The inclusion of Borba et al1. article reporting two different dosages of chloroquine diphosphate to evaluate its efficacy and safety in COVID-19 needs some critical corrections. Table 1 (and all over the report) states that the interventions were hydroxychloroquine in high doses and standard doses. As pointed out in the title of Borba et al. paper, published by JAMA Network Open, interventions were diphosphate chloroquine for 10 days (total dose 20g, equivalent to 12g chloroquine base) and for 5 days (total dose 4.5g, equivalent to 2.7g chloroquine base). Chloroquine diphosphate is more toxic than hydroxychloroquine2. On the other side, Borba et al. article did not comply with the inclusion and exclusion criteria defined by the authors of the systematic review and meta-analysis. There was no proper control group in the study, and chloroquine diphosphate was used as an adjuvant to the obligatory administration of azithromycin, ceftriaxone and, in 90% of the cases, oseltamivir, all three drugs with cardiac side effects. Almost ¼ of the included participants were not diagnosed with COVID-19 (in 2 weeks of treatment, 3 patients without COVID-19 died). It is likely that all included participants were treated before being diagnosed with COVID-19, and there was no report on the timing of initiation of treatment after symptom onset between groups. Borba et al. did not report the incidence of non-cardiac adverse effects (such as vomiting and diarrhea, causes of dehydration and hypokalemia). It´s difficult to make straight causal attributions given the study's design, even in a dosage regimen of chloroquine diphosphate 8 times superior to the one used to treat malaria. Except for the CloroCovid-19 trial in Brazil, Watson et al.3 concluded that “pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity”. However, it must be remembered that the simulation did not consider the deleterious effects of the 2019-nCoV and associated comorbidities in fragile patients treated with a cocktail of other drugs. In the Brazilian trial, chloroquine diphosphate was administrated in patients possibly using other drugs (e.g. digitalis, antidiabetics and diuretics) with significant and potentially lethal interactions resulting in hypokalemia, conduction disorders, heart rhythm changes and deaths.

1. Borba MGS, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Brito M, et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA Netw Open. 2020; 3(4):e208857–e. https://doi.org/10.1001/j...
2. Liu, J., Cao, R., Xu, M. et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 6, 16 (2020). https://doi.org/10.1038/s... .
3. Watson JA, Tarning J, Hoglund RM, Baud FJ, Megarbane B, Clemessy JL, White NJ. Concentration-dependent mortality of chloroquine in overdose. Elife. 2020 Jul 8;9:e58631. https://doi: 10.7554/eLife.58631