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Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.
Metadata
JournalZool ResNot FoundDate
2020-Sep-18
Type
Journal Article
Volume
2020-Sep-18 / 41 : 503-516
Author
Song TZ 1, 2, Zheng HY 1, 2, Han JB 2, Jin L 1, 2, Yang X 2, Liu FL 1, Luo RH 1, Tian RR 1, Cai HR 3, Feng XL 2, Liu C 4, Li MH 2, 4, Zheng YT 1, 2, 5
Affiliation
  • 2. Kunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
  • 3. Department of Respiratory and Critical Care Medicine, Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu 210008, China.
  • 4. National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
  • 5. National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China. E-mail: [email protected]ail.kiz.ac.cn.
Doi
PMIDMESH
Age Factors
Aging
Animals
Betacoronavirus
Coronavirus Infections
Cytokines
Inflammation
Lung
Macaca mulatta
Monkey Diseases
Pandemics
Pneumonia, Viral
Severe Acute Respiratory Syndrome
T-Lymphocytes
Viral Load
Virus Replication
Abstract
As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b + and CD8 + cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b + cells, and persistent infiltration of CD8 + cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.
Keywords: COVID-19 Elderly Immune response Non-human primate animal model
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