According to current guidelines, can hydroxychloroquine be used to treat or prevent COVID‑19?

Hydroxychloroquine Should NOT Be Used for COVID-19 Treatment or Prevention

Current guidelines unanimously recommend against using hydroxychloroquine for COVID-19, whether for treatment or prophylaxis, due to lack of efficacy and significant risk of harm. 1

Treatment of COVID-19

Clear Recommendation Against Use

• Hydroxychloroquine with or without azithromycin is NOT generally recommended for COVID-19 treatment due to the possibility of serious side effects and lack of clinical benefit. 1

• The American College of Physicians explicitly states clinicians should NOT use hydroxychloroquine alone or in combination with azithromycin for treating COVID-19 patients, citing insufficient evidence about benefits and known harms. 1

• High-certainty evidence from 9 randomized trials involving 8,208 participants demonstrates that hydroxychloroquine makes little or no difference to death from any cause (RR 1.09,95% CI 0.99 to 1.19). 2

Evidence of Lack of Efficacy

• Hydroxychloroquine makes little or no difference to viral clearance at day 14 (RR 1.00,95% CI 0.91 to 1.10) and probably results in little to no difference in progression to mechanical ventilation (RR 1.11,95% CI 0.91 to 1.37). 2

• A randomized trial of 423 nonhospitalized adults with early COVID-19 found no significant reduction in symptom severity over 14 days with hydroxychloroquine compared to placebo (difference: -0.27 point, 95% CI -0.61 to 0.07; P = 0.117). 3

• Meta-analysis of randomized controlled trials shows no significant effect on mortality rates, clinical cure, or virologic response. 4

Documented Harms

• Hydroxychloroquine probably results in an almost three-fold increased risk of adverse events (RR 2.90,95% CI 1.49 to 5.64) compared to standard care. 2

• Medication adverse effects occurred in 43% of participants receiving hydroxychloroquine versus 22% receiving placebo (P < 0.001). 3

• The combination of hydroxychloroquine and azithromycin did not result in clinical improvement or viral clearance, and several patients presented with prolonged QT intervals. 1

• QT prolongation is a significant concern, particularly when combined with azithromycin, potentially leading to ventricular arrhythmias. 5, 6

Prophylaxis Against COVID-19

Post-Exposure Prophylaxis

• Hydroxychloroquine should NOT be used for post-exposure prophylaxis in people exposed to SARS-CoV-2. 1

• One trial of 821 participants with exposure to confirmed COVID-19 found very uncertain effects on preventing confirmed COVID-19 (2.4% developed disease at 14 days), but hydroxychloroquine probably increases the risk of adverse events compared with placebo (RR 2.39,95% CI 1.83 to 3.11). 2

• A cluster-randomized trial of 2,525 participants in Spain found no difference in the risk of symptomatic confirmed COVID-19 between hydroxychloroquine and standard care. 2

Pre-Exposure Prophylaxis

• There is NO available evidence supporting hydroxychloroquine for prophylaxis in the general population at risk of COVID-19 exposure. 1

Clinical Context: Only Consider in Research Settings

• If hydroxychloroquine is to be used at all, it should ONLY be in the context of a well-designed clinical trial with informed consent, shared decision-making with patients and families, and appropriate monitoring for adverse effects. 1

• The Korean Association for the Study of the Liver explicitly states that further studies with well-designed clinical trials are needed to confirm any antiviral effect, acknowledging that clinical trials have shown conflicting results. 1

Common Pitfalls to Avoid

• Do NOT combine hydroxychloroquine with azithromycin outside of clinical trials, as this increases the risk of QT prolongation and cardiac complications without providing clinical benefit. 1, 5

• Do NOT prescribe hydroxychloroquine based on early in vitro studies or low-quality observational data, as high-quality randomized controlled trials have definitively shown lack of efficacy. 4, 2

• Do NOT use hydroxychloroquine as a substitute for evidence-based COVID-19 treatments (such as remdesivir, dexamethasone in appropriate patients, or monoclonal antibodies when indicated). 1

• Avoid the misconception that hydroxychloroquine might work in "low-risk" patients or at lower doses—this hypothesis remains unproven and should only be tested in rigorous clinical trials. 7

Monitoring Concerns if Inappropriately Used

• If hydroxychloroquine has already been prescribed, obtain baseline ECG to assess for QT prolongation, check electrolytes (particularly potassium and magnesium), and screen for G6PD deficiency in at-risk populations. 6

• Be aware that retinal toxicity is a concern with prolonged use beyond 2 years, though this is less relevant for short-term COVID-19 treatment courses. 6