1.The title does not correspond to the objective present in the abstract, which only considers the evaluation of hydroxychloroquine in patients with covid-19. The abstract does not reflect all aspects of the study. The objective, the characteristics of the patients and the difference between the groups are not well described. The results are contradictory, suggesting that azithromycin (and not hydroxychloroquine) had a better effect in the treatment group.

2.The introduction points out the justification for conducting the research and choosing the topic addressed. However, the lack of specific objectives and clear hypotheses does not provide adequate understanding about the purpose of the research, and it is necessary to insert these elements to direct the reader. For example, the objective presented at the end of the introduction does not agree with the title of the study, which includes azithromycin as a variable of interest.

3.The study was conducted as an open, non-randomized clinical trial, compromising the investigation of the drug's efficacy and not providing sufficient evidence for what was concluded in the final considerations. The absence of a placebo group and the lack of randomization of individuals compromises the validity of the study, which may result in overestimation of the results.

• Some data are not detailed enough to replicate the study. It is relevant to describe in detail the control group used for comparison purposes, as well as the outcomes that were intended to be analyzed. For the analysis context, it is necessary to add to the baseline, clinical characteristics in addition to age and sex, such as: chronic conditions associated with worse outcomes in infection with the new coronavirus (hypertension, diabetes, obesity). In addition, the authors did not indicate whether the clinical trial consisted of a parallel or factorial design, an important characteristic for decision making. The proportion of allocation was also not explained.

• Another point to be considered was the lack of blinding in the study. An alternative would be to blind at least the evaluators, to provide greater rigor to the research. It would also be relevant to better explain the choice of recruitment and treatment sites for the groups, since, considering the scope of the publication worldwide, it is possible that there is a lack of knowledge about the proposed health service.

In the procedures section, the researchers claim to have performed the standardized clinical examination, but do not specify the content of this assessment. Regarding the Swab Collection, information was vague as to whether it occurred daily and what it meant "when possible" (as well as the justification for what made the procedure unviable in a systematic way). With regard to drug intervention, it would be important to better establish the criteria for initiating the intervention, the clinical judgment and which antibiotics were being used. Likewise, it was not clear whether this treatment was being offered to all groups or just to controls.

• The authors classify the participants into three groups (asymptomatic, upper respiratory tract infection and lower respiratory tract infection), however, they do not provide the proportion of these symptoms per analyzed group (this information is only shown in table 1, in the results), making it impossible the future distinction between reliable results or attributed to chance.

• The primary outcome is clear, however, there is a caveat with regard to the proposed identification of the virus after the sixth day of entry into the protocol, since the baseline considered was in relation to treatment and not to the onset of symptoms, and this aspect is directly related to the viral load that was intended to be analyzed.

• There are inconsistencies with regard to secondary outcomes, the study states that these were: virological clearance over the study period and clinical follow-up (body temperature, respiratory rate, length of hospital stay and mortality) and the occurrence of side effects. What effects were these? If mortality was pointed out as a secondary outcome, why was the only death reported in the study excluded?

• Objectives or methods do not show the intention to investigate the use of Hydroxychloroquine in conjunction with Azithromycin. However, this was one of the outcomes presented in the study, causing some confusion, not making it clear to the reader if it was a hypothesis to be investigated or if it was the result of chance. Regarding statistical analysis, for clinical studies, it is interesting to have information in addition to the p value, such as: the confidence interval and the effect size.

4.The results section has inconsistencies. Table 2 shows the comparison of the hydroxychloroquine group with the control group. In Table 3, the intervention group is divided between people treated with hydroxychloroquine alone and people treated with hydroxychloroquine and azithromycin, implying that azithromycin may have presented itself as a confounding factor in the result of the analysis presented in Table 2.

5.Regarding the limitations of the study, it was necessary to list limitations that compromise the quality of the study: for example: the lack of randomization, lack of blinding, absence of a more detailed description of the patients' characteristics and specific reasons that led them to the ICU or death , resulting in the loss of that data. In the discussion, it is necessary to better list the potential biases, the presence or not of heterogeneity between the groups and the confounding factors that could compromise the results and conclusions of the study. Regarding the generalization of the study, the authors indicate that patients with COVID-19 should use hydroxychloroquine + azithromycin to cure the infection. However, in view of what has already been exposed, the study design allows us to reach this conclusion, as it does not guarantee its internal validity and external validity. In addition, the methodology is not reproducible.