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Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5

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. Her...

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Detalles Bibliográficos
Autores principales: Imbiakha, Brian, Ezzatpour, Shahrzad, Buchholz, David W., Sahler, Julie, Ye, Chengjin, Olarte-Castillo, Ximena A., Zou, Anna, Kwas, Cole, O’Hare, Katelyn, Choi, Annette, Adeleke, Richard Ayomide, Khomandiak, Solomiia, Goodman, Laura, Jager, Mason C., Whittaker, Gary R., Martinez-Sobrido, Luis, August, Avery, Aguilar, Hector C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516498/
https://www.ncbi.nlm.nih.gov/pubmed/37738347
http://dx.doi.org/10.1126/sciadv.adj1736
Descripción
Sumario: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.