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An illustration of a medical disposable syringe filled with the COVID-19 vaccine.

Booster shots for the COVID-19 vaccine are on ongoing discussion in the U.S., and now the FDA has given the green light to eligible Americans to mix and match the boosters for any of the three available vaccines.

If you’re at high risk for severe COVID-19, you can now receive one of three boosters — Pfizer, Moderna, or Johnson & Johnson — no matter which vaccine you received first. For example, if you got the Johnson & Johnson vaccine, you can now choose to get a Pfizer booster, or if you got the Moderna vaccine, you can now choose the Johnson & Johnson booster. Since there are no specific guidelines on which booster to choose, it’s best to ask your health care provider for guidance.

Who Is Considered High-Risk and Should Get a COVID-19 Booster?

There are several factors that can put you at higher risk of COVID-19, including underlying medical conditions, according to the CDC. These conditions include:

  • Cancer
  • Chronic kidney disease
  • Chronic lung disease
  • Dementia or other neurological conditions
  • Diabetes (type 1 or type 2)
  • Down syndrome
  • Heart conditions
  • HIV
  • Immunocompromised state
  • Liver disease
  • Overweight and obesity
  • Pregnancy
  • Sickle cell disease and thalassemia
  • Smoking
  • Transplant recipients
  • Stroke
  • Substance use disorders

Note that certain people with some of these conditions already qualified for a third COVID-19 vaccine dose, including cancer, transplant recipients, and the immunocompromised. Read more below about the difference between getting a booster and getting a third dose.

Moderna and Pfizer

The Moderna and Pfizer boosters are recommended for the following groups.

  • Individuals 65 years of age and older
  • Individuals 18 through 64 years of age at high risk of severe COVID-19
  • Individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19 (for instance, health care workers, teachers and daycare staff, grocery workers, and those in homeless shelters or prisons)

The panel has discussed but has thus far not supported Pfizer and Moderna boosters for the general population ages 18 to 65, per NPR.

Johnson & Johnson

On the other hand, because the Johnson & Johnson vaccine has been shown to have lower efficacy than the Pfizer and Moderna shots, the FDA committee recommended that everyone who received the Johnson & Johnson vaccine receive an additional shot. Although this is being called a booster, some experts argue that the Johnson & Johnson vaccine should have included two doses (separated by about two months) from the start, per The New York Times.

Booster Shot vs. Third Dose: What’s the Difference?

Generally, the only difference is the purpose of the dose. (However, in the case of the Moderna booster shot, the dose is also different. The booster dose is half that of the original dose.)

In August, the FDA adjusted the emergency use authorizations (EUAs) for the Pfizer and Moderna vaccines to allow for an extra dose to be given to certain immunocompromised individuals. The amendment applies to solid organ transplant recipients or those diagnosed with conditions considered to have an equivalent level of immunocompromise.

This includes many people with inflammatory or autoimmune conditions who take immunosuppressant or immunomodulating medications.

In this case, you should wait at least 28 days between your second and third doses, but your doctor will be able to best determine the right timing of vaccination, per the CDC.

“The purpose of a third dose is to try to accomplish in these individuals what two doses accomplished in everybody else,” David Aronoff, MD, Director of the Division of Infectious Diseases at Vanderbilt University School of Medicine in Nashville, Tennessee, previously told CreakyJoints. “It’s essentially saying, ‘Because your immune system is suppressed, you may not respond normally to this vaccine. So for you, the normal regimen is a three-dose regimen, not a two-dose regimen.’”

Booster shots, on the other hand, are meant to increase immunity when antibody levels wane over time. The booster shots are being focused on those who may need extra protection the most.

The Moderna vaccine booster differs from the Pfizer and Johsnon & Johnson vaccine boosters in that its COVID-19 vaccine booster shot is a half-dose of the initial shot. It contains only 50 micrograms of mRNA, compared to 100 micrograms in each initial shot, per NPR.

During the CDC committee meeting for the Pfizer vaccine, scientists showed models indicating that even if booster shots slightly increased protection against hospitalization, they could prevent more than 2,000 hospitalizations per million doses given, according to the New York Times.

Will Immunocompromised People Need a Third Dose AND a Booster?

If you are immunocompromised and got a third dose of the COVID-19 vaccine, it’s too early to say whether you may also need a booster (technically a fourth dose) down the line. It’s possible in the future, but there is not yet data to recommend this. The guidance surrounding the COVID-19 vaccine is constantly evolving as more research emerges.

“Most likely, a fourth vaccine dose will be needed in immunocompromised patients, but we’re waiting on data from studies,” Daniel Arkfeld, MD, a rheumatologist with Keck Medicine of USC, told CreakyJoints previously. “I expect that will probably happen.”

Which Vaccines Will Be Given as a Booster?

This is where things get a little confusing.

  • If you’re immunocompromised (due to, say, taking immunosuppressant medications) both the Moderna and Pfizer vaccines are available as a third dose, at least 28 days after you received your second dose.
  • If you’re high-risk for severe COVID-19 but not immunocompromised (due to, say, obesity or diabetes), all three boosters are available in the U.S. The Pfizer and Moderna boosters are recommended six months after you received your second dose. Booster doses for Johnson & Johnson are recommended at least two months after receiving your original vaccination.

