Efficacy of antioxidant therapy in mild to moderate SARS-CoV-2 infection: A pilot experimental arm of the CanTreatCOVID adaptive platform trial

Hosseini et al., medRxiv, doi:10.64898/2026.08.21.26360704, CanTreatCOVID, NCT05614349, Aug 2026
Hospitalization 52% improvement lower risk ← → higher risk Recovery 42% Recovery, complete al.. 68% Recovery, sustained al.. 67% Recovery, return to us.. 43% Recovery, return to.. b 64% Antioxidants  CanTreatCOVID  EARLY TREATMENT RCT Is early treatment with antioxidants beneficial for COVID-19? RCT 81 patients in Canada Lower hospitalization (p=0.38) and improved recovery (p=0.13), not sig. c19early.org Hosseini et al., medRxiv, August 2026 0 0.5 1 1.5 2+ RR
Zinc for COVID-19
2nd treatment shown to reduce risk in July 2020, now with p = 0.00000012 from 41 studies, recognized in 23 countries.
Lower risk for mortality, hospitalization, progression, recovery, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,600+ studies for 220+ treatments. c19early.org
Meta-analysis
RCT 81 outpatients showing ~2-3x higher odds of favorable recovery outcomes with antioxidant treatment (selenium 300 µg, zinc 40 mg, lycopene 45 mg, vitamin C 1.5 g).
With 81 patients the trial is too small to reach statistical significance, however sustained alleviation was close and showed a 96% Bayesian probability of superiority.
If the point estimates remained the same, significance would be reached after enrolling ~6-50 more patients, depending on the outcome.
Authors indicate the trial was stopped early without providing the reason. The same trial enrolled 716 patients for paxlovid. The platform's sample-size calculation was ~2,413 patients per arm for 80% power. The prespecified stopping criteria are not mentioned in the paper and none appear to have been triggered. There is no indication that authors are currently running a larger trial.
There were no hospitalizations or deaths in the antioxidant arm compared to 2/40 (5%) in usual care.
Treatment was relatively late, ~3-4 days after symptom onset (2.7 days at enrollment plus medication delivery).
No serious adverse events were reported. Authors suggest the improvements may be due to the complementary redox-buffering and immune-supporting roles of the treatments during acute viral infection.
Results were delayed ~16 months after trial completion.
This study is excluded in the after exclusion results of meta-analysis: combined treatments may contribute significantly to the effect seen.
Important missing comments or errors? Let us know.
Study covers vitamin C, selenium, and zinc.
risk of hospitalization, 51.8% lower, RR 0.48, p = 0.38, treatment 0 of 41 (0.0%), control 2 of 40 (5.0%), adjusted per study, odds ratio converted to relative risk, hospitalization or death, Bayesian, day 28.
risk of no recovery, 41.9% lower, RR 0.58, p = 0.13, treatment 8 of 40 (20.0%), control 13 of 36 (36.1%), NNT 6.2, adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, not recovered, day 14.
risk of no recovery, 68.1% lower, RR 0.32, p = 0.16, treatment 0 of 40 (0.0%), control 2 of 36 (5.6%), adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, no complete alleviation of all symptoms, day 14.
risk of no recovery, 66.8% lower, RR 0.33, p = 0.05, treatment 2 of 40 (5.0%), control 7 of 36 (19.4%), NNT 6.9, adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, no sustained alleviation of all symptoms, day 14.
risk of no recovery, 43.1% lower, RR 0.57, p = 0.10, treatment 9 of 40 (22.5%), control 14 of 36 (38.9%), NNT 6.1, adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, failure to return to usual health, day 14.
