Deficient Radiation Transcription Response in COVID-19 Patients

Stanislav Polozov; Lourdes Cruz-Garcia; Grainne O'Brien; Veronika Goriacha; Farah Nasser; Penelope Jeggo; Serge Candéias; Christophe Badie

doi:10.1016/j.adro.2023.101215

Deficient Radiation Transcription Response in COVID-19 Patients

Adv Radiat Oncol. 2023 Mar 25;8(4):101215. doi: 10.1016/j.adro.2023.101215. eCollection 2023 Jul-Aug.

Authors

Stanislav Polozov¹, Lourdes Cruz-Garcia², Grainne O'Brien³, Veronika Goriacha¹, Farah Nasser², Penelope Jeggo³, Serge Candéias⁴, Christophe Badie²

Affiliations

¹ Science Limited, St. Ives, Cambridgeshire, United Kingdom.
² Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Radiation, Chemical & Environmental Hazards, Harwell Campus, UK Health Security Agency, Didcot, Oxfordshire, United Kingdom.
³ Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, United Kingdom.
⁴ Commissariat à l'Energie Atomique et aux Energies Renouvelables, Centre National de la Recherche Scientifique, Interdisciplinary Research Institute - Grenoble, Laboratory of Chemistry and Biology of Metals, Unité mixte de Recherche 5249, 38054, Grenoble, France.

Abstract

Purpose: The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalized patients is complex due to the heterogeneous course of COVID-19. Low-dose radiation therapy is known to dampen localized chronic inflammation and has been suggested to be used to reduce lung inflammation in patients with COVID-19. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk.

Methods and materials: We generated gene expression profiles from circulating leukocytes of hospitalized patients with COVID-19 and healthy donors.

Results: The p53 signaling pathway was found to be dysregulated, with mRNA levels of p53, ATM, and CHK2 being lower in patients with COVID-19. Several key p53 target genes involved in cell cycle arrest, apoptosis, and p53 feedback inhibition were upregulated in patients with COVID-19 while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53-dependant genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 hours after x-ray exposure ex vivo to both low (100 mGy) or high (2 Gy) doses.

Conclusions: SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19.