Decatur (GA): The Task Force for Global Health; 2021 Nov 11 . Available from: https://brightoncollaboration.us/wp-content/uploads/2021/11/TTS-Updated-Brighton-Collaboration-Case-Defintion-Draft-Nov-11-2021.pdf
• Janssen Inc. Product monograph - JCOVDEN^™ COVID-19 vaccine. August 5, 2022.
• Medicago Inc. Product monograph - COVIFENZ^®COVID-19 vaccine. February 24, 2022.
• ModernaTX, Inc. Product monograph - SPIKEVAX^™. July 14, 2022.
• ModernaTX, Inc. Product monograph - SPIKEVAX^™ Bivalent. February 23, 2023
• National Advisory Committee on Immunization. COVID-19 vaccine statements. Accessed September 2022 from: https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci.html#covid-19
• Novavax, Inc. Product monograph - NUVAXOVID^™. February 17, 2022.
• Pfizer Canada ULC. Product monograph - COMIRNATY^® Original & Omicron BA.4/BA.5. December 9, 2022.
• Pfizer Canada ULC. Product monograph - COMIRNATY^™. June 1, 2022.
• Public Health Ontario. Recommendations: Fourth COVID-19 vaccine dose for long-term care home residents and older adults in other congregate settings. December 29, 2021. Accessed February 2022 from: https://www.publichealthontario.ca/-/media/Documents/nCoV/Vaccines/2022/01/covid-19-oiac-4th-dose-recommendations-older-adults-ltc.pdf?sc_lang=en