- Mark Abramowicz, M.D., President: no disclosure or potential conflict of interest to report
- Jean-Marie Pflomm, Pharm.D., Editor in Chief: no disclosure or potential conflict of interest to report
- Brinda M. Shah, Pharm.D., Consulting Editor: no disclosure or potential conflict of interest to report
- Michael Viscusi, Pharm.D., Associate Editor: no disclosure or potential conflict of interest to report
- Describe the recommendations for extending the interval between the first and second primary doses of mRNA COVID-19 vaccines.
Primary-Series Dosing Interval for mRNA Vaccines
The CDC has issued new guidance allowing for an interval of up to 8 weeks between the first and second primary doses of an mRNA COVID-19 vaccine in certain patients 12-64 years old.1 Product labeling currently recommends a 3-week interval between the first two doses of the Pfizer/BioNTech mRNA vaccine (Comirnaty) and a 4-week interval between the first two doses of the Moderna mRNA vaccine (Spikevax). The new guidance is based on data suggesting that a longer interval can decrease the risk of myocarditis and may improve vaccine efficacy.
MYOCARDITIS – The mRNA COVID-19 vaccines have been associated with myocarditis and/or pericarditis. Myocarditis occurs more frequently with the Moderna vaccine than with the Pfizer vaccine. Its incidence is highest in males 12-39 years old following their second primary dose, but even in this cohort, it is rare (<0.05% with either vaccine).2
SAFETY DATA – A retrospective population cohort study estimated rates of myocarditis in persons who received at least one dose of an mRNA COVID-19 vaccine in Ontario, Canada over a period of ~8.5-months. The incidence of myocarditis with a second primary dose was significantly greater when the interval from the first dose was ≤30 days than when it was ≥56 days (unadjusted relative risk 5.5 [95% CI 3.1-9.6] with the Pfizer vaccine and 5.2 [95% CI 2.6-10.0] with the Moderna vaccine).3
EFFICACY DATA – In an observational study in 589 healthcare workers in the UK who received 2 doses of the Pfizer vaccine, neutralizing antibody and T-cell responses were greater with a longer interval between doses (6-14 weeks) than with a shorter interval (2-5 weeks).4 In case-control studies in Canada and England, longer dosing intervals were associated with higher vaccine efficacy rates, but these studies were completed before the emergence of the Omicron variant of SARS-CoV-2.5,6
RECOMMENDATIONS – According to the CDC, an 8-week interval between the first and second doses of an mRNA COVID-19 vaccine primary series may be optimal for certain persons ≥12 years old, especially males 12-39 years old. A standard 3- or 4-week interval between the first two doses should still be used in adults ≥65 years old, persons who are moderately or severely immunocompromised, and those who require more rapid protection because of high levels of community spread of SARS-CoV-2 infection or a high risk of severe COVID-19.1
- CDC. Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States. February 22, 2022. Available at: https://bit.ly/38i7CIH. Accessed March 3, 2022.
- D Moulia. Myocarditis and COVID-19 vaccine intervals: international data and policies. ACIP Meeting. February 4, 2022. Available at: https://bit.ly/3IxhPjZ. Accessed March 3, 2022.
- SA Buchan et al. Epidemiology of myocarditis and pericarditis following mRNA vaccines in Ontario, Canada: by vaccine product, schedule and interval. medRxiv 2021 December 5 (preprint). Available at: https://bit.ly/36PBg9S. Accessed March 3, 2022.
- RP Payne et al. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Cell 2021; 184:5699.
- DM Skowronski et al. Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada. medRxiv 2021 October 26 (preprint). Available at: https://bit.ly/3K2i9rh. Accessed March 3, 2022.
- G Amirthalingam et al. Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England. Nat Commun 2021; 12:7217.
Booster Immunization in Persons Who Are Immunocompromised
The CDC has made the following updates to its recommendations for booster vaccination against COVID-19 in persons who are moderately to severely immunocompromised1:
- The recommended length of time between completion of a 3-dose primary series of an mRNA vaccine (Pfizer/BioNTech or Moderna) and administration of a booster mRNA vaccine dose has been reduced from 5 months to 3 months.
- Persons who have received 1 or 2 doses of the Johnson & Johnson (Janssen) vaccine should continue their vaccination series with an mRNA vaccine until they have received 3 total vaccine doses. An mRNA vaccine should be given ≥4 weeks after an initial Johnson & Johnson vaccine dose and/or ≥2 months after a second vaccine dose of any type. If the completed series will include only one mRNA vaccine dose, it should be a primary dose (Pfizer 30 mcg/0.3 mL or Moderna 100 mcg/0.5 mL). If the completed series will include 2 mRNA vaccine doses, one should be a primary dose and the other a booster dose (Pfizer 30 mcg/0.3 mL or Moderna 50 mcg/0.25 mL).
The Pfizer and Moderna vaccines are preferred over the Johnson & Johnson vaccine for all persons, including those who are immunocompromised. The Johnson & Johnson vaccine can still be offered to persons who would otherwise remain unvaccinated because they have a contraindication or objection to receipt of an mRNA vaccine.1
Increased Dosage of Tixagevimab/Cilgavimab (Evusheld)
The FDA has amended its Emergency Use Authorization (EUA) for the investigational long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) to increase the recommended dose of each drug from 150 mg to 300 mg.1 Evusheld is authorized for IM pre-exposure prophylaxis of COVID-19 in persons ≥12 years old who weigh ≥40 kg and have either a history of a severe adverse reaction that prevents their vaccination against COVID-19 or moderate or severe immune compromise.2
The revision was based on in vitro data showing that the neutralizing activity of Evusheld is reduced against the SARS-CoV-2 Omicron variants BA.1 (by 12- to 30-fold vs the ancestral virus) and BA.1.1 (by 176-fold). Evusheld retains a greater degree of neutralizing activity against the BA.2 Omicron variant (5.4-fold reduction vs the ancestral virus).3
The new recommended dosage of Evusheld is 300 mg of tixagevimab and 300 mg of cilgavimab administered as consecutive IM injections into separate sites (preferably one in each gluteal muscle). Patients who have already received 150-mg doses of the two drugs should receive an additional 150-mg dose of each as soon as possible. The duration of protection provided by an initial dose of Evusheld remains to be established; the FDA will recommend an interval for repeat dosing in the coming months based on changes in the prevalence of different SARS-CoV-2 variants.1,3
- FDA Drug Safety Communication. FDA authorizes revisions to Evusheld dosing. February 24, 2022. Available at: https://bit.ly/3K5AcNc. Accessed March 3, 2022.
- Tixagevimab and cilgavimab (Evusheld) for pre-exposure prophylaxis of COVID-19. Med Lett Drugs Ther 2022; 64:1.
- FDA. Fact sheet for health care providers: Emergency Use Authorization for Evusheld (tixagevimab co-packaged with cilgavimab). February 2022. Available at: https://bit.ly/3IWpQjg. Accessed March 3, 2022.
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