COVID-19 Vaccines

Please see the April 13, 2021 CDC Health Alert concerning the J&J COVID-19 vaccine and rare blood clots.

(Updated April 16, 2021)

The chart below provides dosing, storage, adverse effects, and efficacy information for COVID-19 vaccines available or submitted for approval in the U.S. and/or Canada. The American Society of Health System Pharmacists has resources related to COVID-19 vaccines at https://www.ashp.org/COVID-19/Vaccines?loginreturnUrl=SSOCheckOnly. See end of chart for links to the fact sheets and product labeling.

Vaccine/Type/Status

Dosing

Storage/Stabilitye

Adverse Effects

Efficacyd

BNT162b2
(Pfizer-BioNTech)/mRNA

U.S.: Emergency Use Authorization

Canada: authorized by interim order.

Two 0.3 mL doses (0, 21 days) IM for ≥16 years of age18,19

Requires dilution with 1.8 mL of NS per vial.18,19

Special dry ice shipper: see footnote b for storage/handling

Ultracold freezer (-70°C±10°C) Mfr expiration date (undiluted)19

Freezer (-20°C±5°C): ≤2 weeks.19

Thawing (required before diluting): may take ~two to three hours in the refrigerator, or 30 minutes at room temperature. Allow vial to reach room temperature before diluting. Do not refreeze.18,19

Refrigerator (2°C to 8°C): 5 days undiluted; 6 hours once diluted (vial or pre-drawn syringe)18,19,32

Room Temp (up to 25°C): 2 hours, undiluted, 6 hours once diluted (vial or pre-drawn syringe), minimizing light exposure18,19,32

Most (>95%) adverse effects were mild to moderate.5

Local/injection site: mild to moderate pain in >65% of patients. Severe pain in <1%. Redness and swelling much less common.5

Systemic: fatigue (<60%), headache (≤52%), myalgia (≤37%), chills (≤35%), arthralgia (≤22%), fever ≥38°C (≤16%).5 Less common: diarrhea (<11%), vomiting.17 Any severe event after first dose ≤0.9%, and <2% after the second dose, except fatigue (3.8%) and headache (2%).5

Recipients can expect local adverse effects to resolve within one to two days.5 Systemic effects occur within the first one to two days, then resolve quickly.5 Participants were allowed to use analgesics/antipyretics.5

Appears better tolerated in older (>55 years of age) vs younger adults.5

Four cases of Bell’s palsy occurred in the vaccine group.17

Anaphylaxis reported.18,19

Lymphadenopathy (16%) may interfere with imaging (e.g. mammography) for four to six weeks after vaccination.35

54.2% effective between dose one and two, starting ~14 days after the first dose.17 Israeli data suggests a 33% reduction in positive COVID tests (as opposed to symptomatic disease) in those ≥60 years of age.26

80% reduction in hospitalization after one dose in age >80 years (U.K. data).

95% effective (95% CI 90.3% to 97.6%) seven days after the second dose (n=43,448).5 NNVf = 71. 94.7% effective in adults ≥65 years of age.5

One severe COVID-19 case (nonhospitalized) in the vaccine group vs nine in the placebo group (88.9% effective after first dose).17

Immunocompromised patients were excluded from trials.5

Pediatric studies ongoing.17

In vitro data suggest efficacy against the new UK and South African variants.27-28

Immunogenicity (Phase I study):a produced neutralizing antibody response ≥ natural infection in adults 18 to 85 years of age.1

mRNA-1273
(Moderna)/mRNA

U.S.: Emergency Use Authorization

Canada: authorized by interim order

Two 0.5 mL doses (0, 1 month [days 26 to 36]) IM for ≥18 years of age21-23

Does not require dilution.21,22

Shipping and long-term storage: -50°C to -15°C until mfr expiration date6

Refrigerator (2°C to 8°C): 30 days after thawing (prior to first use). After 30 days, contact manufacturer for guidance before discarding.6
In-use vial/pre-drawn syringe: 12 hours 39

Room temperature: (8°C to 25°C): Unused vial: 12 hours;21,22,32
In-use vial/pre-drawn syringe: 12 hours39

