COVID-19, Vaccines, Prevention

by David O. Freedman, M.D. last updated 2022-01-11 08:42:20.109708-05:00 © Antimicrobial Therapy, Inc.
COVID-19 Post-exposure Prophylaxis, Primary Prevention, Vaccines

Primary Prevention, Prophylaxis

  • Primary prevention / pre-exposure prophylaxis for at risk individuals
    • Evusheld (tixagevimab + cilgavimab), administered as two separate consecutive intramuscular injections (one injection per monoclonal antibody, given in immediate succession), may only be used as PRE-exposure prophylaxis for adults and pediatric individuals (12 years of age and older weighing at least 40 kg) who are not currently infected with SARS-CoV-2 and who have not recently been exposed to an individual infected with SARS-CoV-2, and who have:
      • Moderate to severely compromised immune systems due to a medical condition or due to taking immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination (examples of such medical conditions or treatment s can be found in the fact sheet for health care providers) or
      • A history of severe adverse reactions to a COVID-19 vaccine and/or component(s) of those vaccines, therefore vaccination with an available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended.
    • Evusheld is approved through an EUA for pre-exposure prophylaxis, but is NOT approved for post-exposure prophylaxis nor for treatment of active, current SARS-CoV-2 infection
    • In the pivotal, RC clinical trial, Evusheld recipients had a  77% reduced risk of developing COVID-19 compared to those who received a placebo.  The estimated durability of Evusheld is up to 6 months protection.
  • Primary prevention / post-exposure prophylaxis for previously uninfected household contacts:
    • REGEN-COV, administered 1200 mg as REGEN-COV (600 mg Casirivimab + 600 mg Imdevimab ) subcutaneously one time, OR  Bamlanivimab (700 mg) and etesevimab (1400 mg), administered intravenously together, may only be used as post-exposure prophylaxis for adults and pediatric individuals (12 years of age and older weighing at least 40 kg) who are:
      • At high risk for progression to severe COVID-19, including hospitalization or death and
      • Not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, people with immunocompromising conditions, including those taking immunosuppressive medications) and
        • Have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC), or
        • Who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes or prisons)
    • Relative risk reduction 81.4% relative risk reduction in COVID-19 infection (N Engl J Med, Aug 4, 2021)

Vaccine Preferences (US)

