Summary of COVID-19 vitamin C studies

1. Ried et al., Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial

237 patient vitamin C early treatment RCT: 31% improved recovery (p=0.008).
RCT 237 patients in Turkey, 162 treated with IV vitamin C in addition to HCQ/AZ/zinc/vitamin D used for all patients, showing significantly faster recovery with the addition of IV vitamin C. 97% of patients were vitamin D deficient, and lower vitamin D levels were associated with ICU admission and longer hospital stay. Only 1 of 237 hospitalized patients died (average age 63, range 22-99) - a 70-year-old patient with heart and lung disease and severely deficient vitamin D levels (6 nmol/L). IV vitamin C (sodium ascorbate) was given as 50 mg/kg every six hours on day 1, followed by 100 mg/kg every six hours (four times daily, 400 mg/kg/day) for seven days. NCT04395768.
Nov 2021, Cureus, https://www.cureus.com/articles/76496-therapies-to-prevent-progression-of-covid-19-including-hydroxychloroquine-azithromycin-zinc-and-vitamin-d3-with-or-without-intravenous-vitamin-c-an-international-multicenter-randomized-trial, https://c19p.org/ried

2. Uz et al., Role of intravenous vitamin C on outcomes in hospitalized patients with moderate or severe COVID-19: a real life data of Turkish patients

270 patient vitamin C late treatment study: 84% lower mortality (p=0.05).
Retrospective 270 moderate/severe hospitalized COVID-19 patients, showing lower mortality with high (25 g/day) or low-dose (2 g/day) intraveneous vitamin C.
Nov 2024, Inflammopharmacology, https://link.springer.com/10.1007/s10787-024-01597-7, https://c19p.org/uz

3. Gao et al., The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study

76 patient vitamin C late treatment study: 86% lower mortality (p=0.04).
Retrospective 76 COVID-19 patients, 46 treated with intravenous high-dose vitamin C, showing lower mortality and improved oxygen requirements with treatment. Dosage was 6g intravenous infusion per 12hr on the first day, and 6g once for the following 4 days.
Feb 2021, Aging, https://www.aging-us.com/article/202557/text, https://c19p.org/gao3

4. Kumari et al., The Role of Vitamin C as Adjuvant Therapy in COVID-19

150 patient vitamin C late treatment RCT: 36% lower mortality (p=0.45), 20% lower ventilation (p=0.67), 26% faster recovery (p=0.0001), and 24% shorter hospitalization (p=0.0001).
RCT 150 hospitalized patients in Pakistan showing 26% faster recovery, p < 0.0001. 36% lower mortality, not statistically significant due to the small number of events. Dosage was 50 mg/kg/day of intravenous vitamin C.
Nov 2020, Cureus, https://www.cureus.com/articles/45284-the-role-of-vitamin-c-as-adjuvant-therapy-in-covid-19, https://c19p.org/kumari

5. Seely et al., Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial

90 patient vitamin C late treatment RCT: 14% improved recovery (p=0.41).
Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..
Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seely

6. Yang et al., Traditional Chinese medicine together with high-dose vitamin C improves the therapeutic effect of western medicine against COVID-19

20 patient vitamin C late treatment RCT: 33% faster recovery (p<0.0001) and 36% faster viral clearance (p<0.0001).
Prospective study of 60 patients in China with three arms: SOC, SOC+TCM, and SOC+TCM+high dose vitamin C, showing successively faster recovery with the addition of TCM and the addition of high dose vitamin C. TCM included inhaled vitamin C 10g, 3-7 times per day. IV vitamin C 10g/60kg twice a day, and oral vitamin C 3g three times a day. Group C vs. group A includes combined treatment with TCM, while group C vs. group B both include vitamin C (high vs. low dose).
Jan 2022, American J. Translational Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8829592/, https://c19p.org/yang2

