Coronaviruses and stress: from cellular to global

Near the end of 2019, SARS-CoV-2, a novel highly contagious coronavirus phylogenetically related to the SARS virus, entered the human population with lethal consequences. This special issue devoted to the resulting disease COVID-19 was not planned but instead the articles accumulated organically as researchers in the cell stress response field noticed similarities among the pathophysiology of COVID-19 infections and the responses that they studied in contexts unrelated to viral infection. We preface the issue with an introductory article which begins with a brief review of the structure and biology of SARS-CoV-2. As we collected and compared the COVID-19 articles, several shared themes emerged. In the second part of the introduction, each article is summarized briefly and the common themes that link each into a spontaneously arising chain of ideas and hypotheses are emphasized. These themes include growing evidence of molecular mimicry among the viral proteins and the proteins of patients. The realization that much of the consequences of such immune mimicry may play out on the plasma membrane of vascular endothelial cells raised the specter of autoimmune-induced vascular endothelial damage in multiple organs. Proposals of new therapeutic approaches have coalesced around the theme of inducing protection of the vascular endothelium. New chemical treatments that are proposed include stannous chloride, inducers of the gasotransmitter hydrogen sulfide such as sodium thiosulfate and inducers of the cytoprotective stress protein heme oxygenase. Oxygen delivered by ventilators is already in extensive use to provide life support for patients with severe COVID-19. Two articles propose to advance the use of oxygen to the level of a therapeutic treatment early in the detection of the virus in infected patients by delivering oxygen under elevated pressure in hyperbaric chambers. At elevated blood plasma concentrations, hyperbaric oxygen is capable of achieving results far beyond the capability of ventilators as it promotes the activation of transcription factors that control the establishment of inducible cellular defense systems.