  • Vaccine information is divided into summary tables for US and WHO authorized vaccines and individual vaccine pages. See below. For complete information covering efficacy, adverse effects, and mix and match dosing considerations for primary and booster doses: see Pfizer, Moderna, Janssen/J&J, NovavaxAstraZeneca, SinoPharm, Sinovac, Sputnik, Bharat.
  • Important Note:
    • Other than hypertransmissibility and high peak viral loads, current understanding of SARS-CoV-2 infection with the currently predominant Omicron variant, is incomplete.
      • Most knowledge of clinical, epidemiologic, therapeutic, and diagnostic aspects of infection and COVID-19 are based on studies done in the pre-Omicron era and most recommendations based on references that pre-date Omicron should be interpreted in that context. 
      • We will continue to update COVID-19 information and recommendations based on new developments.
  • Vaccine Efficacy (VE) Against the Omicron Variants
    • VE based on breakthrough infections and hospitalizations in the Omicron era is increasingly difficult to calculate due to the variability in vaccine types, numbers of doses, and spacing of doses in the general population, and due to the decentralized data collection mechanisms in countries with federal structures (including the US).
    • Available observational and laboratory-based data (neutralizing titers) continue to support the need for triple vaccination in those with no history of prior infection.
    • Several robust studies estimate a 4- to 6-fold reduction in neutralizing antibody titers and an approximately 20% drop in vaccine efficacy (VE) against symptomatic illness due to Omicron to <75%  in persons triple vaccinated with the Pfizer vaccine although VE against hospitalization remains >90%.
    • The duration of vaccine efficacy in triple vaccinated persons remains unclear, but T-cell immunity which protects against severe disease appears to last at least 6 months.
    • Recipients of 2 doses of mRNA vaccine appear to have zero or minimal neutralizing antibody titers against Omicron
      • booster doses of non-mRNA vaccines are unproven in preventing population transmission with Omicron.
  • Bottom-line vaccination messaging for the three vaccines currently approved in the US :
    • Only mRNA vaccines (Pfizer, Moderna) should be used
      • Janssen/J&J has been demoted to second-line for uncommon situations due to wide availability of mRNA vaccines and complete absence of life-threatening adverse effects
      • In resource limited environments Janssen/J&J vaccine with ease of storage will still save lives when other vaccines not available.
    • Three doses of mRNA vaccine or a heterolgous adenovirus then mRNA series are the only current effective strategies against the Omicron variant; prior COVID infection likely can substitute for 1 of the 3 vaccines doses.
    • mRNA vaccine partially reduces the ability to infect somebody else with Omicron but not to the extent to which transmission blocking occurred in the pre-delta variant era.
    • A third vaccine dose in immunocompromised persons is not a booster but rather an additional primary dose to induce initial immunity in those unable to achieve it in the first place.
      • Dose 4  as a booster in the immunocompromised population is now recommended.
  • Direct in vitro comparison of vaccines. Pre-Omicron functional antibody testing with a panel of 9 SARS-CoV-2 viral variant spike proteins (n = 196 subjects) revealed marked differences in vaccine responses 2 to 3 months after full vaccination in Mongolia.
    • For example, low-blocking antibody levels were stimulated by the Sinopharm (15%), Gamaleya (26%), and AstraZeneca (38%) vaccines in comparison to the Pfizer (88%) vaccine.  Vaccine efficacy (VE) cannot be extrapolated from these data and vaccinees were enrolled retrospectively.
  • Against pre-Omicron SARS-COV-2 variants, substantial data indicate that the Moderna vaccine has both a VE and durability advantage over the Pfizer vaccine (likely due to the higher mRNA dose in the primary series), and that a single dose of Janssen/J&J vaccine, which is no longer a preferred vaccine in the US is inadequate. Comparison data after the 3rd dose (6-month booster) of mRNA vaccines are not yet available
    • Two primary doses of an adenovirus vectored vaccine (Astra Zeneca or Janssen) are robust in preventing severe disease in the short run, but given an mRNA vaccine for dose 2 is a significantly superior strategy.
    • Adenovirus vaccines are progressively less favored by guideline making bodies in countries where vaccine supplies are ample.
  • Sinovac vs. Pfizer: RCT from Hong Kong of a third dose of the Sinovac vaccine (n = 40) versus the Pfizer vaccine (n = 40) in nonresponders to 2 doses of the Sinovac vaccine (age range: 34-73 years).
    • The Pfizer vaccine elicited significantly higher neutralizing antibodies (nAbs; 95% against delta variant)  than the Sinovac vaccine (49% against delta variant).

Authorized Vaccines

U.S. FDA Authorization

  • The following COVID-19 vaccines have U.S. FDA authorization
  • Janssen/J&J vaccine is now considered second line only to be used in extenuating circumstances
  • See individual vaccine pages for complete summaries: Pfizer, Moderna, J&J

Pfizer-BioNTech COVID-19 Vaccine (Comirnaty, mRNA BNT162b2)

Moderna COVID-19 Vaccine (Spikevax, mRNA-1273) Janssen COVID-19 Vaccine
(Janssen/Johnson & Johnson,
Ad26.COV2.S). No longer a preferred vaccine in the US.

See vaccine page for full details

See vaccine page for full details See vaccine page for full details

≥ 12 yrs in US/Canada/EU. ≥ 18yrs
most other countries. 5-11 year old authorization for pediatric dose (10 μg) in US/Canada. Three dose series for age <5 yrs; EUA in expected end Q2 2022.

≥ 18 yrs (100 µg in USA/Canada/EU). ≥ 12 yrs in Canada/EU (100 µg per dose)

≥ 18 yrs

Type Lipid nanoparticle (LNP) encapsulated mRNA Lipid nanoparticle (LNP) encapsulated mRNA Non-replicating adenovirus vector
Primary Dosing in persons >12 years (including immunocompromised; including additional primary dose)
0.3 mL IM (30 µg); 2 doses 21 days apart (indefinite delay is acceptable). Higher nAb titers with increased dosing interval to 12 weeks.
Severe immunocompromise: additional primary dose (dose 3, 0.3 mL; 30 µg) 28 days after dose 2
0.5 mL IM (100 µg); 2 doses 28 days apart (indefinite delay is acceptable). Not approved in US for ages 12-17.
Severe immunocompromise:  additional primary dose (100 µg; dose 3) 28 days after dose 2. However give 50 µg as additional primary dose 2 months after a primary dose of Janssen/J&J.
0.5 mL IM (5 X 1010 virions) x 1 dose including immunocompromised persons.
Primary Dosing in persons 5-11 years (including immunocompromised; including additional primary dose)

0.2 mL IM (10 µg) pediatric preparation; 2 doses 21 days apart (indefinite delay is acceptable).

