Effectiveness of two and three doses of BNT162b2 against hospital and ED admissions for BA.1 and BA.2 infection

In a recent study posted to Preprints with The Lancet*, researchers compared the effectiveness of two and three-dose regimens of coronavirus disease 2019 (COVID-19) vaccine BNT1262b against Omicron BA.1 and BA.2-related hospital and emergency department (ED) admissions.

Study: BNT162b2 Effectiveness and Durability Against BA.1 and BA.2 Hospital and Emergency Department Admissions in a Large US Health System: A Test-Negative Design.  Image Credit: LookerStudio/Shutterstock
Study: BNT162b2 Effectiveness and Durability Against BA.1 and BA.2 Hospital and Emergency Department Admissions in a Large US Health System: A Test-Negative Design. Image Credit: LookerStudio/Shutterstock


There is a lack of data regarding vaccine effectiveness (VE) against Omicron sub-variants BA.1 and BA.2. Only a few studies have investigated how Omicron sub-lineage BA.2 became the dominant strain around the world within months of the emergence of Omicron in November 2021. For instance, a Danish study reported increased transmissibility and less vaccine protection for Omicron BA.2 than BA.1. A Swedish study also showed a substantial decrease in the effectiveness of the primary vaccination against BA.2.

About the study

In the present study, researchers evaluated the VE, of both two and three-regimens of BNT1262b, against Omicron BA.1 and BA.2 sub-variants across hospital and ED admissions in the adult population (≥18 years) of California between December 27, 2021, and June 4, 2022.

They used a test-negative study design to analyze electronic health records (EHRs) of all these individuals retrieved from Kaiser Permanente Southern California medical centers across Southern California, US. A test-negative design mandated that these patients had an acute respiratory infection (ARI)-related hospital admission. This reduced bias in the study results and ensured all the hospital and ED admissions were for COVID-19 only.

Further, the researchers estimated SARS-CoV-2 variant-specific VEs computing odds ratio (OR) using adjusted logistic regression models among those hospitalized and admitted to EDs but not subsequently hospitalized. All the hospitalized and ED admitted patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection also had an ARI. The team confirmed the presence of SARS-CoV-2 infection using a reverse transcription-polymerase chain reaction (RT-PCR) test. Further, the team distinguished BA.1 and BA.2 cases using several methods, such as genome sequencing, spike (S) gene target failure (SGTF), and variant predominance periods.

Study findings

The authors analyzed EHRs of 1056 Omicron BA.2-infected, and 7435 BA.1-infected hospital and ED admitted patients. The average age of the study cohort was 55 years. Of the 16,994 study participants, 5,813 were cases of hospitalization, and 11,817 were admitted to ED but not hospitalized. Among SARS-CoV-2-positive hospitalized patients, 92% were BA.1 cases, and 8% were BA.2-infected, whereas 14% of ED admitted patients were BA.2-infected and 86% were BA.1 cases .

The results showed that after two vaccine doses, VE against hospitalization and ED admission for BA.1 were 40% and 29%, respectively. Likewise, VE against hospitalization and ED admission for BA.2 were 56 and 16%, respectively. Overall, the VE of two doses against hospitalization and ED admission was limited against BA.1 and BA.2 and ranged between 16 and 56%.

Within six months following a second dose, VE against hospitalization and ED admission declined to 56% and 12% for BA.2. From this time, VE against hospital admission for BA.2 did not decrease further. It consistently remained at 56% from less than six months to more than six months, although with wide confidence intervals (CI) values. Hence, the authors could not make definitive conclusions about the durability of the vaccine-induced immune responses between the two-time points for BA.2 cases. On the other hand, three BNT1262b doses conferred higher protection, ie, over 70% protection against hospitalization for BA.1 and BA.2, but it remained under 30% against BA.2-related ED admissions.

The virological characteristics of Omicron BA.2 and BA.1 sub-variants vary significantly. Accordingly, BA.2 has higher transmissibility and increased immune evading properties, which explain most of the study findings. Consistent with study findings, studies evaluating breakthrough infections (BTIs) by BA.2 have shown a lower (only 17%) rate of BTIs in triple-vaccinated individuals compared to 50% in those who received two doses.

Previous studies had similar findings for VE against severe BA.2-related outcomes like the current study. However, a Swedish study has shown VE variations against severe COVID-19 due to Omicron BA.1 and BA.2 sub-lineages. The observed differences were likely due to how the two studies defined severe COVID-19 outcomes. More importantly, the time of prevalence of BA.2 varied between the US and Sweden; the two nations have different hospitalization criteria.

Lastly, the current study had a small sample size of immunocompromised individuals (896/16,944), and immune status modulates the waning of VE against hospital and ED admissions. Therefore, the authors observed minimal VE differences among the immunocompromised participants and the remaining study population.


To summarize, the study evidenced that two doses of the BNT162b2 vaccine provided limited protection against Omicron BA.1- and BA.2-related hospital and ED admissions, emphasizing the need for booster doses to bolster immunity against Omicron. Although three doses offered over 70% protection against BA.1- and BA.2-related hospitalization, Omicron-specific vaccines could likely improve protection against the less severe outcomes, such as ED visits, especially for BA.2 cases.

*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.


Leave a Comment