Individuals who previously received only the original, wild-type COVID-19 vaccines, with the last dose at least 6 months ago, had little protection against COVID-19 outcomes, and a BNT162b2 BA.4/5 bivalent booster restored protection, according to study findings published in Lancet Respiratory Medicine.
Investigators conducted a clinical trial (ClinicalTrials.gov Identifier: NCT04848584) to evaluate the effectiveness of the Pfizer-BioNTech BNT162b2 BA.4/5 bivalent vaccine against BA.4/5-related and XBB-related disease, based on medical record of adults at least 18 years of age in the Kaiser Permanente Southern California health care system.
The test-negative case-control study enrolled patients who were diagnosed with acute respiratory infection and were tested for SARS-CoV-2 infection from August 31, 2022, to April 15, 2023. The participants were unvaccinated against COVID-19 or received at least 2 doses of a wild-type mRNA COVID-19 vaccine (ie, vaccine with mRNA encoding the original Wuhan-Hu-1 virus strain). Cases were defined as having a positive SARS-CoV-2 polymerase chain reaction test.
The cohort included 123,419 patient encounters, including 24,246 encounters involving individuals who had COVID-19 and 99,173 encounters involving individuals who tested negative for COVID-19 (ie, control individuals). The encounters comprised 4131 critical illnesses, 14,529 hospital admissions, 63,566 emergency department or urgent care visits, and 45,324 in-person outpatient encounters with an acute respiratory infection diagnosis and documented SARS-CoV-2 PCR test. Participants’ median age was 52 years (interquartile range, 36-68) and 62% were female.
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A BNT162b2 BA.4/5 bivalent booster restored protection against a range of COVID-19 outcomes, including against XBB-related sublineages, with the most substantial protection observed against hospital admission and critical illness.
Among the COVID-19 cases, 20,555 infections were BA.4/5-related (1724 inpatient, 8964 emergency department or urgent care, and 9867 outpatient) and 3691 were XBB-related (91 inpatient, 1285 emergency department or urgent care, and 2315 outpatient).
In estimating the relative effectiveness of the BNT162b2 BA.4/5 bivalent booster, the researchers found that having the booster vs only having received 2 or more doses of a wild-type mRNA vaccine provided an additional 50% (95% CI, 23-68) protection against critical illness, an additional 39% (95% CI, 28-49) against hospital admission, an additional 35% (95% CI, 30-40) against emergency department or urgent care visits, and an additional 28% (95% CI, 22-33) against outpatient encounters. Waning effectiveness after vaccination with the BNT162b2 BA.4/5 bivalent dose (from 0 to 3 months post-vaccination to 4 to 7 months post vaccination) was seen only in outpatient encounters and was not found in emergency department or urgent care visits, hospital admission, or critical illness outcomes.
In the relative effectiveness analyses that were stratified by omicron sublineage (BA.4/5-related vs XBB-related), a similar performance was observed for a BNT162b2 BA.4/5 bivalent booster across sublineages. Effectiveness against hospital admission was 56% (95% CI, 12-78) for XBB-related infections compared with 40% (95% CI, 27-50) for BA.4/5-related infections; effectiveness against emergency department or urgent care visits was 34% (95% CI, 21-45) vs 36% (95% CI, 30-41); and effectiveness against outpatient encounters was 29% (95% CI, 19-38) vs 27% (95% CI, 20-33). A BNT162b2 BA.4/5 bivalent booster’s absolute effectiveness against XBB-related strains also was comparable to its effectiveness against BA.4/5-related infections.
Study limitations include potential unmeasured confounding, potential misclassification of cases as being related to COVID-19 when they were not, and potential misclassification of previous infection. In addition, the researchers could not differentiate between XBB sublineages or provide XBB.1.5-specific estimates or estimate differences in effectiveness between BA.4/5, BQ.1, and BQ.1.1 strains. Furthermore, the long-term effectiveness of the BNT162b2 BA.4/5 bivalent vaccine was not evaluated.
“By mid-April, 2023, individuals previously vaccinated only with wild-type vaccines had little protection against COVID-19 — including hospital admission,” said the investigators. “A BNT162b2 BA.4/5 bivalent booster restored protection against a range of COVID-19 outcomes, including against XBB-related sublineages, with the most substantial protection observed against hospital admission and critical illness,” the study authors concluded.
Disclosure: This study was sponsored by Pfizer. 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.
