Oxidative Biomarkers Associated with the Pulmonary Manifestation of Post-COVID-19 Complications

Kamil Siekacz; Anna Kumor-Kisielewska; Joanna Miłkowska-Dymanowska; Małgorzata Pietrusińska; Krystian Bartczak; Sebastian Majewski; Adam Stańczyk; Wojciech J Piotrowski; Adam J Białas

doi:10.3390/jcm12134253

Oxidative Biomarkers Associated with the Pulmonary Manifestation of Post-COVID-19 Complications

J Clin Med. 2023 Jun 25;12(13):4253. doi: 10.3390/jcm12134253.

Authors

Kamil Siekacz¹, Anna Kumor-Kisielewska¹, Joanna Miłkowska-Dymanowska¹, Małgorzata Pietrusińska¹, Krystian Bartczak¹, Sebastian Majewski¹, Adam Stańczyk², Wojciech J Piotrowski¹, Adam J Białas^{1

3}

Affiliations

¹ Department of Pneumology, Medical University of Lodz, 90-419 Lodz, Poland.
² Department of Clinical Pharmacology, Medical University of Lodz, 90-419 Lodz, Poland.
³ Department of Pulmonary Rehabilitation, Regional Medical Center for Lung Diseases and Rehabilitation, Blessed Rafal Chylinski Memorial Hospital for Lung Diseases, 91-520 Lodz, Poland.

Abstract

Introduction: The role of mitochondria in post coronavirus disease 2019 (post-COVID-19) complications is unclear, especially in the long-term pulmonary complications. This study aims to investigate the association between post-COVID-19 pulmonary complications and mitochondrial regulatory proteins in the context of oxidative stress.

Methodology: Patients who had recovered from COVID-19 were enrolled. According to the evidence of persistent interstitial lung lesions on computed tomography (CT), patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(-)). We randomly selected 80 patients for investigation (40 subjects for each group). Biomarkers levels were determined by enzyme-linked immunosorbent assay (ELISA).

Results: The serum concentrations of mitochondrial regulatory proteins were significantly higher in the P(+) group, including PTEN-induced kinase 1 (PINK1): 1.62 [1.02-2.29] ng/mL vs. 1.34 [0.94-1.74] ng/mL (p = 0.046); Dynamin-1-like protein (DNM1L): 1.6 [0.9-2.4] ng/mL IQR vs. 0.9 [0.5-1.6] ng/mL (p = 0.004); and Mitofusin-2 (MFN2): 0.3 [0.2-0.5] ng/mL vs. 0.2 [0.1-0.3] ng/mL IQR (p = 0.001). Patients from the P(+) group also had higher serum levels of chemokine ligand 18 (PARC, CCL18), IL-6, and tumour necrosis factor-alpha (TNF-α) cytokines than the P(-) group. The concentration of interferon alpha (IFN-α) was decreased in the P(+) group. Furthermore, we observed statistically significant correlations between the advanced glycation end product (sRAGE) and TNF-α (Pearson's factor R = 0.637; p < 0.001) and between serum levels of DNM1L and IFN-α (Pearson's factor R = 0.501; p = 0.002) in P(+) patients.

Conclusions: Elevated concentrations of mitochondrial biomarkers in post-COVID-19 patients with long-term pulmonary complications indicate their possible role in the pathobiology of COVID-19 pulmonary sequelae. Oxidative stress is associated with the immune response and inflammation after COVID-19. TNF-α could be a promising biomarker for predicting pulmonary complications and may be a potential target for therapeutic intervention in patients with post-COVID-19 complications.

Keywords: CCL18; DNM1L; IFN-α; PINK1; SARS-CoV-2; TNF-α; mitophagy; oxidative stress; post-COVID-19; pulmonary fibrosis; sRAGE.

Grants and funding

This research received no external funding. The costs of this study were defrayed from the regular finances of the Department of Pneumology, Medical University of Lodz.