As the multi-systemic components of COVID-19 emerge, parallel etiologies can be drawn between SARS-CoV-2 infection and radiation injuries. While some SARS-CoV-2-infected individuals present as asymptomatic, others exhibit mild symptoms that may include fever, cough, chills, and unusual symptoms like loss of taste and smell and reddening in the extremities (e.g., "COVID toes", suggestive of microvessel damage). Still others alarm healthcare providers with extreme and rapid onset of high-risk indicators of mortality that include acute respiratory distress syndrome (ARDS), multi-organ hypercoagulation, hypoxia and cardiovascular damage. Researchers are quickly refocusing their science to address this enigmatic virus that seems to unveil itself in new ways without discrimination. As investigators begin to identify early markers of disease, identification of common threads with other pathologies may provide some clues. Interestingly, years of research in the field of radiation biology documents the complex multi-organ nature of another disease state that occurs after exposure to high doses of radiation: the acute radiation syndrome (ARS). Inflammation is a key common player in COVID-19 and ARS, and drives the multi-system damage that dramatically alters biological homeostasis. Both conditions initiate a cytokine storm, with similar pro-inflammatory molecules increased and other anti-inflammatory molecules decreased. These changes manifest in a variety of ways, with a demonstrably higher health impact in patients having underlying medical conditions. The potentially dramatic human impact of ARS has guided the science that has identified many biomarkers of radiation exposure, established medical management strategies for ARS, and led to the development of medical countermeasures for use in the event of a radiation public health emergency. These efforts can now be leveraged to help elucidate mechanisms of action of COVID-19 injuries. Furthermore, this intersection between COVID-19 and ARS may point to approaches that could accelerate the discovery of treatments for both.