Severe immunocompromise:  Additional primary dose (dose 3, 0.2 mL; 10µg): at least 28 days after dose 2.

 Not approved.  Not approved.
Booster Dosing (US guidelines presented; wide national variations regarding boosters)

0.3 ml IM  (30 µg) same as primary dose in persons aged >12 years, 5 months after completion of primary series. For immunocompromised adults this is dose 4 (30 µg) to be given 6 months after dose 3.


Pfizer vaccine (30 µg) can be used to boost a primary series of Moderna or Janssen/J&J vaccine in approved age groups.


For children 5-11 months no booster doses are recommended, including in immunocompromised persons.

0.25 ml, (half-primary dose; 50 µg) IM 5
months after completion of primary series in persons >18 years. For immunocompromised this is dose 4 (50 µg) to be given 5 months after dose 3.  Moderna vaccine (50 µg) can be used to boost a primary series of Pfizer or Janssen/J&J vaccine.

0.5 ml IM (same as dose 1) given at least 2 months after the first Janssen/J&J dose—may be give to all persons aged ≥ 18 years, including immunocompromised persons but An mRNA vaccine is preferred for this dose in previous Janssen/J&J vaccinees. No additional doses recommended 5 months later as with mRNA vaccine.  

WHO Authorization

  • The following COVID-19 vaccines have WHO and/or other regulatory authorization
  • These vaccines also satisfy U.S. vaccination requirements for entry into the United States
  • See individual vaccine pages for complete summaries: NovavaxAstraZeneca, SinoVac, SinoPharm, Bharat
Vaccine AstraZeneca COVID-19 Vaccine 
(Vaxvevria, Covishield (India), AZD1222,
SinoVac COVID-19 Vaccine (CoronaVac) Sinopharm/Beijing
Institute of Biological Products COVID-19 Vaccine (BBIBP-CorV)
Bharat COVID-19 Vaccine (Covaxin) Novavax COVID-19 Vaccine (Nuvaxovid, Covovax (India), NVX-CoV2373). FDA EUA application to be filed in late January 2022
  See vaccine page for full details See vaccine page for full details See vaccine page for full details See vaccine page for full details See vaccine page for full details
Age ≥ 18 yrs. Trial for age 6-17 yrs currently paused. Many countries not using in adults under 60 due
to thrombosis AE.
≥ 18 yrs ≥ 18 yrs ≥ 18 yrs  ≥ 18 yrs
Type Nonreplicating chimpanzee adenovirus vector Inactivated Inactivated Inactivated  Recombinant protein subunit
Primary Dosing in adults (including immunocompromised; including additional primary dose
0.5 mL IM; 2 doses 4-12 wks apart (UK & EU) and 4 wks in US trial. 8-12 wks under WHO EUL 2 doses 14 or 28 days apart 2 doses 14 or 21 days apart 2 doses 28 days apart  2 doses 21 days apart
Booster Dosing (WHO guidelines presented; wide national variations regarding boosters)
No application in process. Booster recommendations may be to use an mRNA vaccine Booster at 6 months after Dose 2 implemented in several countries. WHO recommends 3rd dose for persons over 60 and 1-3 months after dose 2 in immunocompromised but labels as 3rd dose in a primary series. WHO EUL recommends 3rd dose for persons over 60 and 1-3
months after dose 2 in
immunocompromised but labels as 3rd dose in a primary series.
No recommendation  No recommendation

Development Scorecard

  • Current vaccine scorecard
    • 333 candidates, 117 in clinical trials, 36 in Phase III.  23 in use in at least 1 country. Tables above list those in current use in multiple countries or with authorization from FDA, EMA, or WHO EUL.
      • All current vaccines express similar antigenic components related to the original SARS CoV-2 strain isolated in China.  Three doses of mRNA vaccines clearly induce neutralizing antibody effective against all known variants. 
        • Trials of modified vaccines to include antigenic determinants derived from the delta and omicron variants have yet to reach Phase 2.

