There is limited evidence regarding early treatment of SARS-CoV-2 infection to mitigate symptom progression. The objective of this multicentre, single health system randomised clinical factorial open-label trial was to examine whether high-dose zinc and/or high-dose ascorbic acid reduced the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida were enrolled. The trial was conducted from April 27, 2020, to October 14, 2020. Patients were randomised 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. 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, hospitalisations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. A total of 214 patients were randomised, 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 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.
In this randomised clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the two supplements did not significantly decrease the duration of symptoms compared with standard of care.