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 July 04, 2022.
Last Updated: March 26, 2022
Last Reviewed: March 26, 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.

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 is 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 will 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 will follow the World Health Organization (WHO) classification based on the Greek alphabet naming system. Five major SARS-CoV-2 VOCs have thus far been identified: Alpha, Beta, Gamma, Delta, and Omicron. 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 due to the vaccine effectively responding to the SARS-CoV-2 antigens. 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. Viral vector vaccines may be offered to patients aged ≥18 years with contraindications to mRNA vaccination or if mRNA vaccines are unavailable. 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 third doses: The NACI recommends that populations with moderate to severe immune deficiency complete a 3-dose mRNA vaccine-based primary series. In this population, if a patient previously received a 1- or 2-dose viral vector vaccine primary series, the third dose of an mRNA vaccine should be offered ≥28 days after the previous dose.

A third dose of an mRNA vaccine should also be recommended to patients ≥6 months after completion of the primary series if they are at the highest or increased risk of waning protection following their primary series, at the highest or increased risk of severe COVID-19, or essential to maintain health-care system capacity. These populations include adults living in long-term care or other congregate settings that provide care for seniors; individuals aged ≥50 years; adults identifying as First Nations, Inuit, or Métis; frontline health-care workers who have direct in-person contact with patients and who were vaccinated with a very short interval between doses; and those who completed the primary series of either the AZD1222 or Ad26.COV2.S vaccines.

A third dose of an mRNA vaccine should also be offered to patients aged 18 to 49 years ≥6 months after completion of the primary series if they have individual risk factors for increased risk of severe COVID-19, including social determinants of health.

A third dose of an mRNA vaccine is not currently recommended for patients aged 5 to 17 years.

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 SARS-CoV-2 infection in patients aged ≥5 years.

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) Children aged <5 years: The safety and efficacy of tozinameran has not yet been established in this population.

2) Patients aged 12 to 29 years: Patients in this age range should be preferentially offered tozinameran (Pfizer) over elasomeran (Moderna) to mitigate the potential risk of myocarditis with the latter.

3) Pregnant patients: The safety and efficacy of tozinameran has not yet been established in this population. A phase II/III study (ClinicalTrials.gov identifier: NCT04754594) in this population is underway.

Preliminary data from the Vaccine Adverse Event Reporting System have been published, which to date 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. 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.

4) Breastfeeding patients: It is unknown whether tozinameran is excreted in human breast milk, and therefore a risk to the breastfed child cannot be excluded or established. 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 vaccine series (see “Immunization schedule” below).

4. Immunization schedule:

1) Primary series, persons aged ≥12 years: Tozinameran 30 microg is given after dilution as a 0.3-mL IM injection in the deltoid muscle on days 0 and 21. Due to emerging evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. A third dose of tozinameran 30 microg is recommended 6 months after completion of the primary series in those at high or increased risk (see “Recommendations for third doses” 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.

3) Primary series, immunocompromised patients: For patients aged ≥12 years with moderate or severe immune deficiency, tozinameran 30 microg is given after dilution as a 0.3-mL IM injection in the deltoid muscle on days 0, 21, and 49.

4) 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.

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

Third 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 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).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 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). 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.

