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. 2023 Jan 20:10:1085988.
doi: 10.3389/fmed.2023.1085988. eCollection 2023.

Biomarkers in long COVID-19: A systematic review

Yun-Ju Lai  1 , Shou-Hou Liu  2 , Sumatchara Manachevakul  1 , Te-An Lee  2   3 , Chun-Tse Kuo  2 , Dhimiter Bello  4
Affiliations

Biomarkers in long COVID-19: A systematic review

Yun-Ju Lai et al. Front Med (Lausanne). .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the literature search. Adapted from Page et al. (17).
FIGURE 2
FIGURE 2
Study quality of the 28 articles in the systematic review assessed by the modified REMARK questionnaire (Supplementary Table 3).
FIGURE 3
FIGURE 3
Biomarkers significantly associated with different comparison groups. The Venn diagram presents the 13 biomarkers that were reported by two or more eligible studies. Red indicates up-regulated, while blue refers to down-regulated biomarkers. A detailed list of abbreviations in Figure 3 can be found in Supplementary Table 2.
FIGURE 4
FIGURE 4
Biomarkers of long COVID symptoms. The Venn diagram presents the 41 biomarkers that were reported by two or more eligible studies. Red indicates up-regulated, while blue refers to down-regulated biomarkers. A detailed list of abbreviations in Figure 4 can be found in Supplementary Table 2.
See this image and copyright information in PMC

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