COVID-19 booster vaccines were highly effective against breakthrough infection and adverse outcomes during the Delta-predominant period and offered a lesser degree of protection during the Omicron period, researchers reported in Open Forum Infectious Diseases.
Researchers assessed real-world evidence to identify trends in COVID-19 mRNA booster effectiveness in patients with and without immune dysfunction during the Delta- and Omicron-predominant periods of the pandemic. The researchers conducted a retrospective cohort study using individual-level data from the National COVID Cohort Collaborative. Participants completed primary COVID-19 mRNA vaccination from December 10, 2020, to May 27, 2022.
The analysis included the 2 SARS-CoV2 mRNA vaccines (Pfizer-BioNTech [BNT162b2] and Moderna [mRNA-1273]). Primary vaccination was regarded as completion of 2 doses for the mRNA vaccines in the primary analyses, and a booster vaccination was defined as an additional dose of mRNA vaccine after the primary vaccines. A vaccine breakthrough infection was defined as a COVID-19 diagnosis 14 days or more after vaccination.
The analyses were stratified by: (1) time interval since full vaccination; (2) immune dysfunction severity; (3) booster received during the Delta-predominant period (June 20, 2021, to December 19, 2021); and booster received during the Omicron-predominant period (December 20, 2021, to May 27, 2022).
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While COVID-19 cases and deaths are receding, continued vigilance [and] annual or periodic vaccine administration will both complement and reduce the need for therapeutics among highly vulnerable persons with immune dysfunction.
A total of 2,199,464 patients from 27 sites completed at least 2 doses of mRNA vaccination, of whom 949,457 (43.2%) received a booster vaccine (median interval from primary vaccine to booster dose, 7.7 months). Participants had a median age of 49 years at completion of 2 mRNA vaccine doses and 60% of participants were female. An immune dysfunction diagnosis was identified in 385,167 (17.5%) patients, and 2.1% had moderate to severe immune dysfunction.
The rate of overall breakthrough infections was 5.7% (n=106,878) in the Delta-predominant period and 14.4% (n=321,033) in the Omicron-predominant period.
For patients without immune dysfunction, 3 doses of mRNA vaccine were highly effective against breakthrough infection at 6 months after primary vaccination in the Delta period (range, 69%-81%; hazard ratio [HR] range, 0.31 [95% CI, 0.26-0.36] to 0.19 [95% CI, 0.18-0.21]), with reduced effectiveness in the Omicron period (range, 33% to 39% protection; HR range, 0.67 [95% CI, 0.63-0.71] to 0.61 [95% CI, 0.60-0.62]).
A booster vaccine resulted in a significant decrease in the risk of COVID-19-related hospitalization and invasive ventilation/death in the Delta and Omicron periods. The risk reduction for hospitalization and severe outcomes in the propensity score–matched models were reduced from 79% (HR, 0.21; 95% CI, 0.19-0.22) and 90% (HR, 0.10; 95% CI, 0.08-0.13), respectively, in the Delta period, to 43% (HR, 0.57; 95% CI, 0.55-0.58) and 54% (HR, 0.46; 95% CI, 0.41-0.52), respectively, in the Omicron period.
Having 3 doses of mRNA vaccine resulted in a more than 75% decrease in hospitalization and severe outcomes for patients with mild and moderate to severe immune dysfunction in the Delta-predominant period. In the Omicron-predominant period, effectiveness declined to 50% and 54% in hospitalization and severe outcomes, respectively, in patients with mild immune dysfunction, and to 37% and 37%, respectively, in those with moderate to severe immune dysfunction.
Study limitations include the reliance on electronic medical record data mostly from large academic medical centers and likely underestimation of the prevalence of breakthrough infection. In addition, antivirals, monoclonal antibodies, or immunomodulatory therapies as pre-emptive therapies to slow COVID-19 progression were available for high-risk and hospitalized patients during the Delta and Omicron periods.
“While COVID-19 cases and deaths are receding, continued vigilance [and] annual or periodic vaccine administration will both complement and reduce the need for therapeutics among highly vulnerable persons with immune dysfunction,” the investigators concluded.
Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