>90% of adverse effects mild to moderate.4

Local/injection site: mild to moderate pain in >80% of patients. Severe pain in 2.8% of patients after the first dose and in 4.1% after the second dose.4

Systemic: fatigue (68.5%), headache (63%), myalgia (59.6%), chills (43.4%), arthralgia (44.8%), fever (14.8%).4 Less common: nausea, vomiting, diarrhea. Severe adverse events after 2nd dose: fatigue (9.7%), myalgia (8.6%), arthralgia (5.1%), headache (5.5%).4

Median duration of adverse effects was two days (three for local effects after 2nd dose).4 Participants were allowed to use analgesics/antipyretics.4

Appears better tolerated in older (≥65 years of age) vs younger patients.4

Three cases of Bell’s palsy occurred in the vaccine group, one in the placebo group.4

Anaphylaxis reported.22,36

Lymphadenopathy (16%) may interfere with imaging (e.g. mammography) for four to six weeks.35

Delayed-type hypersensitivity reaction (e.g., large, red area near injection site about a week after shot) is not a contraindication to subsequent vaccination.37 May be itchy, painful, warm, or swollen, and can also involve fingers, elbow, or palm. More common with first shot.37

92.1% effective between dose one and two, starting ~14 days after the first dose.4 Protection beyond 28 days after a single dose unknown.4

94.1% effective (95% CI 89.3% to 96.8%) 14 days after second dose (n=27,817).4 NNVf = 80. No cases of severe COVID-19 in the vaccine group vs 30 in the placebo group (starting 14 days after the 2nd dose).4

~25% of patients were ≥65 years of age, 9.4% had diabetes, ~6.5% had severe obesity, ~5% had significant heart disease, and ~5% had chronic lung disease.4

In vitro data suggest efficacy against the new UK and South African variants, but efficacy against the South African variant might wane.24,25 Use of a third dose (of the same vaccine, or a new one modified to target this variant) is being studied.24

Immunogenicity (Phase I study):a produced neutralizing antibody response in adults comparable to natural infection, even in patients >70 years of age.2,13 Minimal Th2 response.2,13

Ad26.COV2.S
Janssen (J&J)/
/Viral vector (non-replicating)

U.S.: Emergency Use Authorization

Canada:authorized by interim order

One 0.5 mL IM dose for ≥18 years of age9,31 (two-dose regimen also being studied)

If arrives frozen, refrigerate, or for immediate use, thaw at room temperature (max 25°C). May take 2 hours to thaw.9

Refrigerator (2°C to 8°C): Mfr expiration date (unused vial);11,31 In-use vial/pre-drawn syringe: 6 hrs.11,31,32

Room temperature (9°C to 25°C): Unused vial: 12 hours. In-use vial/pre-drawn syringe: 2 hours (Canada: 3 hours)11,31,32

Phase III data:9

  • Most adverse effects were mild to moderate.9
  • Local/injection site: occurred in 58.6% of patients 18 to 59 years of age, and in 33.3% of patients ≥65 years of age, most commonly injection site pain.9 <1% were severe.9 Systemic: most commonly headache (30.4% to 44.4%), fatigue (29.7% to 43.8%), and myalgia (24% to 39.1%), with better tolerability in patients ≥65 years of age.9 Other adverse effects included fever and nausea.9
  • Anaphylaxis reported.9,31
  • Use in U.S. has been paused pending investigation of six cases of cerebral venous sinus thrombosis and thrombocytopenia in young women after vaccination.40

For preventing moderate to severe/critical COVID-19 disease 28 days post-vaccination, efficacy was 72% in the U.S., 68.1% in Brazil, and 64% in South Africa (n=29,371).9 There were no COVID-19 deaths in the vaccine group.9 Overall, it was 85.4% effective for preventing severe/critical COVID-19.9

Immunogenicity (Phase I/IIa study):a Produced neutralizing antibody response in >95% of patients.10 No or minimal Th2 response.10 Robust CD8+ response.10

ChAdOx1-S*
(AstraZeneca)/Viral vector (non-replicating)

Phase III data published.

