Comparing SARS-CoV-2 Omicron BA.2 and BA.5 vaccine breakthrough infections

In a recent study posted to the medRxiv* preprint server, investigators explored the likelihood of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 and BA.5 vaccine breakthrough infections.

Study: SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal. Image Credit: CROCOTHERY/Shutterstock


The SARS-CoV-2 Omicron BA.5 lineage was first discovered in February 2022 in South Africa, shortly after the discovery of the BA.4 lineage. Soon after, both have taken over as the predominant SARS-CoV-2 variants in South Africa, with an increase in coronavirus disease 2019 (COVID-19) incidences in other nations like Portugal.

On 8 May 2022, Doutor Ricardo Jorge of the Portuguese National Institute of Health (INSA) predicted that 37% of SARS-CoV-2 cases in Portugal would be associated with BA.5. At the end of May, it was anticipated that BA.5 might overtake all other SARS-CoV-2 lineages in Portugal. This estimation was based on the 13% projected growth advantage per day and a doubling period of roughly six days of the Omicron BA.5 lineage. Further, Omicron BA.4 and BA.5 were reclassified by the European Center for Disease Prevention and Control (ECDC) from variants of interest (VOI) to variants of concern (VOC) as of 12 May 2022. 

Clarifying the impact of SARS-CoV-2 vaccination and prior infections on the likelihood of infection and critical post-infection outcomes is pertinent given the circulation of numerous Omicron lineages. Alternative study methods that only incorporate infected patients and measure the vaccine's relative effect might be helpful in the setting of substantially vaccinated communities when it is challenging to construct a negative control cohort.

About the study

The present research draws on an earlier assessment of the severity and effectiveness of the SARS-CoV-2 variant vaccination to investigate the comparative efficacy of the COVID-19 vaccine towards Omicron sublineages.

To compare the effectiveness of the complete primary and booster doses of the COVID-19 vaccine against infection, COVID-19-linked hospitalization, and death, the team conducted case-case and cohort studies covering the time of Omicron BA.2/BA.5 lineage replacement across Portugal utilizing electronic health records and SARS-CoV-2 laboratory monitoring data. They categorized SARS-CoV-2 variants using spike gene target failure (SGTF) or whole-genome sequencing (WGS).

The authors adopted two different strategies to conduct the study. Initially, they performed a case-case analysis to assess the chances of a SARS-CoV-2 vaccine breakthrough infection between Omicron BA.5- and BA.2-infected people. Secondly, the scientists leveraged a cohort study design to examine the vaccine efficiency following COVID-19 against infection-related death and hospitalization in BA.5- and BA.2-infected subjects. Instead of considering uninfected persons in comparisons, post-infection vaccine efficacy (VEp) was calculated by comparing the likelihood of catastrophic outcomes in vaccinated infected and unvaccinated infected individuals.


Out of the 27,702 samples collected between 25 April and 10 June 2022, 55.5% were categorized as BA.2 and the rest as BA.5. The present investigation demonstrated no variations in probabilities of vaccination between BA.5 and BA.2 cases throughout the Portuguese adult population by a case-case analysis method, indicating equivalent vaccine efficacy against BA.5 and BA.2 infection. The investigators found no proof of diminished vaccine efficacy for the initial complete vaccination or booster shot against BA.5 compared to BA.2 infection.

Comparing BA.5 cases to BA.2, the vaccine-induced immunity against SARS-CoV-2 reinfection was less effective. Across BA.5-infected people, COVID-19 booster vaccination was linked to an 88% and 77% decrease in the probability of COVID-19-related death and hospitalization, respectively. However, a heightened risk reduction was identified for BA.2 patients, with 94% and 93% for SARS-CoV-2-linked mortality and hospital admission, respectively. While the researchers discovered that BA.5 patients who received a booster vaccination had 3.4 times greater odds of being hospitalized than BA.2 cases, the first booster had a moderate protective impact in lowering the likelihood of hospital admission.


The study findings offer significant evidence that might inform public health policies in Portugal and other nations where the SARS-CoV-2 Omicron BA.5 lineage is spreading more widely. It implies that the rise in COVID-19 instances observed in countries with elevated BA.5 frequency may be associated with the increased immune escape of BA.5. 

In addition, the study data showed that irrespective of vaccination status, the Omicron BA.5 lineage was linked to higher probabilities of reinfection than Omicron BA.2. SARS-CoV-2 booster vaccine provided significant protection against catastrophic outcomes after BA.5 infection, albeit being less effective than BA.2.

In short, the current work enables the detection of COVID-19-related hospital admissions and deaths and provides a reliable categorization of SARS-CoV-2 outcomes centered on electronic health record linkage. It gives a thorough overview of the risk of BA.5 vaccine breakthrough infection, hospitalization, and mortality. 

The team demonstrated that vaccinations were less effective in lowering the risk of catastrophic outcomes for BA.5 than for BA.2, thus offering proof to alter public health interventions during the BA.5 wave. Further, they restricted the analysis to the transitional time between BA.2 and BA.5 and a short period afterward, thereby reducing the likelihood of biases brought about by shifting testing practices.

*Important notice

medRxiv publishes 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.

Journal reference:
  • Irina Kislaya, et al. (2022). SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal. medRxivdoi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Electronic Health Record, Frequency, Gene, Genome, Hospital, immunity, Laboratory, Mortality, Omicron, Public Health, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Vaccine

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Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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