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Blood Biomarkers of Long COVID: A Systematic Review
Callum Thomas1,2, Mark A Faghy3,4,5, Corinna Chidley3
1Biomedical and Clinical Science Research Theme, School of Human Sciences, University of Derby, Derby, UK. C.Thomas@derby.ac.uk.
Insights
No single blood biomarker definitively indicates Long COVID (LC). Instead, a combination of biomarkers related to inflammation, vascular, and metabolic systems may be key for understanding this complex condition.
Area of Science:
- Biomedical Science
- Immunology
- Pathophysiology
Background:
- Long COVID (LC) affects millions globally, with unknown underlying mechanisms.
- Existing blood biomarker research for LC lacks consensus due to varying definitions and study designs.
Purpose of the Study:
- To systematically review and consolidate current knowledge on blood biomarkers associated with Long COVID.
- To align biomarker research with the World Health Organization's (WHO) clinical definition of LC.
Main Methods:
- Systematic literature search adhering to PRISMA guidelines across major databases (Cochrane, Embase, PubMed, Web of Science) until January 2024.
- Inclusion of observational, cross-sectional, and randomized controlled studies meeting specific participant and control group criteria.
- Quality assessment using the REMARK questionnaire.
Main Results:
- Included 46 studies (4415 participants) identifying 525 potential blood biomarkers for LC.
- Three key biomarker subtypes associated with LC: immunological/inflammatory dysfunction, endothelial/vascular dysfunction, and metabolic/clotting abnormalities.
Conclusions:
- No single biomarker is sufficient for LC diagnosis; a multi-system biomarker profile is likely more informative.
- Highlights the need for standardized LC definitions and longitudinal studies to capture the condition's dynamic nature.
- Further research on LC biomarkers, with robust comparator groups and longitudinal data, is crucial for developing effective treatments.
Background:
Long coronavirus disease (COVID; LC) affects millions of people worldwide. The exact mechanisms which result in a broad, undulating and detrimental symptom profile remain unknown. Blood biomarkers associated with LC have been described; however, consensus on these remains elusive, in part due to a lack of continuity between studies on a universally accepted definition of LC. This systematic review aimed to consolidate current knowledge of blood biomarkers associated with the prevalence of LC on the basis of the World Health Organisation (WHO) clinical definition of this condition.
Eligibility Criteria For Selecting Studies:
Observational, cross-sectional, and randomised control studies published in the English language that studied blood biomarkers associated with the WHO definition of LC. All studies included participants who were ≥ 18 years old and group sizes ≥ 10 participants, and were compared against a control group without any known co-morbidities.
Methods:
A systematic literature search was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered on Prospero (ID: CRD42022373121). The Cochrane, Embase, PubMed and Web of Science databases were searched from inception to January 2024. Search results were gathered using Rayyan software and data extracted using Microsoft Excel. The reporting recommendations for tumour markers prognostic studies (REMARK) questionnaire was used to assess the quality of the included studies.
Results:
A total of 45 observational and one interventional study comprising 4415 participants were included in this review which identified 525 blood biomarkers thought to be associated with LC. Three blood biomarker subtypes were associated with the development of LC: (1) immunological and inflammatory dysfunction, (2) endothelial/vascular dysfunction and (3) metabolic and clotting abnormalities.
Discussion And Conclusions:
Our data are consistent with previous findings; however, no single biomarker was sufficiently associated with LC prevalence and instead a profile of biomarkers across various physiological systems may be more clinically useful. In all, 196 studies were excluded due to a lack of an adequately healthy comparator group and/or failure to meet the WHO LC definition. This demonstrates a need for further research incorporating a universal LC definition across all disease severity groups and symptom profiles, and longitudinal data reflecting the relapsing and remitting nature of this condition. Further investigation into blood biomarkers of LC, including clear reporting of healthy comparator groups and the investigation of acute and chronic biomarker changes, within the context of medical practice, may support the development of curative/restorative approaches.
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