Canada: authorized by interim order

*Canada: also manufactured by Serum Institute of India (Covishield)

Two 0.5 mL doses (0 and 4 to 12 weeks) IM for ≥18 years of age8,30

Refrigerator(2°C to 8°C): Mfr expiration date (unused vial); 48 hours (punctured vial)8,30

Room temperature (≤30°C): 6 hours (punctured vial). Vial can be re-refrigerated, but the cumulative storage at room temperature cannot exceed 6 hours, and the total cumulative storage time cannot exceed 48 hours8,30

Meningococcal conjugate (MenACWY) vaccine used as comparator to maintain blinding in regard to adverse effects.3

Transverse myelitis occurred in three patients (one placebo). A possible vaccine relationship was not ruled out in one case.20

Local/injection site (Phase II/III study): pain and tenderness occurred most often.15

Systemic (Phase II/III study): occurred in most patients, most commonly fatigue, headache, feverishness, and myalgia.15 Other systemic side effects were malaise and chills. Few patients confirmed fever.15 Better tolerated in older patients.15 Adverse effects peaked day after vaccination.3

Current evidence does not suggest thrombosis risk, except cerebral sinus vein thrombosis with low platelets (rare; 1 in 250,000 to 500,000)34

Anaphylaxis reported.37

Among patients who received two full dosesc 4 to 12 week apart, in the UK and Brazil (n=10,468):8,30

  • 59.5% effective ≥15 days after second dose)8,30
  • No cases of severe COVID-19 occurred in the COVID-19 vaccine group.8,30
  • Limited data in patients ≥65 years.8,30

Efficacy better with 12-week interval.8,30

80% reduction in hospitalization after one dose in age >80 years (UK data).33

Immunogenicity:a produced neutralizing antibody response in adults 18 to ≥70 years of age.15 Immunogenicity was not affected by acetaminophen.3

NVX-CoV2373
(Novavax)/Protein subunit, adjuvanted

Phase III; rolling review process in U.S. and Canada14

Two doses IM (0, 21 to 28 days)7

Refrigerator (2°C to 8°C)7

Occurred in most patients, especially after the second dose. Mean duration was ≤2 days.29

Local/injection site (Phase I/IIa study): pain and tenderness (mild to moderate) occurred most often.29

Systemic (Phase I/IIa study): headache, fatigue, and myalgia occurred most often. A few patients experienced severe adverse effects (fatigue, myalgia, arthralgia) after the second dose. Other systemic side effects were nausea and malaise.29

In UK, 89.3% effective overall, and 95.6% effective against original strain.14 Up to 60% effective against South African variants.14

Immunogenicity (Phase I/IIa study):a Produced neutralizing antibody response similar to convalescent hospitalized patients. Minimal Th2 response.29

  1. Neutralizing antibodies and Th1 CD4+ polarization are thought to be desirable. Neutralizing antibodies were associated with protection in non-human primate studies. Th1 polarization means that there is more of a response by Th1 CD4+ helper T cells than Th2 CD4+ helper T cells. Th2>Th1 response was associated with immunopathologic lung damage (“enhanced respiratory disease”) in preclinical SARS-CoV-1 and MERS vaccine studies.12
  2. Pfizer vaccine storage and dry ice safety handling resources at https://www.cvdvaccine-us.com/product-storage-and-dry-ice.
  3. Some other patients in the studies received only a half-dose for the first dose due to manufacturing error.16,20
  4. Efficacy = Based on reduction of documented COVID-19 infections (COVID-19 symptoms plus confirmatory test for SARS-CoV2 test [polymerase chain reaction]).17,19,20 This means we do not know if the vaccine prevents asymptomatic infection.
  5. USP: Vaccines should be prepared in accordance with the manufacturer’s labeling. This means that USP engineering controls, risk levels, and beyond-use dating is not required. See https://www.usp.org/compounding.
  6. NNV is the number needed to vaccinate to prevent one symptomatic case.

Abbreviations: IM = intramuscular; NS = normal saline; UK = United Kingdom

The CDC has interim recommendations for COVID-19 vaccine administration errors and deviations available at https://cdc.gov/vaccines/covid-19/downloads/covid19-vaccine-errors-deviations-poster.pdf.

