SARS-CoV-2 and COVID-19: between pathophysiology complexity and therapeutic uncertainty.

First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe and the United States. COVID-19 is a new clinical syndrome characterized by respiratory symptoms with variable degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome aggravated by thrombosis in pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: the early infection phase, the pulmonary phase and the hyperinflammation phase. Although current understanding of COVID-19 treatment mainly derives from small uncontrolled trials that are affected by a number of biases, strong background noise and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antivirals, antimalarials, immunomodulators, anticoagulants, antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the international and Italian dramatic experiences, here we review the changing evolution of the disease and focus on current treatments uncertainties and new promising therapies.