| First Author | Imbiakha B | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 38 | Pages | eadj1736 |
| PubMed ID | 37738347 | Mgi Jnum | J:341174 |
| Mgi Id | MGI:7532183 | Doi | 10.1126/sciadv.adj1736 |
| Citation | Imbiakha B, et al. (2023) Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5. Sci Adv 9(38):eadj1736 |
| abstractText | Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity and mortality, and less is known about more recent Omicron VOC. Here, we show that in contrast to Omicron BA.1, BA.5-infected mice exhibited high levels of morbidity and mortality, correlating with higher early viral loads. Neither Omicron BA.1 nor BA.5 replicated in brains, unlike most prior VOC. Only Omicron BA.5-infected mice exhibited substantial weight loss, high pathology scores in lungs, and high levels of inflammatory cells and cytokines in bronchoalveolar lavage fluid, and 5- to 8-month-old mice exhibited 100% fatality. These results identify a rodent model for pathogenesis or antiviral countermeasure studies for circulating SARS-CoV-2 Omicron BA.5. Further, differences in morbidity and mortality between Omicron BA.1 and BA.5 provide a model for understanding viral determinants of pathogenicity. |
