FAQ Module: COVID-19
Frequently Asked Questions on COVID-19 Epidemiology, Prevention, and Clinical Management

Released: June 01, 2022

Expiration: May 31, 2023

Arthur Kim
Arthur Kim, MD
Sharon R. Lewin
Sharon R. Lewin, AO, FRACP, PhD, FAHMS
Renslow Sherer
Renslow Sherer, MD

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Any suggestions regarding boosters for those who have had COVID-19, then were vaccinated, and are now eligible for a booster?

Short Answer: The patient should receive the standard booster.

Renslow Sherer, MD (May 23, 2022):
For the BNT162b2 (Pfizer BioNTech) vaccine, a booster dose is available for everyone aged 5 years or older, 5 months after completing the primary series. For the mRNA-1273 (Moderna) vaccine, a booster dose is available for adults aged 18 years or older, 5 months after the last dose in their primary series.

For the Ad26.COV2.S (Janssen) vaccine, a booster dose is available for everyone aged 18 years or older, 2 months after their first dose.

Any of these 3 COVID-19 vaccines can be used for the booster dose for those aged 18 years or older, but the CDC gives preference to patients receiving a booster with 1 of the 2 mRNA vaccines.CDC Booster BNT162b2 is the only authorized booster vaccine for children aged 5 to less than 18 years.

The CDC has recently approved second boosters for adults aged 50 years or older, people aged 12 years or older with moderate to severe immunocompromise, and people who received 2 doses of the Ad26.COV2.S vaccine. The second booster must be an mRNA vaccine and can be administered 4 months or more after the first booster.CDC Booster

What should be the timing of boosters for those with breakthrough COVID-19 infections after vaccination?

Short Answer: There are no specific data for this scenario, but there is no reason to alter the standard booster interval.

Renslow Sherer, MD (January 7, 2022):
COVID-19 vaccines, although highly effective, are not 100% effective at preventing COVID-19.CDC Breakthrough Infections A breakthrough infection occurs when a fully vaccinated person becomes infected with SARS-CoV-2. Everyone aged 18 years or older should get a booster dose, and those aged 12-17 years can get a booster dose with the BNT162b2 vaccine if that was the vaccine they originally received.CDC Booster Adults aged 50 years or older, people aged 12 years or older with moderate to severe immunocompromise, and people who received 2 doses of the Ad26.COV2.S vaccine can get a second booster.CDC Booster

For an otherwise healthy patient who has received 2 doses of the BNT162b2 vaccine, would you recommend a booster of BNT162b2 or mRNA-1273?

Short Answer: Either is acceptable, and the CDC does not give preference to one over the other with the exception of BNT162b2 being the only authorized booster for children aged 5 to less than 18 years. Current evidence suggests that the antibody responses following boosters with these 2 regimens are robust, durable, and comparable between the BNT162b2 and mRNA-1273.

Renslow Sherer, MD (May 23, 2022):
Any of the COVID-19 vaccines currently authorized in the United States can be given as a booster for those aged 18 years or older.CDC Booster For patients who received their primary series with BNT162b2 or mRNA-1273, they may receive either of those vaccines as a booster. For those aged 5-17 years, only the BNT162b2 vaccine is authorized as a booster.

In a preliminary report by Atmar and colleagues,Atmar 2021 using BNT162b2 or mRNA-1273 as a booster increased the neutralizing antibody activity substantially more than using Ad26.COV2.S did.

Even though any of the 3 currently available COVID-19 vaccines may be used as a booster for those aged 18 years or older, preference should be given to receiving an mRNA vaccine booster with either BNT162b2 or mRNA-1273.CDC Booster For adults aged 50 years or older receiving a second booster, the second booster must be an mRNA vaccine. For people aged 12-17 years receiving a second booster, the vaccine must be BNT162b2.CDC Booster

Would you recommend a booster dose for an otherwise healthy 60-year-old patient?

Short Answer: Based on guidance from the FDA and CDC, all patients aged 18 years or older who completed their primary vaccine series are eligible for a booster dose. Certain populations can get a second booster.

Renslow Sherer, MD (May 23, 2022):
Studies have demonstrated that after completing a primary COVID-19 vaccination series, protection against the virus and the ability to prevent infection with variants may decrease over time.CDC Booster The CDC recommends that individuals aged 5 years or older receive an authorized booster and that adults aged 50 years or older, people aged 12 years or older with moderate to severe immunocompromise, and people aged 50 years or older who received 2 doses of the Ad26.COV2.S vaccine receive a second booster.CDC Booster 

Is there utility in measuring antibody levels in clinical practice to guide vaccine boosters?

Short Answer: No, antibody levels should not be used to guide the need for COVID-19 vaccine booster doses. There are variations between laboratories and antibody tests, and the heterogeneity does not allow for accurate interpretation of what the antibody levels mean.