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 8Low 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: A Qatari study involving 385,853 patients who had received ≥1 dose and 265,410 patients who had received both doses of tozinameran demonstrated a vaccine efficacy of 89.5% (95% CI, 85.9-92.3) against infection with the Alpha VOC ≥14 days after administration of the second dose. Vaccine efficacy was 100% (95% CI, 81.7-100) against severe/critical COVID-19 or death from Alpha VOC infection.Evidence 9Moderate Quality of Evidence (moderate confidence that we know the true effects of the intervention). Quality of Evidence lowered due to short duration of follow-up. Abu-Raddad LJ, Chemaitelly H, Butt AA; National Study Group for COVID-19 Vaccination. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N Engl J Med. 2021 May 5. doi: 10.1056/NEJMc2104974. Epub ahead of print. PMID: 33951357; PMCID: PMC8117967. The same study also examined vaccine efficacy against the Beta VOC, with endpoints of infection and severe/critical COVID-19 or death. Vaccine efficacy of tozinameran against infection with the Beta VOC ≥14 days after administration of the second dose was 75.0% (95% CI, 70.5-78.9); vaccine efficacy against severe/critical COVID-19 or death was 100% (95% CI, 73.7–100).Evidence 10Moderate Quality of Evidence (moderate confidence that we know the true effects of the intervention). Quality of Evidence lowered due to Quality of Evidence lowered due to short duration of follow-up. Abu-Raddad LJ, Chemaitelly H, Butt AA; National Study Group for COVID-19 Vaccination. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N Engl J Med. 2021 May 5. doi: 10.1056/NEJMc2104974. Epub ahead of print. PMID: 33951357; PMCID: PMC8117967. Serum neutralization assays against the Gamma VOC show a 6.7-fold decrease in antibody titers to this variant; large-scale clinical efficacy data are currently lacking.Evidence 11Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias from small sample size and indirectness. Abdool Karim SS, de Oliveira T. New SARS-CoV-2 Variants - Clinical, Public Health, and Vaccine Implications. N Engl J Med. 2021 May 13;384(19):1866-1868. doi: 10.1056/NEJMc2100362. Epub 2021 Mar 24. PMID: 33761203; PMCID: PMC8008749. After a single dose of tozinameran, vaccine efficacy against the Delta VOC was 35.6% (95% CI, 22.7-46.4); the efficacy after 2 doses increased to 88.0% (95% CI, 85.3-90.1).Evidence 12Moderate Quality of Evidence (moderate confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. 2021 Aug 12;385(7):585-594. doi: 10.1056/NEJMoa2108891. Epub 2021 Jul 21. PMID: 34289274; PMCID: PMC8314739.

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 males 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 disease 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:

1) Shipping: In order to preserve the efficacy of tozinameran, its temperature must be maintained between −90 and −60 degrees Celsius. The vaccine is shipped in multiple-dose vials within an insulated thermal shipping container on dry ice.

2) Storage: Undiluted multiple-dose vials of tozinameran should be maintained between −90 and −60 degrees Celsius until ready to be thawed for patient use or the expiry date, whichever occurs first. Undiluted multiple-dose vials may also be stored at −25 to −15 degrees Celsius for a cumulative time of 2 weeks. Undiluted multiple-dose vials stored at −25 to −15 degrees Celsius may be returned once to the recommended storage temperature of −90 to −60 degrees Celsius. Undiluted multiple-dose vials may be thawed in the refrigerator at 2 to 8 degrees Celsius and stored there for ≤1 month. If the vaccine is required for immediate use, it may be thawed at room temperature (≤25 degrees Celsius) for ≤30 minutes. Instructions for dilution and preparation of a thawed multiple-dose vial: covid-vaccine.canada.ca. Once diluted, the multiple-dose vial must be used within 6 hours or discarded. Vials should never be refrozen once thawed.

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 SARS-CoV-2 infection in patients aged ≥12 years.

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) Children aged ≤11 years: The safety and efficacy of elasomeran have not yet been established in this population.

2) Patients aged 12 to 29 years: Patients in this age range should be preferentially offered tozinameran over elasomeran to mitigate the potential risk of myocarditis with elasomeran. Third doses of elasomeran are only authorized for use in patients aged ≥18 years.

3) Pregnant patients: The safety and efficacy of elasomeran have not yet been established in this population. If pregnant women have been vaccinated with elasomeran, they should be encouraged to enroll in a postauthorization registry and monitoring program (contact Moderna Medical Information at 1-866-663-3762).

Preliminary data from the Vaccine Adverse Event Reporting System have been published, which to date 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. 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.

