Biomarkers in long COVID-19: A systematic review

Yun-Ju Lai; Shou-Hou Liu; Sumatchara Manachevakul; Te-An Lee; Chun-Tse Kuo; Dhimiter Bello

doi:10.3389/fmed.2023.1085988

Biomarkers in long COVID-19: A systematic review

Front Med (Lausanne). 2023 Jan 20:10:1085988. doi: 10.3389/fmed.2023.1085988. eCollection 2023.

Authors

Yun-Ju Lai¹, Shou-Hou Liu², Sumatchara Manachevakul¹, Te-An Lee^{2

3}, Chun-Tse Kuo², Dhimiter Bello⁴

Affiliations

¹ School of Nursing, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA, United States.
² Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
³ Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁴ Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA, United States.

Abstract

Purpose: Long COVID, also known as post-acute sequelae of COVID-19, refers to the constellation of long-term symptoms experienced by people suffering persistent symptoms for one or more months after SARS-CoV-2 infection. Blood biomarkers can be altered in long COVID patients; however, biomarkers associated with long COVID symptoms and their roles in disease progression remain undetermined. This study aims to systematically evaluate blood biomarkers that may act as indicators or therapeutic targets for long COVID.

Methods: A systematic literature review in PubMed, Embase, and CINAHL was performed on 18 August 2022. The search keywords long COVID-19 symptoms and biomarkers were used to filter out the eligible studies, which were then carefully evaluated.

Results: Identified from 28 studies and representing six biological classifications, 113 biomarkers were significantly associated with long COVID: (1) Cytokine/Chemokine (38, 33.6%); (2) Biochemical markers (24, 21.2%); (3) Vascular markers (20, 17.7%); (4) Neurological markers (6, 5.3%); (5) Acute phase protein (5, 4.4%); and (6) Others (20, 17.7%). Compared with healthy control or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 were decreased, and 5 required further determination in the long COVID patients. Of these, up-regulated Interleukin 6, C-reactive protein, and tumor necrosis factor alpha might serve as the potential diagnostic biomarkers for long COVID. Moreover, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein whereas those with pulmonary symptoms exhibited a higher level of transforming growth factor beta.

Conclusion: Long COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.

Keywords: CRP; IL-6; TNF-α; biomarker; long COVID.

Publication types

Systematic Review

Grants and funding

This work was funded in part by the University of Massachusetts Lowell (Faculty start-up D50210000000022 to Y-JL).