Long COVID and health-related quality of life: a systematic review of immune, inflammatory, and metabolic markers

Dinara Turebekova, Bakhyt Kosherova, Zhaniya Dauletkaliyeva, Yelena Shayakhmetova, Alexandr Marchenko, Dmitriy Solyanov, Vaiva Hendrixson, Irina Kadyrova

Frontiers in Public Health, 2026

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.3389/fpubh.2026.1846407
Data confidence 70 medium
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Abstract

Introduction Long COVID is known to be associated with prolonged multiple organ symptoms and decreased health-related quality of life (HRQoL), but the pathogenesis and relationship between immune, inflammatory, and metabolic biomarkers and HRQoL remains poorly understood. This systematic review aims to synthesize the evidence on the health-related quality of life of patients with Long COVID and to summarize the reported associations between health-related outcomes and biomarkers. Methods We conducted a systematic search in PubMed, Web of Science, and Scopus in search of studies that evaluated immune, inflammatory, or metabolic biomarkers and HRQoL in patients with Long COVID. This review included case–control and cohort studies with a control group. The Rayyan tool was used to select studies, and full-text articles were evaluated for compliance with the criteria. Information was obtained on biomarkers, analytical methods, tools for assessing the HRQoL, and the relationship between HRQoL and biomarkers. Due to the high heterogeneity of the methods, the results were summarized in a descriptive form. Results Ten studies were included, involving 1,078 patients with Long COVID and 768 healthy controls. Most studies that used various methods to assess HRQoL consistently reported long-term deterioration after COVID, with the greatest deterioration observed in the areas of physical functioning, vitality, fatigue, daily activities, pain, discomfort, and respiratory distress. The most frequently measured markers were related to inflammation and endothelial/coagulation pathways, including CRP, hsCRP, IL-6, TNF- α , D-dimer, and VCAM-1. Autoimmune, metabolic, intestinal barrier, and omics-based markers were measured less frequently, but indicated phenotype-specific biological heterogeneity. Only a few studies have identified a direct link between biomarkers and HRQoL. Lower HRQoL indicators were associated with increased neurotoxicity, decreased calcium levels, systemic inflammation, endothelial dysfunction, and signals from individual autoantibodies. Conclusion Our results indicate that Long COVID is consistently associated with a long-term decline in HRQoL, especially in the physical and functional areas. The available data indicate the presence of a strong signal regarding inflammatory processes and endothelial coagulation, while autoimmune, metabolic, and genetic data indicate phenotype-specific heterogeneity. Systematic review registration Unique identifier: CRD420251239371, URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251239371 .