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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8902108/
https://www.ncbi.nlm.nih.gov/pubmed/35280492
http://dx.doi.org/10.21037/jtd-21-1284
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author 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
author_facet 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
author_sort Chen, Liping
collection PubMed
description 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.
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spelling pubmed-89021082022-03-10 Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19 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 J Thorac Dis Original Article 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. AME Publishing Company 2022-02 /pmc/articles/PMC8902108/ /pubmed/35280492 http://dx.doi.org/10.21037/jtd-21-1284 Text en 2022 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
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
Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19
title Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19
title_full Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19
title_fullStr Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19
title_full_unstemmed Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19
title_short Co-infecting pathogens can contribute to inflammatory responses and severe symptoms in COVID-19
title_sort co-infecting pathogens can contribute to inflammatory responses and severe symptoms in covid-19
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8902108/
https://www.ncbi.nlm.nih.gov/pubmed/35280492
http://dx.doi.org/10.21037/jtd-21-1284
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