COVID-19, Vaccines
by David Freedman
last updated
2023-05-02 16:13:46
© Antimicrobial Therapy, Inc.
COVID-19 Vaccines, Vaccination Schedules
Introduction
- CDC’s latest recommendations (April 19, 2023) are that monovalent (original) mRNA vaccines are no longer recommended in the US.
- Almost the entire US population already has antibody against SARS-CoV-2 from previous infection or vaccination.
- Unvaccinated individuals need only to receive a single dose of a bivalent vaccine, rather than multiple doses of the original monovalent mRNA vaccines.
- A single additional bivalent vaccine dose for adults >65 years and 1 or more additional doses for people who are immunocompromised are now recommended.
- The updated FDA EUA states that most immunocompromised persons who have received a bivalent COVID-19 vaccine may receive a single additional dose of a bivalent vaccine >2 months following a dose of a bivalent vaccine, and additional doses may be administered at the discretion of, and at intervals determined by, their healthcare provider.
- All persons >6 yrs should receive a bivalent mRNA vaccine, regardless of previous completion of a monovalent primary series.
- Persons >6 yrs who have already received a bivalent mRNA vaccine need no further doses unless they are >65 years or immunocompromised.
- For young children, multiple doses continue to be recommended and vary by age, vaccine, and which vaccines were previously received. See Pfizer COVID-19 Vaccine and Moderna COVID-19 Vaccine
- Dosing for the moderately and severely immunocompromised remains complex (see table below) despite efforts to simplify the general immunization regimens.
- 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.
- Novavax remains monovalent only.
- Novavax remains authorized for use as a 2-dose primary series and as a booster dose in certain very limited situations.
- The Novavax booster dose (only if no previous boosters) must be administered >6 mos after a primary series of COVID-19 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 study and will be considered by ACIP in June 2023.
- Need for updates to current bivalent formulation remain uncertain.
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.
- 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:
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- Persons age >6 months should receive >1 dose of bivalent mRNA vaccine.
- Persons age >6 yrs who are unvaccinated or previously received only monovalent vaccine doses are recommended to receive 1 bivalent mRNA vaccine dose
- However persons >65 years may receive 1 additional bivalent mRNA vaccine dose.
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- CDC schedule for immunocompromised persons (see Immunocompromised, HIV below).
U.S. CDC COVID-19 Vaccination Schedules
- See Pfizer COVID Vaccine and Moderna COVID-19 Vaccine for <12 years of age schedule
- In general, persons should receive the age-appropriate vaccine product and dosage based on their age on the day of vaccination in accordance with the recommended intervals for that age group; certain 4 and 5 yr olds present exceptions.
- Normal Persons (not moderately or severely immunocompromised)
COVID-19 vaccination history | Bivalent vaccine | Bivalent doses indicated | Dosage (mL/ug) | Interval between doses |
Unvaccinated | Moderna | 1 | 0.5 mL/50 ug | NA |
Unvaccinated | Pfizer BioNTech | 1 | 0.3 mL/30 ug | NA |
1 or more doses monovalent mRNA (no doses bivalent mRNA) | Moderna | 1 | 0.5 mL/50 ug | >8 weeks after last monovalent dose |
1 or more doses monovalent mRNA (no doses bivalent mRNA) | Pfizer BioNTech | 1 | 0.3 mL/30 ug | >8 weeks after last monovalent dose |
Ever received 1 dose bivalent mRNA (regardless of monovalent vaccine history) | NA; previously received 1 bivalent vaccine dose | NA | NA | NA |
- Persons age 65 years and older have the option to receive 1 additional bivalent mRNA vaccine dose >4 months after the first dose of a bivalent mRNA vaccine. If Moderna is used, administer 0.5 mL/50 ug; if Pfizer is used, administer 0.3 mL/30 ug
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
- People ages >6 yrs years who previously received 1 or more doses of a monovalent mRNA vaccine may receive either bivalent Moderna or bivalent Pfizer vaccine.
- See individual vaccines pages for younger children.
- Janssen/J&J is a last resort vaccine (relatively increased toxicity) 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 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.
Moderately or Severely Immunocompromised, HIV
Ages 12 and up
- See Pfizer COVID Vaccine and Moderna COVID-19 Vaccine for <12 years of age schedule
COVID-19 vaccination history | Bivalent vaccines | # Bivalent doses indicated | Dosage (mL/ug) | Interval between doses |
Unvaccinated | Moderna† | 3 | 0.5 mL/50 ug | Dose 1 & Dose 2: 4 weeks Dose 2 & Dose 3: >4 weeks |
Unvaccinated | Pfizer BioNTech‡ | 3 | 0.3 mL/30 ug | Dose 1 & Dose 2: 4 weeks Dose 2 & Dose 3: >4 weeks |
1 dose monovalent Moderna | Moderna† | 2 | 0.5 mL/50 ug | Dose 1: 4 weeks after monovalent dose Dose 1 & Dose 2: >4 weeks |
2 doses monovalent Moderna | Moderna† | 1 | 0.5 mL/50 ug | >4 weeks after last monovalent dose |
3 doses monovalent Moderna | Moderna | 1 | 0.5 mL/50 ug | >8 weeks after last monovalent dose |
3 doses monovalent Moderna | Pfizer BioNTech | 1 | 0.3 mL/30 ug | >8 weeks after last monovalent dose |
3 doses monovalent Moderna and 1 dose bivalent mRNA | NA | See footnote | NA | NA |
1 dose monovalent Pfizer | Pfizer BioNTech‡ | 2 | 0.3 mL/30 ug | Dose 1: 3 weeks after monovalent dose Dose 1 & Dose 2: >4 weeks |
2 doses monovalent Pfizer | Pfizer BioNTech‡ | 1 | 0.3 mL/30 ug | >4 weeks after last monovalent dose |
3 doses monovalent Pfizer | Moderna | 1 | 0.5 mL/50 ug | >8 weeks after last monovalent dose |
3 doses monovalent Pfizer | Pfizer BioNTech‡ | 1 | 0.3 mL/30 ug | >8 weeks after last monovalent dose |
3 doses monovalent Pfizer and 1 dose bivalent mRNA | NA | See footnote | NA | NA |
- Footnotes
- Immunocompromised persons ages >12 yrs have the option to receive 1 additional dose of Moderna (0.5 mL/50 ug); or Pfizer (0.3 mL/30 ug; gray cap ) >>2 months following the last recommended bivalent dose. Further additional dose(s) may be administered, informed by clinical judgement and personal preference and circumstances > 2 months after the last vaccine dose.
- ‡Pfizer-COVID-19 Vaccine is also authorized in this age group with this vaccination history (0.3 mL/30 ug).
- †Moderna COVID-19 Vaccine is also authorized in this age group with this vaccination history (0.5 ml/50 ug).
- If possible, COVID-19 vaccines should be administered >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.
- On a case-by-case basis, providers may administer Moderna, Novavax, and Pfizer vaccines outside of the FDA and CDC dosing intervals using a risk-benefit approach together with clinical experience and judgement.
- 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.
- If antibody testing is done, vaccination should be completed as recommended regardless of the antibody test result.
- Prior receipt of a COVID-19 vaccine will not affect the results of SARS-CoV-2 viral tests (nucleic acid amplification or antigen tests).
Comments
- 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