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# Ivermectin for COVID-19 - The Evidence Ledger

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### [Ivermectin for COVID-19](/c/ivermectin-covid)

MechanismPLAUSIBLEOutcomeREFUTED

Claimed

Ivermectin improves survival or recovery in COVID-19.

What holds up

Real in-vitro antiviral activity in cell culture with a proposed importin-mediated mechanism, but the inhibitory concentrations far exceed safely achievable human plasma levels and no in-vivo antiviral activity was ever demonstrated. The Caly et al. in-vitro finding is genuine. The large RCTs are consistent with each other: TOGETHER found no reduction in hospitalization or prolonged ED observation; both ACTIV-6 ivermectin arms found no improvement in time to recovery; PRINCIPLE found hospitalizations and deaths identical between groups with no long-term benefit; I-TECH found no reduction in progression to severe disease. The Cochrane review gives moderate-certainty evidence of no benefit in outpatients.

What it does not show

Multiple large replicated RCTs (TOGETHER, two ACTIV-6 arms, PRINCIPLE, I-TECH) consistently found no survival or recovery benefit; no outcome evidence supports the claim as stated. It does not show improved survival or recovery in any tested setting. The Elgazzar preprint, which powered the early positive meta-analyses, was withdrawn by Research Square for ethical and data-integrity concerns and must be excluded from any honest synthesis. PRINCIPLE's roughly two-day faster self-reported recovery fell below its own pre-specified clinically meaningful threshold.

Evidence for

Caly L et al., Antiviral Res 2020;178:104787, PMID 32251768, Elgazzar A et al., Research Square 2020, DOI 10.21203/rs.3.rs-100956 (withdrawn 2021-07-14)

Sources

VERIFIED Reis G et al., N Engl J Med 2022;386(18):1721-1731, PMID 35353979. VERIFIED Naggie S et al., JAMA 2022;328(16):1595-1603, PMID 36269852. VERIFIED Naggie S et al., JAMA 2023;329(11):888-897, PMID 36807465. VERIFIED Hayward G et al., J Infect 2024;88(4):106130, PMID 38431155. VERIFIED Caly L et al., Antiviral Res 2020;178:104787, PMID 32251768. RETRACTED Elgazzar A et al., Research Square 2020, DOI 10.21203/rs.3.rs-100956 (withdrawn 2021-07-14). PENDING Lim SCL et al., JAMA Intern Med 2022, DOI 10.1001/jamainternmed.2022.0189. PENDING Popp M et al., Cochrane Database Syst Rev 2022;6:CD015017, PMID 35726131.

## 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

PLAUSIBLEReal in-vitro antiviral activity in cell culture with a proposed importin-mediated mechanism, but the inhibitory concentrations far exceed safely achievable human plasma levels and no in-vivo antiviral activity was ever demonstrated. The Caly et al. in-vitro finding is genuine. The large RCTs are consistent with each other: TOGETHER found no reduction in hospitalization or prolonged ED observation; both ACTIV-6 ivermectin arms found no improvement in time to recovery; PRINCIPLE found hospitalizations and deaths identical between groups with no long-term benefit; I-TECH found no reduction in progression to severe disease. The Cochrane review gives moderate-certainty evidence of no benefit in outpatients.admindisplayed2026-10-08T23:52:30.437Z

Outcome gradeJustificationGraded byStateGraded at

REFUTEDMultiple large replicated RCTs (TOGETHER, two ACTIV-6 arms, PRINCIPLE, I-TECH) consistently found no survival or recovery benefit; no outcome evidence supports the claim as stated. It does not show improved survival or recovery in any tested setting. The Elgazzar preprint, which powered the early positive meta-analyses, was withdrawn by Research Square for ethical and data-integrity concerns and must be excluded from any honest synthesis. PRINCIPLE's roughly two-day faster self-reported recovery fell below its own pre-specified clinically meaningful threshold.admindisplayed2026-10-08T23:52:30.438Z

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