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0 0.5 1 1.5 2+ Mortality -157% Improvement Relative Risk Mortality (b) -169% Clinical improvement ≥.. -35% Clinical improvemen.. (b) -32% Vitamin C for COVID-19  Zheng et al.  LATE TREATMENT Is late treatment with vitamin C beneficial for COVID-19? Retrospective 397 patients in China (February - February 2020) Higher mortality (p=0.33) and worse improvement (p=0.17), not sig. Zheng et al., Open Medicine, September 2021 Favors vitamin C Favors control

No significant benefit of moderate-dose vitamin C on severe COVID-19 cases

Zheng et al., Open Medicine, doi:10.1515/med-2021-0361
Sep 2021  
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Retrospective 397 severe COVID-19 patients in China, showing worse outcomes with vitamin C treatment, without statistical significance. IV vitamin C 2-4g/day. Subject to confounding by indication and immortal time bias. Exclusion criteria were (a) the duration of hospitalization was less than 3 days; (b) vitamin C treatment started before admission; and (c) the length of vitamin C use was less than 3 days. Includes vitamin C use started at any time during hospitalization, for many patients this was >15 days later (Figure A2). Duration of treatment varied widely (Figure A1). Treatment was determined by clinicians according to the condition of each patient.
This is the 33rd of 64 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.00000022. 17 studies are RCTs, which show efficacy with p=0.00000014. This study is excluded in the after exclusion results of meta analysis: substantial unadjusted confounding by indication likely; immortal time bias may significantly affect results; treatment start times unknown, treatment may not have started at baseline.
risk of death, 157.0% higher, HR 2.57, p = 0.33, treatment 12 of 70 (17.1%), control 7 of 327 (2.1%), adjusted per study, propensity score matching.
risk of death, 169.0% higher, HR 2.69, p = 0.07, treatment 12 of 70 (17.1%), control 7 of 327 (2.1%), adjusted per study, IPTW.
clinical improvement ≥ 2 points, 35.1% worse, HR 1.35, p = 0.17, treatment 18 of 70 (25.7%), control 16 of 327 (4.9%), adjusted per study, inverted to make HR<1 favor treatment, propensity score matching.
clinical improvement ≥ 2 points, 31.6% worse, HR 1.32, p = 0.11, treatment 18 of 70 (25.7%), control 16 of 327 (4.9%), adjusted per study, inverted to make HR<1 favor treatment, IPTW.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Zheng et al., 22 Sep 2021, retrospective, China, peer-reviewed, 10 authors, study period 13 February, 2020 - 29 February, 2020.
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No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
Shaoping Zheng, Qiaosen Chen, Hongbo Jiang, Chunxia Guo, Jinzhuo Luo, Sumeng Li, Hua Wang, Huadong Li, Xin Zheng, Zhihong Weng
Open Medicine, doi:10.1515/med-2021-0361
There is no specific drug for coronavirus disease 2019 (COVID-19). We aimed to investigate the possible clinical efficacy of moderate-dose vitamin C infusion among inpatients with severe COVID-19. Data of 397 adult patients with severe COVID-19 admitted to a designated clinical center of Wuhan Union Hospital (China) between February 13 and February 29, 2020, were collected. Besides standard therapies, patients were treated with vitamin C (2-4 g/day) or not. The primary outcome was all-cause death. Secondary outcome was clinical improvement of 2 points on a 6-point ordinal scale. About 70 participants were treated with intravenous vitamin C, and 327 did not receive it. No significant association was found between vitamin C use and death on inverse probability treatment weighting (IPTW) analysis (weighted hazard ratio [HR], 2.69; 95% confidence interval [CI], 0.91-7.89). Clinical improvement occurred in 74.3% (52/70) of patients in the vitamin C group and 95.1% (311/327) in the no vitamin C group. No significant difference was observed between the two groups on IPTW analysis (weighted HR, 0.76; 95% CI, 0.55-1.07). Our findings revealed that in patients with severe COVID-19, treatment with moderate dose of intravenous vitamin C had no significant benefit on reducing the risk of death and obtaining clinical improvement.
Conflict of interest: The authors report no conflict of interest. Appendix
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Hemilä, Chalker, Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a metaregression analysis, J Intensive Care
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Mousavi, Bereswill, Heimesaat, Immunomodulatory and antimicrobial effects of vitamin C, Eur J Microbiol Immunol (Bp)
Nabzdyk, Bittner, Vitamin C in the critically ill -indications and controversies, World J Crit Care Med
Patel, Dial, Wu, Gauthier, Wu et al., Dietary antioxidants significantly attenuate hyperoxia-induced acute inflammatory lung injury by enhancing macrophage function via reducing the accumulation of airway HMGB1, Int J Mol Sci
Stuart, Lee, Leacy, Prognostic score-based balance measures can be a useful diagnostic for propensity score methods in comparative effectiveness research, J Clin Epidemiol
Wiersinga, Rhodes, Cheng, Peacock, Prescott, Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review, JAMA
Yan, Fu, Jia, Ma, Tao et al., Nrf2/Keap1/ARE signaling mediated an antioxidative protection of human placental mesenchymal stem cells of fetal origin in alveolar epithelial cells, Oxid Med Cell Longev
Late treatment
is less effective
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