Vaccines: COVID-19

How to Cite This Chapter: Komorowski AS, Mourad O, Loeb M. Vaccines: COVID-19. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.18.53.14. Accessed December 06, 2022.
Last Updated: October 10, 2022
Last Reviewed: October 10, 2022
Chapter Information

Authors’ note: Approvals for different vaccinations to prevent coronavirus disease 2019 (COVID-19) are changing on a rapid basis and differ between jurisdictions. The textbook chapter that follows summarizes vaccines offered approvals in Canada as of the date of the last update of this chapter. The judgment of professional and international organizations assessing the same body of evidence differs across jurisdictions, which may reflect different confidence in the data and different values and preferences associated with different outcomes.

Epidemiology, symptoms, diagnosis, and treatment of COVID-19: see Coronavirus Disease 2019 (COVID-19).

Vaccine PlatformsTop

mRNA vaccines currently approved for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consist of an mRNA molecule encapsulated in a lipid nanoparticle. The mRNA molecule itself encodes for the SARS-CoV-2 spike glycoprotein. The lipid nanoparticle is cationic and contains cholesterol for stability. Cholesterol is necessary to protect the mRNA from degradation once injected and allows its uptake into the cell, where endosomal release of the mRNA occurs. The mRNA is then translated into protein by ribosomes in a process that occurs outside—and independently—of the host cell nucleus. The resultant noninfectious SARS-CoV-2 spike glycoproteins are subsequently presented on the host cell surface for immune recognition by circulating lymphocytes. After being used by the cytoplasmic ribosomes to produce the spike glycoprotein, the mRNA is degraded. Of note, it is not biologically plausible for the mRNA component of the vaccine to integrate into human DNA, as human cells lack the reverse transcriptase and integrase enzymes required to accomplish this task.

Viral vector vaccines currently approved for use against SARS-CoV-2 consist of a recombinant, replication-deficient animal virus encoding for the SARS-CoV-2 spike glycoprotein. Upon injection, the viral vector is taken up into target cells and cellular ribosomes translate the recombinant sequence into the trimeric prefusion SARS-CoV-2 spike glycoprotein. The resultant noninfectious SARS-CoV-2 spike glycoproteins are subsequently presented on the host cell surface for immune recognition by circulating lymphocytes.

Protein subunit vaccines currently approved for use against SARS-CoV-2 consist of a recombinant SARS-CoV-2 spike glycoprotein produced in an insect cell line, along with an adjuvant to stimulate the immune response upon injection.

Plant-based virus-like particle (VLP) vaccines currently approved for use against SARS-CoV-2 contain noninfectious SARS-CoV-2 VLPs consisting of SARS-CoV-2 spike glycoproteins stabilized in prefusion conformation and embedded in a lipid envelope. VLPs are produced by delivering the genetic sequence into nontransgenic plants via a bacterial vector using agroinfiltration.

General ConsiderationsTop

1. Role of vaccination in those with previous SARS-CoV-2 infection: The Canadian National Advisory Committee on Immunization (NACI) recommends vaccination to those with previous clinical or microbiologic evidence of SARS-CoV-2 infection, due to the risk of SARS-CoV-2 reinfection and waning immune response over time.

2. Role of microbiologic testing prior to administration of SARS-CoV-2 vaccines: Testing with polymerase chain reaction (PCR), rapid antigen detection tests, or serology are not required prior to immunization with a SARS-CoV-2 vaccine.

3. Postvaccination serologic testing: Serology is not required after immunization with a SARS-CoV-2 vaccine in order to document seroconversion.

4. Concern for infection with SARS-CoV-2 after immunization with a SARS-CoV-2 vaccine: Receipt of a vaccine does not interfere with PCR or rapid antigen testing for SARS-CoV-2 in the case that a clinician suspects infection with a circulating strain of SARS-CoV-2 in a previously vaccinated patient. Microbiologic testing can also distinguish between adverse events following immunization and natural infection with SARS-CoV-2.

5. Vaccine efficacy against SARS-CoV-2 variants of concern (VOCs): SARS-CoV-2 has a high baseline rate of mutation due to its RNA genome, allowing “escape mutants” to be produced, which are no longer bound by neutralizing antibodies from prior vaccination. VOC nomenclature in this chapter follows the World Health Organization (WHO) classification based on the Greek alphabet naming system. The effect of VOCs on vaccine efficacy is described in the “Vaccine efficacy” subsection of each Health Canada–approved vaccine below.

6. Prevention of SARS-CoV-2 transmission by vaccination: Vaccinated individuals may harbor the virus in the nasopharyngeal mucosa but remain asymptomatic. SARS-CoV-2 vaccines reduce the viral load shed from the nasopharynx of vaccinated individuals asymptomatically harboring the virus in the nasopharynx to varying degrees, depending on the infecting strain.

7. Comparison of efficacy for SARS-CoV-2 vaccines: Different randomized controlled trials of SARS-CoV-2 vaccines have different efficacy endpoints and populations in which they were studied (Table 10.7-1).

8. Vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with viral vector vaccines: VITT is an adverse event occurring after administration of viral vector vaccines (AZD1222 and Ad26.COV2.S). For information regarding the incidence with each specific vaccine, go to the Adverse Events section for the individual vaccine. VITT occurs more frequently in younger patients and in women, with onset 4 to 42 days after vaccination, typically after administration of the first vaccine dose. Patients may present with arterial or venous clots, including atypical clots such as those observed in cerebral sinus venous thrombosis. VITT should be suspected in an individual 4 to 42 days after viral vector vaccination with persistent, severe headache; focal neurologic deficits; hemorrhage; petechiae; ecchymosis; dyspnea; abdominal pain; or swelling and erythema in a limb. For futher information see the Ontario COVID-19 Science Table brief: www.covid19-sciencetable.ca. Patients who have experienced VITT with a first dose of a viral vector vaccine should not receive a second dose of a viral vector vaccine. As an adverse event following vaccination, any case of VITT should be reported to the provincial public health authority and Health Canada.

9. Preferential administration of mRNA vaccines: The NACI recommends that mRNA vaccines (tozinameran [Pfizer] or elasomeran [Moderna]) be offered preferentially to patients aged ≥12 years without contraindications to mRNA vaccines. Protein subunit or VLP vaccines may be offered to patients aged ≥18 years with contraindications to mRNA vaccination, if mRNA vaccines are unavailable, or if the patient is unwilling to receive an mRNA vaccine. Viral vector vaccines should be offered to patients aged ≥18 years only when all other authorized vaccines are contraindicated. Patients who began the primary SARS-CoV-2 vaccination series with a viral vector vaccine and do not have a contraindication to mRNA vaccines precluding their use should complete the primary series with an mRNA vaccine.

10. Recommendations for subsequent booster doses following completion of a primary series: The NACI recommends that populations with moderate to severe immune deficiency complete a 3-dose mRNA vaccine-based primary series, whereas immunocompetent patients are considered to complete the primary series after 2 doses. Any dose received after completion of the primary series should be referred to as a “booster dose” in the relevant population.

In immunocompromised patients, an mRNA vaccine is preferred for administration of a first booster dose (ie, the fourth overall dose) ≥6 months after completion of the primary series. As per the NACI recommendations, if elasomeran (Moderna) is used as a booster dose, a higher 100-microg dose may be considered in this population due to potential for higher vaccine efficacy.

In immunocompetent patients, the first booster dose (ie, the third overall dose) is recommended and should be offered ≥6 months after completion of the primary series, with an mRNA vaccine preferred. In patients aged 16 to 29 years, tozinameran (Pfizer) is preferred over elasomeran (Moderna) due to the higher rate of vaccine-associated myocarditis/pericarditis with the latter in this age group. The NVX-CoV2373 (Novavax) vaccine may be considered for administration as a booster dose within the same time period noted above as per the NACI; however, NVX-CoV2373 is not currently authorized by Health Canada for this purpose. The Ad26.COV2.S (Johnson & Johnson/Janssen) vaccine may be offered as a booster dose only when all other authorized options are contraindicated. The CoVLP (Medicago) vaccine is not currently authorized for use as a booster dose in Canada. Second booster doses are not currently authorized by Health Canada and constitute off-label use: they are strongly recommended by the NACI for community-dwelling adults aged ≥80 years and for any adults living in long-term care or congregate living settings. First Nations, Inuit, and Métis populations, as well as those aged ≤70 years can consider second booster doses. The use of booster doses in immunocompetent patients aged 12 to 15 years constitutes off-label use but should be offered to those at high risk of severe COVID-19, those in congregate settings, and those who belong to racialized groups because of their heightened epidemiologic risk for adverse COVID-19 outcomes.

Vaccines Currently Approved for Use in CanadaTop

Tozinameran (Pfizer-BioNTech) mRNA Vaccine

Tozinameran (marketed by Pfizer-BioNTech as Comirnaty, previously known in developmental stages as BNT162b2) contains mRNA encoding for the SARS-CoV-2 spike glycoprotein encapsulated in lipid nanoparticles.