7. Madamombe et al., Factors associated with COVID-19 fatality among patients admitted in Mashonaland West Province, Zimbabwe 2020-2022: a secondary data analysis

672 patient vitamin C early treatment study: 53% lower mortality (p=0.0004).
Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with vitamin C treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombe

8. Sharif et al., Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study

vitamin C prophylaxis study: 46% lower severe cases (p=0.001).
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifc

9. Coppock et al., Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial

66 patient vitamin C late treatment RCT: 50% greater improvement (p=0.16) and 22% higher hospital discharge (p=0.07).
RCT with 66 very late stage (8 days from symptom onset) hospitalized patients, 44 treated with vitamin C and 22 control patients, showing no significant differences with treatment.
Mar 2022, Life, https://www.mdpi.com/2075-1729/12/3/453, https://c19p.org/coppock

10. Hess et al., High-dose intravenous vitamin C decreases rates of mechanical ventilation and cardiac arrest in severe COVID-19

100 patient vitamin C late treatment study: 20% lower mortality (p=0.54), 40% lower ventilation (p=0.05), and 27% lower ICU admission (p=0.11).
Retrospective 100 severe condition hospitalized patients in the USA, 25 treated with high dose IV vitamin C, showing lower mechanical ventilation and cardiac arrest, and increased length of survival with treatment. 3g IV vitamin C every 6h for 7 days.
Mar 2022, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-022-02954-6/fulltext.html, https://c19p.org/hess

11. Guan et al., High-dose Vitamin C Intake and COVID-19 Related Symptoms During the SARS-CoV-2 Pandemic

2,621 patient vitamin C prophylaxis study: 31% fewer symptomatic cases (p=0.007).
Retrospective 2,746 individuals in China showing significantly lower incidence of COVID-19 symptoms and fever with higher vitamin C intake, with a dose response relationship.
May 2024, The American J. the Medical Sciences, https://www.sciencedirect.com/science/article/pii/S0002962924012229, https://c19p.org/guan2

12. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments

15,968 patient vitamin C prophylaxis study: 28% lower mortality (p=0.002).
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3c

13. Tehrani et al., An investigation into the Effects of Intravenous Vitamin C on Pulmonary CT Findings and Clinical Outcomes of Patients with COVID 19 Pneumonia A Randomized Clinical Trial

44 patient vitamin C late treatment RCT: 87% lower mortality (p=0.13) and 18% shorter hospitalization (p=0.23).
RCT 54 late stage patients, 18 treated with IV vitamin C (2g every 6h for 5 days), showing significant relative improvements in oxygen saturation and respiratory rate.
Nov 2021, Urology J., https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/6863, https://c19p.org/tehrani3

14. Aldwihi et al., Patients’ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia

738 patient vitamin C prophylaxis study: 36% lower hospitalization (p=0.006).
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihic

15. Hamidi-Alamdari et al., Methylene blue for treatment of hospitalized COVID-19 patients: a randomized, controlled, open-label clinical trial, phase 2

80 patient vitamin C late treatment RCT: 44% lower mortality (p=0.38) and 38% shorter hospitalization (p=0.004).
RCT 80 hospitalized patients with severe COVID-19, 40 treated with methylene blue + vitamin C + N-acetylcysteine, showing lower mortality, shorter hospitalization, and significantly improved SpO2 and respiratory distress with treatment.
Mar 2021, Clinical and Translational Investigation, https://www.clinicalandtranslationalinvestigation.com/frame_esp.php?id=375, https://c19p.org/hamidialamdari

16. Asoudeh et al., The association between dietary intakes of zinc, vitamin C and COVID-19 severity and related symptoms: A cross-sectional study

250 patient vitamin C prophylaxis study: 69% lower severe cases (p=0.003).
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher vitamin C intake.
Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudeh

17. Tu et al., Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study

180 patient vitamin C late treatment study: 83% lower mortality (p<0.0001).
Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing lower mortality with vitamin C treatment in unadjusted results.
Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tuc

