COVID-19 treatment options: a difficult journey between failed attempts and experimental drugs.

Since its outbreak in China in December 2019 a novel Coronavirus, named SARS-CoV-2, has spread worldwide causing many cases of severe pneumonia, referred to as COVID-19 disease, leading the World Health Organization to declare a pandemic emergency in March 2020. Up to now, no specific therapy against COVID-19 disease exists. This paper aims to review COVID-19 treatment options currently under investigation. We divided the studied drugs into three categories (antiviral, immunomodulatory and other drugs). For each molecule, we discussed the putative mechanisms by which the drug may act against SARS-CoV-2 or may affect COVID-19 pathogenesis and the main clinical studies performed so far. The published clinical studies suffer from methodological limitations due to the emergency setting in which they have been conducted. Nevertheless, it seems that the timing of administration of the diverse categories of drugs is crucial in determining clinical efficacy. Antiviral drugs, in particular Remdesivir, should be administered soon after symptoms onset, in the viraemic phase of the disease; whereas, immunomodulatory agents, such as tocilizumab, anakinra and steroids, may have better results if administered in pneumonia/hyperinflammatory phases. Low-molecular-weight heparin may also have a role when facing COVID-19-related coagulopathy. Up to now, treatment choices have been inferred from the experience with other coronaviruses or viral infection outbreaks. Hopefully, in the near future, new treatment strategies will be available thanks to increased knowledge on SARS-CoV2 virus and COVID-19 pathogenesis. In the meanwhile, further well-designed clinical trials are urgently needed to establish a standard of care in COVID-19 disease.