1. Indications: Tozinameran is approved for use for the prevention of COVID-19 in patients aged ≥6 months. A bivalent version of the vaccine is approved for use as a booster dose for the prevention of COVID-19 in patients aged ≥12 years. The bivalent formulation contains mRNA encoding the spike glycoproteins for the reference strain, Omicron BA.4 (B.1.1.529.4), and Omicron BA.5 (B.1.1.529.5) variants.

2. Contraindications: Tozinameran is contraindicated in those with allergy or hypersensitivity to vaccine components. The nonmedicinal ingredients used in tozinameran are 1,2-distearoyl-sn-glycero-3-phosphocholine, ALC-0315, ALC-0159, cholesterol, dibasic sodium phosphate dihydrate, monobasic potassium phosphate, potassium chloride, sodium chloride, sucrose, and water for injection.

3. Special populations:

1) Patients aged 6 months to 29 years: Patients in this age range should be preferentially offered tozinameran (Pfizer) over elasomeran (Moderna) to mitigate the potential risk of myocarditis/pericarditis with the latter.

2) Pregnant patients: A phase II/III study (ClinicalTrials.gov identifier: NCT04754594) in this population is underway.

Data from the Vaccine Adverse Event Reporting System as well as from a systematic review of maternal and fetal outcomes following SARS-CoV-2 vaccination have not shown any obvious safety signals among patients who have received an mRNA vaccine.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Shimabukuro TT, Kim SY, Myers TR, et al; CDC v-safe COVID-19 Pregnancy Registry Team. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med. 2021 Jun 17;384(24):2273-2282. doi: 10.1056/NEJMoa2104983. Epub 2021 Apr 21. PMID: 33882218; PMCID: PMC8117969.Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). De Rose DU, Salvatori G, Dotta A, Auriti C. SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes. Viruses. 2022 Mar 5;14(3):539. doi: 10.3390/v14030539. PMID: 35336947; PMCID: PMC8951373. The Society of Obstetricians and Gynecologists of Canada (SOGC) has issued a statement that pregnant individuals should be offered any Health Canada–approved SARS-CoV-2 vaccination at any time during pregnancy provided there are no contraindications to vaccination.

3) Breastfeeding patients: Data from a systematic review of maternal and fetal outcomes following SARS-CoV-2 vaccination have not shown any obvious safety signals among patients who have received an mRNA vaccine.Evidence 3Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness).De Rose DU, Salvatori G, Dotta A, Auriti C. SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes. Viruses. 2022 Mar 5;14(3):539. doi: 10.3390/v14030539. PMID: 35336947; PMCID: PMC8951373. The SOGC has issued a statement that breastfeeding individuals should be offered any Health Canada–approved SARS-CoV-2 vaccination at any time provided there are no contraindications to vaccination.

4) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune deficiency may have a diminished serologic response to vaccination and should receive a 3-dose primary vaccine series (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged ≥12 years: Tozinameran 30 microg is given as a 0.3-mL IM injection in the deltoid muscle on days 0 and 21. Two formulations are authorized for use, one of which requires dilution prior to injection, while the other does not: refer to package instructions prior to administering vaccination to ensure that an appropriate dose is administered. Due to evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. Subsequent booster doses of univalent or bivalent formulations of tozinameran 30 microg are recommended 6 months after completion of the primary series (see “Recommendations for subsequent booster doses following completion of a primary series” in General Considerations above).

2) Primary series, persons aged 5 to 11 years: Tozinameran 10 microg is given after dilution as a 0.2-mL IM injection in the deltoid muscle on days 0 and 21. Due to evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56.

3) Primary series, persons aged 6 months to 5 years: Tozinameran 10 microg is given after dilution as a 0.2-mL IM injection in the deltoid muscle on days 0, 21, and 77.

4) Primary series, immunocompromised patients: For patients aged ≥12 years with moderate or severe immune deficiency, tozinameran 30 microg is given as a 0.3-mL IM injection in the deltoid muscle on days 0, 21, and 49. For patients aged 6 months to 11 years with moderate or severe immune deficiency, tozinameran 10 microg is given after dilution as a 0.2-mL IM injection in the deltoid muscle on days 0, 21, and 49. Two formulations are authorized for use in patients aged ≥12 years, one of which requires dilution prior to injection, while the other does not: refer to package instructions prior to administering vaccination to ensure that an appropriate dose is administered.

5) Missed doses: There is no information available with respect to missed doses and their effect on immune response to tozinameran. According to the NACI, if a second dose is administered between days 19 and 21, it is considered within the recommended dosing schedule. If the second dose is administered prior to day 19, an additional dose should not be given. The primary series does not need to be repeated if >21 days have elapsed since the first dose.

6) Vaccine interchangeability: The NACI recommends that individuals who received a first dose of tozinameran should be offered tozinameran for their primary series, if available. If tozinameran is not readily available or the product used for the first dose is unknown, elasomeran is considered interchangeable and should be used to complete the vaccination series. The same principle applies to booster doses, where eligible.

5. Vaccine efficacy:

1) Short-term efficacy: Tozinameran was 95% effective (95% CI, 90.3-97.6) at preventing SARS-CoV-2 infection ≥7 days after the second dose (in participants without clinical or microbiologic evidence of infection at baseline).Evidence 4Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Polack FP, Thomas SJ, Kitchin N, et al; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577. Epub ahead of print. PMID: 33301246. Vaccine efficacy was consistent across age, sex, race, and ethnicity demographics.

An Israeli study involving 1,193,236 participants showed similar efficacy data: at ≥7 days after the second dose, tozinameran was 92% effective (95% CI, 88-95) at preventing symptomatic SARS-CoV-2 infection; 88% effective (95% CI, 55-100) at preventing hospitalization; and 92% effective (95% CI, 75-100) at preventing severe COVID-19. Efficacy was also seen after administration of the first dose: tozinameran was 72% effective at preventing COVID-19–related death (95% CI, 19-100) for days 14 to 20 after the first dose.Evidence 5Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med. 2021 Feb 24. doi: 10.1056/NEJMoa2101765. Epub ahead of print. PMID: 33626250.

Adolescents: In the United States, a study was conducted to assess vaccine efficacy in 2260 patients aged 12 to 15 years. At >7 days after the second dose, vaccine efficacy of tozinameran at preventing SARS-CoV-2 infection was 100% (95% CI, 75.3-100). Vaccine efficacy after the first dose was 75% (95% CI, 7.6-95.5).Evidence 6Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Olson SM, Newhams MM, Halasa NB, et al; Overcoming COVID-19 Investigators. Effectiveness of Pfizer-BioNTech mRNA Vaccination Against COVID-19 Hospitalization Among Persons Aged 12-18 Years - United States, June-September 2021. MMWR Morb Mortal Wkly Rep. 2021 Oct 22;70(42):1483-1488. doi: 10.15585/mmwr.mm7042e1. PMID: 34673751. Among patients aged 12 to 18 years in the United States, vaccine effectiveness of the complete primary series of tozinameran against hospitalization due to COVID-19 was 93% (95% CI, 83%-97%).Evidence 7Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Frenck RW Jr, Klein NP, Kitchin N, et al; C4591001 Clinical Trial Group. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. 2021 May 27;NEJMoa2107456. doi: 10.1056/NEJMoa2107456. Epub ahead of print. PMID: 34043894; PMCID: PMC8174030.

Children: In a phase II/III trial of 2268 patients aged 5 to 11 years, vaccine efficacy of a 2-dose primary series was 90.7% (95% CI, 67.7-98.3%).Evidence 8Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Walter EB, Talaat KR, Sabharwal C, et al; C4591007 Clinical Trial Group. Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2022 Jan 6;386(1):35-46. doi: 10.1056/NEJMoa2116298. Epub 2021 Nov 9. PMID: 34752019; PMCID: PMC8609605. This study met the prespecified noninferiority immunobridging criteria when comparing serologic response of children aged 6 months to 5 years with those aged 16 to 25 years, with a geometric mean titer ratio of 1.04 (95% CI, 0.93-1.18).Evidence 9Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Walter EB, Talaat KR, Sabharwal C, et al; C4591007 Clinical Trial Group. Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2022 Jan 6;386(1):35-46. doi: 10.1056/NEJMoa2116298. Epub 2021 Nov 9. PMID: 34752019; PMCID: PMC8609605. Similar immunobridging noninferiority criteria were met for patients aged 6 months to 5 years according to Health Canada regulatory filings; however, these data have yet to be published.

