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# Hydroxychloroquine for COVID-19 - The Evidence Ledger

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### [Hydroxychloroquine for COVID-19](/c/hydroxychloroquine-covid)

MechanismPLAUSIBLEOutcomeREFUTED

Claimed

Hydroxychloroquine improves survival or recovery in COVID-19.

What holds up

Genuine in-vitro activity via endosomal pH elevation and ACE2 glycosylation interference, consistent with known pharmacology, but required concentrations exceed achievable free plasma levels and animal models showed no benefit. RECOVERY randomized 4,716 hospitalized patients and found no 28-day mortality difference, with the hydroxychloroquine arm closed for futility; SOLIDARITY found no mortality benefit, and the joint RECOVERY plus SOLIDARITY estimate rules out any material benefit. Outpatient RCTs (Skipper, Ann Intern Med; Mitja, Clin Infect Dis) found no symptom-resolution or hospitalization benefit. A cardiac safety signal (QT prolongation, arrhythmia risk) emerged in observational and small prospective data.

What it does not show

Large replicated RCTs (RECOVERY, SOLIDARITY, plus outpatient trials) consistently show no mortality, hospitalization, or recovery benefit; no outcome evidence supports the claim as stated. It does not show improved outcomes in any setting tested, inpatient or outpatient, early or late. The in-vitro rationale never translated to human benefit; the RECOVERY authors noted the in-vitro inhibitory concentrations were higher than free plasma levels achieved in malaria treatment. Nothing in the RCT record supports efficacy; the evidence supports absence of benefit with moderate-to-high certainty.

Evidence for

Mercuro NJ et al., JAMA Cardiol 2020 (QT prolongation signal)

Sources

VERIFIED Horby P et al. (RECOVERY Collaborative Group), N Engl J Med 2020;383(21):2030-2040, PMID 33031652. PENDING Pan H et al. (WHO SOLIDARITY Trial Consortium), N Engl J Med 2021, DOI 10.1056/NEJMoa2023184. PENDING Skipper CP et al., Ann Intern Med 2020;173:623-631, DOI 10.7326/M20-4207. PENDING Mitja O et al., Clin Infect Dis 2021;73(11):e4073-e4081, DOI 10.1093/cid/ciaa1009. PENDING Mercuro NJ et al., JAMA Cardiol 2020 (QT prolongation signal).

## Grade history (append-only)

Every grade change is kept, never overwritten, so the current grade and every prior one stay visible.

Mechanism gradeJustificationGraded byStateGraded at

PLAUSIBLEGenuine in-vitro activity via endosomal pH elevation and ACE2 glycosylation interference, consistent with known pharmacology, but required concentrations exceed achievable free plasma levels and animal models showed no benefit. RECOVERY randomized 4,716 hospitalized patients and found no 28-day mortality difference, with the hydroxychloroquine arm closed for futility; SOLIDARITY found no mortality benefit, and the joint RECOVERY plus SOLIDARITY estimate rules out any material benefit. Outpatient RCTs (Skipper, Ann Intern Med; Mitja, Clin Infect Dis) found no symptom-resolution or hospitalization benefit. A cardiac safety signal (QT prolongation, arrhythmia risk) emerged in observational and small prospective data.admindisplayed2026-10-08T23:52:30.442Z

Outcome gradeJustificationGraded byStateGraded at

REFUTEDLarge replicated RCTs (RECOVERY, SOLIDARITY, plus outpatient trials) consistently show no mortality, hospitalization, or recovery benefit; no outcome evidence supports the claim as stated. It does not show improved outcomes in any setting tested, inpatient or outpatient, early or late. The in-vitro rationale never translated to human benefit; the RECOVERY authors noted the in-vitro inhibitory concentrations were higher than free plasma levels achieved in malaria treatment. Nothing in the RCT record supports efficacy; the evidence supports absence of benefit with moderate-to-high certainty.admindisplayed2026-10-08T23:52:30.443Z

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