18. Zhao et al., High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study

110 patient vitamin C early treatment PSM study: 72% lower progression (p=0.03) and 8% slower viral clearance (p=0.79).
PSM retrospective 110 patients, 55 treated with high-dose IV vitamin C, showing lower progression to severe disease with treatment. Patients in each group were in different time periods, time based confounding is likely due to SOC improving over time. ChiCTR2000033050.
Apr 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.638556/full, https://c19p.org/zhao4

19. Kumar et al., Efficacy of intravenous vitamin C in management of moderate and severe COVID-19: A double blind randomized placebo controlled trial

60 patient vitamin C ICU RCT: 23% lower mortality (p=0.6) and 21% lower ventilation (p=0.6).
RCT 60 ICU patients in India, showing no significant difference in outcomes with vitamin C. Mortality was lower in the vitamin C arm despite having more severe cases at baseline (87% vs. 67%). 1 gram intravenous vitamin C 8 hourly for four days.
Aug 2022, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_2437_21, https://c19p.org/kumar5

20. Tan et al., Efficacy of diammonium glycyrrhizinate combined with vitamin C for treating hospitalized COVID-19 patients: a retrospective, observational study

161 patient vitamin C late treatment study: 25% lower combined mortality/intubation (p=0.74) and 73% lower progression (p=0.002).
PSM retrospective 207 hospitalized patients in China, 46 treated with diammonium glycyrrhizinate and vitamin C, showing lower risk of ARDS with treatment.
Jul 2021, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcab184/6329274, https://c19p.org/tan3

21. Bejan et al., DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

9,748 patient vitamin C prophylaxis study: 34% lower mortality (p=0.33), 25% lower ventilation (p=0.47), 15% lower ICU admission (p=0.65), and no change in hospitalization (p=1).
Retrospective 9,748 COVID-19 patients in the USA showing lower risk of mortality, ventilation, and ICU admission with vitamin C prophylaxis, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanc

22. Rahman et al., Clinical & Demographical Status of Hospitalized and Non-Hospitalized Covid-19 Cases: A Multicenter Hospital Based Study in Bangladesh

600 patient vitamin C early treatment study: 40% lower hospitalization (p=0.0001).
Retrospective 416 non-hospitalized and 184 hospitalized COVID-19 patients in Bangladesh, showing higher acetaminophen and lower vitamin C usage for hospitalized patients. Confounding may be significant and baseline details per treatment group are not provided, however fever and symptomatic patients were more common in the non-hospitalized group. Note there is an alignment mismatch in Table 1.
Nov 2023, Molecular Mechanism Research, https://ojs.as-pub.com/index.php/MMR/article/view/133, https://c19p.org/rahman5

23. Adhikari et al., Intravenous Vitamin C for Patients Hospitalized With COVID-19 Two Harmonized Randomized Clinical Trials

1,560 patient vitamin C late treatment RCT: 28% lower mortality (p=0.19) and 35% higher ventilation (p=0.04).
Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C. Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here [Adhikari, Adhikari]. eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival): LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical). REMAP-CAP shows 12% and 7% probability of superiority of vitamin C. Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more..
Oct 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2811212, https://c19p.org/adhikari2b

24. Doocy et al., Clinical progression and outcomes of patients hospitalized with COVID-19 in humanitarian settings: A prospective cohort study in South Sudan and Eastern Democratic Republic of the Congo

144 patient vitamin C late treatment study: 63% lower mortality (p=0.22).
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with vitamin C treatment.
Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocy

25. Simsek et al., Effects of high dose vitamin C administration in Covid-19 patients

139 patient vitamin C late treatment study: 44% lower mortality (p=0.19) and 10% lower ICU admission (p=0.66).
Retrospective 139 hospitalized patients in Turkey, 58 treated with high dose vitamin C, showing improved kidney functioning with treatment. Mortality was lower with treatment, but not reaching statistical significance with the small sample size.
Sep 2021, Annals of Medical Research, https://www.annalsmedres.org/index.php/aomr/article/view/3910, https://c19p.org/simsekc

