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
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. NCT04342728 (history)
. A secondary analysis concludes that vitamin C increases recovery rate by 71% (p
= 0.036) [pubpeer.com]
. See also [patrickholford.com]
risk of death, 204.2% higher, RR 3.04, p = 0.49, treatment 1 of 48 (2.1%), control 0 of 50 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of hospitalization, 30.6% lower, RR 0.69, p = 1.00, treatment 2 of 48 (4.2%), control 3 of 50 (6.0%), NNT 55.
recovery time, 17.9% lower, relative time 0.82, p = 0.15, treatment mean 5.5 (±3.7) n=48, control mean 6.7 (±4.4) n=50, mean time to a 50% reduction in symptoms, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Thomas et al., 12 Feb 2021, Randomized Controlled Trial, USA, peer-reviewed, 11 authors, trial NCT04342728 (history)
Abstract: Original Investigation | Public Health
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
Suma Thomas, MD, MBA; Divyang Patel, MD, MS; Barbara Bittel, BSN, RN; Kathy Wolski, MPH; Qiuqing Wang, MS; Anirudh Kumar, MD, MS; Zachary J. Il’Giovine, MD;
Reena Mehra, MD, MS; Carla McWilliams, MD; Steve E. Nissen, MD; Milind Y. Desai, MD, MBA
IMPORTANCE There is limited evidence regarding early treatment of novel severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression.
OBJECTIVE To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity
or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2
Question Do high-dose zinc, high-dose
ascorbic acid, and/or a combination of
the 2 reduce the duration of symptoms
of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2)?
Findings In this randomized clinical trial
of 214 patients with confirmed SARS-
DESIGN, SETTING, AND PARTICIPANTS This multicenter, single health system randomized clinical
CoV-2 infection receiving outpatient
factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection
care, there was no significant difference
confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and
in the duration of symptoms among the
Florida. The trial was conducted from April 27, 2020, to October 14, 2020.
Meaning These findings suggest that
INTERVENTION Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc
gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care.
treatment with zinc, ascorbic acid, or
both does not affect SARS-CoV-2
OUTCOMES The primary end point was the number of days required to reach a 50% reduction in
symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point
scale for each symptom). Secondary end points included days required to reach a total symptom
severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed
medications, and adverse effects of the study supplements.
RESULTS A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132
(61.7%) women. The study was stopped for a low conditional power for benefit with no significant
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difference among the 4 groups for the primary end point. Patients who received usual care without
supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared
with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5
(3.4) days for the group receiving both (overall P = .45). There was no significant difference in
secondary outcomes among the treatment groups.
CONCLUSIONS AND RELEVANCE In this randomized clinical trial of ambulatory patients diagnosed
with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination
of the 2 supplements did not significantly decrease the duration of symptoms compared with
standard of care.
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