The European Center for Disease Prevention and Control (ECDC) said in a report that variants BA4 and BA5 could lead to a surge in cases across the continent, risking a rise in hospital and ICU pressure.
The EU body is pressing all countries to "remain vigilant" for signs that the strains are emerging - while encouraging over 80s to receive a second booster jab.
It also urged countries to put plans in place for those over 60 and other vulnerable groups to receive a second booster.
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The BA4 and BA5 strains were first detected in South Africa in January and February of this year, respectively.
They have since become the popular strain in that country, while BA5 is expected to be the most common variant in Portugal by May 22, according to the ECDC.
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Both new variants of concern can evade immunity awarded by both a previous Covid infection and a vaccine, "particularly if this is waned over time," health officials said, encouraging booster shots for the elderly and vulnerable.
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However, the report said there was currently "no indication of any change in severity for BA4/BA5 compared to previous Omicron lineages."
The ECDC said: "The presence of these variants could cause a significant overall increase in COVID-19 cases in the EU/EEA in the coming weeks and months.
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"The overall proportion of BA.4 and BA.5 in the EU/EEA is currently low but the high growth advantages reported suggest that these variants will become dominant in the EU/EEA in the coming months.
"Based on the limited data currently available, no significant increase in infection severity compared to the circulating lineages BA.1 and BA.2 is expected.
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"However, as in previous waves, if COVID-19 case numbers increase substantially, some level of increased hospital and ICU admissions is likely to follow.
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"ECDC encourages countries to remain vigilant for signals of BA.4 and BA.5 emergence."
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It added: "For all age groups, it remains a priority to improve Covid-19 vaccine uptake of the primary course and first booster dose in populations who have yet to receive them."
It comes as figures published today show COVID levels continued to decline in England last week, falling to their lowest levels since the start of December before Omicron took off.
The Office for National Statistics (ONS) estimates 1.2million, or one in 45 people, were carrying the virus on any given day in the week to May 7, down a quarter on the previous week.
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