First Generation COVID-19 Vaccine Protection Wanes Over Time


Investigators estimate that the effectiveness was higher after 1 or 2 booster doses compared with the primary series alone.

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The first generation of COVID-19 mRNA vaccines was associated with protection against the Omicron BA.4/BA.5 virus, but the protection waned over time, according to the results of a study published in Jama Network Open.

In the study, vaccine effectiveness that was associated with protection against medically attended COVID-19 illness lowered over time since the last dosage. Investigators estimated that vaccine effectiveness was higher after 1 or 2 booster doses compared with the primary series alone.

They conducted the study in 10 states using data from emergency-department (ED) and urgent-care visits and hospitalization between December 16, 2021, and August 20, 2022. Individuals included in the study were adults with COVID-19-like illness and molecular testing for SARS-CoV-2.

The data were analyzed between August 2, 2022, and September 21, 2022.

The vaccine effectiveness with protection against COVID-19 was estimated and stratified by care setting and vaccine doses, with 2, 3, or 4 doses compared with 0 as the reference group. Among individuals who were hospitalized with COVID-19, clinical and demographic characteristics and in-hospital outcomes were compared across sublineage periods.

During the period when the BA.4 and BA.5 variants were prominent, 82,229 eligible ED and urgent-care encounters were recorded for COVID-19-like illnesses. Of those, there were 3583 positive test results.

Investigators found that estimated vaccine effectiveness against hospitalization was approximately 25% for those who had 2 vaccine doses and at 150 days or more after receiving the doses.

For 3 doses, the number was 68% for 7 to 119 days after receiving the vaccine and 36% for 120 days or more. For those aged 65 years and older who received 4 doses, the vaccine effectiveness was 66% at 7 to 59 days after vaccination and 57% at 60 days or more after vaccination.

Among individuals with COVID-19 who were admitted to a hospital or intensive care unit (ICU), in-hospital death occurred in 21.4% of individuals during the BA.1 period and 14.7% during the BA.4 and BA.5 periods.

Investigators also found that among ED and urgent-care encounters, individuals with COVID-19 were less likely to have received at least 1 booster does compared with controls. Additionally, among those aged 50 years or older with COVID-19, approximately 11.4% had received 4 doses of a vaccine compared with 19.6% without COVID-19.

They also found that individuals who were hospitalized with COVID-19 were less likely to have received at least 1 booster dose and more likely to be older compared with individuals without COVID-19.

Investigators also noted several limitations, including that the patient sample was not available for genomic characterization directly.

Furthermore, investigators combined estimated vaccine effectiveness against ICU admission and death, which could have affected the results, because of differences in vaccine effectiveness for the individual outcomes.

These findings provide a baseline for the bivalent vaccine efficiency analysis, investigators said.


Link-Gelles R, Levy ME, Natarajan K, Reese SE, et al. Estimation of COVID-19 mRNA vaccine effectiveness and COVID-19 illness and severity by vaccination status during Omicron BA.4 and BA.5 sublineage periods. JAMA Netw Open. 2023;6(3):e232598. doi:10.1001/jamanetworkopen.2023.2598

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