Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

  1. Izumi Kimura
  2. Daichi Yamasoba
  3. Tomokazu Tamura
  4. Naganori Nao
  5. Yoshitaka Oda
  6. Shuya Mitoma
  7. Jumpei Ito
  8. Hesham Nasser
  9. Jiri Zahradnik
  10. Keiya Uriu
  11. Shigeru Fujita
  12. Yusuke Kosugi
  13. Lei Wang
  14. Masumi Tsuda
  15. Mai Kishimoto
  16. Hayato Ito
  17. Rigel Suzuki
  18. Ryo Shimizu
  19. MST Monira Begum
  20. Kumiko Yoshimatsu
  21. Jiei Sasaki
  22. Kaori Sasaki-Tabata
  23. Yuki Yamamoto
  24. Tetsuharu Nagamoto
  25. Jun Kanamune
  26. Kouji Kobiyama
  27. Hiroyuki Asakura
  28. Mami Nagashima
  29. Kenji Sadamasu
  30. Kazuhisa Yoshimura
  31. Jin Kuramochi
  32. Gideon Schreiber
  33. Ken J Ishii
  34. Takao Hashiguchi
  35. The Genotype to Phenotype Japan (G2P-Japan) Consortium
  36. Terumasa Ikeda
  37. Akatsuki Saito
  38. Takasuke Fukuhara
  39. Shinya Tanaka
  40. Keita Matsuno
  41. Kei Sato
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Abstract

After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.

Highlights

  • Spike L452R/Q/M mutations increase the effective reproduction number of BA.2

  • BA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infections

  • BA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2

  • BA.4/5 is more pathogenic than BA.2 in hamsters

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