How Do You Mix and Match Vaccines?

Mixing and matching vaccines (say, getting Moderna as a first dose and Pfizer as a second dose) has been used in Europe and other places, particularly in the case of shortages, according to Yale Medicine. Switching has also been permitted for the third dose for immunocompromised people if necessary, and has now been granted emergency use for individuals who are eligible for any of the three boosters.

Mix-and-Match Boosters for the Johnson & Johnson Vaccine

Mixing and matching vaccines is less of an issue when it comes to the Pfizer and Moderna vaccines, because the effectiveness is similar. It may be more critical with the Johnson & Johnson vaccine. Early research shows this may lead to a stronger immune response compared to a Johnson & Johnson booster.

Preliminary findings have shown that Johnson & Johnson recipients who receive a Moderna vaccine booster see a 76-fold increase in antibody levels within 15 days, compared with just a fourfold rise with a Johnson & Johnson booster, per an October 2021 pre-print study posted on MedRxiv.

If you’ve already received your Johnson & Johnson vaccine, you can receive one of the following boosters at least two months after receiving your original vaccination:

  • Johnson & Johnson vaccine: full single booster dose
  • Moderna vaccine: with half the dose authorized as booster dose
  • Pfizer vaccine: full dose

Mix-and-Match Boosters for the Pfizer and Moderna Vaccines

A Pfizer booster raised antibody levels by 35-fold. That said, the trial only looked at antibody levels, which don’t show the full picture of how vaccines can protect individuals.

If you’ve already received your Pfizer or Moderna vaccine, you can receive one of the following boosters at least six months after your original vaccination:

  • Johnson & Johnson vaccine: full single booster dose
  • Moderna vaccine: with half the dose authorized as booster dose
  • Pfizer vaccine: full dose

The FDA plans on updating fact sheets for each vaccine to include specific instructions on booster doses.

Where Do You Get the Booster Dose?

If you’re not sure whether you qualify for a COVID-19 booster based on your underlying medical conditions, talk to your doctor to determine if you need a booster dose.

Pfizer, Moderna, and Johnson & Johnson booster shots should be available where vaccines are already being offered, including pharmacies, health departments, clinics, and some doctor’s offices.

What Should I Tell My Loved Ones Who Are Eligible?

If you’re immunocompromised because of an inflammatory or autoimmune condition and already received your third COVID-19 vaccine dose, you’re likely doing many things to bolster your protection and reduce your risk of getting sick. If you have people in your life who are now eligible for a COVID-19 booster shot, you should encourage them to get one — to protect themselves, of course, but also to help keep you safe too.

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Atmar RL, et al. Heterologous SARS-CoV-2 Booster Vaccinations – Preliminary Report. MexRxiv. October 13, 2021. https://doi.org/10.1101/2021.10.10.21264827.

Centers for Disease Control and Prevention. CDC expands eligibility for COVID-19 booster shots. https://www.cdc.gov/media/releases/2021/p1021-covid-booster.html.

Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals. U.S. Food & Drug Administration. August 12, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised.

FDA Authorizes Booster Dose of Pfizer-BioNTech COVID-19 Vaccine for Certain Populations. U.S. Food & Drug Administration. September 22, 2021. https://www.fda.gov/news-events/press-announcements/fda-authorizes-booster-dose-pfizer-biontech-covid-19-vaccine-certain-populations.

Hensley S. Experts recommend that FDA should authorize Moderna COVID vaccine booster. NPR. October 14, 2020. https://www.npr.org/sections/health-shots/2021/10/14/1046079675/experts-recommend-that-fda-should-authorize-moderna-covid-vaccine-booster.

Interview with Amesh A. Adalja, MD, a Senior Scholar at Johns Hopkins Center for Health Security

Interview with Daniel Arkfeld, MD, a rheumatologist with Keck Medicine of USC

Interview with David Aronoff, MD, Director of the Division of Infectious Diseases at Vanderbilt University School of Medicine in Nashville, Tennessee

Interview with  S. Louis Bridges, Jr., MD, PhD, Physician-in-Chief and Chief of the Division of Rheumatology

Joint Statement from HHS Public Health and Medical Experts on COVID-19 Booster Shots. CDC Newsroom. U.S. Centers for Disease Control and Prevention. August 18, 2021. https://www.cdc.gov/media/releases/2021/s0818-covid-19-booster-shots.html.

LaFraniere S, et al. F.D.A. Panel Unanimously Recommends Johnson & Johnson Booster Shots. The New York Times. October 15, 2021. https://www.nytimes.com/2021/10/15/health/johnson-johnson-vaccine-booster.html.

Mandavilli A, et al. The C.D.C. chief overruled her own agency’s panel and recommended Pfizer boosters for workers at risk. The New York Times. September 23, 2021. https://www.nytimes.com/2021/09/23/health/pfizer-booster-cdc-fda-authorize.html.

Park A. CDC Panel Outlines Who Should Get Pfizer-BioNTech COVID-19 Booster Shots, And Who Should Wait. Time. September 23, 2021. https://time.com/6101259/cdc-pfizer-booster-shot/.

People with Certain Medical Conditions. COVID-19. U.S. Centers for Disease Control and Prevention. August 20, 2021. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html.

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