Hydroxychloroquine and chloroquine were widely used for the treatment of malaria. Currently, they are still used in rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders. Because of its effects on inhibiting pH-dependent steps of the replication of several viruses, they have been suggested as a possible treatment in the context of the COVID-19 pandemic in 2019/2020.
- We are uncertain whether the use of antimalarials as part of the treatment of COVID-19 has any effect on outcomes critical for decision-making (e.g. mortality or need of mechanical ventilation) as the certainty of the evidence has been assessed as very low.
- The addition of antimalarials may not even increase the number of patients achieving SARS-CoV-2 clearance, but the certainty of the available evidence is low.
- Adding antimalarials to standard treatment may increase the risk of serious adverse effects.
Interactive Summary of Findings (iSoF) table:
The evidence supporting this summary is publicly available through the L·OVE (Living OVerview of Evidence) platform. Use this link to access L·OVE and activate email notifications of new articles addressing this question.
Appendix 1. References
1. Gautret et al
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents [Internet] 2020 March 20 [Accessed March 26] Available from:.
Epistemonikos | DOI
2. Chen, Hongzhou et al (NCT04261517)
Chen Jun, Liu Danping. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Journal of Zhejiang University (Medical Science) [Internet] 2020 [Accessed March 26] ;49(1):0-0.:
3. Hongzhou Lu, Shanghai Public Health Clinical Center. Efficacy and Safety of Hydroxychloroquine for Treatment of Pneumonia Caused by 2019-nCoV ( HC-nCoV ). ClinicalTrials.gov [Internet] registration number: NCT04261517 [Accessed March 26].
Appendix 2. Search strategy
((coronavir* OR coronovirus* OR “corona virus” OR “virus corona” OR “corono virus” OR “virus corono” OR “sars-coronavirus” OR hcov* OR (wuhan* AND (virus OR viruses OR viral) OR coronav*) OR (covid* AND (virus OR viruses OR viral)) OR cv19 OR “cv-19” OR “cv 19” OR “n-cov” OR ncov* OR “sars-cov-2” OR “mers-cov” OR “mers cov” OR “sars-cov” OR “sars cov”)) AND ((antimalari* OR “anti-malarial” OR “anti-malarials” OR “anti-malaria”) OR (chloroquine* OR CQ OR Aralen) OR (hydroxychloroquine* OR HCQ OR Plaquenil))
Minor modifications were conducted to the Epistemonikos strategy in order to adapt it to other databases.
Appendix 3. Forest plots
Appendix 5. Summary of Findings table (GRADE), static version.
|Antimalarials for the treatment of SARS-CoV-2 infection|
|Intervention||Addition of antimalarials (hydroxychloroquine or chloroquine) to standard treatment (as defined by the studies)|
|Comparison||Placebo or no treatment (added to standard treatment as defined by the studies)|
|Absolute effect*||Certainty of evidence (GRADE)||Key messages|
1 trial 
|On trial reported that all participants were still alive at 2 weeks of follow-up.||⨁○○○1,2
|We are uncertain whether the addition of antimalarials to standard treatment decreases mortality as the certainty of the evidence has been assessed as very low.|
|Mechanical ventilation||The outcome mechanical ventilation or extracorporeal membrane oxygenation has not been reported by the analyzed evidence.||—||—|
|Extracorporeal membrane oxygenation||The outcome extracorporeal membrane oxygenation has not been reported by the analyzed evidence.||—||—|
|Length of hospital stay||The outcome length of hospital stay has not been reported in the evidence analyzed.||—||—|
2 trials [2,3]
No studies were found evaluating respiratory failure or acute respiratory distress syndrome, however, indirect evidence was found:
The trials reported that the group receiving antimalarials had less progression of lung disease*** compared to the control group (RR 0.46, 95% CI 0.15 to 1.39).
|We are uncertain whether the addition of antimalarials to standard treatment decreases respiratory failure as the certainty of the evidence has been assessed as very low.|
|Serious adverse effects||—
2 trials [2,3]
|No studies were found evaluating serious adverse effects, however indirect evidence was found:
The trials reported that the group receiving antimalarials presented more total adverse effects**** compared to the control group (RR 1.65, 95% CI 0.50 to 5.50).
|The addition of antimalarials to standard treatment may increase the incidence of serious adverse effects (low certainty of evidence)|
|SARS-CoV-2 clearance*****||RR 0.93
(0.73 a 1.18)
—30 patients/ 1 trial 
(252 less to 168 more)
|The addition of antimalarials to standard treatment may not increase SARS-CoV-2 clearance (low certainty of evidence)|
95 CI%: 95% confidence interval
RR: Relative risk.
GRADE: Evidence grades Grading of Recommendations Assessment, Development and Evaluation.
*The risk WITHOUT antimalarials is based on the risk in the control group of the trials. The risk WITH antimalarials (and its confidence interval) is calculated from relative effect (and its confidence interval).
**** Total adverse effects evaluated at 2 weeks  and 6 days  of follow-up, including diarrhea, anemia, elevated creatinine, transient AST elevation, rash and headache.
2 The certainty of the evidence was downgraded in two levels for imprecision, since it cannot be ruled out that the observed effect is a product of chance, given the low number of events and sample size (n = 30).
3 The certainty of the evidence was downgraded in one level for imprecision since different decisions would be taken at each end of the confidence interval.
4 The certainty of the evidence was downgraded in one level for indirectness since the reported outcomes correspond to surrogates of respiratory failure and serious adverse effects. There is also controversy about indirectness regarding hydroxychloroquine therapeutic dose (400 mg qd). However, we did not downgrade for this factor because we did not find convincing evidence or consensus regarding the optimal dose.