Study Finds Vaccine Effectiveness Lowers as Time Increases From Last Dose

A study published in JAMA Network Open found that vaccine effectiveness (VE) was reliant on the time since the previous dose, with the estimated VE higher after receiving 1 or 2 booster doses compared with those who received the primary dose alone.

The vaccine for the COVID-19 virus has prevented hospitalizations and deaths in the United States, but newer variants of the virus have evaded vaccine-induced immunity, making monitoring VE important in the continued public health strategies and policies. This study aimed to estimate VE associated with first-generation mRNA vaccines against BA.4 and BA.5 omicron subvariants.

Data were collected from 9 VISION Network health care systems from 10 states, which included 268 hospitals, 292 emergency departments (ED), and 140 urgent care (UC) clinics. VE was estimated by assessing ED and UC encounters and hospitalizations that had 1 or more discharge codes in line with COVID-19–like illness as well as a molecular test.

Adults that were 18 years or older and had a medical encounter that was related to COVID-19 and SARS-CoV-2 molecular testing were included in this study, and only completed hospitalizations were included.

Vaccination status was collected through state and local immunization information systems, electronic medical records, and claims data, with only mRNA vaccines being considered for this study. Those who had not received any doses of the mRNA vaccine prior to the index date were considered unvaccinated. Patients were excluded if they had only received 1 dose of the mRNA vaccine, had received a non-mRNA vaccine, or had an immunocompromising condition.

There were 82,229 patients with ED or UC encounters included in the study, with a median (IQR) age of 51 (33-70) years and a total of 60.4% of female patients; there were 19,114 encounters with a positive COVID-19 test result. A total of 15.7% of encounters were from Hispanic patients, 12.5% were from non-Hispanic Black patients, and 59.3% were from non-Hispanic White patients.

Patients who had COVID-19 were less likely to have a booster dose compared with the controls (32.3% vs 41.9%) but were similar in age (median age, 50 [33-69] years vs 52 [30-70]); 11.4% of patients aged less than 50 years who had ED or UC encounters had received a second booster compared with 19.6% of patients without COVID-19.

The study included 21,007 hospitalizations with a median patient age of 71 (58-81) years, and 53.4% were women. A total of 17.1% of patients had a positive COVID-19 test result. Patients hospitalized for COVID-19 were less likely to have received at least a booster dose compared with the controls (41.2% vs 47.1%) and were more likely to be older. A total of 10.3% of patients aged 50 years or older with COVID-19 had a second dose compared with 15.8% without COVID-19.

The estimated VE for the previous receipt of 2 vaccine doses at least 150 days earlier (median, 424 [326-470] days) compared with unvaccinated was 28% (95% CI, 24%-31%). VE for a third dose that was received 7 to 119 days earlier was 62% (95% CI, 54%-68%) but was only 32% (95% CI, 29%-36%) when taken at least 120 days earlier (median, 228 [197-257] days).

Estimated VE was 25% (95% CI, 17%-32%) for people who previously received 2 vaccine doses at least 150 days earlier. A fourth dose was associated with greater protection in adults aged 65 years or older compared with a later third dose at 7 to 59 days (66%; 95% CI, 53%-75%) and 60 days or longer (57%; 95% CI, 44%-66%) after receiving the fourth dose. VE was highest or similar against COVID-19–related intensive care unit admission or in-hospital death in patients aged 65 years or older who had a fourth dose.

Receiving a third dose within the previous 7 to 119 days was found to be associated with greater protection compared with completing 2 doses 150 or more days before in patients with ED and UC encounters (rVE, 49%; 95% CI, 39%-58%) and hospitalizations (rVE, 57%; 95% CI, 35%-72%).

Genomic characterization could not be done directly due to patient samples not being available. The study contained all individuals because prior infection was likely underreported, but this may have biased results toward the null if some protection against reinfection or severity occurs with initial infection.

The researchers concluded that the VE for patients who had received a third or fourth dose recently was higher against ED or UC visits, hospitalization, and intensive care unit admission or death compared with those who had 2 doses. However, this waned during the period where BA.4 and BA.5 were predominant.

Reference

Link-Gelles R, Levy ME, Natarajan K, 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