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

被引：11

作者：

Imbiakha, Brian ^{[1
]}

Ezzatpour, Shahrzad ^{[2
]}

Buchholz, David W. ^{[1
]}

Sahler, Julie ^{[1
]}

Ye, Chengjin ^{[3
]}

Olarte-Castillo, Ximena A. ^{[1
,4
]}

Zou, Anna ^{[1
]}

Kwas, Cole ^{[1
]}

O'Hare, Katelyn ^{[1
]}

Choi, Annette ^{[1
]}

Adeleke, Richard Ayomide ^{[1
]}

Khomandiak, Solomiia ^{[1
]}

Goodman, Laura ^{[4
,5
]}

Jager, Mason C. ^{[6
]}

Whittaker, Gary R. ^{[1
,5
]}

Martinez-Sobrido, Luis ^{[3
]}

August, Avery ^{[1
]}

Aguilar, Hector C. ^{[1
,2
]}

机构：

[1] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA

[2] Cornell Univ, Coll Agr & Life Sci, Dept Microbiol, Ithaca, NY 14853 USA

[3] Texas Biomed Res Inst, San Antonio, TX 78227 USA

[4] Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA

[5] Cornell Univ, Coll Vet Med, Dept Publ & Ecosyst Hlth, Ithaca, NY 14853 USA

[6] Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 38期

基金：

美国国家卫生研究院;

关键词：

T-CELLS; DENDRITIC CELLS; INFECTION; COVID-19; IMMUNITY; REVEALS; SIGNATURES; CYTOKINES;

D O I：

10.1126/sciadv.adj1736

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

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