risk of no recovery, 63.8% lower, RR 0.36, p = 0.08, treatment 2 of 40 (5.0%), control 6 of 36 (16.7%), NNT 8.6, adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, failure to return to usual activity, day 14.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hosseini et al., 26 Aug 2026, Randomized Controlled Trial, Canada, preprint, 24 authors, trial NCT05614349 (history) (CanTreatCOVID). Contact: benita.hosseini@utoronto.ca.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org August 2026 Canada Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Nepal China Uzbekistan Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea Saudi Arabia Algeria Morocco Yemen Poland India Venezuela DR Congo Madagascar Thailand Uganda Egypt Nigeria Taiwan Zambia Bolivia Fiji Bosnia-Herzegovina Jordan Georgia Switzerland Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Trinidad and Tobago Mongolia Czechia Israel Belarus North Macedonia Hong Kong Qatar Panama Serbia CAR Syria Canada favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org August 2026 Canada Angola Colombia Kenya Mozambique Myanmar South Africa Peru Philippines Vietnam Japan Nepal China Uzbekistan Iran Bangladesh Ethiopia Ghana Germany Mexico South Korea Saudi Arabia Algeria Morocco Yemen Poland India Venezuela DR Congo Madagascar Thailand Uganda Egypt Nigeria Zambia Bolivia Fiji Jordan Georgia Switzerland Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore Iceland New Zealand Mongolia Czechia Israel Belarus North Macedonia Hong Kong Qatar Panama Serbia CAR Canada favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Abstract: ## Efficacy of antioxidant therapy in mild to moderate SARS-CoV-2 infection: A pilot experimental arm of the CanTreatCOVID adaptive platform trial Banafshe Hosseini* 1,2,3,26 , David Jenkins 4,5 , Peter Daley 6,7 , Kerry McBrien 8,9 , Srinivas Murthy 10 , Amanda Condon 11 , Bruno R. da Costa 12,13 , Michelle Greiver 2,14 , Peter Jüni 12 , Peter Selby 2,3,15 , Norman Umali 1 , Meichen Liu 1 , Haolun Shi 16 , Kawsika Sivayoganathan 1 , Darshna Patel 17,18 , Melanie Paquette 17,18 , Helen Hue My Nguyen 18,19 , Marc Malty 18,20 , Aleksandra Nedeljkovic 18,21 , Nerissa Situ 18,22 , Gabriel So 18,23 , Ethan Belo 18,24 , Yueyang Han 16 , Andrew D. Pinto 1,2,3,25 /i1 Affiliations /i1 1. Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada /i1 2. Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada /i1 3. Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada /i1 4. Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 5. Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, Ontario, Canada 6. Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada. /i1 7. Eastern Regional Health Authority, St. John's, Newfoundland and Labrador, Canada. /i1 8. Department of Family Medicine, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada /i1 9. Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. /i1 10. Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. /i1 11. Department of Family Medicine, University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada /i1 12. Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom 13. Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. /i1/i1 14. Department of Family and Community Medicine, North York General Hospital, Toronto, Ontario, Canada. /i1 15. Addiction Programs, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. /i1 16. Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada 17. Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 18. Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada 19. Faculty of Science, York University, Toronto, Ontario, Canada 20. Department of Health Sciences, Wilfrid Laurier University, Waterloo, Ontario, Canada 21. Health and Life Science Faculty, Humber Polytechnic, Toronto, Ontario, Canada 22. School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada 23. Department of Health Sciences, Wilfrid Laurier University, Waterloo, Ontario, Canada 24. Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada It is made available under a CC-BY-NC-ND 4.0 International license . is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) medRxiv preprint doi:..
DOI record: { "DOI": "10.64898/2026.08.21.26360704", "URL": "http://dx.doi.org/10.64898/2026.08.21.26360704", "abstract": "<jats:p>\n Background: Although the acute phase of the COVID–19 pandemic has passed, SARS–CoV–2 continues to cause outpatient morbidity. Antioxidant micronutrients support immune regulation and may offer a low–cost, scalable adjunctive treatment in early infection. \nObjective: To evaluate a pilot combination antioxidant therapy within CanTreatCOVID.\nMethods: This pilot sub–protocol enrolled non–hospitalized adults across five Canadian provinces (September 5th, 2024–March 31st, 2025) with mild–to–moderate SARS–CoV–2 infection within five days of symptom onset. Participants were randomized to usual care plus a 10–day antioxidant regimen (selenium 300 μg, zinc 40 mg, lycopene 45 mg, vitamin C 1.5 g) or usual care alone. Pilot objectives assessed feasibility, retention, adherence, and safety. The primary outcome was hospitalization or death within 28 days; exploratory outcomes included recovery and symptom measures by day 14.