Clinical manifestations of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include gastrointestinal signals and symptoms . Individuals with previous clinical conditions that usually enroll gut dysbiosis have been identified as being at high risk to develop more severe infectious phenotypes . Actually, intestinal dysbiosis has been observed in infected patients and potentially linked to systemic hyperinflammation . These observations suggest that a previous gut dysbiosis may be aggravated by SARS-CoV-2 infection and related to progression of the coronavirus disease 2019 (COVID-19) into more severe stages . While COVID-19's pathophysiology is not fully understood, it seems relevant to consider the interactions of candidate therapeutic drugs with the host, gut microbiota, and SARS-CoV-2 . Here we summarize scientific evidence supporting the potential relevance of these interactions and suggest that unfavorable clinical data on hydroxychloroquine administration in COVID-19 may have been influenced by the dose provided and its impact on gut dysbiosis . The proposition is based on preliminary data on gut microbiota composition from individuals with inactive systemic lupus erythematosus under exclusive continuous hydroxychloroquine treatment, displaying a direct correlation between drug doses and markers typically associated with gut dysbiosis.