Third Vaccine Dose Protects Immunocompromised from Severe COVID-19

A new CDC study of COVID-19 patients in 18 states provides evidence backup to what has been observed: A third mRNA vaccine dose significantly reduces hospitalization risks, even among immunocompromised patients. Find out how effective the “booster” doses were and how the VE differed between immunocompetent and immunocompromised adults.

ATLANTA – While protection still lags somewhat among immunocompromised adults receiving COVID-19 vaccines, getting a third “booster” dose provides them improved protection against hospitalization.

Third doses of an mRNA COVID-19 vaccine have been recommended for all adults in the United States by the national Centers for Disease Control and Prevention (CDC), but it has not been clear how effective those are in preventing hospitalization, especially among the immunocompromised.

In a Morbidity and Mortality Weekly Report study of hospitalized adults, CDC-led researchers found that, compared with receipt of 2 mRNA COVID-19 vaccine doses, receipt of a third dose increased vaccine effectiveness against hospitalization among adults without immunocompromising conditions, from 82% to 97% and from 69% to 88% for those who are immunocompromised.

The research was conducted in a multistate network, significantly higher VE was observed in adults who received a third mRNA vaccine dose either as part of a primary vaccine series (immunocompromised persons) or as a booster dose (immunocompetent persons) compared with those who had received 2 doses.

“These findings underscore the importance of immunocompromised adults obtaining a third mRNA vaccine dose ≥28 days after the second vaccine dose and of immunocompetent adults receiving a third (booster) dose currently recommended ≥5 months after the second dose,” the authors advised.

This study was conducted during a period of SARS-CoV-2 Delta variant predominance, according to the report, which suggests that VE against the B.1.1.529 (Omicron) variant of SARS-CoV-2 might be lower than for other variants that have circulated widely, possibly because of immune evasion.

“Early evidence suggests that a third mRNA vaccine dose elicits markedly stronger neutralizing antibody responses to the Omicron variant compared with responses to 2 vaccine doses), and increases VE against severe disease following infection with the Omicron variant,” the authors explain, adding, “The effectiveness of 3 doses of COVID-19 mRNA vaccines against a range of disease severity associated with the Omicron variant needs to be carefully evaluated in different populations.”

Background information in the articles notes that COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) provide protection against infection with SARS-CoV-2, the virus that causes COVID-19, and are highly effective against COVID-19–associated hospitalization among eligible persons who receive 2 doses. “However, vaccine effectiveness (VE) among persons with immunocompromising conditions is lower than that among immunocompetent persons (2), and VE declines after several months among all persons,” the CDC researchers caution.

The study focused on 2,952 adults--1,385 COVID-19 case-patients and 1,567 COVID-19–negative controls --hospitalized at 21 U.S. hospitals during August 19–December 15, 2021. Researchers compared the effectiveness of mRNA vaccines against COVID-19–associated hospitalization between 1,251 adults eligible for but who had not received a third vaccine dose and 312 vaccine-eligible adults who received a third dose ≥7 days before illness onset.

Results indicate that, among 1,875 adults without immunocompromising conditions -- including 1,065 [57%] unvaccinated, 679 [36%] 2-dose recipients, and 131 [7%] 3-dose [booster] recipients) -- VE against COVID-19 hospitalization was higher among those who received a booster dose (97%; 95% CI = 95%–99%) compared with that among 2-dose recipients (82%; 95% CI = 77%–86%) (p <0.001).

Among 1,077 adults with immunocompromising conditions -- including 324 [30%] unvaccinated, 572 [53%] 2-dose recipients, and 181 [17%] 3-dose recipients -- VE was higher among those who received a third dose to complete a primary series (88%; 95% CI = 81%–93%) compared with 2-dose recipients (69%; 95% CI = 57%–78%) (p <0.001).

Limitations of the report include the following:

  • 2-dose and 3-dose vaccine recipients were similar in terms of most demographic and clinical characteristics but might have differed in terms of exposure risk for SARS-CoV-2 infection or risk factors for severe COVID-19. VE associated with newly emergent variants, including Omicron, was not assessed.
  • VE was not assessed against SARS-CoV-2 infection or mild illness.
  • Most 3-dose mRNA vaccine recipients were vaccinated within several weeks of enrollment and durability of protection will require future analysis.
  • VE associated with a fourth mRNA vaccine dose recommended as a booster dose in immunocompromised individuals ≥5 months after dose 3, was not assessed.
  • Although medical centers in 18 states were included in the analysis, patients might not be representative of the general U.S. population.

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