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Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we...

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Autores principales: Shen, Xu-Rui, Li, Qian, Li, Hui-Ling, Wang, Xi, Wang, Qi, Zheng, Xiao-Shuang, Geng, Rong, Zhang, Yu-Lan, Li, Bei, Jiang, Ren-Di, Liu, Mei-Qin, Zhu, Yan, Zhang, Wei, Yang, Xing-Lou, Peng, Ke, Zhou, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704563/
https://www.ncbi.nlm.nih.gov/pubmed/34960752
http://dx.doi.org/10.3390/v13122483
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author Shen, Xu-Rui
Li, Qian
Li, Hui-Ling
Wang, Xi
Wang, Qi
Zheng, Xiao-Shuang
Geng, Rong
Zhang, Yu-Lan
Li, Bei
Jiang, Ren-Di
Liu, Mei-Qin
Zhu, Yan
Zhang, Wei
Yang, Xing-Lou
Peng, Ke
Zhou, Peng
author_facet Shen, Xu-Rui
Li, Qian
Li, Hui-Ling
Wang, Xi
Wang, Qi
Zheng, Xiao-Shuang
Geng, Rong
Zhang, Yu-Lan
Li, Bei
Jiang, Ren-Di
Liu, Mei-Qin
Zhu, Yan
Zhang, Wei
Yang, Xing-Lou
Peng, Ke
Zhou, Peng
author_sort Shen, Xu-Rui
collection PubMed
description Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.
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spelling pubmed-87045632021-12-25 Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis Shen, Xu-Rui Li, Qian Li, Hui-Ling Wang, Xi Wang, Qi Zheng, Xiao-Shuang Geng, Rong Zhang, Yu-Lan Li, Bei Jiang, Ren-Di Liu, Mei-Qin Zhu, Yan Zhang, Wei Yang, Xing-Lou Peng, Ke Zhou, Peng Viruses Article Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19. MDPI 2021-12-11 /pmc/articles/PMC8704563/ /pubmed/34960752 http://dx.doi.org/10.3390/v13122483 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shen, Xu-Rui
Li, Qian
Li, Hui-Ling
Wang, Xi
Wang, Qi
Zheng, Xiao-Shuang
Geng, Rong
Zhang, Yu-Lan
Li, Bei
Jiang, Ren-Di
Liu, Mei-Qin
Zhu, Yan
Zhang, Wei
Yang, Xing-Lou
Peng, Ke
Zhou, Peng
Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis
title Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis
title_full Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis
title_fullStr Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis
title_full_unstemmed Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis
title_short Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis
title_sort antibody-dependent enhancement of sars-cov-2 infection of human immune cells: in vitro assessment provides insight in covid-19 pathogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704563/
https://www.ncbi.nlm.nih.gov/pubmed/34960752
http://dx.doi.org/10.3390/v13122483
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