Booster dose: An Israeli study examined the benefit of a third dose of tozinameran in people aged >60 years at ≥5 months after completion of the primary vaccine series. Rates of confirmed infection in the third dose group ≥12 days after vaccination was lower by a factor 11.3, and rates of severe illness were lower by a factor 19.5.Evidence 10Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness).Bar-On YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. N Engl J Med. 2021 Oct 7;385(15):1393-1400. doi: 10.1056/NEJMoa2114255. Epub 2021 Sep 15. PMID: 34525275; PMCID: PMC8461568. A second Israeli study found that the test positivity rate in patients aged >40 years who received a third dose was reduced by 48% to 68% after 7 to 13 days and by 70% to 84% after 14 to 20 days after receiving the third dose.Evidence 11Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Patalon T, Gazit S, Pitzer VE, Prunas O, Warren JL, Weinberger DM. Short Term Reduction in the Odds of Testing Positive for SARS-CoV-2; a Comparison Between Two Doses and Three doses of the BNT162b2 Vaccine. medRxiv. Published August 31, 2021. doi:10.1101/2021.08.29.21262792. The bivalent formulation of tozinameran has not yet been evaluated in a clinical trial.

2) Long-term efficacy: There is no current information regarding the durability of long-term efficacy or safety in individuals who have received the vaccine. This information is legally required to be collected and reported as part of postauthorization monitoring.

3) Role in preventing transmission: A study of vaccinated health-care workers analyzed the effect of a single dose of tozinameran on PCR detection of asymptomatic SARS-CoV-2 infection in the nasopharynx. A 4-fold decrease in PCR detection was noted in health-care workers ≥12 days after having received their first dose relative to unvaccinated health-care workers (P = 0.004).Evidence 12Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the method of determination of transmissibility (indirectness). Jones NK, Rivett L, Seaman S, et al; Cambridge COVID-19 Collaboration. Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection. Elife. 2021 Apr 8;10:e68808. doi: 10.7554/eLife.68808. PMID: 33830018; PMCID: PMC8064747. 

4) Efficacy against SARS-CoV-2 VOCs: In a retrospective, test-negative South African study examining 133,437 PCR results, the 2-dose tozinameran vaccine efficacy against the Omicron VOC was found to be 70% (95% CI, 62-76).Evidence 13Moderate Quality of Evidence (moderate confidence that we know the true effects of the intervention). Quality of Evidence lowered due to indirectness. Collie S, Champion J, Moultrie H, Bekker LG, Gray G. Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa. N Engl J Med. 2022 Feb 3;386(5):494-496. doi: 10.1056/NEJMc2119270. Epub 2021 Dec 29. PMID: 34965358; PMCID: PMC8757569.

6. Adverse events: Adverse events stratified by dose and reported in the phase III clinical trial of tozinameran: Table 10.7-2.

Adverse events were more common after the second dose of the vaccine. Serious adverse events were reported by <1% of the clinical trial participants.

Myocarditis after the administration of tozinameran, particularly in adolescents and young adults, occurs at a rate of 35 per 1,000,000 doses in patients aged 16 to 17 years, and 20.6 per 1,000,000 doses in patients aged 18 to 24 years. According to Israeli data, a crude rate after the first dose is estimated at 5 per 1,000,000 doses, and after the second dose, at 24 per 1,000,000 doses; largely in men aged 16 to 19 years.Evidence 14Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from small sample size and indirectness. Myocarditis and Pericarditis Following COVID-19 mRNA Vaccines. Public Health Ontario statement. June 18, 2021. Data suggest that this is self-limiting in most cases and does not have long-term sequelae. The rate among recipients of tozinameran is lower than that among elasomeran recipients.

7. Shipping and storage: As multiple formulations of tozinameran are authorized for use in Canada, including some multiple-dose vials that require dilution prior to injection and some that do not, consulting the safety data sheet and the shipping and handling guidance available at comirnaty.ca is recommended.

Elasomeran (Moderna) Vaccine

Elasomeran (marketed by Moderna as Spikevax, known in developmental stages as mRNA-1273 vaccine) contains mRNA encoding for the SARS-CoV-2 spike glycoprotein encapsulated in lipid nanoparticles.

1. Indications: Elasomeran is approved for use for the prevention of COVID-19 in patients aged ≥6 months. A bivalent version of the vaccine is approved for use as a booster dose for the prevention of COVID-19 in patients aged ≥18 years. The bivalent formulation contains mRNA encoding the spike glycoproteins for both the reference strain and the Omicron BA.1 (B.1.1.529.1) variant.

2. Contraindications: Elasomeran is contraindicated in those with allergy or hypersensitivity to vaccine components. The nonmedicinal ingredients used in elasomeran are 1,2-distearoyl-sn-glycero-3-phosphocholine, acetic acid, cholesterol, lipid SM-102, polyethylene glycol 2000, sodium acetate, sucrose, tromethamine, tromethamine hydrochloride, and water for injection.

3. Special populations:

1) Patients aged 6 months to 29 years: Patients in this age range should be preferentially offered tozinameran over elasomeran to mitigate the potential risk of myocarditis/pericarditis with elasomeran. Booster doses of elasomeran are only authorized for use in patients aged ≥18 years.

3) Pregnant patients: Data from the Vaccine Adverse Event Reporting System as well as from a systematic review of maternal and fetal outcomes following SARS-CoV-2 vaccination have not shown any obvious safety signals among patients who have received an mRNA vaccine.Evidence 15Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Shimabukuro TT, Kim SY, Myers TR, et al; CDC v-safe COVID-19 Pregnancy Registry Team. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med. 2021 Jun 17;384(24):2273-2282. doi: 10.1056/NEJMoa2104983. Epub 2021 Apr 21. PMID: 33882218; PMCID: PMC8117969.Evidence 16Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness).De Rose DU, Salvatori G, Dotta A, Auriti C. SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes. Viruses. 2022 Mar 5;14(3):539. doi: 10.3390/v14030539. PMID: 35336947; PMCID: PMC8951373.

4) Breastfeeding patients: Data from a systematic review of maternal and fetal outcomes following SARS-CoV-2 vaccination have not shown any obvious safety signals among patients who have received an mRNA vaccine.Evidence 17Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). De Rose DU, Salvatori G, Dotta A, Auriti C. SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes. Viruses. 2022 Mar 5;14(3):539. doi: 10.3390/v14030539. PMID: 35336947; PMCID: PMC8951373. The SOGC has issued a statement that breastfeeding individuals should be offered any Health Canada–approved SARS-CoV-2 vaccination at any time provided there are no contraindications to vaccination.

5) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune deficiency may have a diminished serologic response to vaccination, and should receive a 3-dose primary vaccines series (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged ≥18 years: Elasomeran 100 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0 and 28. Due to evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. Subsequent booster doses of elasomeran are recommended 6 months after completion of the primary series (see “Recommendations for subsequent booster doses following completion of a primary series” in General Considerations above).

A reduced dose of elasomeran 50 microg is recommended for univalent booster doses in patients aged 30 to 69 years, while an elasomeran dose of 100 microg is recommended for univalent booster doses in patients aged ≥70 years. If a patient is receiving a bivalent elasomeran booster, the only dose available is 50 microg. Tozinameran is preferred over elasomeran for completion of the primary series in patients aged 18 to 29 years due to lower rates of myocarditis in this age group. A notable exception is based on fall 2022 guidance: the NACI is recommending the use of elasomeran bivalent booster doses over tozinameran in eligible patients aged 18 to 29 years.

2) Primary series, persons aged 12 to 18 years: Elasomeran 100 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0 and 28. Due to evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. Booster doses of elasomeran are not currently authorized in this population and are considered off-label use; those potentially eligible for booster doses in this age group should be offered tozinameran.

3) Primary series, persons aged 6 to 11 years: Elasomeran 50 microg is given as a 0.25-mL IM injection of the 0.20 mg/mL concentration or as a 0.5-mL IM injection of the 0.10 mg/mL concentration in the deltoid muscle on days 0 and 28. Due to evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. Booster doses are not currently authorized or recommended in this population.

4) Primary series, persons aged 6 months to 5 years: Elasomeran 25 microg is given as a 0.25-mL IM injection in the deltoid muscle on days 0 and 28. Booster doses are not currently authorized or recommended in this population.

5) Primary series, immunocompromised patients: For patients aged ≥12 years with moderate or severe immune deficiency, elasomeran 100 microg is given after dilution as a 0.5-mL IM injection in the deltoid muscle on days 0, 28, and 56. Tozinameran is preferred over elasomeran for patients aged 18 to 29 years due to lower rates of myocarditis in this age group.

6) Missed doses: There is no information available with respect to missed doses and their effect on immune response. According to the NACI, if a second dose is administered between days 21 and 28, it is considered within the recommended dosing schedule. If >28 days have elapsed since the first dose, the second dose should be administered at the earliest convenience; in such a case, the primary series does not need to be repeated.

7) Vaccine interchangeability: The NACI recommends that individuals who received a first dose of elasomeran should be offered elasomeran for their second dose. If elasomeran is not readily available or the product used for the first dose is unknown, tozinameran is considered interchangeable and should be used to complete the vaccination series. The same principle applies to booster doses, where eligible.

