Principal Component Analysis of Cytokine Signature in COVID-19 and Long COVID, 2026, Korobova et al.

Chandelier

Senior Member (Voting Rights)

Authors: Zoia R. Korobova, Areg A. Totolian

Abstract​

Despite the activity of the COVID-19 pandemic being lower in the recent years, new COVID-associated threat, known long COVID (LC), has emerged.
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.

We analyzed data of cytokine multiplex analysis of 289 patients with COVID-19, 44 patients with LC and 51 healthy donors.
Using principal component analysis (PCA) we identified cyotkines with the highest importance rate, and further investigated relationship between them with the use of 3D mapping.
As a result, 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.

The coordinated interactions within these clusters reveal a complex immunopathology behind LC, but leave an opening for further interpretation
 
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A total of 289 samples were obtained from patients with PCR verified COVID-19 who were hospitalized with an official COVID-19 diagnosis at two medical institutions in Saint Petersburg, Russia

A separate LC group (n = 44) was defined according to WHO criteria for post-COVID condition, comprising individuals with persistent psychoneurological symptoms […] and were predominantly female (72.7%, n = 32). […] We acknowledge this gender imbalance as a limitation for the interpretation and generalizability of the results, particularly regarding male populations.

Additionally, plasma samples were included from 51 healthy donors with no history of COVID-19, collected during the initial phase of the pandemic (January to March 2020). Median age for healthy donors comprised 49 (24–69).

We did not adjust for confounding factors like age, sex, or comorbidities, which differed between variant groups and the Long COVID cohort. These demographic and clinical differences may have influenced the cytokine profiles independently of the viral strain or post-acute condition.
 
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