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.

Details

Title
Persistent Symptoms and Association With Inflammatory Cytokine Signatures in Recovered Coronavirus Disease 2019 Patients
Author
Sean Wei Xiang Ong 1 ; Siew-Wai Fong 2 ; Young, Barnaby Edward 3 ; Yi-Hao, Chan 2 ; Lee, Bernett 4 ; Amrun, Siti Naqiah 2 ; Chee, Rhonda Sin-Ling 2 ; Yeo, Nicholas Kim-Wah 2 ; Tambyah, Paul 5 ; Pada, Surinder 6 ; Seow Yen Tan 7 ; Ding, Ying 8 ; Laurent Renia 2 ; Yee-Sin, Leo 9 ; Ng, Lisa F P 10 ; David Chien Lye 9 

 National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore 
 A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 
 National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 
 Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 
 National University Health System, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 
 Ng Teng Fong General Hospital, Singapore 
 Changi General Hospital, Singapore 
 National Centre for Infectious Diseases, Singapore 
 National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 
10  A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, United Kingdom 
Publication year
2021
Publication date
Jun 2021
Publisher
Oxford University Press
e-ISSN
23288957
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3171167769
Copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.