5. Vaccine efficacy:

1) Short-term efficacy: Elasomeran was 94.5% effective (95% CI, 86.5-97.8) at preventing SARS-CoV-2 infection ≥14 days after the second dose (in participants without clinical or microbiologic evidence of infection at baseline).Evidence 18Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020 Dec 30:NEJMoa2035389. doi: 10.1056/NEJMoa2035389. Epub ahead of print. PMID: 33378609; PMCID: PMC7787219. Vaccine efficacy was consistent across age, sex, race, and ethnicity demographics.

Adolescents: In phase II/III trial of adolescents aged 12 to 17 years, elasomeran was 93.3% effective (95% CI, 47.9-99.9) at preventing SARS-CoV-2 infection >14 days after administration of the second dose.Evidence 19Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from small sample size and indirectness. Ali K, Berman G, Zhou H, et al. Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents. N Engl J Med. 2021 Dec 9;385(24):2241-2251. doi: 10.1056/NEJMoa2109522. Epub 2021 Aug 11. PMID: 34379915; PMCID: PMC8385554.

Children: In a randomized controlled trial of 4016 children aged 6 to 11 years, elasomeran was 88.0% effective (95% CI, 70.0-95.8) at preventing SARS-CoV-2 infection ≥14 days after administration of the first dose.Evidence 20Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from small sample size and indirectness. Creech CB, Anderson E, Berthaud V, et al; KidCOVE Study Group. Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age. N Engl J Med. 2022 May 26;386(21):2011-2023. doi: 10.1056/NEJMoa2203315. Epub 2022 May 11. PMID: 35544369; PMCID: PMC9127699. An estimate of vaccine efficacy after the second dose was not able to be performed due to small event rates and short follow-up. Immunobridging noninferiority criteria were met for patients aged 6 months to 5 years according to Health Canada regulatory filings; however, these data have yet to be published.

Booster dose: In an interim analysis of 814 patients, neutralizing antibody responses against the Omicron VOC were superior when participants were vaccinated with a bivalent elasomeran booster dose compared with a univalent elasomeran booster dose, with a geometric mean titer ratio of 1.75 (97.5% CI, 1.49-2.04).Evidence 21Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from small sample size and indirectness.Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, McGhee N, Tomassini JE, Chen X, Chang Y, Sutherland A, Montefiori DC, Girard B, Edwards DK, Feng J, Zhou H, Baden LR, Miller JM, Das R. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. N Engl J Med. 2022 Sep 16. doi: 10.1056/NEJMoa2208343. Epub ahead of print. PMID: 36112399.

2) Long-term efficacy: There is no current information regarding the durability of long-term efficacy or safety in individuals who have received the vaccine. This information is legally required to be collected and reported as part of postauthorization monitoring.

3) Role in preventing transmission: Elasomeran trial data showed lower viral shedding in vaccine recipients compared with those who received placebo, a surrogate measure for transmissibility.

4) Efficacy against SARS-CoV-2 VOCs: In a test-negative case-control study from England, vaccine efficacy of elasomeran against symptomatic disease caused by the Omicron VOC was analyzed. Vaccine efficacy was 75.1% at 2 to 4 weeks after the second dose (95% CI, 70.8-78.7) among patients with the Omicron VOC, declining to 14.9% after ≥25 weeks (95% CI, 3.9-24.7), and increasing to 66.3% 2-4 weeks after administration of a third dose of elasomeran (95% CI, 63.7-68.8).Evidence 22Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Andrews N, Stowe J, Kirsebom F, et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N Engl J Med. 2022 Mar 2:NEJMoa2119451. doi: 10.1056/NEJMoa2119451. Epub ahead of print. PMID: 35249272; PMCID: PMC8908811.

6. Adverse events: Adverse events stratified by dose and reported in the phase III clinical trial of elasomeran: Table 10.7-3.

Adverse events were more common after the second dose of the vaccine. Most serious adverse events were reported by <2% of the clinical trial participants. In study participants ≥65 years of age, serious adverse events with an incidence ≥2% occurred exclusively after administration of the second dose of vaccine.

Multiple jurisdictions have reported cases of myocarditis after the administration of elasomeran, occurring at a rate of 35 per 1,000,000 doses in patients aged 16 to 17 years, and 20.6 per 1,000,000 doses in patients aged 18 to 24 years. According to Israeli data, a crude rate after the first dose is estimated at 5 per 1,000,000 doses, and after the second dose, at 24 per 1,000,000 doses; largely in men aged 16 to 19 years.Evidence 23Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from small sample size and indirectness. Myocarditis and Pericarditis Following COVID-19 mRNA Vaccines. Public Health Ontario statement. June 18, 2021. Data suggest that this disease is self-limiting in most cases and does not have long-term sequelae. The rate among recipients of elasomeran is higher than that among tozinameran recipients.

7. Shipping and storage: As multiple formulations of elasomeran are authorized for use in Canada, consulting the safety data sheet and up-to-date shipping and handling guidance at modernacovid19global.com is recommended.

AZD1222 ChAdOx1-S (Oxford-AstraZeneca) Vaccines

The AZD1222 ChAdOx1-S vaccine (marketed by AstraZeneca as Vaxzevria) consists of a recombinant, replication-deficient chimpanzee adenovirus encoding for the SARS-CoV-2 spike glycoprotein. Each vaccine dose contains 5 × 1010 viral particles.

1. Indications: The AZD1222 vaccine is recommended for the prevention of SARS-CoV-2 infection in patients aged ≥18 years.

While the vaccine has been approved for patients aged >18 years, the NACI recommends using an mRNA vaccine to complete the primary series, unless mRNA vaccines are contraindicated or unavailable, because of the risk of VITT with AZD1222. For recommendations with respect to the interchangeability of SARS-CoV-2 vaccines marketed by different manufacturers, see "Immunization schedule" below.

2. Contraindications: The AZD1222 vaccine is contraindicated in those with allergy or hypersensitivity to vaccine components. The nonmedicinal ingredients used in the AZD1222 vaccine are ethanol, EDTA, L-histidine, L-histidine hydrochloride monohydrate, magnesium chloride hexahydrate, polysorbate 80, sodium chloride, sucrose, and water for injection.

3. Special populations:

1) Children aged <18 years: The safety and efficacy of the AZD1222 vaccine has not yet been established in this population.

2) Pregnant patients: The SOGC has issued a statement that pregnant individuals should be offered a Health Canada–approved SARS-CoV-2 vaccination at any time during pregnancy provided there are no contraindications to vaccination. mRNA vaccines are strongly preferred over AZD1222 by the NACI.

3) Breastfeeding patients: The SOGC has issued a statement that breastfeeding individuals should be offered a Health Canada–approved SARS-CoV-2 vaccination at any time provided there are no contraindications to vaccination. mRNA vaccines are strongly preferred over AZD1222 by the NACI.

4) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate to severe immune deficiency may have a diminished serologic response to vaccination, and should receive a 3-dose primary vaccine series (see “Immunization schedule” below). mRNA vaccines are strongly preferred over AZD1222 for immunocompromised patients, unless contraindications or lack of availability preclude their use; patients should be offered AZD1222 only when all other eligible vaccines are unavailable or contraindicated.

4. Immunization schedule:

1) Primary series, persons aged ≥18 years: The AZD1222 vaccine is given as a 0.5-mL IM injection in the deltoid muscle, with the first dose given on day 0, and the second dose given between days 28 and 84, with the NACI recommending the second dose between days 56 and 84. In patients who had a longer interval (≥12 weeks) between doses, vaccine efficacy was 81.3% (95% CI, 60.3-91.2), compared with those with a short interval between doses (<6 weeks), in whom vaccine efficacy was 55.1% (95% CI, 33.0-69.9).Evidence 24Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from low indirectness (lack of follow-up), inconsistency (dosing error), and imprecision (small proportion of patients ≥65 years of age, a clinically relevant demographic). Voysey M, Costa Clemens SA, Madhi SA, et al; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021 Feb 19:S0140-6736(21)00432-3. doi: 10.1016/S0140-6736(21)00432-3. Epub ahead of print. PMID: 33617777; PMCID: PMC7894131. The NACI recommends a booster dose using an approved mRNA vaccine 6 months after completion of the primary series in those at high or increased risk (see "Recommendations for subsequent booster doses following completion of a primary series” in General Considerations above).

2) Primary series, immunocompromised patients: For patients aged ≥18 years with moderate or severe immune deficiency, tozinameran or elasomeran mRNA vaccines are strongly preferred, unless mRNA vaccines are contraindicated or unavailable. Tozinameran is preferred over elasomeran for patients aged 18 to 29 years due to lower rates of myocarditis in this age group. Immunocompromised patients who begin their primary series with AZD1222 should receive 2 doses of the AZD1222 vaccine given as a 0.5-mL IM injection in the deltoid muscle on days 0 and 28, followed by a third dose of an mRNA vaccine at the recommended dosage for the patient’s age on day 56.

