In a recent study published in Preprints with The Lancet *, researchers compared the effectiveness of the two- and three-dose regimens of the 2019 coronavirus disease vaccine BNT1262b (COVID-19) with Omicron BA.1 and BA.2 related to hospital and emergency department (ED) admissions.
Study: BNT162b2 Effectiveness and Durability Against Hospital and Emergency Department Admissions BA.1 and BA.2 in a Large U.S. Health System: A Negative Test Design. Image credit: LookerStudio / Shutterstock
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There is a lack of data on vaccine efficacy (VE) against Omicron BA.1 and BA.2 subvariants. Only a few studies have investigated how Omicron BA.2 underlining became the dominant strain worldwide a few months after the advent of Omicron in November 2021. For example, a Danish study reported ‘greater transmissibility and less vaccine protection for Omicron BA.2. that BA.1. A Swedish study also showed a substantial decrease in the effectiveness of primary vaccination against BA.2.
About the study
In the present study, the researchers evaluated the VE, of both two- and three-regimens of BNT1262b, against Omicron BA.1 and BA.2 subvariants through hospital and ED admissions to the adult population (≥ 18 years old) from California between December. 27 of 2021 and 4 of June of 2022.
They used a negative test study design to analyze the electronic health records (EHR) of all these people recovered from Kaiser Permanente Medical Centers in Southern California in Southern California, USA. A negative test design forced these patients to have a hospital admission related to an acute respiratory infection (ARI). This reduced the bias in the study results and ensured that all hospital and ED admissions were for COVID-19 only.
In addition, the researchers estimated the specific VEs of the SARS-CoV-2 variant by calculating the probability ratio (OR) using adjusted logistic regression models between those hospitalized and admitted to ED but not subsequently hospitalized. All patients hospitalized and admitted to the emergency department with coronavirus 2 (SARS-CoV-2) infection of confirmed severe acute respiratory syndrome also had an IRA. The team confirmed the presence of SARS-CoV-2 infection by a reverse transcription-polymerase chain reaction (RT-PCR) test. In addition, the team distinguished the cases of BA.1 and BA.2 by various methods, such as genome sequencing, gene target failure (SGTF), and variant predominance periods.
Study results
The authors analyzed the EHRs of 1056 patients infected with Omicron BA.2 and 7435 hospitalized patients and ED infected with BA.1. The mean age of the study cohort was 55 years. Of the 16,994 participants in the study, 5,813 were hospitalization cases and 11,817 were admitted to the emergency department but not hospitalized. Among SARS-CoV-2-positive hospitalized patients, 92% were cases of BA.1 and 8% were infected with BA.2, while 14% of patients admitted to ED were infected with BA.2 and 86% were cases of BA.1. .
The results showed that after two doses of vaccine, VE against hospitalization and admission to ED for BA.1 were 40% and 29%, respectively. Likewise, the EV against hospitalization and admission to ED for BA.2 were 56 and 16%, respectively. Overall, two-dose EV against hospitalization and ED admission was limited against BA.1 and BA.2 and ranged from 16 to 56%.
In the six months following a second dose, EV versus hospitalization and ED admission was reduced to 56% and 12% for BA.2. From that moment on, the EV versus hospital admission for BA.2 did not decrease further. It remained steady at 56% from less than six months to more than six months, albeit with broad confidence interval (CI) values. Therefore, the authors were unable to draw definitive conclusions about the durability of vaccine-induced immune responses between the two time points for BA cases.2. On the other hand, three doses of BNT1262b conferred superior protection, i.e. more than 70% protection against hospitalization for BA.1 and BA.2, but remained below 30% against ED income related to BA.2.
The virological characteristics of the Omicron BA.2 and BA.1 subvariants vary significantly. Consequently, BA.2 has higher transmissibility and increased immune evasion properties, which explain most of the study findings. According to the results of the study, studies evaluating advanced infections (ITV) for BA.2 have shown a lower rate (only 17%) of ITV in triple vaccinated individuals compared to 50% in those who received two doses.
Previous studies had similar findings for VE versus severe BA.2-related outcomes as the current study. However, a Swedish study has shown variations in VE versus severe COVID-19 due to Omicron BA.1 and BA.2 underlining. The observed differences are probably due to how the two studies defined the severe outcomes of COVID-19. More importantly, the prevalence time of BA.2 varied between the US and Sweden; the two nations have different hospitalization criteria.
Finally, the current study had a small sample size of immunocompromised individuals (896 / 16,944) and the immune status modulated the decrease in EV versus hospital and ED admissions. Therefore, the authors observed minimal differences in VE between immunocompromised participants and the rest of the study population.
Conclusions
In summary, the study showed that two doses of the BNT162b2 vaccine provided limited protection against hospital and ED admissions related to Omicron BA.1 and BA.2, emphasizing the need for booster doses to enhance immunity against Omicron. Although three doses offered more than 70% protection against BA.1- and BA.2-related hospitalization, specific Omicron vaccines could probably improve protection against less serious outcomes, such as visits to the hospital. ED, especially for cases of BA.2.
* Important news
Preprints with The Lancet publish preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.