Fact Sheets and Product Labeling

References

  1. Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med 2020;383:2439-50.
  2. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2: preliminary report. New Engl J Med 2020;383:1920-31.
  3. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCOV-19 vaccine against SARS-CoV-2: a preliminary report of a phase1/2, single-blind, randomised controlled trial. Lancet 2020;396:467-78.
  4. FDA. FDA Briefing document. Moderna COVID-19 vaccine. Vaccines and Related Biological Products Advisory Committee Meeting. December 17, 2020. https://www.fda.gov/media/144434/download. (Accessed February 7, 2021).
  5. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-15.
  6. CDC. Moderna COVID-19 vaccine questions. Last reviewed April 6, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/moderna-faqs.html. (Accessed April 15, 2021).
  7. Novavax. Clinical trial protocol. A phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of a SARS-Co-V-2 recombinant spike protein nanoparticle vaccine (SARS-CoV-2 rS) with Matrix-M1 adjuvant in adult participants ≥18 years. November 16, 2020. https://www.novavax.com/sites/default/files/2020-12/Novavax_2019nCoV-301_Protocol_%20Phase%203-Redacted.pdf. (Accessed February 25, 2021).
  8. Product monograph for Covishield/COVID-19 Vaccine (ChAdOx1-S). Verity Pharmaceuticals. Mississauga, ON L4W 4Y9. (Accessed March, 2021).
  9. FDA. Fact sheet for healthcare providers administering vaccine (vaccination providers). Emergency use authorization (EUA) of the Janssen COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). February 27, 2021. https://www.fda.gov/media/146304/download. (Accessed February 27, 2021).
  10. Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1-2a trial of Ad26.COV2.S. N Engl J Med 2021 Jan 13.. doi: 10.1056/NEJMoa2034201.
  11. CDC.  Janssen COVID-19 vaccine (Johnson & Johnson).  Page last reviewed March 11, 2021.  https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/index.html.  (Accessed March 19, 2021).
  12. FDA. Development and Licensure of Vaccines to Prevent COVID-19; Guidance for Industry. June 20, 2020. https://www.fda.gov/media/139638/download. (Accessed February 7, 2021).
  13. Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med 2020;383:2427-38.
  14. Novavax. Press release Novavax announces start of rolling review by multiple regulatory authorities for COVID-19 vaccine authorization. February 4, 2021. https://ir.novavax.com/node/15531/pdf. (Accessed February 7, 2021).
  15. Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet 2020;396:1979-93.
  16. Anon. AstraZeneca, Oxford acknowledge manufacturing error in potential COVID-19 vaccine. November 26, 2020. https://www.nasdaq.com/articles/astrazeneca-oxford-acknowledge-manufacturing-error-in-potential-covid-19-vaccine-2020-11. (Accessed February 7, 2021).
  17. FDA. FDA Briefing document. Pfizer-BioNTech COVID-19 vaccine. Vaccines and Related Biological Products Advisory Committee meeting. December 10, 2020. https://www.fda.gov/media/144245/download. (Accessed February 7, 2021).
  18. Product monograph for Pfizer-Biontech COVID-19 vaccine. Pfizer Canada. Kirkland, QC H9J 2M5. February 2021.
  19. FDA. Fact sheet for healthcare providers administering vaccine (vaccination providers). Emergency use authorization (EUA) of the Pfizer-Biontech COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). Revised February 25, 2021. https://www.fda.gov/media/144413/download. (Accessed March 19, 2021).
  20. Voysey M, Costa Clemens SA, Madhi SA, et al. Safety and efficacy of the ChAdOx1CoV-19 vaccine (AZS1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111.
