Kei Sato, Virtual COVID 19 Symposium May 11, 2022

Kei Sato, PhD, Professor, Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Japan, Evolution of SARS-CoV-2 – Delta, Omicron, and more greek alphabet(s)?

Dr. Sato's group, a part of the G2P-Japan Consortium, has contributed many significant studies since the COVID-19 pandemic regarding the phenotypes of SARS-CoV2 variants or mutations, such as L452R spike mutation increasing infectivity and evading cellular immunity, Mu variant highly resistant to neutralization, P681R mutation causing the high fusogenicity and pathogenicity of Delta. Since the Omicron variant emerged, the group specifically focused on the "pathogenicity" and "neutralization" features of Omicron. They found that Omicron was highly resistant to vaccine-induced immunity, but the spike was less efficiently cleaved, leading to poor cell entry. Also, Omicron was more transmissible but less pathogenic. The Omicron BA.2 variant had more substitution mutations than Omicron BA.1 variant. Utilizing a split luciferase, GFP-CoV2 spike expressing cells, and ACE2 expressing cells in the cell-based fusion assay, the group demonstrated that BA.2 spike was more fusogenic than BA.1 spike and induced larger syncytia than BA.1 spike. The Omicron BA.1 variant had much lower S cleavage spike cleavage efficiency and fusogenicity compared with the Delta variant. The BA.2 variant had higher pathogenicity, more efficient spreads, and induced more inflammation in the animal lungs than BA.1 variant. However, the clinically isolated BA.2 variant had similar pathogenicity to BA.1 variant.