新型冠状病毒奥密克戎株BA.1和BA.2在金黄地鼠模型中的致病性及传染力研究

Pathogenicity and transmissibility of SARS-CoV-2 Omicron BA.1 and BA.2 in golden hamster

目的比较新型冠状病毒(SARS-CoV-2)奥密克戎(Omicron)BA.1、BA.2在金黄地鼠中的致病性及传播能力差异。方法6~8周龄雄性金黄地鼠,体质量(107.00±18.88)g,共24只,其中,12只金黄地鼠感染10^(6)CCID_(50)/100μl病毒液(6只感染Omicron BA.1,6只感染Omicron BA.2)24 h后作为供体,与8只健康金黄地鼠(作为受体,每种病毒株4只受体)共同饲养2 h,用于接触传播研究,同时供体用于致病力研究,4只金黄地鼠作为空白对照。所有动物在实验周期内每天进行体质量监测,供体动物于感染后第1天开始采集鼻咽拭子及肛拭子,受体动物于接触当天开始采集鼻咽拭子。采用RT-PCR对动物鼻咽拭子、肺、鼻甲组织病毒载量进行检测,同时用苏木精伊红(HE)染色评估肺组织损伤程度,进而评估2种病毒株在金黄地鼠中的致病力及传播力。结果SARS-CoV-2 Omicron BA.1与BA.2均未导致严重的肺损伤,同时未引起明显的体质量变化,Omicron BA.1感染金黄地鼠体质量:初始(121.61±8.21)g,实验结束(131.53±8.02)g;Omicron BA.2感染金黄地鼠体质量:初始(88.15±1.74)g,实验结束(90.42±9.95)g。肺组织病毒核酸拷贝数[Omicron BA.1感染金黄地鼠(7.64±0.74)log_(10)拷贝/ml,Omicron BA.2感染金黄地鼠(7.79±0.25)log_(10)拷贝/ml];鼻甲病毒核酸拷贝数[Omicron BA.1感染金黄地鼠(6.63±0.63)log_(10)拷贝/ml,Omicron BA.2感染金黄地鼠(6.92±0.14)log_(10)拷贝/ml],差异均无统计学意义,表明两者致病性无明显差异。在传播能力方面,Omicron BA.2的传播能力略高于Omicron BA.1,健康金黄地鼠分别与感染病毒的金黄地鼠共同饲养2 h后,50.0%(2/4)金黄地鼠体内可检测到Omicron BA.1,100.0%(4/4)金黄地鼠体内可检测到Omicron BA.2,且受体Omicron BA.2金黄地鼠肺组织核酸拷贝数[(6.83±1.54)log_(10)拷贝/ml]显著高于受体Omicron BA.1金黄地鼠肺组织核酸拷贝数[(2.26±2.61)log_(10)拷贝/ml],P<0.05。结论SARS-CoV-2 Omicron BA.1、BA.2在金黄地鼠模型中均可通过接触传播感染,两者的致病力相似但传播力不同。

Objective To compare the pathogenicity and transmissibility of SARS-CoV-2 Omicron BA.1 and BA.2 in the golden hamsters.Methods A total of 24 male golden hamsters aged 6-8 weeks and weighed(107.00±18.88)g were used in this study,of which,12 were used as donors 24 hours after infection with 10^(6) CCID_(50)/100μl venom(6infected with Omicron BA.1,and 6 infected with Omicron BA.2).Eight healthy golden hamsters(receptors,4 receptors per virus strain)were co-housing for 2 h for contact transmission study.In contrast,the donor was used for pathogenicity study,and 4 golden hamsters were used as blank controls.All animals were monitored daily for body mass during the experimental cycle,with nasopharyngeal swabs and anal swabs beginning on day 1 after infection for donor animals and nasopharyngeal swabs beginning on the day of exposure for recipient animals.The viral load of swabs,lung and turbinate tissues were detected by RT-PCR,and the degree of lung injury was evaluated by HE staining to evaluate the pathogenicity and transmissibility of the two virus strains in golden hamsters.Results SARS-CoV-2 Omicron BA.1 and BA.2 did not cause severe lung injury.Body mass changes[Omicron BA.1,D0(121.61±8.21)g vs D5(131.53±8.02)g;Omicron BA.2,D0(88.15±1.74)g vs D5(90.42±9.95)g],viral nucleic acid copy number in lung tissue[Omicron BA.1(7.64±0.74)log_(10) copies/ml,Omicron BA.2(7.79±0.25)log_(10) copies/ml]and the viral nucleic acid copy number of turbinate[Omicron BA.1(6.63±0.63)log_(10) copies/ml,Omicron BA.2(6.92±0.14)log_(10) copies/ml]showed no significant difference in pathogenicity between the two groups.In terms of transmission capacity,the transmission capacity of Omicron BA.2 was slightly higher than that of Omicron BA.1.After feeding healthy golden hamsters with infected golden hamsters for 2 h,Omicron BA.1 was detected in 50.0%(2/4)of golden hamsters.Omicron BA.2 was detected in 100.0%(4/4)of golden hamsters.The copy number of nucleic acid in lung tissue of receptor Omicron BA.2[(6.83±1.54)log_(10) copies/ml]was significantly higher than that of receptor Omicron BA.1[(2.26±2.61)log_(10) copies/ml],P<0.05.Conclusion SARS-CoV-2 Omicron BA.1 and BA.2 can be transmitted by contact in the golden hamster model,and their pathogenicity is similar,while their transmissibility is slightly different.