  21. FDA. Fact sheet for healthcare providers administering vaccine (vaccination providers). Emergency use authorization (EUA) of the Moderna COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). March 31, 2021. https://www.fda.gov/media/144637/download. (Accessed April 15, 2021).
  22. Product monograph for Moderna COVID-19 vaccine (Canada). Moderna Therapeutics. Cambridge, MA 02139. February 2021.
  23. Personal communication (written). P. Raper. Medical Information. Moderna. Cambridge, MA 02139. January 5, 2021.
  24. Tanne JH. Covid-19: Moderna plans booster doses to counter variants. BMJ 2021;372:n232.
  25. Wu K, Werner AP, Moliva JI, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. medRxiv 2021.01.25.427948 https://doi.org/10.1101/2021.01.25.427948. (Accessed February 7, 2021).
  26. Mahase E. Covid-19: reports from Israel suggest one dose of Pfizer vaccine could be less effective than expected. BMJ 2021;372:n217.
  27. Muik A, Wallisch AK, Sanger B, et al. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera. medRxiv 2021.01.18.426984 https://doi.org/10.1101/2021.01.18.426984. (Accessed February 7, 2021).
  28. Xie X, Liu Y, Liu J, et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K, and N501Y variants by BNT162b2 vaccine-elicited sera. Nat Med 2021 Feb 8. doi: 10.1038/s41591-021-01270-4.
  29. Keech C, Albert G, Cho A, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med 2020;383:2320-32.
  30. Product monograph for AstraZeneca COVID-19 Vaccine (ChAdOx1-S).  AstraZeneca Canada.  Mississauga, ON L4Y 1M4.  (Accessed March 2021).
  31. Product monograph for Janssen COVID-19 vaccine. Janssen.Toronto, ON M3C 1L9. (Accessed March 2021).
  32. USP.  COVID-19 vaccine handling toolkit:  operational considerations for healthcare practitioners.  March 2021-Version 3.0.  https://www.usp.org/covid-19/vaccine-handling-toolkit.  (Accessed March 19, 2021).
  33. Iacobucci G.  Covid-19:  single dose of Pfizer and Oxford vaccines cuts risk of hospital admission by 80% in over 80s, data suggest.  BMJ 2021:372:n612.
  34. Thrombosis Canada.  Thrombosis Canada updated statement on AstraZeneca vaccine and blood clots.  March 18, 2021.  https://thrombosiscanada.ca/tc-updated-statement-march-18/#:~:text=%C2%A0Toronto,%20Ontario%20(March%2018,%202021)%E2%80%93%20Thrombosis%20Canada%20has,that%20is%20associated%20with%20thrombocytopenia%20(low%20blood%20platelets).  (Accessed March 24, 2021).
  35. NCCN: Cancer and COVID-19 Vaccination.  Recommendations of the NCCN COVID-19 vaccination Advisory Committee.  Version 2.0.  March 10, 2021.  https://www.nccn.org/covid-19/pdf/COVID-19_Vaccination_Guidance_V2.0.pdf.    (Accessed March 19, 2021).
  36. CDC COVID-19 Response Team, Food and Drug Administration.  Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine-United States, December 21, 2020-January 10, 2021.  MMWR Morb Mortal Wkly Rep 2021;70:125-9.
  37. Blumenthal KG, Freeman EE, Saff RR, et al.  Delayed large local reactions to mRNA-1273 vaccine against SARS-CoV-2.  N Engl J Med 2021 March 3.  doi:  10.1056/NEJMc2102131.
  38. FDA News.  Severe allergy added to EMA’s list of AstraZeneca vaccine side effects.  March 16, 2021.  https://www.fdanews.com/articles/201861-severe-allergy-added-to-emas-list-of-astrazeneca-vaccine-side-effects.  (Accessed March 20, 2021).
  39. USP. Beyond use date in vial or syringe for COVID-19 vaccines (factsheet). Updated April 6, 2021. https://www.usp.org/covid-19/vaccine-handling-toolkit.  (Accessed April 15, 2021).
  40. FDA. Joint CDC and FDA statement on Johnson & Johnson COVID-19 vaccine. April 13, 2021. https://www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-johnson-johnson-covid-19-vaccine.  (Accessed April 15, 2021).

Cite this document as follows: Clinical Resource, COVID-19 Vaccines. Pharmacist’s Letter/Prescriber’s Letter. March 2021. [370301]

Related Articles