Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19

Journal of Thoracic Disease

article

Liping Chen¹  Lihan Shen²  Weichen Wu³  Wenda Guan¹  Jinchao Zhou¹  Gengyan Luo³  Qimin Chen²  Hongxia Zhou²  Zhenxuan Deng²  Yaoqing Chen³  Wenjing Zhao³  Wenxiang Jin¹  Minshan Qiu²  Qianwei Zheng²  Yutao Wang¹  Chen Liu⁵  Xiangxiang Bai⁵  Deyin Guo³  Edward C. Holmes⁶  Nanshan Zhong¹  Mang Shi³  Zifeng Yang¹ 

[1] 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;Department of Critical Care Medicine, Dongguan Institute of Respiratory and Critical Care Medicine, Dongguan People’s Hospital;School of Medicine, Sun Yat-sen University;KingMed Virology Diagnostic & Translational Center;Novogene Bioinformatics Technology Co., Ltd.;Sydney Institute for Infectious Diseases, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney;State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology

关键词: Total infectome;    COVID-19;    co-infection;    inflammatory responses;    meta-transcriptomics;   

DOI  :  10.21037/jtd-21-1284

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: 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. Methods: 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. Results: Eight pathogens, SARS-CoV-2, Aspergillus fumigatus (A. fumigatus), Mycoplasma orale (M. orale), Myroides odoratus (M. odoratus), Acinetobacter baumannii (A. baumannii), Candida tropicalis, 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. Conclusions: 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.

【 授权许可】

Unknown