COVID-19, Vaccines

by David O. Freedman, M.D. last updated 2022-11-27 15:18:49.882316-05:00 © Antimicrobial Therapy, Inc.
COVID-19 Vaccines, Vaccination Schedules

Introduction

  • CDC vaccination recommendations updated as of Sept 1, 2022 for new bivalent booster vaccines.
  • Official CDC vaccine acronyms: 
    • 1vCOV-mRNA (Pfizer or Moderna), 
    • 2vCOV-mRNA (Pfizer or Moderna)
    • 1vCOV-aPS (Novavax only)
  • Omicron-containing booster vaccines (all booster doses now bivalent) should retain neutralization for original SARS-CoV-2, induce a strong response against BA.5 and induce broad cross-neutralization against future variants.
  • Pfizer-BioNTech COVID-19 Vaccine, Bivalent (original and Omicron BA.4/BA.5), is restricted to use in individuals ≥5 years  as a one-time only booster >2 months after
    • primary vaccination with any monovalent vaccine
    • the most recent monovalent booster dose with any vaccine.
  • Identical indications for Moderna COVID-19 Vaccine, Bivalent, but for age >6 years.
  • Only monovalent and not bivalent vaccines for primary series doses if unvaccinated
  • Novavax is monovalent only; not useable for boosters
    • A monovalent Novavax booster dose may be used in limited situations if  >18 years with a complete primary series of any COVID-19 vaccine, have not received any previous booster doses, and are unable or unwilling to receive an mRNA vaccine.  The monovalent Novavax booster dose (only if no previous boosters) must be administered >6 mos after primary series not at >2 mos as with mRNA first boosters.

  • See below and individual vaccine page for vaccine doses, efficacy, adverse effects, and mix and match dosing : see Pfizer, Moderna, Janssen/J&J, NovavaxAstraZeneca

Indications for Vaccination (US)

  • All US persons age >6 mos should be vaccinated regardless of a history of symptomatic or asymptomatic SARS-CoV-2 infection, presence of long COVID, or history of a SARS-Cov2 breakthrough infection. As of September 1, 2022 all previous booster guidelines are superseded. For normal hosts:
    • Age >12 yrs: 2 primary monovalent doses (Moderna, Pfizer, or Novavax) followed by 1 bivalent mRNA
      booster dose >2 months later.
      • A single (no further boosters subsequently) bivalent mRNA booster dose >2 months from the previous monovalent vaccine dose for recipients of:
        • Primary (monovalent) series only
        • Primary series + 1 booster; or
        • Primary series + 2 boosters 
      • Only bivalent vaccine should be used for boosters after a primary series;
        • Heralds apparent move to annual COVID/influenze vaccine programs
      • No monovalent vaccine boosters per previously recommended schedules/intervals
      • CDC up-to-date status: 1) a primary series and receipt of the most recent booster dose recommended by CDC required.
    • Children ages 6–11 yrs: A 2-dose primary monovalent series and 1 bivalent mRNA booster dose (Moderna or Pfizer-BioNTech).  Bivalent booster dose >2 months aftlelr completion of primary series.
    • Children 5 yrs old: Use only Pfizer for bivalent booster after primary series as per 6-11 year olds.
    • Children 6 mos-4 yrs:  Monovalent Moderna=2 doses and Pfizer=3 doses for primary series. No boosters of any kind at present.
  • CDC schedule for immunocompromised persons (see Immunocompromised, HIV below).

U.S. CDC COVID-19 Vaccination Schedules

COVID19-vaccination-schedule-most-people-10-23-22.png

EMA-approved COVID-19 Vaccines

  • EMA-approved vaccines (non-FDA approved)
    • VidPrevatyn (Sanofi;GSK), monovalent adjuvanted protein vaccine based on the Beta Variant, is EMA approved (>18 yrs) to be given once as boosters for persons given mRNA or adenovirus vaccines.  
    • Wait >4 months after a previous vaccine dose.
  • Complete list of EMA Approved Covid-19 Vaccines

WHO-approved COVID-19 Vaccines

Efficacy, Duration of Protection

  • Time since most recent COVID-19 vaccine dose is likely more important than cumulative number of doses.
    • With continued viral evolution, after the primary series and the critical first booster, each booster dose stands on its own induces high VE against hospitalization for 3-6 months
  • Against hospitalization
    • 2021: 2 doses of original monovalent mRNA vaccine had VE of >90%; VE remained high through early Omicron.
    • BA.5 era: VE (median days since most recent dose) of monovalent mRNA vaccines against hospitalization in immunocompetent persons >18 years is 25% after 2 doses (445d), 34% after 3 doses (229d), and for persons >50 yrs 60% after 4 doses (84d).
  • Against symptomatic infection
    • 3 doses of monovalent mRNA vaccine (compared to unvaccinated) in the BA.5 era has VE which drops from ~50% at 2 wks post-vaccination to 20% at 3 months.
    • 4 doses of monovalent mRNA vaccine (compared to 3 doses; no 4th dose) has VE drops which drops from ~50% at 2 weeks post dose 4 to ~35% at 3 months.
  • Bivalent boosters
    • Clinical data to date derived from human immunogenicity (no efficacy data) studies on BA.1 (not BA.4/5) containing bivalent vaccines only
      • Immune responses to BA.1 were modestly superior in bivalent boostees compared to recipients of the original monovalent boosters.
    • Mouse data only: modest superiority of boosting with BA.4/5 bivalent vaccine vs. monovalent vaccine
    • The 2-month interval for a bivalent booster in persons already multiply boosted is arbitrary and considerable evidence on boosters in general indicates a longer interval is be optimal; further study is required.

