While most Americans who initially received two shots of the Pfizer or Moderna COVID-19 vaccines will be able to get a single booster shot when they are eligible, federal health guidelines will also allow a few million Americans with compromised immune systems to eventually get a fourth dose as early as next year.
Back in August, the FDA and the Centers for Disease Control and Prevention authorized and recommended anfor some "moderately and several immunocompromised" patients who were vaccinated with two doses of Moderna or Pfizer.
Now some of those people will be eligible to receive a fourth shot — a "booster" six months after they received their third "additional" dose.
That group includes people who are taking medications that can suppress their immune systems for organ transplants or cancer, the CDC says, as well as people facing significant immunodeficiency from diseases like advanced or untreated HIV.
Around 3 million "additional" doses were administered under that guidance, before Pfizer's booster shots for a broader group of Americans were authorized and recommended last month. Around 2.3% of American adults are immunocompromised, the CDC estimated in August, though only a fraction of these 7 million adults would need an "additional" dose.
To date, close to 14 million Americans have now received either a "booster" or "additional" dose of COVID-19 vaccine.
"We use the term 'additional' dose to refer to a subsequent vaccine dose in people who likely did not mount a protective immune response after their primary vaccination," the CDC's Dr. Sujan Reddy said at a recent webinar with providers.
The CDC's guidance does not apply to recipients of Johnson & Johnson's Janssen COVID-19 vaccine, who are only recommended to receive a single additional dose in all situations, though federal health officials have said they planned to allow for flexibility in providers looking to improve protection for their severely immunocompromised patients.
"I think for these immunocompromised groups specifically, we're hoping that this is a clinical decision that the provider makes with the patient," the CDC's Dr. Amanda Cohn told the agency's Advisory Committee on Immunization Practices earlier this month.
"We believe the number of individuals who received a Janssen vaccine who are immunocompromised is likely very low, but they exist," Cohn added.
Adult recipients of Johnson & Johnson's shot can get a booster of any of the three COVID-19 vaccines at least two months after they were first vaccinated. Some early data from antibodies measured in a government-backed study suggests these people might get better protection by seeking out second doses from Moderna or Pfizer, instead of Johnson & Johnson.
However, both the trial's scientists and the FDA have cautioned the data was insufficient to draw direct comparisons between the combinations. Scientists also suspect protection from Johnson & Johnson's vaccine comes from other parts of the immune system that were not yet measured in the study's preliminary results.
"There are reasons to think that they might, at the end of the day, all come out in the wash as being close to one another," Dr. Peter Marks, the FDA's top vaccines official, said on a recent call hosted by the Infectious Diseases Society of America.
Some deciding whether to switch away from a second dose of Johnson & Johnson will also have to weigh the risks of rare heart inflammation side effects, myocarditis and pericarditis, associated with the mRNA-based vaccines from Pfizer and Moderna. Cases have been seen largely in young males and typically require hospitalization, although many recover within a day.
The guidance for immunocompromised people is just one of several complexities that the FDA and CDC have sought to iron out in recent weeks, as it has rolled out newfor all three vaccines.
Federal health officials also say they are launching outreach efforts to providers to prevent mix-ups around the size of Moderna's booster shot, which is just half the size of its original 100 microgram doses.
"We knew that having a 50 microgram and a 100 microgram boost would be potentially confusing," said Marks.
"If you're going to give an immunocompromised individual a third dose of Moderna, it should be the 100 microgram dose, just like all the other primary series doses," Marks added.
The CDC is also mulling guidance on booster shots for people who were vaccinated outside the United States with vaccines that are greenlighted by the World Health Organization, but not yet authorized by the FDA, like the vaccine developed by AstraZeneca.
"We do consider those people fully vaccinated. But at the moment, we don't have booster recommendations for that population," said Reddy. "We continue to work with our international colleagues to try to figure that out, but at the moment we have no recommendation for that."