3) Missed doses: There is no information available with respect to missed doses and their effect on immune response. The NACI has not yet made recommendations with respect to missed doses as of the date of the last update of this chapter.

4) Vaccine interchangeability: AZD1222 is not recommended to begin or complete a primary SARS-CoV-2 vaccination series unless the patient has contraindications or mRNA vaccine supplies are limited. Due to emerging data on favorable reactogenicity and in order to mitigate the risk of VITT associated with viral vector vaccines, the NACI currently recommends that patients who have received a first dose of AZD1222 receive either tozinameran or elasomeran to complete their vaccine series.

5. Vaccine efficacy:

1) Short-term efficacy: Participants in the pooled efficacy analysis for AZD1222 either received 2 standard doses (5 × 1010 viral particles per dose), or 1 reduced dose (2.2 × 1010 viral particles per dose) followed by 1 standard dose. The reduced dose/standard dose regimen was the result of a difference in concentration determination in one of the studies. Of those trial participants who received 2 standard doses, the AZD1222 vaccine was 62.1% effective (95% CI, 39.96-76.08) at preventing symptomatic, PCR-confirmed SARS-CoV-2 infection ≥15 days after the second dose.Evidence 25Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from low indirectness (lack of follow-up), inconsistency (dosing error), and imprecision (small proportion of patients ≥65 years of age, a clinically relevant demographic). Voysey M, Clemens SAC, Madhi SA, et al; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8. Erratum in: Lancet. 2021 Jan 9;397(10269):98. PMID: 33306989; PMCID: PMC7723445. There were no hospitalizations for COVID-19 (data cutoff December 7, 2020) in participants ≥15 days after receipt of the second dose.Evidence 26Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from low indirectness (lack of follow-up), inconsistency (dosing error), and imprecision (small proportion of patients ≥65 years of age, a clinically relevant demographic). Voysey M, Clemens SAC, Madhi SA, et al; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8. Erratum in: Lancet. 2021 Jan 9;397(10269):98. PMID: 33306989; PMCID: PMC7723445. Short-term efficacy data should be interpreted with caution for AZD1222, as the trial population used for vaccine efficacy calculation excluded 51% of participants; an unexpected significant difference in vaccine efficacy was found between the participants who received the reduced dose/standard dose (90.0%; 95% CI, 67.4-97.0) versus those who received 2 standard doses; there was wide variability in dosing interval between study participants; and only 9.7% of clinical trial participants were ≥65 years of age.

2) Long-term efficacy: There is no current information regarding the durability of long-term efficacy or safety in individuals who have received the vaccine. This information is legally required to be collected and reported as part of postauthorization monitoring.

3) Role in preventing transmission: Two standard AZD1222 doses reduce SARS-CoV-2 PCR positivity rates in the nasopharynx by 54.1% (95% CI, 44.7-69.1).Evidence 27Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the risk of bias from low indirectness (lack of follow-up), inconsistency (dosing error), and imprecision (small proportion of patients ≥65 years of age, a clinically relevant demographic). Voysey M, Costa Clemens SA, Madhi SA, et al; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021 Feb 19:S0140-6736(21)00432-3. doi: 10.1016/S0140-6736(21)00432-3. Epub ahead of print. PMID: 33617777; PMCID: PMC7894131.

4) Efficacy against SARS-CoV-2 VOCs: In a test-negative case-control study from England, vaccine efficacy of AZD1222 against symptomatic disease caused by the Omicron VOCs was analyzed. The primary series of AZD1222 was ineffective at preventing symptomatic disease at 20 to 24 weeks from the second dose.Evidence 28Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Andrews N, Stowe J, Kirsebom F, et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N Engl J Med. 2022 Mar 2:NEJMoa2119451. doi: 10.1056/NEJMoa2119451. Epub ahead of print. PMID: 35249272; PMCID: PMC8908811. AZD1222 was not effective (vaccine efficacy 46.7%) at preventing symptomatic disease at 5 to 9 weeks after administration of a third dose (95% CI, 34.2-56.7).Evidence 29Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Andrews N, Stowe J, Kirsebom F, et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N Engl J Med. 2022 Mar 2:NEJMoa2119451. doi: 10.1056/NEJMoa2119451. Epub ahead of print. PMID: 35249272; PMCID: PMC8908811.

6. Adverse events: Adverse events stratified by dose and reported in the phase III clinical trial of the AZD1222 vaccine: Table 10.7-4.

Adverse events were more common after the first dose of the vaccine. Serious adverse events were reported by 0.7% of the clinical trial participants who received AZD1222. Two serious adverse events may have been related to AZD1222: pyrexia (n = 1), occurring 2 days after dose 1, and transverse myelitis (n = 1), occurring 14 days after dose 2.

VITT is projected to occur at a rate between 1 per 26,000 and 1 per 100,000 AZD1222 vaccinations.

7. Shipping and storage:

1) Shipping: The AZD1222 vaccine should be maintained at temperatures between 2 and 8 degrees Celsius during shipping and should not be frozen. It is shipped in multiple-dose vials.

2) Storage: The AZD1222 vaccine should not be stored frozen. Multiple-dose vials may be stored between 2 and 8 degrees Celsius. During refrigerated storage, unopened vials should be protected from light. Opened vials may be maintained at room temperature (max allowable temperature, 30 degrees Celsius) for up to 6 hours. Vials may be refrigerated (2-8 degrees Celsius) after opening for a maximum of 48 hours. If an opened vial is maintained at room temperature for a cumulative time of >6 hours or at refrigeration temperature for a cumulative time of >48 hours, it should be discarded.

Ad26.COV2.S (Johnson & Johnson/Janssen) Vaccine

The Ad26.COV2.S vaccine (marketed by Johnson & Johnson/Janssen Inc. as Jcovden) consists of a recombinant, replication-deficient adenovirus type 26 encoding for the SARS-CoV-2 spike glycoprotein in a stabilized conformation. The vaccine is produced in the PER.C6 TetR cell line. Each vaccine dose contains 5 × 1010 viral particles.

1. Indications: The Ad26.COV2.S vaccine is recommended for the prevention of SARS-CoV-2 infection in patients aged ≥18 years.

While the vaccine has been approved for patients aged ≥18 years, currently the NACI recommends using an mRNA vaccine for the primary vaccine series, unless mRNA vaccines are contraindicated or unavailable, because of the risk of VITT with Ad26.COV2.S. For recommendations with respect to the interchangeability of SARS-CoV-2 vaccines marketed by different manufacturers, see “Immunization schedule” below.

2. Contraindications: The Ad26.COV2.S vaccine is contraindicated in those with allergy or hypersensitivity to vaccine components. The nonmedicinal ingredients used in the Ad26.COV2.S vaccine are 2-hydroxypropyl-beta-cyclodextrin, citric acid monohydrate, ethanol, hydrochloric acid, polysorbate 80, sodium chloride, sodium hydroxide, trisodium citrate dihydrate, and water for injection.

3. Special populations:

1) Children aged <18 years: The safety and efficacy of the Ad26.COV2.S vaccine has not yet been established in this population.

2) Pregnant patients: The SOGC has issued a statement that pregnant individuals should be offered any Health Canada–approved SARS-CoV-2 vaccination at any time during pregnancy provided there are no contraindications to vaccination. mRNA vaccines are strongly preferred over Ad26.COV2.S by the NACI.

3) Breastfeeding patients: The SOGC has issued a statement that breastfeeding individuals should be offered any Health Canada–approved SARS-CoV-2 vaccination at any time provided there are no contraindications to vaccination. mRNA vaccines are strongly preferred over Ad26.COV2.S by the NACI.

4) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune deficiency may have a diminished serologic response to vaccination. Two populations of immunosuppressed patients were included in the phase III clinical trial of Ad26.COV2.S: those on chronic, low-dose immunosuppression (≤20 mg prednisone equivalent) and those with stable HIV infection.

Immunocompromised patients who receive an Ad26.COV2.S vaccine primary series are strongly recommended to receive a second dose of an mRNA vaccine. mRNA vaccines are strongly preferred over Ad26.COV2.S for immunocompromised patients, unless contraindications or lack of availability preclude their use.

4. Immunization schedule:

1) Primary series, persons aged ≥18 years: The Ad26.COV2.S vaccine is given as a single 0.5-mL IM injection in the deltoid muscle on day 0. The NACI recommends consideration of a second dose using an approved mRNA vaccine 6 months after completion of the primary Ad26.COV2.S vaccine series. The Ad26.COV2.S vaccine does not require reconstitution or dilution prior to administration.

