肥胖对非人类灵长类动物对SARS-CoV-2感染的急性反应和COVID-19急性后后遗症的影响

IF 4.9 1区 医学 Q1 MICROBIOLOGY
PLoS Pathogens Pub Date : 2025-07-24 eCollection Date: 2025-07-01 DOI:10.1371/journal.ppat.1012988
Kristin A Sauter, Gabriela M Webb, Lindsay Bader, Craig N Kreklywich, Diana L Takahashi, Cicely Zaro, Casey M McGuire, Anne D Lewis, Lois M A Colgin, Melissa A Kirigiti, Hannah Blomenkamp, Cleiton Pessoa, Matthew Humkey, Jesse Hulahan, Madeleine Sleeman, Robert C Zweig, Sarah Thomas, Archana Thomas, Lina Gao, Alec J Hirsch, Maayan Levy, Sara Cherry, Steven E Kahn, Mark K Slifka, Daniel N Streblow, Jonah B Sacha, Paul Kievit, Charles T Roberts
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引用次数: 0

摘要

SARS-CoV-2感染的长期不良后果,称为“长COVID”或COVID急性后后遗症(PASC),是COVID-19总体疾病负担的主要组成部分。既往肥胖和代谢性疾病增加了急性疾病的严重程度,但SARS-CoV-2感染也有助于新发代谢性疾病的发展。由于COVID大流行是在全球肥胖流行的背景下发生的,一个重要的问题是,已有的肥胖在多大程度上改变了对SARS-CoV-2感染的长期反应。我们利用一种非人灵长类动物模型,比较了在6个月的时间过程中,感染SARS-CoV-2 δ型变异对瘦和肥胖/胰岛素抵抗的成年雄性恒河猴的影响。虽然对SARS-CoV-2感染的一些纵向反应,包括总体病毒动力学、SARS-CoV-2特异性IgG诱导、细胞因子谱和病毒RNA的组织持久性,在瘦肉和肥胖动物之间没有明显差异,但其他反应,包括中和Ab动力学、肺病理、体重、胰岛素敏感性程度、脂肪细胞因子谱、体温和夜间活动水平,在瘦肉和肥胖动物中存在显著差异。此外,在感染SARS-CoV-2后,瘦动物的几个参数发生了变化,与肥胖动物相似。值得注意的是,在大多数动物中存在多个参数的持续变化,这表明PASC可能比人类研究中自我报告的症状估计的更为普遍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.

Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.

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来源期刊
PLoS Pathogens
PLoS Pathogens MICROBIOLOGY-PARASITOLOGY
自引率
3.00%
发文量
598
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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