Principal component analysis of cytokine signature in COVID-19 and Long COVID

Introduction: Despite the activity of the COVID-19 pandemic being lower in the recent years, COVID-associated threat, long COVID (LC). Its clinical presentation includes nearly 200 symptoms affecting cardiovascular, respiratory, nervous systems, endocrine organs, urinary tract, and gastrointestinal systems. Cytokines serve as important biomarkers for assessing the level of immune system involvement and dysregulation in LC. Most studies on cytokine network and cytokine interactions usually address more traditional methods of statistical analysis with comparison criteria, discriminant analysis, regression. But multiplex cytokine analysis includes dozens of parameters, and requires complex assessment of the network as a whole. Methods: We analyzed data of cytokine multiplex analysis of 289 patients with COVID-19, 44 patients with LC and 51 healthy donors. PCA we identified cyotkines with the highest importance rate, and further investigated between them with the use of 3D mapping. Results: Three key clusters were identified: cluster A - IL-13, CCL7/MCP-3, IL-4; cluster B - IL-18, CCL2/MCP-1, CCL4/MIP-1β, CXCL8/IL-8, M-CSF, and cluster C - sCD40L, CXCL1/GROα, PDGF-AA, EGF, FGF-2, FLT-3L, IL-7, IL-17F. Discussion: The coordinated interactions within these clusters reveal a complex immunopathology behind LC: clsuter A repsresenting local immune responses, cluster B for neuroinflammatory processes, and cluster C for changes in the blood vessels. The results, however, leave an opening for further investigatoin and interpretation.