Biomarkers in long COVID-19: A systematic review

The study aimed to systematically evaluate blood biomarkers that may serve as indicators or therapeutic targets for long COVID, also known as post-acute sequelae of COVID-19. This condition refers to a range of long-term symptoms experienced by individuals who continue to suffer from symptoms for one or more months following SARS-CoV-2 infection.

Key Findings:

  1. Association of Biomarkers with Long COVID: The study identified 113 biomarkers significantly associated with long COVID, categorized into six biological classifications:
    • Cytokine/Chemokine (38 biomarkers, 33.6%)
    • Biochemical markers (24 biomarkers, 21.2%)
    • Vascular markers (20 biomarkers, 17.7%)
    • Neurological markers (6 biomarkers, 5.3%)
    • Acute phase protein (5 biomarkers, 4.4%)
    • Others (20 biomarkers, 17.7%)
  2. Variation in Biomarker Levels: Compared to healthy controls or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 decreased, and 5 required further determination in long COVID patients.
  3. Potential Diagnostic Biomarkers: Up-regulated biomarkers such as Interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) might serve as potential diagnostic biomarkers for long COVID. Additionally, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein, while those with pulmonary symptoms had higher levels of transforming growth factor beta.
  4. Elevated Inflammatory Biomarkers: The study found significant associations between specific biomarkers and long COVID symptoms, indicating that long COVID patients present elevated inflammatory biomarkers after initial infection. The up-regulated IL-6, CRP, and TNF-α were highlighted as a potential core set of biomarkers for long COVID​​.

Conclusion: The findings underscore the importance of further investigations to identify a core set of blood biomarkers for diagnosing and managing long COVID patients in clinical practice. This research contributes to the growing understanding of the biological underpinnings of long COVID and its potential diagnostic and therapeutic implications.

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