Zinc, Vitamin C Don’t Reduce Duration of COVID-19 Symptoms

Empty pharmacy shelves can give testament to which drugs were touted to reduce COVID-19 symptoms or even “cure” the infection. A new study of two products that have been among the most popular – ascorbic acid and zinc – found no evidence that either drug – or a combination – reduced the duration of symptoms of SARS-CoV-2 infection. Here are more details.

CLEVELAND – High-dose zinc and vitamin C have flown off drugstore shelves during the COVID-19 pandemic, despite little evidence of their effectiveness in reducing the duration of symptoms of severe acute respiratory syndrome coronavirus 2.

Now, a randomized clinical trial of 214 patients with confirmed SARS-CoV-2 infection receiving outpatient care demonstrates no benefit from the products, individually or in combination. An article in JAMA Network Open describes how no significant difference in the duration of symptoms among the four groups was identified.

Cleveland Clinic researchers from Ohio and Florida write that their findings suggest that treatment with zinc, ascorbic acid, or both does not affect SARS-CoV-2 symptoms.

“There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression,” the authors write, explaining why they sought 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 COVID-19.

Enrolled in the multicenter, single health system randomized clinical factorial open-label trial were 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay; most, 62% were women, and they had an average age of 45.2. Participants received outpatient care in sites in Ohio and Florida from April 27, 2020, to Oct. 14, 2020.

Researchers randomized patients 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.

Defined as 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; each symptom was rated on a 4-point scale. 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.

The authors advise that their study was halted for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. At that point, patients who received usual care without supplementation had 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). No significant difference in secondary outcomes among the treatment groups was determined.

Another recent study, published in JAMA Internal Medicine, used the IQVIA National Prescription Audit Weekly to determine with alleged COVID-19 treatments were the biggest sellers in U.S. pharmacies.

The study followed 17 potential COVID-19 treatments as listed by the National Institutes of Health's (NIH's) "COVID-19 Treatment Guidelines" and the American Society of Health-system Pharmacists' "Assessment of Evidence for COVID-19–related Treatments” from March 14, 2020, to Dec. 18, 2020.

National Centers for Disease Control and Prevention researchers tracked prescriptions being ordered at 50% or higher rates above pre-pandemic times. They found that ivermectin, chloroquine, zinc, and hydroxychloroquine had the highest percentage changes in dispensed prescriptions during a peak week at 583.4%, 494.4%, 403.3%, and 185.5%, respectively, with ivermectin peaking twice.

The longest time a prescription stayed at least 50% above its baseline was 32 weeks (zinc), followed by 30 (vitamin C), and 12 (ivermectin), the authors report.

The study points out that ivermectin had two dispensing peaks, despite never being recommended by the NIH. “Zinc also peaked twice during the weeks ending Apr 10 and Aug 7 before rising again through Dec 11 despite its lack of NIH endorsement,” they add.

Researchers note that another non-endorsed drug, dexamethasone, decreased in dispensing in mid-March before increasing to 25% above baseline at the end of July and then above 50% through mid-December. Hydroxychloroquine, chloroquine, and lopinavir-ritonavir's peaks during COVID-19 case increases in March and April 2020 did not recur, because studies showed the drugs' lack of efficacy, the researchers write.

"These trends in prescribing practices suggest that clinicians consider the most recent recommendations from the National Institutes of Health and the US Food and Drug Administration before prescribing unproven therapies for COVID-19 to outpatients outside of clinical trials,” the study concludes.

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