Advanced Pipeline

  • A preliminary analysis (press release) indicates that 1 booster dose of a candidate adjuvanted recombinant protein vaccine targeting the original SARS-CoV-2 parent strain virus (Sanofi/GSK joint venture) given between 4 and 10 months after a complete primary vaccination schedule of another vaccine elicited a 9- to 43-fold range increase in nAbs for all age groups tested (n = 521). Results were similar whether the primary vaccine received was AstraZeneca, Janssen/J&J, Moderna, or Pfizer.
  • Some investigators believe that a heterologous boost with an inactivated vaccine after priming with either an mRNA vaccine or an adenovirus-vectored vaccine may provide a more long-term immune response. A Phase 3 trial of this vaccine candidate as a 2-dose primary series is also underway as populations around the world are increasingly exposed to COVID-19 variants; results are expected in the first quarter of 2022.


  • Definition of fully-vaccinated person for purposes of public health, mandates or US entry.  US FDA-authorized/approved vaccine: ≥ 2 weeks following receipt of the second dose in a 2-dose series (Moderna [aged ≥ 18 years: 0.5 mL; 100 µg] or Pfizer [aged 5-11 years: 0.2 mL; 10 µg or aged ≥ 12 years: 0.3 mL; 30 µg]) or ≥ 2 weeks following receipt of 1 dose of a single-dose series (Janssen/J&J [aged ≥ 18 years: 0.5 mL; 5x1010 viral particles]).  Boostered persons will likely to be classified shortly as "persons fully up-to-date on vaccination".
  • SARS-Cov-2 experienced persons: 
    • Independent high-quality studies indicate that previously SARS-CoV-2–infected persons have an equal or better neutralizing antibody response including against viral variants after 1 dose of mRNA vaccine when compared to persons who received 2 doses but had not had SARS-CoV-2 infection.
    • A second vaccine dose in previously infected persons does not induce a further titer rise against early SARS-CoV-2 strains but appears beneficial in increasing antibody titers against Omicron. Almost certainly 1 vaccine dose appears adequate for those with previous COVID-19. 
    • In vitro data indicates memory B cells persist for >1 year and that reactivity against T-cell epitopes found in the omicron variants is intact in doubly vaccinated persons for 6 months or more.
      • Natural immunity induced by earlier variants appears weak against omicron.
  • Quarantine and vaccination: 
    • No quarantine (applies to exposed persons fully up-to-date on vaccination) is recommended for the following persons, but they should test on day 5; if the test result is positive or symptoms develop, they should isolate;
      • Aged ≥ 18 years and received all recommended COVID-19 vaccine doses
      • Aged 5-17 years and completed a COVID-19 primary vaccination series
      • Any aged persons with confirmed COVID-19 within the past 90 days (positive viral test result); no test recommended on day 5.
    • Persons already in quarantine because of an exposure should not be vaccinated until quarantine is over.
  • Additional considerations
    • 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 the wide variety of antibody assays have variable targets (not all related to vaccine response) and performance. 
      • With no correlate of immunity; +ve IgG only minimally reassuring, -ve IgG unhelpful in patients whose ability to mount a B-cell response is uncertain such as transplant recipients and people on anti-B cell therapies.
    • Persons with recent (time period now undefined) documented acute symptomatic or asymptomatic SARS-CoV-2 infection should be vaccinated.
      • Risk of reinfection likely increases with time following initial infection. 
      • In acute illness, including for those who develop SARS-CoV-2 infection after the first vaccine dose but before receipt of the second dose, vaccination should be deferred until criteria for discontinuing isolation have been met
    • Currently available vaccines are not recommended for outbreak management or for post-exposure prophylaxis (vaccination to prevent the development of SARS-CoV-2 infection in a person with an exposure).
    • The majority of persons are protected by 12 days after the first dose but this single-dose immunity may well be very transient without a second dose.
    • If Dose 2 is administered no more than 4 days before the minimum (21 or 28 day) interval it is considered valid; however, a dose inadvertently administered > 4 days before the minimum interval does not need to be repeated.
    • Other non-COVID vaccines notably influenza vaccine may be administered simultaneously with or at any interval before or after any SARS-CoV-2 vaccine dose.
    • 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. 
      • Adenovirus vaccine DNA in the nucleus has deletions of critical genes therefore cannot replicate and cannot integrate into DNA. 
  • Further detail:

Management of COVID-19