Increased pathogenicity and transmissibility in hamsters of all age groups reveal an underestimated perniciousness of severe acute respiratory syndrome coronavirus 2 EG.1 variant

The evolution and mutation of SARS-CoV-2 is elusive. However, the diverse <i>in vivo</i> pathogenicity and transmissibility of different SARS-CoV-2 Omicron/XBB variants are not well understood. We compared virological attributes of two XBB variants, XBB.1.16 and XBB.1.9.2.1 (EG.1) in new-born, juvenile, adult, middle-aged and senescent Syrian hamsters. In particular, EG.1 has a specific Q613H mutation and causes fatal severe pneumonia in hamsters of all ages. In contrast, all hamsters infected with XBB.1.16 survived and showed milder symptoms. The XBB.1.16 infected hamsters lost significantly less body weight and exhibited lower respiratory viral loads, pro-inflammatory cytokines and lung injury than those with EG.1 infection. In addition, EG.1 is more transmissible than XBB.1.16 in close contact co-housing. Both EG.1 and XBB.1.16 are highly resistant to therapeutic antibodies and convalescent serum. Overall, the unpredictable evolution, global transmission and potential threat of emerging SARS-CoV-2 variants necessitate the updating of prophylactic and therapeutic countermeasures in all age groups.