Chen Liping, Shen Lihan, Wu Weichen, Guan Wenda, Zhou Jinchao, Luo Gengyan, Chen Qimin, Zhou Hongxia, Deng Zhenxuan, Chen Yaoqing, Zhao Wenjing, Jin Wenxiang, Qiu Minshan, Zheng Qianwei, Wang Yutao, Liu Chen, Bai Xiangxiang, Guo Deyin, Holmes Edward C, Zhong Nanshan, Shi Mang, Yang Zifeng
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Critical Care Medicine, Dongguan Institute of Respiratory and Critical Care Medicine, Dongguan People's Hospital, Dongguan, China.
J Thorac Dis. 2022 Feb;14(2):355-370. doi: 10.21037/jtd-21-1284.
The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19.
We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels.
Eight pathogens, SARS-CoV-2, (), (), (), (), , herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens.
For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.
当前的新型冠状病毒肺炎（COVID-19）大流行正在全球范围内对公共卫生构成重大挑战。虽然人们普遍认为严重的COVID-19是由炎症介质过度表达（即“细胞因子风暴”）所致，但共感染病原体是否以及如何促成疾病发病机制仍不清楚。为解决这一问题，我们对重症或危重症COVID-19病例的整个病程进行了跟踪，以确定所有潜在病原体——总的“感染组”——的存在和丰度，以及它们在重症COVID-19背景下如何与宿主免疫系统相互作用。
我们检查了1例重症和3例危重症COVID-19病例以及一组健康对照，从每个病例采集纵向样本（咽拭子、全血和血清）。进行了总RNA测序（宏转录组学）以同时研究每个样本中的病原体多样性和丰度以及宿主免疫反应。采用生物芯片方法测量血清细胞因子和趋化因子水平。
在COVID-19患者中鉴定出的8种病原体，即严重急性呼吸综合征冠状病毒2（SARS-CoV-2）、（此处原文缺失部分病原体名称），在疾病的不同阶段出现。与单独的SARS-CoV-2相比，血清和呼吸道中炎症介质的动态变化与感染组的动态变化相关性更强。相关性分析显示，肺损伤与细胞因子水平直接相关，而细胞因子水平又与SARS-CoV-2和共感染病原体的增殖相关。
对于每位患者而言，导致急性肺损伤和死亡的细胞因子风暴涉及一个动态且高度复杂的感染组，其中SARS-CoV-2是其中一个组成部分。这些结果表明需要采用精准医学方法来研究感染和宿主反应，作为传染病特征描述的标准手段。
