Dataset Information

Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.

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.

SUBMITTER: Song TZ

PROVIDER: S-EPMC7475018 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.

Song Tian-Zhang TZ Zheng Hong-Yi HY Han Jian-Bao JB Jin Lin L Yang Xiang X Liu Feng-Liang FL Luo Rong-Hua RH Tian Ren-Rong RR Cai Hou-Rong HR Feng Xiao-Li XL Liu Chao C Li Ming-Hua MH Zheng Yong-Tang YT

Zoological research 20200901 5

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 ( <i>Macaca mulatta</i>) of varied ages. Results indicated that infected young macaques manifested impaired respirator ...[more]

PMID: 32772513

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Project description:Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%-30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques (Macaca mulatta) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8+ T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8+ T cells declined but showed increased activation, while both the number and activation of effector memory CD4+ T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80+/CD86+ B cells and resting memory B cells (CD27+CD21+) increased significantly. Intermediate monocytes (CD14+CD16+) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4+ T cells, B cells, CD16+CD56+ NK cells, CD14+CD16+ monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection.

Dataset Information

Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.

Publications

Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.

Similar Datasets

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