Choice, Interchangeability

  • The same monovalent vaccine product should be used for all doses of the primary series (Pfizer, Moderna, Novavax).
    • Bivalent Moderna vaccine is not authorized <6 years of age but bivalent Pfizer vaccine is authorized >5 years old
  • Either homologous or heterologous age-appropriate bivalent mRNA vaccine for the bivalent booster dose except Pfizer only in 5 yr olds. 
  • Novavax is a recombinant protein sub-subunit, adjuvanted vaccine made by conventional production; with mRNA vaccines the recipient's body makes the same SARS-CoV-2 protein after injection of the mRNA
  • Janssen/J&J is a last resort vaccine and is not readily available
  • Pre-Omicron data indicate that the Moderna vaccine has both a VE and durability advantage over the Pfizer vaccine (higher mRNA dose in monovalent doses)

Toxicities

Contraindications

  • See individual vaccine pages
  • Recent exposure to SARS-CoV-2 is not a contraindication or precaution to COVID-19 vaccination.

Precautions

  • See individual vaccine pages
  • Recent SARS-CoV-2 infection may allow consideration of delaying a primary series dose or booster dose by 3 months
    • Increased interval may improve immune response to vaccination.
  • Administration of an antiviral drug pre- or post-vaccination unlikely to impair response

Adverse Effects

  • See individual vaccine pages for minor adverse effects
  • Safety similar whether monovalent or bivalent vaccine is used as a 4th dose (2nd booster)
  • Myocarditis: 131 myocarditis cases reported to VAERS after 123 million mRNA booster vaccinations
    • Risk primarily in adolescent and young adult males
    • No increase in children ages 5–11 years following 1st booster
    • Rates are lower following 1st booster dose vs. dose 2 of primary series (and lower following dose 1 vs. dose 2 of primary series)
    • An 8-week interval between the first and second primary series doses of Moderna, Novavax, and Pfizer-BioNTech COVID-19 vaccines may be optimal to reduce myocarditis.

Drug Interactions

  • Influenza (including HD or adjuvanted) and COVID-19 vaccines to be given at the same visit, if eligible.
  • COVID-19 vaccines may be administered without regard to timing of other vaccines.
  • Dose 2 administered no more than 4 days before the minimum (21 or 28 day) interval is valid; however, do not repeat an inadvertent dose administered earlier
  • No minimum interval between COVID-19 vaccination and monkeypox vaccine
  • Consider waiting 4 weeks after monkeypox vaccination before COVID-19 vaccination to minimize myocarditis

Special Populations

Pregnancy, Breastfeeding

  • Vaccinate according to standard recommendations if pregnant, breastfeeding, attempting or contemplating conception
    • Pregnant and recently pregnant persons at increased risk for severe illness and the fetus is at increased risk
  • Benefits outweighs risks of vaccination
  • Antibodies are transferred to the newborn
  • No contraindications to breastfeeding

Immunocompromised, HIV

COVID19-vaccination-schedule-immunocompromised-10-23-22.png

  • Reference: At-A-Glance COVID-19 Vaccination Schedules (CDC)
  • Persons with HIV not at higher risk of severe disease after completing vaccination. 
    • severe disease risk higher if CD4<350 even with vaccination;  ensure up to date with bivalent boosting and educate to seek prompt treatment of infection. 
  • NCCN recommends against Novavax in active cancer patients unless no choice.
    • Self-attestation to moderately or severely immunocompromised status is acceptable
  • New immunocompromise after a 2-dose mRNA primary series do not need additional primary doses;  immunocompromised schedule for the booster dose.
  • Revaccinate HCT or CAR-T-cell therapy recipients with an mRNA vaccine or Novavax >3 months after HCT or CAR-T-cell therapy 
  • Consider revaccination if 1 or more doses of vaccine (primary series and bivalent booster doses) received during short-course treatment with B-cell-depleting therapies (e.g., rituximab, ocrelizumab)  beginning at about 6 months after completion of therapy
  • Administration of vaccines should not be delayed in patients on ongoing immunosuppressives
    • Administer vaccine doses approximately 4 weeks before the next scheduled therapy for patients on ongoing B-cell-depleting therapies
  • In addition to following the recommended COVID-19 vaccination schedule, tixagevimab/cilgavimab (EVUSHELD™), should be administered to the  immunocompromised every 6 months.  See COVID-19, Prophylaxis.
    • No delay of vaccination following tixagevimab/cilgavimab.
    • Delay tixagevimab/cilgavimab for at least 2 weeks after a vaccine dose.

Serologic Testing

  • Antibody testing is not recommended to assess for immunity following COVID-19 vaccination or to assess the need for vaccination in an unvaccinated person
    • No correlates of protection are available and assays vary widely
    • +ve IgG only minimally reassuring, -ve IgG unhelpful in patients whose ability to mount a B-cell response is uncertain

Comments

  • Age-appropriate vaccine product and dosage is based on age on the day of vaccination.
    • a move from a younger age group to an older age group during the primary series, requires the vaccine product and dosage for the older age group
  • Vaccines are not recommended for outbreak management or for post-exposure prophylaxis
  • mRNA vaccines do not have a risk of modifying the vaccine recipient’s genetic makeup as mRNA does not enter cell nucleus where host DNA is located.
  • Vaccine pipeline: https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/
  • See also