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The Omicron variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has rapidly replaced the Delta variant as a dominating SARS-CoV-2variant because of natural selection, which favors the variant with higherinfectivity and stronger vaccine breakthrough ability. Omicron has threelineages or subvariants, BA.1 (B.1.1.529.1), BA.2 (B.1.1.529.2), and BA.3(B.1.1.529.3). Among them, BA.1 is the currently prevailing subvariant. BA.2shares 32 mutations with BA.1 but has 28 distinct ones. BA.3 shares most of itsmutations with BA.1 and BA.2 except for one. BA.2 is found to be able toalarmingly reinfect patients originally infected by Omicron BA.1. An importantquestion is whether BA.2 or BA.3 will become a new dominating "variant ofconcern". Currently, no experimental data has been reported about BA.2 andBA.3. We construct a novel algebraic topology-based deep learning model trainedwith tens of thousands of mutational and deep mutational data to systematicallyevaluate BA.2's and BA.3's infectivity, vaccine breakthrough capability, andantibody resistance. Our comparative analysis of all main variants namely,Alpha, Beta, Gamma, Delta, Lambda, Mu, BA.1, BA.2, and BA.3, unveils that BA.2is about 1.5 and 4.2 times as contagious as BA.1 and Delta, respectively. It isalso 30% and 17-fold more capable than BA.1 and Delta, respectively, to escapecurrent vaccines. Therefore, we project that Omicron BA.2 is on its path tobecoming the next dominating variant. We forecast that like Omicron BA.1, BA.2will also seriously compromise most existing mAbs, except for sotrovimabdeveloped by GlaxoSmithKline.

Omicron BA.2 (B.1.1.529.2): high potential to becoming the next dominating variant