Omicron subvariant BA.5 efficiently infects lung cells

The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell–cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry of BA.5 is uncoupled from mutations at H69/V70 and is associated with efficient receptor recognition in polarized lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that the evolution of Omicron subvariants can result in partial loss of attenuation.

Markus Hoffmann, Lok-Yin Roy Wong, Prerna Arora, Lu Zhang, Cheila Rocha, Abby Odle, Inga Nehlmeier, Amy Kempf, Anja Richter, Nico Joel Halwe, Jacob Schön, Lorenz Ulrich, Donata Hoffmann, Martin Beer, Christian Drosten, Stanley Perlman, Stefan Pöhlmann