# Inflammatory and Angiogenic Mediators Are Differentially Ex-Pressed in Patients with Post-COVID-19 Syndrome with Normal and Abnormal Spirometry Results

## TL;DR

This study finds that inflammatory and angiogenic mediators are differently expressed in post-COVID-19 patients with normal or abnormal lung function, suggesting potential biomarkers for predicting outcomes.

## Contribution

The study identifies specific inflammatory and angiogenic mediators that are differentially expressed in post-COVID-19 syndrome based on spirometry results.

## Key findings

- Abnormal spirometry in post-COVID-19 patients is linked to higher disease severity and specific clinical factors.
- IL-6, IL-12, and VEGF-A are upregulated in post-COVID-19 syndrome compared to healthy controls.
- MMP-9 levels are higher in patients with normal spirometry than in those with abnormal results.

## Abstract

Background: Inflammatory and angiogenic mediators play a key role in post-COVID-19 syndrome pathophysiology. These mediators might be of prognostic value for pulmonary function in this syndrome. Objectives: To determine interleukin-6, -12, and -17, macrophage inflammatory protein-1A (MIP-1A), the vascular endothelial growth factor-A (VEGF-A) gene expression levels, the matrix metalloproteinase-9 (MMP-9) plasma levels, and the association of clinical data with pulmonary function in patients with post-COVID-19 syndrome with normal and abnormal spirometry results. Methods: Demographic/clinical data and blood samples were collected (45 patients). Pulmonary function was evaluated (spirometry), and the gene expression levels of inflammatory and angiogenic mediators (IL-6, IL-12, IL-17, MIP-1A, and VEGF-A) were determined in PBMCs (qPCR). MMP-9 plasma levels were determined (ELISA). Results: Seventeen out of forty-five patients with post-COVID-19 syndrome had abnormal spirometry values, which were associated with arterial hypertension, pneumonia, previous hospitalization, and disease severity (p < 0.05). IL-6, IL-12, and VEGF-A gene expression was upregulated in patients with post-COVID-19 syndrome compared with healthy controls. In patients with normal spirometry values, IL-17 and VEGF-A gene expression was upregulated (p < 0.05), but MIP-1A was downregulated (p < 0.05) (vs. the abnormal spirometry group). MMP-9 serum levels were increased in the normal spirometry group compared with the abnormal one (p < 0.05). Conclusions: Post-COVID-19 syndrome has a complex immune pathophysiology, but potential inflammatory and angiogenic biomarkers, such as IL-6, IL-12, IL-17, MIP-1A, and VEGF-A, are differentially expressed in this syndrome and might be prognostic predictors of post-COVID-19 syndrome associated with pulmonary function alterations.