Moderate and severely immunocompromised individuals, including people with HIV, cancer, and those who take medicines that suppress the immune system, may be at a higher risk of COVID-19.

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These individuals are generally at a higher risk of developing severe and persistent illnesses compared with others. They may also lack adequate protection or immunity against coronavirus infection.

This makes them susceptible to infection even after receiving a two-dose primary mRNA COVID-19 vaccine. This is already evident from the significant number of immunocompromised individuals hospitalized for “vaccine breakthrough infections” and fully vaccinated people who still get SARS-CoV-2 infections. An infection with the virus SARS-CoV-2 is what causes COVID-19 in people.

The Centers for Disease Control and Prevention (CDC) recommends people who are moderately and severely immunocompromised receive three primary doses of Pfizer or Moderna and two boosters. If a person initially had a Janssen vaccine, they should receive another Janssen shot and two boosters.

These extra vaccines and boosters can help protect against serious illness and the need for hospitalization due to COVID-19.

An immunocompromised person receiving their COVID-19 vaccine.Share on Pinterest
miodrag ignjatovic/Getty Images

All vaccines that currently have approval and authorization in the United States — Moderna, Johnson and Johnson’s Janssen, and Pfizer-BioNTech, aid in preventing hospitalization, severe disease, and death from COVID-19.

However, emerging data suggest that these vaccines are less effective in preventing COVID-19 illness and hospitalization in immunocompromised individuals. These people comprise about 2.7% of the adult U.S. population, according to 2013 data.

Generally, immunocompromised people seem to be at a higher risk of developing severe forms of COVID-19. A 2021 study found that these individuals are at risk for prolonged infection. Another 2020 study also noted prolonged viral shedding, or the release of viral particles.

Additionally, a 2020 study found that immunocompromised individuals and people with diabetes are more likely to pass on SARS-CoV-2 to others in their households. A 2021 Israel study found that 40% of hospitalized breakthrough cases consisted of immunocompromised patients. Immunocompromised individuals also comprised 44% of hospitalized breakthrough cases in a similar U.S. study.

Immunocompromised people

The CDC recommends moderate to severely immunocompromised people receive a third dose of Pfizer or Moderna, or two shots of the Janssen vaccine, and then an additional two boosters. These may include those with or who have had:

Individuals with chronic conditions associated with varying immunocompetence, such as chronic kidney disease may also need a third primary vaccine dose. And those with other medical conditions and treatments involving varying immunosuppression may also need a third dose.

A person’s healthcare team can assess the degree of immunocompetence and decide whether and when they should receive their third primary dose.

Benefits

An additional primary dose may prevent serious and life threatening COVID-19 in immunocompromised people who have not developed enough protection from their first two-dose vaccine series.

Studies found that individuals with no detectable antibody response after their first two doses of vaccines, such as solid-organ transplant recipients and chronic dialysis patients, developed a 33–50% antibody response after a third dose.

It is important to note that experts cannot directly associate antibody levels with preventing infection. However, research is currently underway to understand this link further.

Risks

There is currently limited information on the risks of taking additional doses of the COVID-19 vaccine. Studies about their efficacy, safety, and benefits are currently underway.

According to available data, reactions to the third primary dose are similar to the two-dose series, including pain in the injection site and fatigue. Most people report mild to moderate symptoms.

All individuals with an appointment for an additional COVID-19 vaccine dose should bring their vaccination cards. These contain relevant information, including the type of vaccine they initially received and when and where they received their initial two doses.

Currently, the CDC does not advise immunocompromised people to mix and match vaccines, as research on this remains ongoing. For example, an immunocompromised person who received either the Moderna or Pfizer-BioNTech COVID-19 vaccine series should safely receive a third shot of the same mRNA vaccine.

However, if the type of mRNA product is unknown or unavailable, a person may receive any of the two product types for their additional dose. Currently, the Food and Drug Administration’s (FDA) emergency use authorization amendment endorses additional mRNA doses for Pfizer-BioNTech, Moderna, and Johnson and Johnson’s Janssen COVID-19 vaccines.

The CDC recommends slightly different primary vaccine timelines for immunocompromised persons of different age groups depending on the vaccine they receive:

VaccineAge groupTotal dosesSecond doseThird dose
Pfizer5–12+321 days after the first doseat least 28 days after the second dose
Moderna18+328 days after the first doseat least 28 days after the second dose
Janssen18+2Pfizer or Moderna at least 28 days after the first dosenot recommended

The CDC recommends everyone ages 5 and over receives at least one booster. Currently, the organization recommends adults who are 50 years of age or older and immunocompromised people who are 12 years or older receive two boosters.

Booster recommendations

The CDC recommends moderately and severely immunocompromised people follow its booster recommendations:

VaccineAgeFirst boosterSecond booster
Pfizer5-11 at least 3 months after their third dosenot recommended
Pfizer12+at least 3 months after their third at least 4 months after their first booster
Moderna 18+at least 3 months after their third doseat least 4 months after their first booster
Janssen18+at least 2 months after their second primary doseat least 4 months after their first booster

Adults who received an initial shot of Janssen should have a Pfizer or Moderna second shot at least 28 days later. They can then receive a Pfizer or Moderna booster shot at least 2 months after their second vaccine.

Several studies and trials are underway to assess the effectiveness and safety of vaccine boosters in immunocompromised individuals. A recent nationwide survey found that local and systemic reactions due to the third dose in immunocompromised individuals were the same as in previous vaccines. Additionally, most individuals reported better responses from the third dose than the second.

Trials are also evaluating the effectiveness of mixed-dose vaccine schedules and boosters. A preprint of a 2021 study in Germany found people tolerated a mixed-dose booster vaccination of ChAdOx/BNT well. They also had similar side effects to those observable in same-dose boosters. People also had improved immunity responses in both same-dose and mixed-dose boosters.

A similar 2021 preprint found that heterologous, or mixed, vector-mRNA boosted immune response. This means receiving a ChAdOx1-nCoV-19 vector-vaccine for the initial two-dose series and then an mRNA-vaccine booster yielded favorable protection with manageable side effects.

Another 2021 study preprint looking at heterologous schedules, or using a different vaccine product for the second dose than the first dose, found that these produced higher antibody levels than the licensed vaccine schedule.

The National Institutes of Health (NIH) also states that research shows a person with a mixed vaccine primary and booster shot has antibody levels similar to those who receive the same vaccine for all of their shots.

Additionally, levels of CD4 and CD8 T cells, which are types of immune cells that may help against SARS-CoV-2, rose no matter which vaccine a person received, unless they had a Janssen shot as their first vaccine. However, people who had a Janssen shot already had higher levels of CD8 T cells.

Emerging data suggest current COVID-19 vaccines are less effective in preventing illness and hospitalization in immunocompromised people. Therefore, those who are immunocompromised are at a higher risk of developing severe forms of COVID-19.

This population may wish to ensure that close contacts are up-to-date on their vaccinations. They should also continue to take preventive measures such as regular handwashing, mask-wearing, and maintaining social distancing.

The CDC recommends immunocompromised persons have three primary vaccine doses. Those who are 12 years of age and older should have two additional boosters of an mRNA COVID vaccine. People should receive their first booster at least 3 months after their last primary dose and then a second booster at least 4 months later. Immunocompromised children aged 5–11 years should receive one mRNA COVID vaccine booster at least 3 months after their last primary dose.

Any immunocompromised people interested in COVID-19 booster shots but are unsure of which to receive and when can contact their doctor for further guidance.