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. 2022 Jun 16;11(6):1184.
doi: 10.3390/antiox11061184.

Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia

Elisabet Rodríguez-Tomàs  1   2 , Johana C Acosta  1 , Laura Torres-Royo  1 , Gabriel De Febrer  3 , Gerard Baiges-Gaya  2 , Helena Castañé  2 , Andrea Jiménez  2 , Carlos Vasco  3 , Pablo Araguas  1 , Junior Gómez  1 , Bárbara Malave  1 , Miguel Árquez  1 , David Calderón  1 , Berta Piqué  1   4 , Manel Algara  5 , Ángel Montero  6 , Josep M Simó  7 , Xavier Gabaldó-Barrios  7 , Sebastià Sabater  8 , Jordi Camps  2 , Jorge Joven  2 , Meritxell Arenas  1
Affiliations

Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia

Elisabet Rodríguez-Tomàs et al. Antioxidants (Basel). .

Abstract

The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-β1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-β1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-β1 concentrations at 24 h.

Keywords: COVID-19 pneumonia; chemokines; low-dose radiation therapy; paraoxonase-1.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Serum paraoxonase-1 (PON1)-related variables and selected cytokines and immunological markers in patients with COVID-19 pneumonia before and after low-dose radiation therapy (LDRT). (B) Magnitude of change of selected variables, shown as log2fold change. Abbreviations: CCL2, chemokine (C-C motif) ligand 2; CD, cluster of differentiation; IFN-γ, interferón γ; IL, interleukin; LDH, lactate dehydrogenase; PON1, paraoxonase-1; TGF-β1, transforming growth factor beta 1; TNF-α, tumor necrosis factor α.
Figure 2
Figure 2
Statistically significant correlations between the analyzed variables at baseline and at 24 h after low-dose radiation therapy (LDRT). Abbreviations: ALT, alanine aminotransferase; CD, cluster of differentiation; IFN-γ, interferon γ; IL, interleukin; LDH, lactate dehydrogenase; PON1, paraoxonase-1; TGF-β1, transforming growth factor beta 1.
Figure 3
Figure 3
Baseline values of variables showing statistically significant differences between patients with COVID-19 pneumonia according to their SaFI (A) or their percentage of lung parenchymal infiltrates (B). Abbreviations: CD, cluster of differentiation; IFN-γ, interferon γ; IL, interleukin; TGF-β1, transforming growth factor beta 1.
Figure 4
Figure 4
Lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels and receiver operating characteristics plots in patients who died and those who did not.
Figure 5
Figure 5
Selected variables in patients with COVID-19 pneumonia according to whether they showed a SaFI improvement or a worsening after 1 week of low-dose radiation therapy. Abbreviations: CCL2, chemokine (C-C motif) ligand 2; CD, cluster of differentiation; IFN-γ, interferon γ; IL, interleukin; PON1, paraoxonase-1; TGF-β1, transforming growth factor beta 1; TNF-α, tumor necrosis factor α.
See this image and copyright information in PMC

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