COVID-19, Vaccines
by David O. Freedman, M.D.
last updated
2023-03-20 08:09:20.586060-04:00
© Antimicrobial Therapy, Inc.
COVID-19 Vaccines, Vaccination Schedules
Introduction
- Last CDC vaccination recommendations update was December 9, 2022 to include bivalent vaccine doses for ages 6 mos - 4 yrs.
- Official CDC vaccine acronyms:
- 1vCOV-mRNA (Pfizer or Moderna),
- 2vCOV-mRNA (Pfizer or Moderna)
- 1vCOV-aPS (Novavax only)
- Data to February 2023: Additional VE of ~30% against infection 2 mos after bivalent booster (vs previous monovalent booster doses only) against hospitalization from current strains for approximately 3 months.
- IF >5 yrs of age, 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 yrs 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.
- A monovalent Novavax booster dose may be used in limited situations if >18 yrs 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.
- See below and individual vaccine page for vaccine doses, efficacy, adverse effects, and mix and match dosing : see Pfizer, Moderna, Janssen/J&J, Novavax, AstraZeneca
- Data for and against need for annual vaccination against SARS-CoV still under early study.
- Switch to bivalent vaccine for all doses imminent.
- Need for updates to current bivalent formulation remain uncertain.
Indications for Vaccination (US)
- All US persons age >6 mos should be vaccinated with a 2- or 3-dose primary series and booster regardless of a history of symptomatic or asymptomatic SARS-CoV-2 infection, presence of long COVID, or history of a SARS-Cov2 breakthrough infection.
- Defer vaccination until recovery from acute episode and discontinuation of isolation.
- After SARS-CoV-2 infection may consider delaying of next dose by 3 mos from symptom onset or positive test.
- For normal hosts:
- Age >12 yrs: 2 primary monovalent doses (Moderna, Pfizer, or Novavax) followed by 1 bivalent mRNA
booster dose >2 mos later.- A single (no further boosters subsequently) bivalent mRNA booster dose >2 mos 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;
- No monovalent vaccine boosters at any time; superces 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.
- A single (no further boosters subsequently) bivalent mRNA booster dose >2 mos from the previous monovalent vaccine dose for recipients of:
- Children ages 6–11 yrs: A 2-dose primary monovalent series and a one time single bivalent mRNA booster dose (Moderna or Pfizer-BioNTech) >2 mos after completion of primary series or the most recent monovalent booster dose with any vaccine.
- Children 5 yrs old: Use only Pfizer for bivalent booster after primary series as per 6-11 yrs olds.
- Ages 6 mos–4 yrs who receive a complete 2-dose monovalent Moderna primary series to receive 1 bivalent Moderna booster >2 mos after completion of primary series.
- 5 yrs olds may also receive bivalent Pfizer vaccine >2 mos after completion of the Moderna primary series.
- 5 yrs olds may also receive bivalent Pfizer vaccine >2 mos after completion of the Moderna primary series.
- Ages 6 mos–4 yrs: monovalent Pfizer vaccine for the first and second doses, followed by 1 bivalent Pfizer vaccine as the 3rd primary dose >8 wks after the second monovalent primary series dose.
- A bivalent booster dose (4th dose) is now authorized 2 mos after a previous 3-dose monovalent series of Pfizer.
- Age >12 yrs: 2 primary monovalent doses (Moderna, Pfizer, or Novavax) followed by 1 bivalent mRNA
- CDC schedule for immunocompromised persons (see Immunocompromised, HIV below).
U.S. CDC COVID-19 Vaccination Schedules
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 mos after a previous vaccine dose.
- 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.
- Complete list of EMA Approved Covid-19 Vaccines
WHO-approved COVID-19 Vaccines
- For WHO-approved vaccines (non-FDA approved), see WHO COVID-19 Vaccines Emergency Use Listing.
- Links to WHO EUL vaccine package inserts:
- AstraZeneca (Vaxzevria)
- FDA application withdrawn
- Sinopharm (Covilo)
- Janssen/J&J (Jcovden)
- Serum Institute of India (Covishield)
- Sinovac (Coronavac)
- Cansino (Convidecia)
- Bharat (Covaxin)
- AstraZeneca (Vaxzevria)
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 in inducing high VE against hospitalization for 3-6 mos.
