Vitamin C may increase the recovery rate of outpatient cases of SARS-CoV-2 infection by 70%: reanalysis of the COVID A to Z Randomized Clinical Trial
Hemilä et al.
, Vitamin C may increase the recovery rate of outpatient cases of SARS-CoV-2 infection by 70%: reanalysis of the..
, Research Square, doi:10.21203/rs.3.rs-289381/v1 (Preprint) (meta analysis)
Reanalysis of Thomas et al. showing that vitamin C increased the recovery rate by 70%, p
Currently there are 58 vitamin C studies
and meta analysis shows:
Hemilä et al., 2 Mar 2021, preprint, 3 authors.
Abstract: Vitamin C may increase the recovery rate of
outpatient cases of SARS-CoV-2 infection by 70%:
reanalysis of the COVID A to Z Randomized Clinical
Harri Hemilä ( email@example.com )
University of Helsinki, Helsinki, Finland https://orcid.org/0000-0002-4710-307X
University of Otago, Christchurch, New Zealand https://orcid.org/0000-0002-5890-2977
University of Sydney, Sydney, Australia https://orcid.org/0000-0003-1593-3770
Keywords: Ascorbic acid, COVID-19, Common cold, Randomized controlled trials, SARS-CoV-2, Statistics,
Time factors, Treatment outcome, Zinc
Posted Date: March 1st, 2021
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
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Version of Record: A version of this preprint was published at Frontiers in Immunology on May 10th,
2021. See the published version at https://doi.org/10.3389/fimmu.2021.674681.
The COVID A to Z trial (JAMA Netw Open. 2021;4:e210369) is important as it focused specifically on
SARS-CoV-2 coronavirus patients and examined a high dose of vitamin C which was previously predicted
to reduce the duration of respiratory virus infections by about 20%. Unfortunately, there are several
limitations in the trial methods. The COVID A to Z trial was “stopped early for futility”. In the sample size
calculation, the authors assumed a 1.0 day shorter symptoms by intervention. Duration of symptoms
was reduced by 1.2 days in the vitamin C arm compared with the usual care arm. Given that the observed
vitamin C effect was 20% greater than the expected effect (1.2 vs. 1.0), it is illogical to have stopped the
trial early because of “futility”. In this reanalysis we calculated the rate ratio of recovery between the
vitamin C and usual care arms and found that vitamin C increased the rate of recovery by 70% (95% CI
6.8% to 170%, P = 0.025). Furthermore, we calculated quantile treatment effect of vitamin C. At the 60th
percentile level of symptom distribution, duration was 9 days in the usual care arm, and 6 days in the
vitamin C arm, which corresponds to reduction in symptom duration by 3 days (95% CI 3 to 4.6 days; P <
0.001). The analysis of the quantile treatment effect indicates that there may be around 30% reduction in
symptom duration in patients with the longest symptoms. Our reanalysis indicates a need for
methodologically sound trials with larger numbers of patients to investigate the treatment effects of
vitamin C against SARS-CoV-2.
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