Vaccines: SARS-CoV-2 (COVID-19)

How to Cite This Chapter: Komorowski AS, Loeb M. Vaccines: SARS-CoV-2 (COVID-19). McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.18.53.14 Accessed January 25, 2021.
Last Updated: January 14, 2021
Last Reviewed: January 14, 2021
Chapter Information

Authors’ note: Emergency Use Authorizations (EUAs) and 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 EUAs or 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.

General ConsiderationsTop

1. Role of vaccination in those with previous SARS-CoV-2 infection: Current Canadian National Advisory Committee on Immunization (NACI) guidance is that vaccination should be recommended to those with previous clinical or microbiologic evidence of SARS-CoV-2 infection, as there is possible evidence of SARS-CoV-2 reinfection and of waning antibody titers from natural infection.

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.

Vaccines Currently Approved for Use in CanadaTop

Tozinameran (Pfizer-BioNTech BNT162b2) mRNA Vaccine

Tozinameran (marketed by Pfizer-BioNTech, 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 recommended for the prevention of SARS-CoV-2 infection in patients aged ≥16 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 <16 years: The safety and efficacy of tozinameran has not yet been established in this population. The NACI recommends that in cases where a risk-benefit analysis has been undertaken and where informed consent has been obtained tozinameran may be offered to individuals 12 to 15 years of age at very high risk of severe outcomes with COVID-19 (ie, in congregate living facilities or with preexisting conditions known to be associated with increased mortality risk in COVID-19).

2) Pregnant patients: The safety and efficacy of tozinameran has not yet been established in this population.

3) 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.

4) Immunocompromised patients: Patients on immunosuppressive medications or those with immune compromise may have a diminished serologic response to vaccination.

4. Immunization schedule:

1) Tozinameran is given after dilution as a 0.3 mL IM injection in the deltoid muscle on days 0 and 21.

2) There is no information available with respect to missed doses and their effect on immune response to tozinameran. According to current guidance from the US Centers for Disease Control and Prevention (CDC), if a second dose is administered between days 17 and 21, it is considered within the recommended dosing schedule. If the second dose is administered prior to day 17, an additional dose should not be given. If >21 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.

3) As the interchangeability of SARS-CoV-2 vaccines marketed by different manufacturers has not been established, it is currently recommended that a single manufacturer’s vaccine be used to initiate and complete the primary vaccination series.

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 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). 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.

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: There is no current information with respect to whether immunization with tozinameran prevents transmission of SARS-CoV-2 from a vaccinated to an unvaccinated individual (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).

6. Adverse events: Adverse events stratified by dose and reported in the phase III clinical trial of tozinameran: Table 8.8-1.

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

7. Shipping and storage:

1) Shipping: In order to preserve the efficacy of tozinameran, its temperature must be maintained between −80 and −60 degrees Celsius. The vaccine is shipped in multiple-dose vials within an insulated thermal shipping container on dry ice.

2) Storage: Tozinameran must be maintained between −80 and −60 degrees Celsius until it is ready to be thawed for patient use. Undiluted multiple-dose vials may be thawed in the refrigerator at 2 to 8 degrees Celsius and may be stored there for ≤5 days. 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.

Moderna mRNA-1273 Vaccine

The mRNA-1273 vaccine (marketed by Moderna, and hereinafter referred to as “mRNA-1273 vaccine”) contains mRNA encoding for the SARS-CoV-2 spike glycoprotein encapsulated in lipid nanoparticles.

1. Indications: The mRNA-1273 vaccine is recommended for the prevention of SARS-CoV-2 infection in patients aged ≥18 years.

2. Contraindications: The mRNA-1273 vaccine is contraindicated in those with allergy or hypersensitivity to vaccine components. The nonmedicinal ingredients used in the mRNA-1273 vaccine 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 <18 years: The safety and efficacy of the mRNA-1273 vaccine has not yet been established in this population; a phase III study (TeenCOVE study; ClinicalTrials.gov Identifier: NCT04649151) in this population is underway.

2) Pregnant patients: The safety and efficacy of the mRNA-1273 vaccine has not yet been established in this population. If a pregnant woman has been vaccinated with the mRNA-1273 vaccine, these patients should be encouraged to enroll in a postauthorization registry and monitoring program (contact Moderna Medical Information at 1-866-663-3762).

3) Breastfeeding patients: It is unknown whether the mRNA-1273 vaccine is excreted in human breast milk, and therefore a risk to the breastfed child cannot be excluded or established.

4) Immunocompromised patients: Patients on immunosuppressive medications or those with immune compromise may have a diminished serologic response to vaccination.

4. Immunization schedule:

1) The mRNA-1273 vaccine is given as a 0.5 mL IM injection in the deltoid muscle on days 0 and 28. The mRNA-1273 vaccine does not require reconstitution or dilution prior to administration.

2) There is no information available with respect to missed doses and their effect on immune response. According to current guidance from 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.

3) As the interchangeability of SARS-CoV-2 vaccines marketed by different manufacturers has not been established, it is currently recommended that a single manufacturer’s vaccine be used to initiate and complete the primary vaccination series.

5. Vaccine efficacy:

1) Short-term efficacy: The mRNA-1273 vaccine 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 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). 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.

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: Preliminary data show a lower prevalence of transmission among study participants with PCR evidence of SARS-CoV-2 infection before the administration of dose 2 in those who received the mRNA-1273 vaccine. Data are currently insufficient to draw conclusions as to whether individuals vaccinated with the mRNA-1273 vaccine are less likely to transmit SARS-CoV-2 to unvaccinated individuals.

6. Adverse events: Adverse events stratified by dose and reported in the phase III clinical trial of the mRNA-1273 vaccine: Table 8.8-2.

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.

7. Shipping and storage:

1) Shipping: The mRNA-1273 vaccine should be maintained at temperatures between −25 and −15 degrees Celsius during shipping. It is shipped in multiple-dose vials.

2) Storage: The mRNA-1273 vaccine 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 up to 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.

TablesTop

Table 8.8-1. 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 ≥38.0°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 ≥38.0°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-BioNTechCOVID-19 Vaccine [COVID-19 mRNA Vaccine] Product Monograph.

Table 8.8-2. Adverse events with administration of the mRNA-1273 vaccine, 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.

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