Deficient Radiation Transcription Response in COVID-19 Patients.

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.

RAPID GENE EXPRESSION BASED DOSE ESTIMATION FOR RADIOLOGICAL EMERGENCIES.

Gene expression (GE) assays have shown great potential for rapid individual radiation dose exposure assessment. The aim of the present study was to optimise GE-based biological dosimetry protocols for radiological emergencies. Experiments were carried out to validate a newly developed protocol (P2) where several steps were optimised and to compare it with the current validated protocol in place in our laboratory (P1). Several donor blood samples from were exposed ex vivo to of the following doses: 0, 0.5, 1, 2 Gy X-rays. Concomitant measurement of transcription level of genes FDXR, P21, PHPT1, CCNG1 and SESN1 plus HPRT (control) was performed. To summarise, both protocols provided similar dose estimates, P1 being completed in 7 hours while P2 in merely 4 hours. Thus, a significant time shortening was achieved leading to a potential increase of throughput capacity. Hence, this new protocol can be recommended for mass radiation casualties triage purposes.