\nResults: Eighty–one participants were randomized (41 antioxidant; 40 usual care). Retention was high 85.4% antioxidant; 82.5% usual care), and 90.2% of antioxidant participants completed the intervention course. Adverse events were infrequent (9.8% vs 2.5%), with no serious adverse events reported. No deaths occurred in either group; no hospitalizations occurred in the antioxidant arm versus 2/40 (5%) in usual care. By day 14, recovery was reported in 32/40 (80.0%) participants receiving antioxidants versus 23/36 (63.9%) in usual care (OR 2.128; 95% CI 0.7474.871). Sustained alleviation of all symptoms occurred in 38/40 (95.0%) versus 29/36 (80.6%), respectively (OR 3.498; 95% CI 0.872\t—10.017). Return to usual activity by day 14 occurred in 38/40 (95.0%) versus 30/36 (83.3%) (OR 3.113; 95% CI 0.762—9.022). Adjusted between–group differences in dietary intake were not statistically significant.\nConclusions: Combination antioxidant therapy was feasible to deliver in a decentralized outpatient setting, with high adherence and tolerability. While the trial was not powered for definitive efficacy conclusions, consistent directional improvements across symptom outcomes support evaluation of this host-directed antioxidant strategy in larger trials.\nKeywords: Adaptive Platform Trial; Antioxidant Therapy; SARS–CoV–2 ; Outpatient Therapeutics; Micronutrient Supplementation\nTrial registration number: https://clinicaltrials.gov/study/\n <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05614349\">NCT05614349</jats:ext-link>\n </jats:p>", "accepted": { "date-parts": [ [ 2026, 8, 26 ] ] }, "author": [ { "affiliation": [ { "name": "Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing& Knowledge Institute, Unity Health Toronto. Markham Stouffville Hospital, Oak Valley Health. St.Michael's Hospital, University of Toronto & Dalla Lana School of Public Health.;" } ], "family": "Hosseini", "given": "Banafshe", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "first" }, { "affiliation": [ { "name": "Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, Ontario, Canada;" } ], "family": "Jenkins", "given": "David", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada. Eastern Regional Health Authority, St. John's, Newfoundland and Labrador, Canada;" } ], "family": "Daley", "given": "Peter", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Family Medicine, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada;" } ], "family": "McBrien", "given": "Kerry A.", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;" } ], "family": "Murthy", "given": "Srinivas", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Family Medicine, University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada;" } ], "family": "Condon", "given": "Amanda", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom. Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto;" } ], "family": "da Costa", "given": "Bruno R.", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada. Department of Family and Community Medicine, North York General Hospital, Toronto, Ontario, Canada;" } ], "family": "Greiver", "given": "Michelle", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;" } ], "family": "Juni", "given": "Peter", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Family and Community Medicine, University of Toronto, Canada. Addiction Programs, Centre for Addiction and Mental Health, Toronto, Canada. Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Canada;" } ], "family": "Selby", "given": "Peter", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada;" } ], "family": "Umali", "given": "Norman", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada;" } ], "family": "Liu", "given": "Meichen", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada;" } ], "family": "Shi", "given": "Haolun", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada;" } ], "family": "Sivayoganathan", "given": "Kawsika", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Clinical Nutrition and Risk Factor Modification Centre, St.Michael's Hospital, Toronto, Ontario, Canada;" } ], "family": "Patel", "given": "Darshna", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Clinical Nutrition and Risk Factor Modification Centre, St.Michael's Hospital, Toronto, Ontario, Canada;" } ], "family": "Paquette", "given": "Melanie", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada. Faculty of Science, York University, Toronto, Ontario, Canada;" } ], "family": "Nguyen", "given": "Helen Hue My", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada. Department of Health Sciences, Wilfrid Laurier University, Waterloo, Ontario, Canada;" } ], "family": "Malty", "given": "Marc", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada. Health and Life Science Faculty, Humber Polytechnic, Toronto, Ontario, Canada;" } ], "family": "Nedeljkovic", "given": "Aleksandra", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada. School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada;" } ], "family": "Situ", "given": "Nerissa", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada. Department of Health Sciences, Wilfrid Laurier University, Waterloo, Ontario, Canada;" } ], "family": "So", "given": "Gabriel", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Ontario, Canada. Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada;" } ], "family": "Belo", "given": "Ethan", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada;" } ], "family": "Han", "given": "Yueyang", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "affiliation": [ { "name": "Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing& Knowledge Institute, Unity Health Toronto. 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