Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques
Tian‐Zhang Song, 中国科学院昆明动物研究所，中国科学院动物模型与人类疾病机制重点实验室，KIZ-CUHK常见疾病生物资源与分子研究联合实验室，云南 昆明650223，中国, Hong‐Yi Zheng, Jian-Bao Han, Lin Jin, Xiang Yang, Feng‐Liang Liu, Rong‐Hua Luo, Ren‐Rong Tian, Hourong Cai, Xiaoli Feng, Chao Liu, Minghua Li, Yong‐Tang Zheng, 中国科学院昆明动物研究所，昆明国家高等级生物安全灵长类动物实验中心，中国科学院生物安全大科学研究中心，云南 昆明650107，中国, 南京大学附属鼓楼医院呼吸与危重症医学科，江苏 南京210008，中国, 中国科学院昆明动物研究所，国家非人灵长类实验动物资源库，模式动物表型与遗传研究国家重大科技基础设施（灵长类设施），云南 昆明 650107，中国
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 (<i>Macaca mulatta</i>) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup> cells, and persistent infiltration of CD8<sup>+</sup> 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.