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Title: Persistent symptoms and association with inflammatory cytokine signatures in recovered coronavirus disease 2019 patients
Authors: Ong, Sean Wei Xiang
Fong, Siew-Wai
Young, Barnaby Edward
Chan, Yi-Hao
Lee, Bernett
Siti Naqiah Amrun
Chee, Rhonda Sin-Ling
Yeo, Nicholas Kim-Wah
Tambyah, Paul
Pada, Surinder
Tan, Seow Yen
Ding, Ying
Renia, Laurent
Leo, Yee Sin
Ng, Lisa F. P.
Lye, David C.
Keywords: Science::Medicine
Issue Date: 2021
Source: Ong, S. W. X., Fong, S., Young, B. E., Chan, Y., Lee, B., Siti Naqiah Amrun, Chee, R. S., Yeo, N. K., Tambyah, P., Pada, S., Tan, S. Y., Ding, Y., Renia, L., Leo, Y. S., Ng, L. F. P. & Lye, D. C. (2021). Persistent symptoms and association with inflammatory cytokine signatures in recovered coronavirus disease 2019 patients. Open Forum Infectious Diseases, 8(6), ofab156-.
Project: COVID19RF-001 
BMRC IAF 311006 
Journal: Open Forum Infectious Diseases 
Abstract: Background: The complications and sequelae of coronavirus disease 2019 (COVID-19) and their effect on long-term health are unclear, and the trajectory of associated immune dysregulation is poorly understood. Methods: We conducted a prospective longitudinal multicenter cohort study at 4 public hospitals in Singapore. Patients with COVID-19 were monitored for a median of 6 months after recovery from acute infection. Clinical symptoms and radiologic data were collected, along with plasma samples for quantification of immune mediators. The relationship between clinical symptoms and immune cytokine profiles was investigated. Results: Two hundred eighty-eight participants were recruited, and follow-up data were available for 183, 175, and 120 participants at days 30, 90, and 180 postsymptom onset, respectively. Symptoms related to COVID-19 were present in 31 (16.9%), 13 (7.4%), and 14 (11.7%) at days 30, 90, and 180. In a multivariable model, age >65 years, non-Chinese ethnicity, and the severity of acute infection were associated with increased likelihood of persistent symptoms. Recovered COVID-19 patients had elevated levels of proinflammatory interleukin (IL)-17A, stem cell factor, IL-12p70, and IL-1β and pro-angiogenic macrophage inflammatory protein 1β, brain-derived neurotrophic factor, and vascular endothelial growth factor at day 180 compared with healthy controls. Higher levels of monocyte chemoattractant protein-1 and platelet-derived growth factor-BB were detected in patients with persistent symptoms, versus symptom-free patients. Conclusions: Approximately 10% of recovered patients had persistent symptoms 6 months after initial infection. Immune cytokine signatures of the recovered patients reflected ongoing chronic inflammation and angiogenesis. Patients with COVID-19 should be monitored closely for emerging long-term health consequences.
ISSN: 2328-8957
DOI: 10.1093/ofid/ofab156
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: National Centre for Infectious Diseases
Tan Tock Seng Hospital
Yong Loo Lin School of Medicine, National University of Singapore
Rights: © The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact DOI: 10.1093/ofid/ofab156.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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