- Bivalent boosters provide additional moderate increased VE (vs previous monovalent booster doses only) against hospitalization from current strains for approximately 3 months.
- Against hospitalization
- Late Omicron era: VE (median d since most recent dose) of monovalent mRNA vaccines against hospitalization in immunocompetent persons >18 yrs is 25% after 2 doses (445d), 34% after 3 doses (229d), and for persons >50 yrs 60% after 4 doses (84d).
- Absolute VE of 2 or more monovalent doses against hospitalization 19% and 28% for ages 18-64 and >65 respectively
- Relative VE (versus monovalent booster doses only) of bivalent booster at >7d and 2-4 mos since booster in adults >18 yrs: 52% and 31% respectively
- VE against omicron BA.4.6, BA.5, BQ.1, and BQ.1.1:
- Against severe infection over d 15 to 99 after receipt of one monovalent booster dose, VE was 25.2% (during Q2 2022) and the corresponding VE for one bivalent booster dose was 58.7% (during Q4 of 2022)(N Engl J Med, Jan 25, 2023, online ahead of print).
- VE equal in >65 yr group vs 12-64 yrs of age.
- Against severe infection over d 15 to 99 after receipt of one monovalent booster dose, VE was 25.2% (during Q2 2022) and the corresponding VE for one bivalent booster dose was 58.7% (during Q4 of 2022)(N Engl J Med, Jan 25, 2023, online ahead of print).
- Against symptomatic infection
- 4 doses of monovalent mRNA vaccine (compared to 3 doses; no 4th dose) has VE drops which drops from ~50% at 2 wks post dose 4 to ~35% at 3 mos.
- Children <5 yrs VE of ~40% for primary series against symptomatic infection, wanes after 4 mos. Moderna > Pfizer
- Relative VE (versus monovalent booster) of bivalent booster against symptomatic infection at 4-5 months since booster: 41%, 28%, 21% for age 18-49, 50-64, >65 respectively
- Meta-analysis on protection by previous infection and hybrid immunity. Lancet DOI:https://doi.org/10.1016/S0140-6736(22)02465-5
Choice, Interchangeability
- The same monovalent vaccine product should be used for all doses of the primary series (Pfizer, Moderna, Novavax).
- Exceptions: use bivalent Pfizer vaccine for primary dose 3 in ages 6 mos-4 yrs and use heterologous mRNA if homologous not available or possible.
- Bivalent Moderna vaccine is not authorized <6 yrs of age but bivalent Pfizer vaccine is authorized >5 yrs 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 mos
- 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 yrs 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-wks interval between the first and second primary series doses of Moderna, Novavax, and Pfizer-BioNTech COVID-19 vaccines may be optimal to reduce myocarditis.
- No safety signals for ischemic stroke with mRNA vaccines with primary doses or monovalent boosters in US or any other country.
- One small cluster of ischemic stroke after a bivalent booster in persons >65 at a single reporting site in 1 of several US CDC and Pfizer surveillance networks needs further investigation.
- Possible association with concomitant adjuvanted influenza vaccine needs study prior to 2023-24 flu season.
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 d before the minimum (21 or 28 d) 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 wks 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
- If possible, COVID-19 vaccines should be administered at least 2 wks before initiation or resumption of immunosuppressive therapies.
- 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.
- 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 primary series, no additional primary doses; immunocompromised schedule for the booster dose
- Revaccinate HCT or CAR-T-cell therapy recipients with an mRNA vaccine or Novavax >3 mos 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) begining at about 6 mos after completion of therapy.
- Administration of vaccines should not be delayed in patients on ongoing immunosuppressives.
- Administer vaccine doses approximately 4 wks before the next scheduled therapy for patients on ongoing B-cell-depleting therapies
- Tixagevimab/cilgavimab (EVUSHELD™) no longer recommended as prophylaxis
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
- 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 (WHO)
- See also
- Pre- and post-exposure prophylaxis: COVID-19, Prophylaxis
- Treatment and other aspects of COVID-19 management: COVID-19, SARS CoV-2