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

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.

The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view

“…Lower plasmatic levels of IFN-γ, IFN-α2, and MCP-3 (2-, 1.3-, and, respectively, 1.3-fold lower), and higher plasmatic values of CRP (2.6-fold higher) were found in patients with fibrosis compared to those without fibrosis [ 105 ]. Furthermore, increased expression of mitochondrial biomarkers was found in patients with long-term pulmonary sequelae post-COVID-19, further indicating a correlation between oxidative stress induced by a higher inflammatory status and long-term pulmonary complications [ 106 ].…”

Can we predict lung sequelae in post-COVID-19 patients?

“…Biomarkers which have been related to the oxidative stress like TNF-alpha have been associated with prediction of pulmonary complications and could be used as therapeutic targets as well (21). The usage of such biomarkers might not be practical for routine usage and might not be performed widely in different centers.…”

Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID

“…Elevated levels of mitochondrial biomarkers in LC patients with long-term pulmonary sequelae could reveal their feasible role in post-COVID-19 pulmonary pathophysiology. TNF-α could be a valuable and manageable predictor [119].…”