2) Primary series, immunocompromised patients: For patients aged ≥18 years with moderate or severe immune deficiency, tozinameran or elasomeran mRNA vaccines are strongly preferred, unless mRNA vaccines are contraindicated or unavailable. Tozinameran is preferred over elasomeran for patients aged 18 to 29 years due to lower rates of myocarditis in this age group. Immunocompromised patients who received a dose of Ad26.COV2.S vaccine given as a single 0.5-mL IM injection in the deltoid muscle on day 0 should receive an additional dose of an mRNA vaccine at the recommended dosage for the patient’s age on day 28.

5. Vaccine efficacy:

1) Short-term efficacy: The Ad26.COV2.S vaccine was 66.9% effective (95% CI, 59.0-73.4) at preventing moderate to severe/critical COVID-19 ≥14 days after vaccination and 66.1% effective (95% CI, 55.0-74.8) at preventing moderate to severe/critical COVID-19 ≥28 days after vaccination. When stratified by severe and critical COVID-19 cases only, Ad26.COV2.S was 76.7% effective (95% CI, 54.6-89.1) at preventing such cases ≥14 days from vaccination and 85.4% effective (95% CI, 54.2-96.9) at preventing such cases ≥28 days from vaccination. There were no hospitalizations for COVID-19 in vaccinated trial participants in whom SARS-CoV-2 was detected ≥28 days after vaccination. There were no COVID-19–related deaths in trial participants who received the Ad26.COV2.S vaccine.Evidence 30Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Sadoff J, Gray G, Vandebosch A, et al; ENSEMBLE Study Group. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N Engl J Med. 2021 Apr 21. doi: 10.1056/NEJMoa2101544. Epub ahead of print. PMID: 33882225.

2) Long-term efficacy: There is no current information regarding the durability of long-term efficacy or safety in individuals who have received the vaccine. This information is legally required to be collected and reported as part of postauthorization monitoring.

3) Role in preventing transmission: Data are currently insufficient to draw conclusions as to whether individuals vaccinated with the Ad26.COV2.S vaccine are less likely to transmit SARS-CoV-2.

4) Efficacy against SARS-CoV-2 VOCs: Ad26.COV2.S human serum neutralization assays against the Omicron VOC demonstrate no activity.Evidence 31Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to indirectness (surrogate measure of vaccine efficacy).  Cameroni E, Bowen JE, Rosen LE, et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature. 2022 Feb;602(7898):664-670. doi: 10.1038/s41586-021-04386-2. Epub 2021 Dec 23. PMID: 35016195.

6. Adverse events: Adverse events stratified by dose and reported in the phase III clinical trial of the Ad26.COV2.S vaccine: Table 10.7-5.

Thirteen percent of trial participants receiving Ad26.COV2.S had an unsolicited adverse event, the majority of which were low-grade reactogenicity events. Serious adverse events were reported by 0.4% of the clinical trial participants who received Ad26.COV2.S. Three serious adverse events were considered related to Ad26.COV2.S: fever, headache, and asthenia (n = 1); severe injection site pain nonresponsive to analgesics with symptoms ongoing at 10 weeks (n = 1); and type IV hypersensitivity reaction progressing to lip angioedema and resolving within 5 weeks (n = 1).

VITT incidence is projected to occur at a rate of 1 per 500,000 Ad26.COV2.S vaccinations.

7. Shipping and storage:

1) Shipping: The Ad26.COV2.S vaccine should be maintained at temperatures between 2 and 8 degrees Celsius during shipping and should not be frozen. It is shipped in multiple-dose vials.

2) Storage: The Ad26.COV2.S vaccine should not be stored frozen. Multiple-dose vials may be stored between 2 and 8 degrees Celsius. During refrigerated storage, unopened vials should be protected from light. Unopened vials may be maintained at room temperature (max allowable temperature, 25 degrees Celsius) for up to 12 hours. Once opened, vials may be kept refrigerated (2-8 degrees Celsius) for up to 6 hours or at room temperature (max allowable temperature, 25 degrees Celsius) for up to 3 hours. If an opened vial is maintained at room temperature for a cumulative time of >3 hours or at refrigeration temperature for a cumulative time of >6 hours, it should be discarded.

NVX-CoV2373 (Novavax) Vaccine

The NVX-CoV2373 vaccine (marketed by Novavax as Nuvaxovid) consists of recombinant SARS-CoV-2 spike glycoproteins stabilized in prefusion conformation and assembled onto lipid nanoparticles, together with a Quillaja saponaria saponin-based adjuvant. Prior to assembly onto lipid nanoparticles, the recombinant proteins are produced by infection of an engineered baculovirus into moth cell culture.

1. Indications: NVX-CoV2373 is approved for use for the prevention of COVID-19 in patients aged ≥18 years.

2. Contraindications: The NVX-CoV2373 vaccine is contraindicated in those with allergy or hypersensitivity to vaccine components. The nonmedicinal ingredients used in the NVX-CoV2373 vaccine are disodium hydrogen phosphate heptahydrate, polysorbate 80, sodium chloride, sodium dihydrogen phosphate monohydrate, cholesterol, disodium hydrogen phosphate dihydrate, phosphatidylcholine, potassium chloride, and potassium dihydrogen phosphate. Hydrochloric acid and sodium hydroxide are used for pH adjustment during the manufacturing process.

3. Special populations:

1) Children aged <18 years: The safety and efficacy of the NVX-CoV2373 vaccine has not yet been established in this population.

2) Pregnant patients: The SOGC has issued a statement that pregnant individuals should be offered a Health Canada–approved SARS-CoV-2 vaccination at any time during pregnancy provided there are no contraindications to vaccination.

3) Breastfeeding patients: The SOGC has issued a statement that breastfeeding individuals should be offered a Health Canada–approved SARS-CoV-2 vaccination at any time provided there are no contraindications to vaccination.

4) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune compromise may have a diminished serologic response to vaccination and should receive a 3-dose primary vaccines series (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged ≥18 years: NVX-CoV2373 5 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0 and 21. Due to evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. Booster doses of NVX-CoV2373 are not currently authorized by Health Canada in this population and are considered off-label use; however, booster doses have been studied in randomized trials. In patients with contraindications or who are unwilling to receive mRNA vaccines as booster doses, NVX-CoV2373 may be offered ≥6 months after completion of the primary series.

2) Primary series, immunocompromised patients: NVX-CoV2373 is not currently authorized by Health Canada in immunocompromised patients for use as a primary series. The use of NVX-CoV2373 is considered off-label in this population and may be offered to immunocompromised patients with contraindications or who are unwilling to receive mRNA vaccines. In such cases, NVX-CoV2373 5 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0, 21, and 49.

5. Vaccine efficacy:

1) Short-term efficacy: NVX-2373 has been assessed in 2 phase III randomized controlled trials. In one study of 29,949 patients in the United States and Mexico, which occurred mostly during circulation of the Alpha VOC, NVX-CoV2373 was 90.4% (95% CI, 82.9-94.6) effective against PCR-confirmed SARS-CoV-2 infection ≥7 days after the second dose.Evidence 32Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Dunkle LM, Kotloff KL, Gay CL, et al; 2019nCoV-301 Study Group. Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico. N Engl J Med. 2022 Feb 10;386(6):531-543. doi: 10.1056/NEJMoa2116185. Epub 2021 Dec 15. PMID: 34910859; PMCID: PMC8693692. Vaccine efficacy against moderate to severe COVID-19 was 100% (95% CI, 87.0-100); the event rates for this outcome were low in both arms.Evidence 33Low Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness) and low event rate (imprecision). Dunkle LM, Kotloff KL, Gay CL, et al; 2019nCoV-301 Study Group. Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico. N Engl J Med. 2022 Feb 10;386(6):531-543. doi: 10.1056/NEJMoa2116185. Epub 2021 Dec 15. PMID: 34910859; PMCID: PMC8693692. In a phase III study of 15,187 patients in the United Kingdom, NVX-CoV2373 was 89.7% (95% CI, 80.2-94.6) effective in the per-protocol population against the occurrence of PCR-confirmed, symptomatic mild, moderate, or severe COVID-19 ≥7 days after the second dose.Evidence 34Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Heath PT, Galiza EP, Baxter DN, et al; 2019nCoV-302 Study Group. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N Engl J Med. 2021 Sep 23;385(13):1172-1183. doi: 10.1056/NEJMoa2107659. Epub 2021 Jun 30. PMID: 34192426; PMCID: PMC8262625.

2) Long-term efficacy: There is no current information regarding the durability of long-term efficacy or safety in individuals who have received the vaccine. This information is legally required to be collected and reported as part of postauthorization monitoring.

3) Role in preventing transmission: Data are currently insufficient to draw conclusions as to whether individuals vaccinated with the NVX-CoV2373 vaccine are less likely to transmit SARS-CoV-2.

4) Efficacy against SARS-CoV-2 VOCs: Serum neutralization of the Omicron BA.1 and BA.4 VOC sublineages has been successfully demonstrated in patients receiving 2-dose or 3-dose schedules of NVX-CoV2373 in a non–peer reviewed study.Evidence 35Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to indirectness (surrogate measure of vaccine efficacy).Bhiman JN, Richardson SI, Lambson BE, et al. Novavax NVX-COV2373 triggers potent neutralization of Omicron sub-lineages. bioRxiv. 2022:2022.07.14.500148. doi: 10.1101/2022.07.14.500148.