26. Zhang et al., Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients (preprint 8/10/2020)

56 patient vitamin C ICU RCT: 50% lower mortality (p=0.2).
Small RCT for high dose vitamin C for ICU patients showing reduced (but not statistically significant) mortality. Dosage was 12g of vitamin C/50ml every 12 hours for 7 days at a rate of 12ml/hour.
Aug 2020, Annals of Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00792-3, https://c19p.org/zhang

27. Rana et al., Effects of mega dose vitamin C in critically ill COVID-19 patients: a randomized control trial

278 patient vitamin C ICU RCT: 55% lower mortality (p=0.2), 44% lower ventilation (p=0.41), and 37% shorter hospitalization (p=0.91).
RCT 278 COVID-19 ICU patients in Pakistan, showing lower mortality and ventilation, and shorter length of stay with high dose vitamin C treatment, without statistical significance. 30 grams IV vitamin C for four days.
Jun 2023, Biological and Clinical Sciences Research J., http://bcsrj.com/ojs/index.php/bcsrj/article/view/343, https://c19p.org/rana2

28. Hakamifard et al., The effect of vitamin E and vitamin C in patients with COVID-19 pneumonia; a randomized controlled clinical trial

72 patient vitamin C late treatment RCT: 46% lower ICU admission (p=0.46) and 1% shorter hospitalization (p=0.82).
RCT with 38 patients treated with vitamin C and vitamin E, and 34 control patients, showing lower ICU admission with treatment, but not statistically significant.
Apr 2021, Immunopathologia Persa, https://immunopathol.com/Article/ipp-22230, https://c19p.org/hakamifard

29. Kyagambiddwa et al., Thirty-Day Outcomes of Young and Middle-Aged Adults Admitted with Severe COVID-19 in Uganda: A Retrospective Cohort Study

246 patient vitamin C late treatment study: 50% lower mortality (p=0.06).
Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with vitamin C treatment, without statistical significance (p = 0.06).
May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwa

30. Guldemir et al., Clinical characteristics of bus drivers and field officers infected with COVID-19: A cross-sectional study from Istanbul

477 patient vitamin C prophylaxis study: 31% lower hospitalization (p=0.05).
Retrospective 477 COVID+ public transportation workers in Turkey, showing lower risk of hospitalization with vitamin C use in unadjusted results.
Nov 2022, Work, https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-220292, https://c19p.org/guldemir

31. Izzo et al., Combining L-Arginine with Vitamin C Improves Long-COVID Symptoms: The Nationwide Multicenter LINCOLN Study

1,390 patient vitamin C long COVID study: 41% improved recovery (p<0.0001).
Long COVID trial comparing L-arginine + vitamin C with multivitamin treatment (vitamin B1, B2, B6, B12, nicotinamide, folic acid, pantothenic acid), showing significant improvement in symptoms with L-arginine + vitamin C treatment.
Jul 2022, Pharmacological Research, https://www.sciencedirect.com/science/article/pii/S104366182200305X, https://c19p.org/izzo

32. Krishnan et al., Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia

152 patient vitamin C late treatment study: 31% lower mortality (p=0.04).
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanc

33. Labbani-Motlagh et al., High-dose intravenous Vitamin C in early stages of severe acute respiratory syndrome coronavirus 2 infection: A double-blind, randomized, controlled clinical trial

74 patient vitamin C late treatment RCT: 33% lower mortality (p=0.74), 13% longer hospitalization (p=0.49), and 16% lower progression (p=0.12).
RCT 74 patients in Iran, showing no significant differences in outcomes with high dose vitamin C treatment. Tables 1b and 2a show conflicting baseline SOFA scores. The percentages of patients receiving antiviral treatments and corticosteroids are switched between the text and Table 1b. Authors indicate ICU admission was an outcome, but the result is not provided. AKI was lower with treatment, though not reaching statistical significance.
Dec 2022, J. Research in Pharmacy Practice, http://www.jrpp.net/text.asp?2022/11/2/64/363550, https://c19p.org/labbanimotlagh

34. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization

2,148 patient vitamin C prophylaxis study: 25% lower hospitalization (p=0.08) and 17% lower severe cases (p=0.18).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin C prophylaxis, without statistical significance.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerc

35. Majidi et al., The Effect of Vitamin C on Pathological Parameters and Survival Duration of Critically Ill Coronavirus Disease 2019 Patients: A Randomized Clinical Trial

100 patient vitamin C ICU RCT: 14% lower mortality (p=0.03).
RCT 100 ICU patients in Iran, 31 treated with vitamin C, showing lower mortality with treatment.
Dec 2021, Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2021.717816/full, https://c19p.org/majidi

36. Corrao et al., Safety of High-Dose Vitamin C in Non-Intensive Care Hospitalized Patients with COVID-19: An Open-Label Clinical Study

146 patient vitamin C late treatment study: 39% lower mortality (p=0.37), 19% lower combined mortality/ICU admission (p=0.24), 102% higher ICU admission (p=0.51), and 25% shorter hospitalization (p=0.16).
Prospective study of 146 hospitalized COVID-19 patients showing shorter hospitalization with high-dose intravenous vitamin C. 104 patients received 10g of vitamin C intravenously daily for 3 days and 42 patients received only standard care. Mortality was lower with treatment (8.7% vs 14.3%) without statistical significance. Treatment was associated with significantly shorter hospitalization in multivariable analysis (−4.95, p=0.041). No adverse events were reported in the vitamin C group.
Jul 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/13/3987, https://c19p.org/corrao

37. Usanma Koban et al., The factors affecting the prolonged PCR positivity in COVID-19 patients

126 patient vitamin C early treatment study: 33% improved viral clearance (p=0.73).
Retrospective 126 patients in Turkey, showing no significant difference in PCR+ at day 14 with vitamin C treatment.
Jun 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7706&category_id=179&option=com_virtuemart, https://c19p.org/usanmakobanc

38. Patel et al., The significance of oral ascorbic acid in patients with COVID-19

176 patient vitamin C late treatment study: 29% lower mortality (p=0.18).
Retrospective 176 hospitalized patients, 96 treated with oral vitamin C (from 500mg to 1500mg daily), showing lower mortality with treatment.
Sep 2020, Chest Infections, https://journal.chestnet.org/article/S0012-3692(20)32508-3/fulltext, https://c19p.org/patel

39. Coskun et al., The Effect of High-dose Vitamin C Treatment for Acute Respiratory Failure due to Coronavirus Disease Pneumonia on Mortality and Length of Intensive Care Stay: A Retrospective Cohort Study

78 patient vitamin C ICU study: 25% lower mortality (p=0.26), 2% lower ventilation (p=1), no change in ICU admission, and 28% improved recovery (p=0.005).
Retrospective 78 ICU patients in Turkey, showing lower mortality with high-dose vitamin C treatment, without statistical significance. The SOFA score was significantly better with treatment at day 4. Authors incorrectly state that "HDVC treatment did not reduce the short-term mortality...". Mortality was lower with treatment, although not statistically significant given the sample size. 6g of vitamin C daily in 4 equal doses every 6h, for a total of 96h.
Mar 2023, SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital, https://sislietfaltip.org/jvi.aspx?un=SETB-66742&volume=, https://c19p.org/coskun

40. Fogleman et al., A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

66 patient vitamin C late treatment RCT: 4% improved recovery (p=0.83).
Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).
Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/foglemanc

41. Akbar et al., The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank

10,000 patient vitamin C prophylaxis study: 14% fewer cases (p=0.29).
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with vitamin C supplementation, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2c

