In all of the complexity of approved COVID-19 booster shots for adults with any of three vaccines, which involve varying dosages and wait times, some healthcare providers might not have noticed that some patients are eligible for a fourth shot.

The CDC advises, "Moderately and severely immunocompromised people aged ≥18 years who completed an mRNA COVID-19 vaccine primary series and received an additional mRNA vaccine dose may receive a single COVID-19 booster dose (Pfizer-BioNTech, Moderna, or Janssen) at least 6 months after completing their third mRNA vaccine dose. In such situations, people who are moderately and severely immunocompromised may receive a total of four COVID-19 vaccine doses."

The CDC goes on to say that someone who is moderately or severely immunocompromised and has received two doses of an mRNA vaccine, with more than 28 days having elapsed since the second dose, should receive an additional mRNA dose immediately, followed 6 or more months later by a single COVID-19 vaccine booster dose. (If Moderna COVID-19 vaccine is used, the first booster should be 100 µg in 0.5 mL, and the second booster should be 50 µg in 0.25 mL, according to the guidance.)

The advice also varies with the Janssen (Johnson & Johnson) vaccine. Public-health officials note that moderately and severely immunocompromised adults who received a single-dose Janssen COVID-19 vaccine primary series should receive a single COVID-19 booster vaccine (Pfizer-BioNTech, Moderna, or Janssen) at least 2 months (8 weeks) after receiving their initial Janssen primary dose. (If the Moderna vaccine is used in this circumstance, the booster dose and dose volume should be used (50 µg in 0.25 mL.)

"A patient's clinical team is best positioned to determine the appropriate timing of vaccination," according to the CDC. "A person who received one primary dose of Janssen COVID-19 vaccine should not receive more than two COVID-19 vaccine doses."

The issue, according to the guidance, is that patients with immunocompromising conditions and those who take immunosuppressive medications or therapies are at increased risk for severe COVID-19. Although the current FDA-approved or authorized COVID-19 vaccines are not live vaccines and can be safely administered to immunocompromised patients, those recipients might have reduced vaccine effectiveness.

Based on small studies, the CDC has determined that an additional mRNA COVID-19 vaccine dose in some immunocompromised patients who received an mRNA COVID-19 primary vaccine series can enhance antibody response, increasing the proportion of patients who respond.

Immunocompromised patients who have completed a primary vaccine series (i.e., two-dose mRNA vaccine series with Pfizer-BioNTech and Moderna or a single dose of Janssen vaccine) are considered fully vaccinated 2 or more weeks after completion of the series. Public-health officials urge consideration of an additional dose of an mRNA COVID-19 vaccine for patients with the following conditions:

• Receipt of solid-organ transplant and taking immunosuppressive therapy

• Receipt of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic stem-cell transplantation (within 2 years of transplantation or taking immunosuppressive therapy)

• Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome)

• Advanced or untreated HIV infection (people with HIV and CD4 cell counts <200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)

• Active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor blockers, and other biological agents that are immunosuppressive or immunomodulatory

Disease severity, duration, clinical stability, complications, comorbidities, and any potentially immune-suppressing treatment should be considered in determining patients' general level of immune competence. The authors urge against basing the decision for an extra dose solely on age or place of residence, such as long-term care, however.

The CDC also provides some advice on when those patients should be vaccinated relative to their treatment schedules."Whenever possible, mRNA COVID-19 vaccination doses (including the primary series, additional dose, and booster dose) or the single-dose Janssen COVID-19 vaccine (primary or booster) should be completed at least 2 weeks before initiation or resumption of immunosuppressive therapies," advises the agency. "Timing of COVID-19 vaccination should take into consideration current or planned immunosuppressive therapies and optimization of both the patient's medical condition and response to vaccine. A patient's clinical team is best positioned to determine the degree of immune compromise and appropriate timing of vaccination."

Not recommended at this point is the use of serologic testing or cellular immune testing outside of research studies, the CDC emphasizes. "The utility of serologic testing or cellular immune testing to assess immune response to vaccination and guide clinical care (e.g., as part of need assessment for an additional dose) has not been established," the guidance adds.

Even though recipients can choose any booster shot, for immune-compromised patients, the additional mRNA COVID-19 dose should be the same vaccine product as the initial two-dose mRNA COVID-19 primary series (Pfizer-BioNTech or Moderna). "If the mRNA COVID-19 vaccine product given for the first two doses is not available, the other mRNA COVID-19 vaccine product may be administered," the CDC writes. "If a mixed mRNA vaccine primary series was administered (one dose of Pfizer-BioNTech and one dose of Moderna), the person may still receive an additional mRNA dose at least 28 days after the second dose."

So far, expert opinion calls for the additional dose of an mRNA COVID-19 vaccine to be administered at least 28 days after completion of the initial two-dose mRNA COVID-19 primary vaccine series, although public-health officials say that could change with more data.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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