How effective is the bivalent mRNA SARS-CoV-2 vaccine in preventing COVID-19 hospitalizations and deaths?

In a recent study posted to Preprints with The Lancet*, researchers examined the effectiveness of the bivalent messenger ribonucleic acid (mRNA) vaccine against severe outcomes of coronavirus disease 2019 (COVID-19).

Background

Bivalent mRNA vaccines contain components of the ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain and the Omicron BA.4/5 sublineages. The United States (US) Food and Drug Administration approved using Pfizer and Moderna bivalent vaccine boosters in adults in August 2022. The bivalent vaccines were approved for booster vaccination in Israel for those at high risk for severe COVID-19.

Data on the clinical efficacy of bivalent vaccines from randomized controlled trials are lacking. Nevertheless, preliminary evidence from the US indicates significant protection with bivalent boosters against severe illness, with efficacy estimates ranging between 38% and 73%. Still, the effectiveness of bivalent boosters in preventing COVID-19 hospitalization and mortality remains unknown.

About the study

In the present study, researchers evaluated the effectiveness of bivalent mRNA boosters in preventing hospitalizations and deaths associated with COVID-19 in Israel. They used electronic medical record data from a large healthcare organization (Clalit Health Services, CHS) covering two-thirds of Israel’s population aged ≥ 65.

The cohort comprised CHS members aged 65 or older eligible for the bivalent vaccination. Individuals who were infected or vaccinated in the past three months and those who did not complete primary vaccination were excluded. The primary and secondary endpoints of the study were COVID-19-induced hospitalization and death, respectively.

The team extracted information on subjects’ demographics, COVID-19 testing dates and results, vaccination dates, hospitalizations, and mortality. Data on risk factors for severe illness were also collected. They tested all covariates for interactions with bivalent vaccination. Variables meeting the testing criteria were included in the multivariate regression analysis.

A multivariate Cox proportional hazards model was used with time-dependent covariates to estimate the association of covariates with bivalent booster uptake and COVID-19 hospitalization and mortality. The models were adjusted for sociodemographic factors and concurrent illnesses.

Findings

The researchers identified 622,701 individuals who met the inclusion criteria. Of these, 85,314 were boosted with Pfizer’s bivalent mRNA vaccine. The boosted individuals were more likely to be older and male than others in the cohort. The mean age of bivalent vaccine recipients was 77.2. Vaccine uptake was significantly higher among adults over 75 and those of higher socioeconomic status but lower among ultra-orthodox Jewish and Arab individuals.

COVID-19-related hospitalizations occurred in six bivalent vaccine recipients and 297 individuals who did not receive it. The crude event rate was 0.27 per 100,000 person-days at risk, and the adjusted hazard ratio was 0.19. Male sex and age were associated with a higher rate of COVID-19 hospitalization; by contrast, Arabs had a lower hospitalization rate.

Chronic obstructive pulmonary disease (COPD), chronic renal failure (CRF), chronic heart failure (CHF), and a history of stroke were significantly associated with an increased risk for hospitalization. COVID-19-related deaths occurred in one bivalent vaccine recipient and 73 others who were not boosted with the bivalent vaccine. Age, COPD, CHF, and history of stroke showed significant association with elevated mortality risk.

Conclusion

In summary, the researchers noted that bivalent booster vaccination in the eligible population was associated with an 81% decrease in COVID-19-related hospitalizations. It was also associated with an 86% decline in mortality. Notably, there was a low response rate for bivalent vaccination (14%) among eligible subjects, perhaps due to vaccine misinformation, belief that vaccination was unnecessary, or reports of side effects.

Together, these results indicate that bivalent vaccination is associated with a lower risk of severe COVID-19 in older adults and that efforts must increase to encourage vaccination among eligible populations.

*Important notice

Preprints with the Lancet publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.