Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation

Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents com...

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Main Authors: Chioh, Florence Wen Jing, Fong, Siew-Wai, Young, Barnaby Edward, Wu, Kan Xing, Siau, Anthony, Krishnan, Shuba, Chan, Yi-Hao, Carissimo, Guillaume, Teo, Louis L. Y., Gao, Fei, Tan, Ru San, Zhong, Liang, Koh, Angela S., Tan, Seow-Yen, Tambyah, Paul A., Renia, Laurent, Ng, Lisa F. P., Lye, David C., Cheung, Christine
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/151759
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spelling sg-ntu-dr.10356-1517592023-03-05T16:47:12Z Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation Chioh, Florence Wen Jing Fong, Siew-Wai Young, Barnaby Edward Wu, Kan Xing Siau, Anthony Krishnan, Shuba Chan, Yi-Hao Carissimo, Guillaume Teo, Louis L. Y. Gao, Fei Tan, Ru San Zhong, Liang Koh, Angela S. Tan, Seow-Yen Tambyah, Paul A. Renia, Laurent Ng, Lisa F. P. Lye, David C. Cheung, Christine Lee Kong Chian School of Medicine (LKCMedicine) A*STAR Infectious Diseases Labs Singapore Immunology Network, A*STAR Institute of Molecular and Cell Biology, A*STAR Science::Medicine COVID-19 Endothelial Cells Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Ministry of Health (MOH) Nanyang Technological University National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This research is funded by National Medical Research Council (COVID19RF-001, COVID19RF-060, NMRC/TA/0031/2015, MOH-000153, NMRC/OFIRG/0018/2016, NMRC/BnB/0017/2015, MOH-000358), Biomedical Research Council, A*STAR (H20/04/g1/006), National Research Foundation Singapore (NRF2017_SISFP09), Nanyang Technological University (Nanyang Assistant Professorship Start-Up Grant), Ministry of Education - Singapore (MOE2018-T2-1-042) and Agency for Science, Technology and Research (H18/01/a0/017). 2021-07-15T10:18:48Z 2021-07-15T10:18:48Z 2021 Journal Article Chioh, F. W. J., Fong, S., Young, B. E., Wu, K. X., Siau, A., Krishnan, S., Chan, Y., Carissimo, G., Teo, L. L. Y., Gao, F., Tan, R. S., Zhong, L., Koh, A. S., Tan, S., Tambyah, P. A., Renia, L., Ng, L. F. P., Lye, D. C. & Cheung, C. (2021). Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation. ELife, 10, e64909-. https://dx.doi.org/10.7554/eLife.64909 2050-084X 0000-0003-0329-238X 0000-0001-7870-2879 0000-0003-0349-1557 0000-0001-7127-9107 https://hdl.handle.net/10356/151759 10.7554/eLife.64909 33752798 2-s2.0-85103307495 10 e64909 en COVID19RF-001 COVID19RF-060 H20/04/g1/006 NRF2017_SISFP09 MOE2018-T2-1-042 H18/01/a0/017 eLife © 2021, Chioh et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
COVID-19
Endothelial Cells
spellingShingle Science::Medicine
COVID-19
Endothelial Cells
Chioh, Florence Wen Jing
Fong, Siew-Wai
Young, Barnaby Edward
Wu, Kan Xing
Siau, Anthony
Krishnan, Shuba
Chan, Yi-Hao
Carissimo, Guillaume
Teo, Louis L. Y.
Gao, Fei
Tan, Ru San
Zhong, Liang
Koh, Angela S.
Tan, Seow-Yen
Tambyah, Paul A.
Renia, Laurent
Ng, Lisa F. P.
Lye, David C.
Cheung, Christine
Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation
description Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Chioh, Florence Wen Jing
Fong, Siew-Wai
Young, Barnaby Edward
Wu, Kan Xing
Siau, Anthony
Krishnan, Shuba
Chan, Yi-Hao
Carissimo, Guillaume
Teo, Louis L. Y.
Gao, Fei
Tan, Ru San
Zhong, Liang
Koh, Angela S.
Tan, Seow-Yen
Tambyah, Paul A.
Renia, Laurent
Ng, Lisa F. P.
Lye, David C.
Cheung, Christine
format Article
author Chioh, Florence Wen Jing
Fong, Siew-Wai
Young, Barnaby Edward
Wu, Kan Xing
Siau, Anthony
Krishnan, Shuba
Chan, Yi-Hao
Carissimo, Guillaume
Teo, Louis L. Y.
Gao, Fei
Tan, Ru San
Zhong, Liang
Koh, Angela S.
Tan, Seow-Yen
Tambyah, Paul A.
Renia, Laurent
Ng, Lisa F. P.
Lye, David C.
Cheung, Christine
author_sort Chioh, Florence Wen Jing
title Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation
title_short Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation
title_full Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation
title_fullStr Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation
title_full_unstemmed Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation
title_sort convalescent covid-19 patients are susceptible to endothelial dysfunction due to persistent immune activation
publishDate 2021
url https://hdl.handle.net/10356/151759
_version_ 1759856012061310976