The effectiveness of mRNA vaccines during Omicron BA.4/5 predominance

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Mar 21 2023

The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented morbidity and mortality across the globe, the mitigation of which is challenged by the continual emergence of increasingly transmissible and immune-evasive Omicron subvariants such as BA.4/5. Evaluating COVID-19 messenger ribonucleic acid (mRNA) vaccine effectiveness (VE) against novel viral variants could aid in developing updated and more effective vaccines with wider neutralization breath to ultimately improve global preparedness and reduce the health burden of COVID-19.

Study: 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. Image Credit: PeopleImages.com - Yuri A

About the study

In a recent study published in JAMA Network Open, researchers evaluate VE for two, three, and four doses of COVID-19 mRNA first-generation vaccines, including the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines.

VE was assessed among adults against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.4/5 sub-variant of concern (VOC) infections. The relative COVID-19 severity among hospitalized patients with Omicron VOC BA.1 sub-VOC, BA.2 sub-VOC, BA.2.12.1 sub-VOC, or BA.4/5 sub-VOC infections was also assessed.

The current study comprised adult individuals with SARS-CoV-2 infection-like disease. These patients were included based on the International Classification of Diseases, ninth revision (ICD-9), and ICD-10 codes for acute pulmonary clinical diagnosis or COVID-19-associated symptoms such as fever, cough, and breathlessness.

Molecular SARS-CoV-2 testing, which was primarily provided by reverse transcription-polymerase chain reaction (RT-PCR) assay, was performed three weeks or less after BA.4/5 infections and before bivalent booster vaccine authorization doses between June 19, 2022, and August 20, 2022.

The participants were registered with nine VISION network healthcare systems across 10 states. Participant data were obtained from urgent care (UC) and emergency department (ED) encounters and hospital admissions of one or more days duration between December 16, 2021, and August 20, 2022.

The study exposure was COVID-19 mRNA vaccination, whereas study outcomes included SARS-CoV-2 infection-associated UC or ED encounters, hospital admissions, intensive care unit (ICU) admission, or death within four weeks of hospitalization. VE related to immunity levels against medical encounters for SARS-CoV-2 infections was estimated and categorized by the type of care settings and the number of vaccine doses administered.

Among hospitalized COVID-19 patients, clinical and demographic characteristics were retrieved from participants’ electronic health records (EHRs). Within-hospital study outcomes were evaluated and compared across Omicron BA.1, BA.2, and BA.2.12.1 sub-VOC waves. SARS-CoV-2 vaccination status was determined using local or state vaccination data systems, claims information, and EHRs.

Individuals were excluded if they received booster vaccine doses prior to the recommended period for immunocompetent adults or received vaccines with a shorter time interval than recommended. In addition, individuals who received single COVID-19 mRNA vaccination, non-mRNA vaccinations, or were immunocompromised, were excluded.

Multivariable-type logistic regression modeling was performed for the analysis and odds ratios (OR) were determined. Sensitivity analyses were performed by stratifying VE estimates by age, vaccine type, and prior COVID-19 history.

Study findings

During Omicron BA.4/5 predominance, 82,229 UC and ED encounters were reported among individuals suffering from SARS-CoV-2 infection-like disease. Among these individuals, the median participant age was 51 years, 61% of whom were female and 23% had SARS-CoV-2-positive reports. Among the 21,007 hospitalized individuals, the median age was 71 years, 53% of whom were female and 17% had SARS-CoV-2-positive reports.

VE estimates against hospital admission were 25% for two-dose vaccines more than 150 days post-vaccine administration, 68% for seven days to 119 days after receipt of the first booster vaccine dose, and 36% for over 120 days following receipt of the first booster dose.

Among COVID-19 second booster recipients over the age of 65, VE estimates were 66% and 57% at seven to 59 days post-vaccination and over 60 days post-vaccination, respectively.

Among hospitalized COVID-19 patients, ICU admissions or in-hospital deaths occurred in 21% of patients during the BA.1 wave as compared to 15% during the BA.4/5 wave. Sensitivity analyses yielded similar findings.

VE estimates were similar for all study outcomes, which is contrary to several previous studies that have reported greater vaccine-induced immune protection for increasingly severe COVID-19 outcomes. This difference may be due to changes in population immunity levels, behavioral changes including recent reduced mask-wearing and social distancing, as well as confounding factors.

Conclusions

The study findings showed that mRNA COVID-19 vaccines protect against SARS-CoV-2 BA.4/5 infections; however, the protective immunity levels reduced with time. VE estimates were greater among boosted individuals than prime vaccinated individuals. Furthermore, patients hospitalized due to BA.4/5 infections had less severe illness than those hospitalized due to BA.1 infections, despite advancing age.