6. Adverse events: Adverse events stratified by dose and reported in phase III clinical trials of the NVX-CoV2373 vaccine: Table 10.7-6.

The majority of local and systemic adverse events in both clinical trials were mild to moderate and self-limited. Adverse events were more common after the second dose of the vaccine.

7. Shipping and storage:

 1) Shipping: The NVX-CoV2373 vaccine should be maintained at temperatures between 2 and 8 degrees Celsius during shipping and should not be frozen. It is shipped in multiple-dose vials.

2) Storage: The NVX-CoV2373 vaccine should not be stored frozen. Multiple-dose vials may be stored between 2 and 8 degrees Celsius. During refrigerated storage, unopened vials should be protected from light. Once opened, vials may be kept for up to 6 hours between 2 and 25 degrees Celsius.

CoVLP (Medicago) Vaccine

The CoVLP vaccine (marketed by Medicago as Covifenz) is an adjuvanted vaccine containing noninfectious SARS-CoV-2 VLPs consisting of SARS-CoV-2 spike glycoproteins stabilized in prefusion conformation and embedded in a lipid envelope. VLPs are produced by delivering the genetic sequence into nontransgenic Nicotiana benthamiana plants via a bacterial vector using agroinfiltration.

1. Indications: CoVLP is approved for use for the prevention of COVID-19 in patients aged 18 to 64 years.

2. Contraindications: The CoVLP vaccine is contraindicated in those with allergy or hypersensitivity to vaccine components. The nonmedicinal ingredients used in the CoVLP vaccine are DL-alpha-tocopherol, squalene, polysorbate 80, phosphate buffered saline, potassium phosphate monobasic anhydrous, sodium chloride, sodium phosphate dibasic anhydrous, and water for injection. The vaccine may contain trace amounts of polyethylene glycol, kanamycin, and carbenicillin.

3. Special populations:

1) Children aged <18 years: The safety and efficacy of the CoVLP vaccine has not yet been established in this population.

2) Adults aged ≥65 years: The safety and efficacy of the CoVLP vaccine has not yet been established in this population.

3) Pregnant patients: The SOGC has issued a statement that pregnant individuals should be offered a Health Canada–approved SARS-CoV-2 vaccination at any time during pregnancy provided there are no contraindications to vaccination.

4) Breastfeeding patients: The SOGC has issued a statement that breastfeeding individuals should be offered a Health Canada–approved SARS-CoV-2 vaccination at any time provided there are no contraindications to vaccination.

5) Immunocompromised patients: Patients on immunosuppressive medications or those with moderate or severe immune compromise may have a diminished serologic response to vaccination, and should receive a 3-dose primary vaccines series (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged 18 to 64 years: CoVLP 3.75 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0 and 21. 0.25 mL of antigen suspension and 0.25 mL of AS03 adjuvant suspension must be mixed immediately prior to injection in a 1:1 ratio to achieve the final 0.5-mL dose formulation. Due to evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. Booster doses of CoVLP are not currently authorized by Health Canada in this population and are not recommended by the NACI at this time.

2) Primary series, immunocompromised patients: CoVLP is not currently authorized by Health Canada in immunocompromised patients for use as a primary series. The use of CoVLP is considered off-label in this population and may be offered to immunocompromised patients with contraindications or who are unwilling to receive mRNA vaccines. In this population, CoVLP 3.75 microg is given as a 0.5-mL IM injection in the deltoid muscle on days 0, 21, and 49. 0.25 mL of antigen suspension and 0.25 mL of AS03 adjuvant suspension must be mixed immediately prior to injection in a 1:1 ratio to achieve the final 0.5-mL dose formulation.

5. Vaccine efficacy:

1) Short-term efficacy: The CoVLP vaccine was 69.5% effective (95% CI, 56.7-78.8) in the intention-to-treat population at preventing symptomatic COVID-19 ≥7 days after the second dose of vaccination.Evidence 36Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness). Hager KJ, Pérez Marc G, Gobeil P, et al; CoVLP Study Team. Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine. N Engl J Med. 2022 Jun 2;386(22):2084-2096. doi: 10.1056/NEJMoa2201300. Epub 2022 May 4. PMID: 35507508; PMCID: PMC9127773. When stratified by age, the CoVLP vaccine was 68.9% effective (95% CI, 55.0-78.9) at preventing symptomatic COVID-19 ≥7 days after the second vaccine dose in patients aged 18 to 64 years.Evidence 37Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up (indirectness).Hager KJ, Pérez Marc G, Gobeil P, et al; CoVLP Study Team. Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine. N Engl J Med. 2022 Jun 2;386(22):2084-2096. doi: 10.1056/NEJMoa2201300. Epub 2022 May 4. PMID: 35507508; PMCID: PMC9127773. An estimate of vaccine efficacy was unable to be calculated for patients aged ≥65 years in both the intention-to-treat and per-protocol populations, due to low event rates. The majority of infections during the course of the trial were caused by the Gamma and Delta VOCs. No COVID-19–related hospitalizations occurred in the treatment arm, and no COVID-19–related deaths were reported during the trial.

2) Long-term efficacy: There is no current information regarding the durability of long-term efficacy or safety in individuals who have received the vaccine. This information is legally required to be collected and reported as part of postauthorization monitoring.

3) Role in preventing transmission: Data are currently insufficient to draw conclusions as to whether individuals vaccinated with the CoVLP vaccine are less likely to transmit SARS-CoV-2.

4) Efficacy against SARS-CoV-2 VOCs: Data are currently insufficient to draw conclusions as to whether the CoVLP vaccine is effective against the Omicron VOC.

6. Adverse events: Adverse events stratified by dose and reported in phase III clinical trials of the CoVLP vaccine: Table 10.7-7.

Local adverse events were reported in 92.3% of patients overall who received CoVLP vaccine in the clinical trial. Adverse events were typically mild to moderate and self-limiting; 22.7% of patients had an unsolicited adverse event up to 21 days after administration of the second vaccine dose. Two participants reported serious systemic adverse events following the second dose of vaccination, one of whom experienced fever, and the other of whom experienced chills, headache, myalgias, and malaise. Three cases of facial paralysis were reported among patients in the vaccine group; however, data are currently insufficient to determine a causal relationship with vaccination at present.

7. Shipping and storage:

 1) Shipping: The CoVLP vaccine is shipped as separate antigen and AS03 adjuvant vials, which should be maintained at temperatures between 2 and 8 degrees Celsius during shipping and should not be frozen. It is shipped in multiple-dose vials.

2) Storage: The CoVLP vaccine should not be stored frozen. Multiple-dose vials may be stored between 2 and 8 degrees Celsius. During refrigerated storage, unopened vials should be protected from light. Once opened and the components mixed, the vaccine may be kept for up to 6 hours between 20 and 30 degrees Celsius. If refrigerated once mixed, the vaccine must be discarded.

TablesTop

Table 10.7-1. Summary of SARS-CoV-2 vaccines currently approved in Canada

Vaccine type

Population

Primary endpoint

Vaccine efficacy

Hospitalizationsa

Deathsa

Tozinameran (Pfizer-BioNTech)

mRNA

– Age >16 years

– Excluded if prior SARS-CoV-2 infection or if immunocompromised

 

Preventing COVID-19–related death 14-20 days after 1st dose

 

Dose 1: 72% (95% CI, 19-100)

 

 

0

0

Preventing SARS-CoV-2 infection ≥7 days after 2nd dose

 

Dose 2: 95% (95% CI, 90.3-97.6)

Elasomeran (Moderna)

mRNA

– Age >18 years

– Excluded if prior SARS-CoV-2 infection or if pregnant or immunocompromised

 

Preventing SARS-CoV-2 infection ≥14 days after 2nd dose

 

94.5% (95% CI, 86.5-97.8)

0

0

AZD1222 (Oxford-AstraZeneca and COVISHIELD)

Recombinant adenovirus

– Age 18-65 years

– Excluded if prior SARS-CoV-2 infection or if positive NAAT within 14 days of 2nd vaccination

 

Preventing symptomatic SARS-CoV-2 infection 14 days after 2nd dose

 

62.1% (95% CI, 39.96-76.08)

≥21 days after 1st dose: 0

≥21 days after 1st dose: 0

Ad26.COV2.S (Johnson & Johnson)

Recombinant adenovirus

– Age ≥18 years

– Excluded if prior SARS-CoV-2 infection or if pregnant or immunocompromised

Preventing moderate to severe COVID-19

– 14 days: 66.9% (95% CI, 59.0-73.4)

– 28 days: 66.1% (95% CI, 55.0-74.8)

