A pilot double‐blind safety and feasibility randomized controlled trial of high‐dose intravenous zinc in hospitalized COVID‐19 patients

Abstract

Zinc inhibits replication of the SARS-CoV virus. We aimed to evaluate the safety, feasibility, and biological effect of administering high-dose intravenous zinc (HDIVZn) to patients with COVID-19. We performed a Phase IIa doubleblind, randomized controlled trial to compare HDIVZn to placebo in hospitalized patients with COVID-19. We administered trial treatment per day for a maximum of 7 days until either death or hospital discharge. We measured zinc concentration at baseline and during treatment and observed patients for any significant side effects. For eligible patients, we randomized and administered treatment to 33 adult participants to either HDIVZn (n = 15) or placebo (n = 18).We observed no serious adverse events throughout the study for a total of 94 HDIVZn administrations. However, three participants in the HDIVZn group reported infusion site irritation. Mean serum zinc on Day 1 in the placebo, and the HDIVZn group was 6.9 ± 1.1 and 7.7 ± 1.6 µmol/l, respectively, consistent with zinc deficiency. HDIVZn, but not placebo, increased serum zinc levels above the deficiency cutoff of 10.7 µmol/l (p < .001) on Day 6. Our study did not reach its target enrollment because stringent public health measures markedly reduced patient hospitalizations. Hospitalized COVID-19 patients demonstrated zinc deficiency. This can be corrected with HDIVZn. Such treatment appears safe, feasible, and only associated with minimal peripheral infusion site irritation. This pilot study justifies further investigation of this treatment in COVID-19 patients.

Identification of potential pan-coronavirus therapies using a computational drug repurposing platform

“…Predicted drugs in Cluster 3 that are not used for cancer therapy and are not in clinical trials were then assessed for their association with viral replication through literature searches. We found literature documenting that Zinc deficiency has been confirmed in COVID-19 patients, and SARS-CoV-2 replication was reduced when zinc was administered [39] . Ademetionine has also been identified as a repurposing candidate in several studies [7] , [40] .…”

The Role of Complementary and Alternative Medicines in the Treatment and Management of COVID-19

“…Studies show that treatment with zinc as adjuvant therapy was appeared to be feasible and safe for the management of COVID-19. However, the infusion of zinc causes limited infusion site irritation on the periphery [87]. Zinc supplement was found to be efficiently clear the SARS-CoV-2 from the nasopharynx in a lesser time than other symptomatic therapy [88].…”

Nutritional risk of vitamin D, vitamin C, zinc, and selenium deficiency on risk and clinical outcomes of COVID-19: A narrative review

“…They observed that none of the interventions significantly decreased the duration of symptoms compared with standard care. In a pilot randomized controlled trial with hospitalized COVID-19 patients, Patel et al (2021) [132] detected low serum zinc levels in both experimental and placebo groups (6.9 ± 1.1 and 7.7 ± 1.6 mmol/L, respectively). They also observed that a high dose of venous zinc administration (0.24 mg/kg/day of elemental zinc for a maximum of 7 days) was safe and able to increase serum zinc levels above the zinc deficiency cutoff adopted (10.7 mmol/L).…”

“…According to our search, 3 randomized clinical trial studies aimed to investigate the effect of zinc supplementation in patients with COVID-19 [37,131,132]. Abd-Elsalam et al ( 2020) [131] aimed to evaluate the effect of combining chloroquine/hydroxychloroquine and zinc in the treatment of COVID-19 patients.…”