An Open Question: Is It Rational to Inhibit the mTor-Dependent Pathway as COVID-19 Therapy?

In December 2019, a novel coronavirus infection appeared in China (Wuhan City and Hubei Province), causing the first cases of abnormal severe pneumonia. Since then, the SARS-Cov2 infection has become pandemic and the correlated coronavirus disease (COVID-19) has been showing a plethora of pathophysiological manifestations that do not exclusively reduce COVID-19 to the occurrence of severe acute respiratory distress. Although the immunological responses against SARS-Cov2 remain poorly defined it is of note that the critical phase of COVID-19 currently appears, at least in some critical pathophysiological aspects, as a sort of autoimmune disease or as immune response hypersensitivity. Consequently, many authors have proposed various therapeutic approaches based on the modulation/inhibition of abnormal immune response in COVID-19. Recently, the effects of Tocilizumab administration has seemed to indicate that inhibition of the Interleukin (IL)-6 receptor (IL-6R) may result in the recovery of critical COVID-19 patients in the advanced post-alveolitic phase, when extensive pulmonary fibrosis is accompanied by a diffuse interstitial inflammation apparently sustained by a described exacerbated cytokine storm. Such evidence highlights the critical relevance of controlling the IL-6/IL-6R pro-inflammatory pathway in the pathophysiology of COVID-19 in order to mitigate the adverse immune response that is a determinant of the most serious and undesirable phase of SARS-Cov2 infection.In particular, hyper-reactivity was described as a major feature of the critical phase of COVID-19, broadly due to the hyperacute inflammatory context that leads to pulmonary interstitial disease and severe acute respiratory distress.