In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

1st Medical Faculty at Biocev Charles University Vestec Prague Czechia

AMED CREST Japan Agency for Medical Research and Development Tokyo Japan

Center for Animal Disease Control University of Miyazaki Miyazaki Japan

Center for iPS Cell Research and Application Kyoto University Kyoto Japan

Collaboration Unit for Infection Joint Research Center for Human Retrovirus infection Kumamoto University Kumamoto Japan

CREST Japan Science and Technology Agency Kawaguchi Japan

Department of Biomolecular Sciences Weizmann Institute of Science Rehovot Israel

Department of Cancer Pathology Faculty of Medicine Hokkaido University Sapporo Japan

Department of Clinical Pathology Faculty of Medicine Suez Canal University Ismailia Egypt

Department of Global Health Promotion Tokyo Medical and Dental University Tokyo Japan

Department of Medicinal Sciences Graduate School of Pharmaceutical Sciences Kyushu University Fukuoka Japan

Department of Microbiology and Immunology Faculty of Medicine Hokkaido University Sapporo Japan

Department of Veterinary Science Faculty of Agriculture University of Miyazaki Miyazaki Japan

Division of International Research Promotion International Institute for Zoonosis Control Hokkaido University Sapporo Japan

Division of Molecular Pathobiology International Institute for Zoonosis Control Hokkaido University Sapporo Japan

Division of Molecular Virology and Genetics Joint Research Center for Human Retrovirus infection Kumamoto University Kumamoto Japan

Division of Risk Analysis and Management International Institute for Zoonosis Control Hokkaido University Sapporo Japan

Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan

Graduate School of Frontier Sciences The University of Tokyo Kashiwa Japan

Graduate School of Medicine and Veterinary Medicine University of Miyazaki Miyazaki Japan

Graduate School of Medicine The University of Tokyo Tokyo Japan

HiLung Inc Kyoto Japan

Institute for Chemical Reaction Design and Discovery Hokkaido University Sapporo Japan

Institute for Genetic Medicine Hokkaido University Sapporo Japan

Institute for Vaccine Research and Development HU IVReD Hokkaido University Sapporo Japan

International Collaboration Unit International Institute for Zoonosis Control Hokkaido University Sapporo Japan

International Research Center for Infectious Diseases The Institute of Medical Science The University of Tokyo Tokyo Japan

International Vaccine Design Center The Institute of Medical Science The University of Tokyo Tokyo Japan

Interpark Kuramochi Clinic Utsunomiya Japan

Laboratory of Medical Virology Institute for Life and Medical Sciences Kyoto University Kyoto Japan

Laboratory of Virus Control Research Institute for Microbial Diseases Osaka University Suita Japan

Medical Research Council University of Glasgow Centre for Virus Research Glasgow UK

One Health Research Center Hokkaido University Sapporo Japan

Tokyo Metropolitan Institute of Public Health Tokyo Japan

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Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

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