AI Insight
This cross-sectional study of 127 participants examined blood biomarkers in Long COVID patients grouped by disease severity, comparing them to uninfected controls, acutely infected individuals, and spontaneous resolvers. The research found elevated interleukin-12 levels in Long COVID and acute infection groups compared to controls, and reduced basic fibroblast growth factor in mild Long COVID cases versus spontaneous resolvers. While correlation analysis suggested coordinated inflammatory patterns in some Long COVID subgroups, principal component analysis could not identify group-specific cytokine profiles.
Why it matters
The findings suggest persistent immune activation in Long COVID and support the potential for biological subgrouping of patients rather than relying solely on self-reported symptoms. However, the marginal statistical significance and exploratory nature of these results indicate that larger longitudinal studies are needed before these biomarkers can be used for clinical diagnosis or treatment guidance.
Understand the Science
by Callum Thomas, Ruth E. Ashton, Etheresia Pretorius, Rebecca Owen, Massimo Nunes, Jan H. Pretorius, Isaac T. Shawa, Corinna Chidley, Mark A. Faghy
Introduction
Long COVID is a complex pathophysiological condition linked to a heterogenous symptom profile. Dysregulation of 1) immunological and inflammatory responses, 2) endothelial/vascular function, and 3) metabolic and clotting processes have been identified; however, there remains a lack of clinically validated diagnostic biomarkers. The study aim was to investigate dysregulation of cytokines, chemokines and growth factors in confirmed Long COVID cases grouped by disease severity.
Methods
One-hundred-and-twenty-seven participants provided venous blood samples for cytokine profiling utilising Luminex assays. Participants were grouped into those with no knowledge of SARS-CoV-2 infection (n = 21), acute infection within 3-months (n = 22), spontaneous resolvers (>3-months, n = 21) and those with confirmed Long COVID (n = 63). Long COVID severity was grouped according to the post-COVID-19 functional status (PCFS) and defined as those with negligible (4A; n = 9), mild (4B; n = 20), moderate (4C; n = 24), and severe limitations (4D; n = 10). Cytokines were assessed for normality using Shapiro-Wilk tests and differences measured between groups using Kruskal-Wallis tests. Pairwise correlation and principal component analysis were performed.
Results
Interleukin-12 (p40/p70) was 22% greater in the Long COVID group (Median [IQR]: 58 [49] pg/mL, p = 0.046) and 30% greater in the acutely infected group (64 [36] pg/mL; p = 0.039) against non-infected controls (45 [25] pg/mL). Following PCFS classification, fibroblast growth factor-basic was 25% lower in Long COVID 4B versus spontaneous resolvers (24 [7] vs. 32 [24] pg/mL; p = 0.025). Pairwise correlation differences demonstrated that three Long COVID subgroups had strong, positive associations between cytokines when compared to non-infected controls; however, PCA was unable to determine any coordinated cytokine variation that was group specific.
Discussion and conclusions
Elevated interleukin-12 (p40/p70) and reduced basic fibroblast growth factor suggest persistent immune activation and possible subgroup-specific Long COVID; however, these findings were marginally significant and exploratory. A coordinated but partial immunological/inflammatory profile may exist in some of those with Long COVID, suggesting a rationale for subgrouping upon a biological, rather than self-report basis but larger longitudinal studies are required to confirm this hypothesis.