4) Breastfeeding patients: It is unknown whether elasomeran is excreted in human breast milk, and therefore a risk to the breastfed child cannot be excluded or established. 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 emerging evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56.

A third dose of elasomeran is recommended 6 months after completion of the primary series in those at high or increased risk (see “Recommendations for third doses” in General Considerations above). A reduced dose of elasomeran 50 microg is recommended for the third dose in patients aged 30 to 69 years, while an elasomeran dose of 100 microg is recommended for the third vaccine in patients aged ≥70 years. Tozinameran is preferred over elasomeran for any dose in patients aged 18 to 29 years due to lower rates of myocarditis in this age group. Elasomeran does not require reconstitution or dilution prior to administration.

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 emerging evidence that host immune response to vaccination is optimized with a longer interval between doses, the NACI recommends administration on day 0 and 56. A third dose of elasomeran is not currently recommended in this population.

3) 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.

4) 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.

5) 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 third 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 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). 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.

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 17Low 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.

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: Elasomeran human serum neutralization assays against the Alpha VOC illustrate consistently high neutralizing antibody titers from the full set of mutations or from specific key mutations found therein.Evidence 18Low 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. Wu K, Werner AP, Koch M, et al. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine. N Engl J Med. 2021 Apr 15;384(15):1468-1470. doi: 10.1056/NEJMc2102179. Epub 2021 Mar 17. PMID: 33730471; PMCID: PMC8008744. Neutralizing antibody titers against the Beta VOC showed a 6-fold decrease; however, titers remained above the levels shown to protect nonhuman primates in wild-type virus challenge experiments.Evidence 19Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to risk of bias from small sample size and indirectness. Wu K, Werner AP, Koch M, et al. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine - Preliminary Report. N Engl J Med. 2021 Feb 17. doi: 10.1056/NEJMc2102179. Epub ahead of print. PMID: 33596346.

In a test-negative case-control study from England, vaccine efficacy of elasomeran against symptomatic disease caused by the Delta and Omicron VOCs was analyzed. Vaccine efficacy against the Delta variant 2 to 4 weeks after administration of a third dose of elasomeran was >95% (no CI provided).Evidence 20Moderate 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 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 21Moderate 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 males aged 16 to 19 years.Evidence 22Low 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. The preliminary 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:

1) Shipping: Elasomeran should be maintained at temperatures between −25 and −15 degrees Celsius during shipping. It is shipped in multiple-dose vials.

2) Storage: Elasomeran should not be stored on dry ice. During storage, it should be protected from light. Multiple-dose vials may be stored between 2 and 8 degrees Celsius for ≤30 days prior to first use. Vials may be thawed prior to use for 2.5 hours at 2 to 8 degrees Celsius; alternatively, they may be thawed for 1 hour at 15 to 25 degrees Celsius. Once the vial has been punctured with a needle, it should be used within 6 hours or discarded. Vials should never be refrozen once thawed.

AZD1222 ChAdOx1-S (Oxford-AstraZeneca and COVISHIELD) Vaccines

The AZD1222 ChAdOx1-S vaccine (marketed by AstraZeneca) 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 safety and efficacy of the AZD1222 vaccine has not yet been established in this population. 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.

3) Breastfeeding patients: It is unknown whether the AZD1222 vaccine is excreted in human breast milk, and therefore a risk to the breastfed child cannot be excluded or established. 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 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.

