SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery

被引：159

作者：

Frere, Justin J. ^{[1
,2
]}

Serafini, Randal A. ^{[3
]}

Pryce, Kerri D. ^{[3
]}

Zazhytska, Marianna ^{[4
]}

Oishi, Kohei ^{[2
]}

Golynker, Ilona ^{[2
]}

Panis, Maryline ^{[2
]}

Zimering, Jeffrey ^{[3
,5
]}

Horiuchi, Shu ^{[2
]}

Hoagland, Daisy A. ^{[6
]}

Moller, Rasmus ^{[2
]}

Ruiz, Anne ^{[3
]}

Kodra, Albana ^{[4
]}

Overdevest, Jonathan B. ^{[7
]}

Canoll, Peter D. ^{[8
]}

Borczuk, Alain C. ^{[9
]}

Chandar, Vasuretha ^{[10
]}

Bram, Yaron ^{[10
]}

Schwartz, Robert ^{[10
,11
]}

Lomvardas, Stavros ^{[4
]}

Zachariou, Venetia ^{[3
]}

Tenoever, Benjamin R. ^{[2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[2] New York Univ, Grossman Sch Med, Dept Microbiol, New York, NY 10016 USA

[3] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA

[4] Columbia Univ, Brain & Behav Inst, Mortimer B Zuckerman Mind, New York, NY 10027 USA

[5] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 USA

[6] Harvard Med Sch, Dept Immunol, Boston, MA 02115 USA

[7] Columbia Univ, Irving Med Ctr, Dept Otolaryngol Head & Neck Surg, Vagelos Coll Physicians & Surg, New York, NY 10032 USA

[8] Columbia Univ, Irving Med Ctr, Dept Pathol & Cell Biol, Vagelos Coll Physicians & Surg, New York, NY 10032 USA

[9] Weill Cornell Med, Dept Pathol & Lab Med, New York, NY 10021 USA

[10] Weill Cornell Med, Dept Physiol Biophys & Syst Biol, New York, NY 10021 USA

[11] Weill Cornell Med, Div Gastroenterol & Hepatol, Dept Med, New York, NY 10021 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2022年 / 14卷 / 664期

关键词：

SET ENRICHMENT ANALYSIS; COGNITIVE IMPAIRMENT; THALAMIC ACTIVITY; ANIMAL-MODEL; DEPRESSION; CELLS; TRANSCRIPTOME; CONNECTIVITY; SEVERITY; COVID-19;

D O I：

10.1126/scitranslmed.abq3059

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster after either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely affected the olfactory bulb (OB) and olfactory epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month after viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

引用

页数：21

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