He stated Tuesday that while it would take weeks to judge the severity of the new variant, early indications suggested it was not worse than prior strains and even possibly milder.
The Director of the National Institute of Allergy and Infectious Disease told AFP that he is certain that the variant is more transmissible than the Delta variant.
The new variant was discovered in late November by South African officials and was feared to be the most infectious form of the virus yet, and could potentially evade vaccine protection.
South African officials report that the variant causes less-severe infections than previous variants. However, hospitalizations in the Gauteng province where it was first detected have spiked in recent weeks - with local leaders unable to explain why.
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Fauci's statements come as 19 U.S. states have recorded at least one case of the variant, and the nation's vaccination rate reaches 60 percent.
In the U.K., cases are spiking - especially among the vaccinated - and Prime Minister Boris Johnson hopes an enhanced campaign to get Britons booster shots will help curb the Omicron variant.
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"It almost certainly is not more severe than Delta," said Fauci.
"There is some suggestion that it might even be less severe because when you look at some of the cohorts that are being followed in South Africa, the ratio between the number of infections and the number of hospitalizations seems to be less than with Delta."
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He added it was necessary to not over-interpret this data.
"I think that's going to take another couple of weeks at least in South Africa," he expressed.
"As we get more infections throughout the rest of the world, it might take longer to see what the level of severity is."
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Fauci insisted a more transmissible virus that doesn't cause more severe illness and doesn't lead to a surge of hospitalizations and deaths was the "best case scenario."
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"The worst-case scenario is that it is not only highly transmissible, but it also causes severe disease, and then you have another wave of infections that are not necessarily blunted by the vaccine or by people's prior infections," he pressed.
"I don't think that worst-case scenario is going to come about, but you never know."