≥28 days post vaccination: 0

≥28 days post vaccination: 0

Preventing severe to critical COVID-19

– 14 days: 76.7% (95% CI, 54.6-89.1)

– 28 days: 85.4% (95% CI, 54.2-96.9)

NVX-CoV2373 (Novavax)

Recombinant protein subunit

United States and Mexico

– Age ≥18 years

– Excluded if prior SARS-CoV-2 infection or immunocompromised

Preventing symptomatic mild, moderate, or severe COVID-19 >7 days from 2nd dose

90.4% (95% CI, 82.9-94.6)

Not reported

All-cause: 9

United Kingdom

– Age 18-84 years

– Excluded if prior SARS-CoV-2 infection, on immunosuppressive medication, or diagnosis of immunocompromising condition

Preventing symptomatic mild, moderate, or severe COVID-19 >7 days from 2nd dose

89.7% (95% CI, 80.2-94.6%)

0

0

CoVLP (Medicago)

Plant-based viral-like particle

– Age ≥18 years

– Excluded if immunosuppressive condition, immunodeficiency, autoimmune disease, significant neuropsychiatric illness

Preventing symptomatic COVID-19 >7 days from second dose

69.5% (95% CI, 56.7-78.8)

0

0

a Outcomes in experimental arm

COVID-19, coronavirus disease 2019; NAAT, nucleic acid amplification test; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Table 10.7-2. Adverse events with administration of tozinameran, stratified by age of clinical trial participants

Adverse events within 7 days of administration; study participants aged 18-55 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

4.5

5.9

Local swelling

5.8

6.3

Pain at injection site

83.1

77.8

Temperature ≥38°C

3.7

15.8

Fatigue

47.4

59.4

Headache

41.9

51.7

Chills

14.0

35.1

Vomiting

1.2

1.9

Diarrhea

11.1

10.4

New or worsened myalgia

21.3

37.3

New or worsened arthralgia

11.0

21.9

Adverse events within 7 days of administration; study participants aged ≥56 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

4.7

7.2

Local swelling

6.5

7.5

Pain at injection site

71.1

66.1

Temperature ≥38°C

1.4

10.9

Fatigue

34.1

50.5

Headache

25.2

39.0

Chills

6.3

22.7

Vomiting

0.5

0.7

Diarrhea

8.2

8.3

New or worsened myalgia

13.9

28.7

New or worsened arthralgia

8.6

18.9

Adapted from N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577 and the Pfizer-BioNTech COVID-19 Vaccine [COVID-19 mRNA Vaccine] Product Monograph.

Table 10.7-3. Adverse events with administration of elasomeran, stratified by age of clinical trial participants

Adverse events within 7 days of administration; study participants aged 18-64 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

3.0

8.9

Local swelling

6.7

12.6

Pain at injection site

86.9

89.9

Axillary tenderness/swelling

11.6

16.2

Fatigue

38.4

67.6

Headache

35.3

62.8

Chills

9.2

48.6

Nausea/vomiting

9.4

21.4

Fever

0.9

17.4

Myalgia

23.7

61.6

Arthralgia

16.6

45.5

Adverse events within 7 days of administration; study participants aged ≥65 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

2.3

7.5

Local swelling

4.4

10.8

Pain at injection site

74.0

83.2

Axillary tenderness/swelling

6.1

8.5

Fatigue

33.3

58.3

Headache

24.5

46.2

Chills

5.4

30.9

Nausea/vomiting

5.2

11.8

Fever

0.3

10.0

Myalgia

19.7

47.1

Arthralgia

16.4

35.0

Adapted from N Engl J Med. 2020 Dec 30. doi: 10.1056/NEJMoa2035389 and Product Monograph: Moderna COVID-19 Vaccine, mRNA-1273 SARS-CoV-2 vaccine.

Table 10.7-3. Adverse events with administration of elasomeran, stratified by age of clinical trial participants

Adverse events within 7 days of administration; study participants aged 18-64 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

3.0

8.9

Local swelling

6.7

12.6

Pain at injection site

86.9

89.9

Axillary tenderness/swelling

11.6

16.2

Fatigue

38.4

67.6

Headache

35.3

62.8

Chills

9.2

48.6

Nausea/vomiting

9.4

21.4

Fever

0.9

17.4

Myalgia

23.7

61.6

Arthralgia

16.6

45.5

Adverse events within 7 days of administration; study participants aged ≥65 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

2.3

7.5

Local swelling

4.4

10.8

Pain at injection site

74.0

83.2

Axillary tenderness/swelling

6.1

8.5

Fatigue

33.3

58.3

Headache

24.5

46.2

Chills

5.4

30.9

Nausea/vomiting

5.2

11.8

Fever

0.3

10.0

Myalgia

19.7

47.1

Arthralgia

16.4

35.0

Adapted from N Engl J Med. 2020 Dec 30. doi: 10.1056/NEJMoa2035389 and Product Monograph: Moderna COVID-19 Vaccine, mRNA-1273 SARS-CoV-2 vaccine.

Table 10.7-4. Adverse events with administration of the AZD1222 vaccine, stratified by age of clinical trial participants

Adverse events within 7 days of administration; study participants aged 18-64 years from COV001, COV002, and COV003 studies

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

2.6

1.1

Local swelling

2.9

0.9

Pain at injection site

60.3

34.4

Local pruritus

6.5

4.2

Fatigue

64.6

43.0

Headache

61.1

38.3

Chills

37.2

6.5

Nausea

23.9

9.7

Fever

11.6

0.7

Myalgia

52.3

25.6

Arthralgia

28.0

11.6

Adverse events within 7 days of administration; study participants aged ≥65 years from COV001, COV002, and COV003 studies

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

2.3

0.4

Local swelling

2.0

0.8

Pain at injection site

22.8

10.2

Local pruritus

3.5

2.3

Fatigue

40.9

27.0

Headache

31.8

19.9

Chills

10.8

2.0

Nausea

8.0

5.5

Fever

1.0

0.0

Myalgia

22.6

13.7

Arthralgia

13.0

7.4

Adapted from Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1 and Product Monograph: AstraZeneca COVID-19 Vaccine, ChAdOx1-S [recombinant].

Table 10.7-5. Adverse events with administration of the Ad26.COV2.S vaccine versus placebo, stratified by age of clinical trial participants

Adverse events within 7 days of administration; study participants aged 18-59 years

Adverse event reported

Percentage (%)

Local erythema

9.0

Local swelling

7.0

Pain at injection site

58.6

Fatigue

43.8

Headache

44.4

Nausea

15.5

Fever

12.8

Myalgia

39.1

Adverse events within 7 days of administration; study participants aged ≥60 years

Adverse event reported

Percentage (%)

Local erythema

4.6

Local swelling

2.7

Pain at injection site

33.3

Fatigue

29.7

Headache

30.4

Nausea

12.3

Fever

3.1

Myalgia

24.0

Adapted from Product Monograph including Patient Medication Information: Janssen COVID-19 Vaccine: SARS-CoV-2 Vaccine (Ad26.COV2.S, recombinant).

Table 10.7-6. Pooled adverse events with administration of the NVX-CoV2373 vaccine versus placebo, stratified by age of clinical trial participants

Adverse events within 7 days of administration from studies 2019n-501, -301, and -302; study participants aged 18-64 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local tenderness

50.7

69.3

Local erythema

1.0

6.3

Local swelling

0.9

5.8

Pain at injection site

35.2

57.7

Fatigue

24.9

46.8

Headache

25.3

43.4

Nausea or vomiting

6.7

11.3

Fever

0.6

5.7

Myalgia

22.7

46.0

Adverse events within 7 days of administration from studies 2019n-501, -301, and -302; study participants aged ≥65 years

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local tenderness

33.0

54.9

Local erythema

0.8

5.2

Local swelling

0.7

5.7

Pain at injection site

19.3

40.5

Fatigue

16.3

28.6

Headache

15.3

23.6

Nausea or vomiting

3.7

5.1

Fever

0.5

1.9

Myalgia

12.3

26.4

Adapted from Product Monograph including Patient Medication Information: Nuvaxovid COVID-19 Vaccine: SARS-CoV-2 Vaccine (Recombinant protein, Adjuvanted).

Table 10.7-7. Adverse events within 7 days of administration of the CoVLP vaccine versus placebo

Adverse event reported

Dose 1 (%)

Dose 2 (%)

Local erythema

6.8

15.3

Local swelling

18.7

30.0

Pain at injection site

85.0

84.2

Fatigue

36.0

55.1

Headache

39.7

56.2

Chills

13.8

40.9

Fever

1.1

8.6

Malaise

29.0

55.1

Myalgia

42.7

55.0

Arthralgia

15.5

32.9

Axillary swelling

6.4

11.1

Neck swelling

11.5

15.3

Adapted from N Engl J Med. 2022 Jun 2;386(22):2084-2096. doi: 10.1056/NEJMoa2201300.

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