Renslow Sherer, MD (November 18, 2021):
Current data are insufficient to determine an antibody titer threshold that indicates when an individual is protected from SARS-CoV-2 infection.CDC Use of Vaccines There is neither an FDA-approved or -authorized test nor any other scientifically validated strategy that healthcare professionals or patients can use to reliably determine whether a person is protected from infection. Patients and healthcare professionals should follow the current CDC guidance on which populations are eligible to receive a booster dose.CDC Booster

Is there better efficacy with a delayed second dose in a 2-dose COVID-19 vaccine series?

Short Answer: There have been satisfactory outcomes and, in some cases, higher levels of antibody response in persons who received their second dose of BNT162b2 or mRNA-1273 vaccine 2-3 months after their first dose. However, it is important to follow dosing interval guidance based on the science of how the clinical trials were designed and the efficacy outcomes demonstrated.

Renslow Sherer, MD (November 18, 2021):
Patients who receive the second dose of BNT162b2 or mRNA-1273 vaccine no more than 4 days before or at any time after the recommended second dose date are considered to have completed the primary series.CDC Use of Vaccines

If the second dose of an mRNA vaccine is given earlier than the 4-day grace period for that specific vaccine, the second dose should be repeated, and the repeat dose should be spaced based on the date of the dose given in error by the recommended minimum interval.CDC Use of Vaccines

If the second dose of BNT162b2 or mRNA-1273 vaccine is administered at any interval after the recommended interval, the dosing series does not need to be repeated, as there is no maximum interval between the 2 doses.CDC Use of Vaccines

What is the best resource to direct the public to regarding breakthrough COVID-19 infection cases?

Short Answer: The CDC and FDA websites both share raw data that their advisory panels are reviewing. National conferences are another resource for current breakthrough infection data. Credible scientific literature from major medical journals and The Medical Letter are important resources.

Renslow Sherer, MD (November 18, 2021):
The CDC maintains a webpage related to COVID-19 breakthrough infection cases. This webpage hosts a list of sites for the CDC’s systems for monitoring COVID-19 breakthrough infections, including the Coronavirus Disease 2019–Associated Hospitalization Surveillance Network (COVID-NET). COVID-NET follows approximately 10% of the US population in 99 counties in 14 states.CDC COVID-NET The CDC relies on individual states to report breakthrough cases, and currently 49 states have reported ≥1 COVID-19 breakthrough infection to this system.CDC Breakthrough Infections      

Are there data or recommendations for boosters for patients vaccinated with the ChAdOx1-S recombinant vaccine?

Short Answer: The ChAdOx1-S recombinant (AstraZeneca) vaccine is an adenovirus vaccine similar to the Ad26.COV2.S vaccine, and data suggest that a booster dose 2 months after completing the initial ChAdOx1-S recombinant vaccine series would be a reasonable strategy.

Renslow Sherer, MD (May 23, 2022):
The ChAdOx1-S recombinant vaccine was initially developed and studied as a single-dose vaccine, similar to Ad26.COV2.S. However, after review of immunogenicity data in phase I clinical trials that demonstrated substantial increases in neutralizing antibodies following a second dose, the vaccine has been administered and studied as a 2-dose series.Folegatti 2020 The recommended interval between doses is 8-12 weeks. A booster dose is recommended for high-risk groups (eg, older adults, healthcare professionals) 4-6 months after completion of the primary series.WHO Data from an ongoing trial demonstrate increased antibody response during the omicron era after a third (booster) dose.AstraZeneca; Kirsebom 2022

Will a fourth vaccine dose be needed?

Short Answer: A fourth dose is indicated for certain populations.

Sharon R. Lewin, AO, FRACP, PhD, FAHMS (May 23, 2022):
Many countries have authorized a fourth vaccine dose for patients with immunocompromising conditions or those receiving immunosuppressant medications.CDC Use of Vaccines In early January 2022, Israel began offering a fourth vaccine dose to high-risk populations, including persons aged 60 years or older, healthcare workers, and residents of nursing homes.Burki 2022 The CDC recommends that adults aged 50 years or older, people aged 12 years of age or older with moderate to severe immunocompromise, and people aged 50 years or older who received 2 doses of the Ad26.COV2.S vaccine get a second booster.CDC Booster 

When will we have intranasal COVID-19 vaccines?

Short answer: Intranasal COVID-19 vaccines are currently in development.

Sharon R. Lewin, AO, FRACP, PhD, FAHMS (February 3, 2022):
Intranasal COVID-19 vaccines are in development as an alternative to vaccination administered by IM injection. Intranasal vaccination may serve as a primary vaccination or as a booster to an IM vaccination. Preliminary data are promising, but more studies are needed to determine the safety and efficacy of intranasal COVID-19 vaccines.Mao 2022

When will we have COVID-19 vaccines for children younger than 5 years of age?

Short Answer: COVID-19 vaccines for children younger than 5 years of age are coming soon.

Sharon R. Lewin, AO, FRACP, PhD, FAHMS (May 23, 2022):
The FDA has announced plans to review both mRNA-1273 (Moderna) and BNT162b2 (Pfizer) Emergency Use Authorization applications for COVID-19 vaccines for children in June 2022.Moderna PR; Pfizer Strong Response