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 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 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 Use and timing of booster doses in General Considerations above). The AZD1222 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 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 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, 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 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. 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 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, 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: A study of 8534 patients in the United Kingdom showed a clinical efficacy of 70.4% (95% CI, 43.6-84.5) against symptomatic infection with the Alpha VOC.Evidence 27Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to inconsistency (dosing error) and imprecision (small proportion of patients ≥65 years of age, a clinically relevant demographic). Emary KRW, Golubchik T, Aley PK, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial. Lancet. 2021 Apr 10;397(10282):1351-1362. doi: 10.1016/S0140-6736(21)00628-0. Epub 2021 Mar 30. PMID: 33798499; PMCID: PMC8009612. In a study of 2026 HIV-negative adults in South Africa, the AZD1222 vaccine was shown to offer no protection against mild/moderate COVID-19 caused by the Beta VOC, with vaccine efficacy of 10.4% (95% CI, –76.8 to 54.8).Evidence 28Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to inconsistency (dosing error) and imprecision (small proportion of patients ≥65 years of age, a clinically relevant demographic). Madhi SA, Baillie V, Cutland CL, et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med. 2021 Mar 16:NEJMoa2102214. doi: 10.1056/NEJMoa2102214. Epub ahead of print. PMID: 33725432; PMCID: PMC7993410. The effect of the Gamma and Delta VOCs on AZD1222 vaccine efficacy has not yet been studied. A non–peer-reviewed study has examined the efficacy of the AZD1222 vaccine against the Delta VOC. A single dose had an efficacy of 33.5% (95% CI, 20.6-44.3) against the Delta VOC; the efficacy increased to 59.8% (95% CI, 28.9-77.3) with the second vaccine dose.Evidence 29Moderate Quality of Evidence (moderate confidence that we know the true effects of the intervention). Quality of Evidence lowered due to the short duration of follow-up. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. 2021 Aug 12;385(7):585-594. doi: 10.1056/NEJMoa2108891. Epub 2021 Jul 21. PMID: 34289274; PMCID: PMC8314739.

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 30Moderate 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 31Moderate 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.) 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 safety and efficacy of the Ad26.COV2.S vaccine has not yet been established in this population. Pregnant women who have been vaccinated with the Ad26.COV2.S vaccine should be encouraged to enroll in a postauthorization registry and monitoring program (c-viper.pregistry.com). 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.

3) Breastfeeding patients: It is unknown whether the Ad26.COV2.S vaccine is excreted in human breast milk, and therefore a risk to the breastfed child cannot be excluded or established. 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. 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 in those at high or increased risk. 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 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). 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 to unvaccinated individuals.

4) Efficacy against SARS-CoV-2 VOCs: Ad26.COV2.S human serum neutralization assays against the Alpha VOC illustrate a 9-fold decrease in neutralizing antibody titers compared with a canonical strain of the virus at ≥28 days post vaccination; there was, however, only a 3.3-fold decrease in neutralizing antibody titers by ≥70 days post vaccination. Subgroup analysis of vaccine efficacy at the South African trial site, where the Beta VOC predominates as a circulating strain, shows a vaccine efficacy of 64% (95% CI, 41.2-78.7), in line with overall trial results.Evidence 33Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to imprecision (use of entire study population to infer vaccine efficacy against VOC). Vaccines and Related Biological Products Advisory Committee Meeting: February 26, 2021. FDA Briefing Document: Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19COVID Vaccine Ad26.COV2.S VAC31518 (JNJ-78436735). Published February 26, 2021. Accessed March 6, 2021. https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-february-26-2021-meeting-announcement In the final analysis of the Ad26.COV2.S clinical trial, Ad26.COV2.S was not effective at preventing moderate to severe COVID-19 ≥14 days after completion of the primary series (vaccine efficacy −5.7%, 95% CI, −177.7 to 59.2).Evidence 34Low Quality of Evidence (low confidence that we know the true effects of the intervention). Quality of Evidence lowered due to imprecision (low event rates). Sadoff J, Gray G, Vandebosch A, et al; ENSEMBLE Study Group. Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S. N Engl J Med. 2022 Mar 3;386(9):847-860. doi: 10.1056/NEJMoa2117608. Epub 2022 Feb 9. PMID: 35139271; PMCID: PMC8849184. Ad26.COV2.S human serum neutralization assays against the Omicron VOC demonstrate no activity.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).  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.

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 after 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)

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).

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