In the light of collected data, despite the success of the first clinical trials, the latest studies have shown the ineffectiveness of HCQ for the treatment and prevention of COVID-19 infection. So that, if the U.S. Food and Drug Administration (FDA) had initially authorized the use of HCQ in case of emergency [61], in June 2020, the FDA revoked this authorization [62] since the potential HCQ effectiveness in treating COVID-19 was overtaken by severe cardiac adverse events and other serious side effects. In fact, there is the need to consider that in subjects with severe COVID-19, the abundance of inflammatory molecules like interleukins and tumor necrosis factors generate a cytokine storm, leading to a septic shock and multiple organ failure. In hepatic and renal dysfunction, HCQ metabolism and clearance were compromised and its safety is altered. Moreover, recently the Surviving Sepsis Campaign guidelines on the management of critically ill patients with COVID-19 concluded that there was insufficient evidence to recommend the routine use of HCQ in patients admitted in ICU [63]. In the same way, the American College of Physicians practice guidelines do not recommend HCQ for prophylaxis or treatment [64]. International trials like SOLIDARITY (International trial by World Health Organisation) [65], RECOVERY (Randomised Evaluation of Covid-19 Therapy) [66], and DISCOVERY (Trial of Treatments for COVID-19 in Hospitalized Adults) [67] have also stopped the HCQ arm. In particular, the World Health Organisation (WHO), in the SOLIDARITY trial project, has arrested all arms involving HCQ, as evidence showed that it did not reduce the mortality of hospitalized COVID-19 patients compared with SOC. However, this decision was not applied to HCQ use or evaluation in pre- or post-exposure prophylaxis for subjects exposed to COVID-19 [68].