Abstract
The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly replaced the Delta variant as a dominating SARS-CoV-2 variant because of natural selection, which favors the variant with higher infectivity and stronger vaccine breakthrough ability. Omicron has three lineages 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.2 shares 32 mutations with BA.1 but has 28 distinct ones. BA.3 shares most of its mutations with BA.1 and BA.2 except for one. BA.2 is found to be able to alarmingly reinfect patients originally infected by Omicron BA.1. An important question is whether BA.2 or BA.3 will become a new dominating ``variant of concern''. Currently, no experimental data has been reported about BA.2 and BA.3. We construct a novel algebraic topology-based deep learning model trained with tens of thousands of mutational and deep mutational data to systematically evaluate BA.2's and BA.3's infectivity, vaccine breakthrough capability, and antibody 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.2 is about 1.5 and 4.2 times as contagious as BA.1 and Delta, respectively. It is also 30% and 17-fold more capable than BA.1 and Delta, respectively, to escape current vaccines. Therefore, we project that Omicron BA.2 is on its path to becoming the next dominating variant. We forecast that like Omicron BA.1, BA.2 will also seriously compromise most existing mAbs, except for sotrovimab developed by GlaxoSmithKline.