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

Author:

Chioh Florence WJ1,Fong Siew-Wai234,Young Barnaby E156,Wu Kan-Xing1,Siau Anthony1,Krishnan Shuba17,Chan Yi-Hao23ORCID,Carissimo Guillaume23,Teo Louis LY89,Gao Fei89,Tan Ru San89,Zhong Liang89,Koh Angela S89,Tan Seow-Yen10ORCID,Tambyah Paul A11,Renia Laurent123ORCID,Ng Lisa FP23,Lye David C15612,Cheung Christine113ORCID

Affiliation:

1. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

2. A*STAR ID Labs, Agency for Science, Technology and Research, Singapore, Singapore

3. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore

4. Department of Biological Sciences, National University of Singapore, Singapore, Singapore

5. National Centre for Infectious Diseases, Singapore, Singapore

6. Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore

7. Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Campus Flemingsberg, Stockholm, Sweden

8. National Heart Centre Singapore, Singapore, Singapore

9. Duke-NUS Medical School, Singapore, Singapore

10. Department of Infectious Diseases, Changi General Hospital, Singapore, Singapore

11. Department of Medicine, National University Hospital, Singapore, Singapore

12. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

13. Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore

Abstract

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.

Funder

National Medical Research Council

Biomedical Research Council, A*STAR

National Research Foundation Singapore

Nanyang Technological University

Ministry of Education - Singapore

Agency for Science, Technology and Research

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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