Omicron sublineages BA.4 and BA.5 were discovered in South Africa in January and February 2022, respectively, and have since emerged as dominant variants. Both lineages have the amino-acid substitutions L452R, F486V, and R493Q in the spike receptor binding domain. Preliminary research indicates that BA.4 and BA.5 have significantly different antigenic properties than BA.1 and BA.2, particularly BA.1. Furthermore, in recent weeks, the variant proportions for BA.5 have increased, which has been accompanied by an increase in COVID-19 case numbers and test positivity rate.

According to the Portuguese National Institute of Health, BA.5 accounted for 37% of positive cases as of May 8, 2022. BA.5 has a 13% estimated daily growth advantage over BA.2, which is comparable to South Africa’s previously reported 12% daily growth advantage. If this rate of growth continues, by May 22, 2022, BA.5 will be the dominant variant in Portugal.

The observed growth advantage of BA.4 and BA.5 is most likely due to their ability to evade immune protection induced by prior infection and/or vaccination, particularly if this has waned over time. In vitro data from previously infected unvaccinated individuals show that both BA.4 and BA.5 are capable of evading immune protection induced by BA.1 infection. Individuals who have not received an immunization are unlikely to be immune to symptomatic BA.4 or BA.5 infection. Previously, sera from vaccinated individuals performed better in invitro

studies, but protection against the Omicron variant from currently available vaccines waned over time.

At this time, there is no evidence of a severity difference between BA.4/BA.5 and previous Omicron lineages.

These findings suggest that the presence of these variants may result in a significant increase in COVID-19 cases in the EU/EEA in the coming weeks and months. Although the overall proportion of BA.4 and BA.5 is currently low in the EU/EEA, the reported high growth advantages indicate that these variants will become dominant in the EU/EEA in the coming months. According to the available data, there will be no significant increase in infection severity when compared to the circulating lineages BA.1 and BA.2. However, if the number of COVID-19 cases increases significantly, hospital and ICU admissions are likely to increase, as they have in previous waves.

The ECDC advises countries to keep an eye out for signs of BA.4 and BA.5 emergence. Sensitive and representative testing, as well as genomic surveillance and timely sequence reporting, are required for early variant detection. To accurately determine the extent to which these variants may contribute to any observed increases in severe outcomes in the population, such as increases in hospital or ICU admissions, representative testing policies are required.

The ECDC recently determined that the public health benefit of administering a second mRNA COVID-19 booster dose is greatest in those aged 80 and older, and that immediate administration of a second booster dose in this population is optimal in situations of continued high or increasing viral circulation.

Close epidemiological and vaccine effectiveness monitoring is required to detect early signs of increased SARS-CoV-2 circulation or the risk of severe disease among vaccinated individuals. If such signals emerge, a second booster for some or all adults 60 and older, as well as other vulnerable groups, may be considered.

Countries should have plans in place to distribute booster doses to these populations as soon as possible.

Increased COVID-19 vaccine uptake remains a top priority for all age groups.

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