42. Gavrielatou et al., Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis

113 patient vitamin C ICU study: 58% lower mortality (p=0.11).
Retrospective 113 consecutive mechanically ventilated COVID+ ICU patients in Greece, 10 receiving high dose IV vitamin C, showing lower mortality with treatment, without statistical significance (p=0.11). The associated meta analysis includes only 11 studies, while there are currently studies, with mortality results. Authors only include critical patients, however not all studies with critical patients are included, for example [Hamidi-Alamdari, Majidi, Yüksel, Özgünay]. The meta analysis also uses unadjusted results, while PSM, Cox proportional hazards, or KM results are reported by [Al Sulaiman, Gao, Zhang, Zheng]. For [Zhang] authors use 28 day mortality, while the study reports longer term in-hospital mortality.
Feb 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.814587/full, https://c19p.org/gavrielatou

43. Jang et al., Clinical course of COVID-19 patients treated with ECMO: A multicenter study in Daegu, South Korea

19 patient vitamin C late treatment study: 51% improved recovery (p=0.15).
Retrospective 19 COVID-19 ECMO patients in South Korea, showing a higher rate of weaning from ECMO with vitamin C treatment, without statistical significance. Authors perform multivariate analysis but do not provide full results, only reporting p > 0.05.
Dec 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S0147956320304027, https://c19p.org/jang2

44. Behera et al., Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study

215 patient vitamin C prophylaxis study: 18% fewer cases (p=0.58).
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/beherac

45. Vaisi et al., The association between nutrients and occurrence of COVID-19 outcomes in the population of Western Iran: A cohort study

3,955 patient vitamin C prophylaxis study: 38% lower hospitalization (p=0.17) and 10% fewer symptomatic cases (p=0.71).
Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.
May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisic

46. Yüksel et al., Effects of high dose vitamin c on patient outcomes in ARDS patients admitted to intensive care with COVID-19; multi-center retrospective study

86 patient vitamin C ICU PSM study: 19% lower mortality (p=0.04).
PSM retrospective 86 ICU patients on mechanical ventilation in Turkey, showing lower mortality with high dose vitamin C treatment (≥200mg/kg for 4 days).
Sep 2020, Intensive Care Medicine Experimental, 9:S1, 001458, https://icm-experimental.springeropen.com/track/pdf/10.1186/s40635-021-00413-8.pdf, https://c19p.org/yuksel

47. Darban et al., Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial

20 patient vitamin C ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.
Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanc

48. Al Sulaiman et al., Ascorbic Acid as an Adjunctive Therapy in Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study

284 patient vitamin C late treatment PSM study: 15% lower mortality (p=0.27).
Retrospective 158 critically ill patients receiving vitamin C and propensity matched controls, showing mortality OR 0.77 [0.48-1.23], and statistically significantly lower thrombosis, OR 0.42 [0.18-0.94]. 1000mg of vitamin C was given daily.
Apr 2021, Research Square, https://www.researchsquare.com/article/rs-354711/v1, https://c19p.org/alsulaiman2

49. Vishnuram et al., Role of high dose oral liposomal vitamin C in reducing mortality in patients with COVID-19

8,875 patient vitamin C late treatment study: 54% lower mortality (p=0.03).
Retrospective 8,634 hospitalized patients in India, showing lower mortality with high-dose vitamin C in unadjusted results. No group details are provided, the text and table appear to show different results, and some numbers do not match.
Jun 2021, Indian J. Basic and Applied Medical Research, https://www.ijbamr.com/assets/images/issues/pdf/FuXsaN_e2u6D7_ZY1348_LzacYt_766641.pdf, https://c19p.org/vishnuram

