How severe RNA virus infections such as SARS-CoV-2 disrupt tissue and organ barriers—Reconstitution by mesenchymal stem cell-derived exosomes

The host tissue barriers arrange numerous lines of resistance to influx and cell-to-cell spread of pathogenic viruses. However, the highly virulent pathogens are equipped with diverse molecular mechanisms that can subvert the host countermeasures and/or exaggerate the host cell responses to toxic levels leading to severe illnesses. In his review, we discuss the immune-mediated pathogenesis of COVID-19 disease induced by the SARS-Cov-2 coronavirus. SARS-Cov-2 primarily infects type II alveolar epithelial cells. These cells are highly abundant with the ACE2 receptor protein, which occurs to be counterpart of the viral Spike protein and thus facilitates internalization of the virus. Following infection onset, the rapid clinical deterioration occurs about in a week suggesting that the respiratory failure in COVID-19 could result from a unique pattern of immune impairment characterized by severe Cytokine Release Syndrome (known as cytokine storm) leading to macrophage activation syndrome. In addition, the SARS-Cov-2 infection can induce a profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer cells, i.e., all major guardians cell components of the host immune barrier. However, while the numbers of that cells decline in the sequelae of the disease, the presence of persistent hyper-inflammation driving progressive tissue injury, suggests that the deteriorating impact of the systemic reactive responses can be more significant than the virus-induced cytopathic effects on the immunocompetent cells. In this respect, the authors discuss the emerging evidence of beneficial effects of administration of exosomes derived from mesenchymal stem cells—another sentinel-type cells—in management of the hyper-inflammatory response to SARS-CoV-2. Moreover, they also discuss the exosomes-originated mechanisms, which sustain regeneration of the damaged pulmonary lining cells and the vascular endothelial cells in various organs, including the brain.