At the present time, evidence from the first published RCT does not support off-label treatment with LPV/RTV in COVID-19 patients. This result should also discourage the use of other protease inhibitors (e.g. darunavir), at least until results of dedicated RCT are available. Although promising in preclinical studies, remdesivir should be currently provided for treating COVID-19 patients only within RCT (preferentially) or compassionate-use/expanded-access programmes, owing to its investigational nature. Pending high-level supporting evidence, favipiravir and umifenovir should not be provided outside RCT, at least in those countries where they are not approved for other indications. Oseltamivir or zanamivir should be provided only in the presence of suspected/proven concomitant influenza.