50. Suna et al., Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia

323 patient vitamin C late treatment study: 21% lower mortality (p=0.52) and 2% higher ICU admission (p=1).
Retrospective 323 hospitalized patients, 153 treated with vitamin C, showing no significant differences. Patients in each group were in different time periods, with the vitamin C group first. Time based confounding is possible due to improvements in SOC.
May 2021, Med. Clin., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112281/, https://c19p.org/suna

51. Louca et al., Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app

372,720 patient vitamin C prophylaxis study: no change in cases (p=1).
Survey analysis of dietary supplements showing no significant difference in PCR+ cases with vitamin C usage in the UK, however significant reductions were found in the US and Sweden. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucac

52. Fowler et al., SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)

47 patient vitamin C ICU RCT: 19% lower mortality (p=0.75) and 2% worse results (p=0.28).
RCT 47 ICU patients showing no significant differences with vitamin C treatment.
Apr 2024, NCT04344184, https://clinicaltrials.gov/study/NCT04344184, https://c19p.org/fowler

53. Pourhoseingholi et al., Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study

2,468 patient vitamin C late treatment study: 13% lower mortality (p=0.38).
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with vitamin C treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholi

54. Shehab et al., Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection

253 patient vitamin C prophylaxis study: 4% lower severe cases (p=1).
Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with vitamin C prophylaxis in unadjusted analysis. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabc

55. Abdulateef et al., COVID-19 severity in relation to sociodemographics and vitamin D use

427 patient vitamin C prophylaxis study: 19% lower hospitalization (p=0.69).
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefc

56. Salehi et al., Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center study

125 patient vitamin C ICU study: 10% lower mortality (p=0.56).
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with vitamin C treatment in unadjusted results.
Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehic

57. Zangeneh et al., Survival analysis based on body mass index in patients with COVID-19 admitted to the intensive care unit of Amir Al-Momenin Hospital in Arak – 2021

vitamin C ICU study: 4% lower mortality (p=0.86).
Retrospective 193 ICU patients in Iran, showing no significant difference with vitamin C treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangenehc

58. Özgünay et al., The use of vitamin C in the intensive care unit during the COVID-19 pandemic

160 patient vitamin C ICU study: 9% lower mortality (p=0.69) and 1% higher ventilation (p=1).
Retrospective 160 ICU patients, 32 with raised neutrophil/lymphocyte ratio treated with vitamin C, showing no significant differences.
Jul 2021, The European Research J., https://dergipark.org.tr/en/download/article-file/1774154, https://c19p.org/ozgunay

59. Mousaviasl et al., The Effect of a Low Dose of Vitamin C in Patients With COVID-19: A Double-Blind Randomized Controlled Trial

401 patient vitamin C late treatment RCT: 20% lower mortality (p=0.64), 200% higher ventilation (p=1), and 33% higher ICU admission (p=0.79).
RCT 401 hospitalized COVID-19 patients showing no significant differences with low-dose oral vitamin C (1000mg daily for 5 days).
Jul 2023, Disease and Diagnosis, https://ddj.hums.ac.ir/Article/ddj-500, https://c19p.org/mousaviasl

60. Mohseni et al., Do body mass index (BMI) and history of nutritional supplementation play a role in the severity of COVID-19? A retrospective study

603 patient vitamin C prophylaxis study: 44% more cases (p=0.002).
Retrospective 603 patients in Iran, 34 taking vitamin C supplements, showing increased risk of COVID-19 cases in unadjusted results. IR.SHOUSHTAR.REC.1399.015.
Aug 2021, Nutrition & Food Science, https://www.emerald.com/insight/content/doi/10.1108/NFS-11-2020-0421/full/html, https://c19p.org/mohsenic

61. JamaliMoghadamSiahkali et al., Safety and Effectiveness of High-Dose Vitamin C in Patients with COVID-19; A Randomized Controlled open-label Clinical Trial

