To conclude, the HCQ treatment of SARS-CoV-2 infection was not met with its hoped success. This is probably related to the inability of the dosing regimens currently in use to achieve the blood concentration required for the HCQ antiviral activity. Initially, based on physiological pharmacokinetic models, Yao et al. recommended for SARS-CoV-2 infection a loading oral HCQ dose of 400 mg twice daily, followed by a maintenance dose of 200 mg administered twice daily for four days [50]. However, this recommended HCQ dosage regimen was based only on the ratio of free lung trough concentration to in vitro EC50 values (the EC50 of HCQ for SARS-CoV-2 ranged between 0.72 and 17.31µM) and did not consider the tendency of HCQ to accumulate within acidic cellular organelles like endosomes, lysosomes, and Golgi apparatus [69]. In fact, it has been demonstrated that HCQ concentration in lysosomes is higher than the extracellular concentration (80 µM vs. 0.5 µM, respectively) [70]. Based on these results, it was considered necessary to compare the EC50 values obtained in vitro with the plasma concentration and not with the lung concentration. In a study investigating HCQ pharmacokinetics in COVID-19 patients treated with 600 mg/day of HCQ, it was found that the mean blood concentration of HCQ was 0.46 mg/day [32], which was below the lowest estimated levels of 0.48 mg/mL corresponding to the in vitro concentration of 0.72 µM. Further, a plasma concentration predicted for HCQ antiviral EC50 made by Garcia-Cremades et al. found that it should be 4,7 µM corresponding to 1.58 mg/mL, which is much higher than in vivo plasmatic values. To reach this plasma concentration, it should be necessary to take an amount of HCQ higher than 400 mg twice a day for five days or more [71], which would increase the onset of side effects. Thus, the ineffectiveness of HCQ antiviral activity again SARS-CoV-2 can be related to the low current dosing regimens and the impossibility to increase the administered doses due to the increased risk of severe side effects, especially QT prolongation.