60 patient vitamin C late treatment RCT: 25% higher ventilation (p=1) and 31% longer hospitalization (p=0.03).
Small late stage RCT for the addition of vitamin C to HCQ and lopinavir/ritonavir, with 30 treatment and 30 control patients, finding a significant reduction in temperature and a significant improvement in oxygenation after 3 days in the vitamin C group. However, hospitalization time was longer and there was no significant difference in mortality.
Jan 2021, Research Square, https://www.researchsquare.com/article/rs-139942/v1, https://c19p.org/jamalimoghadamsiahkali

62. Özgülteki̇n et al., The effect of high-dose vitamin C on renal functions in COVID–19 patients

43 patient vitamin C ICU study: 5% higher mortality (p=1).
Retrospective 43 ICU patients in Turkey, 21 treated with vitamin C, showing no significant difference in mortality and increased renal failure. Treatment included stage 1 AKI patients. Vitamin C 45-50 g/day for 5 days.
Sep 2022, Kastamonu Medical J., https://www.kastamonumedicaljournal.com/index.php/kmj/article/view/59, https://c19p.org/ozgultekin

63. Li et al., Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection

32 patient vitamin C ICU PSM study: 11% higher mortality (p=1).
PSM retrospective 8 ICU patients treated with vitamin C and 24 matched controls, showing no significant difference. Authors note that "it is possible for the delayed timing of IV vitamin C to have blunted the beneficial effects as these patients may have already progressed to the late fibroproliferative phase or ARDS". IV vitamin C 1.5 grams every 6 hours.
Jun 2021, J. Pharmacy Practice, https://journals.sagepub.com/doi/10.1177/08971900211015052, https://c19p.org/li7

64. Elhadi et al., Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study

465 patient vitamin C ICU study: 12% higher mortality (p=0.15).
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadic

65. Gadhiya et al., Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state

281 patient vitamin C late treatment study: 1% higher mortality (p=0.99).
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyac

66. Mulhem et al., 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study

3,219 patient vitamin C late treatment study: 32% higher mortality (p=0.01).
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhemc

67. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)

15,227 patient vitamin C prophylaxis study: 3% more cases (p=0.86).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtc

68. Zheng et al., No significant benefit of moderate-dose vitamin C on severe COVID-19 cases

397 patient vitamin C late treatment PSM study: 157% higher mortality (p=0.33) and 35% worse improvement (p=0.17).
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.
Sep 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0361/html, https://c19p.org/zheng

69. Baguma et al., Characteristics of the COVID-19 patients treated at Gulu Regional Referral Hospital, Northern Uganda: A cross-sectional study

481 patient vitamin C late treatment study: 48% higher mortality (p=0.54).
Retrospective COVID+ hospitalized patients in Uganda, 385 patients receiving vitamin C treatment, showing higher mortality with treatment, without statistical significance.
Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/bagumac

70. Mahto et al., Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India

689 patient vitamin C prophylaxis study: 26% higher IgG positivity (p=0.49).
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with vitamin C prophylaxis.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoc

71. Su et al., Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China

vitamin C early treatment study: 135% higher progression (p=0.18) and 34% slower improvement (p=0.04).
Retrospective 616 patients in China showing increased risk of disease progression with vitamin C treatment.
Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/suc

72. Thomas et al., Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial

98 patient vitamin C early treatment RCT: 18% faster recovery (p=0.15).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. A secondary analysis concludes that vitamin C increases recovery rate by 71% (p = 0.036) [pubpeer.com]. See also [patrickholford.com].
Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomasc

73. Adhikari et al., Intravenous Vitamin C for Patients Hospitalized With COVID-19 Two Harmonized Randomized Clinical Trials

2,206 patient vitamin C late treatment RCT: 19% higher mortality (p=0.08) and 35% higher ventilation (p=0.04).
Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C. Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here [Adhikari, Adhikari]. eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival): LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical). REMAP-CAP shows 12% and 7% probability of superiority of vitamin C. Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more..
Oct 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2811212, https://c19p.org/adhikari2

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