key: cord-0962537-sd4tr0wk
authors: Finzi, Eric; Harrington, Allan
title: Zinc treatment of outpatient COVID‐19: A retrospective review of 28 consecutive patients
date: 2021-01-27
journal: J Med Virol
DOI: 10.1002/jmv.26812
sha: c131ea1665d48e52f9ff0f3af011fa544c491df9
doc_id: 962537
cord_uid: sd4tr0wk

Previous research has shown that zinc can interfere with proteolytic processing of polyproteins in RNA viruses1 , and the RNA polymerase of SARS-CoV-12 . This article is protected by copyright. All rights reserved.

Previous research has shown that zinc can interfere with proteolytic processing of polyproteins in RNA viruses, 1 and the RNA polymerase of SARS-CoV-1. 2 Coronaviruses frequently cause the common cold.

A recent meta-analysis of seven randomized controlled trials showed that zinc lozenges shortened the mean duration of the common cold by 33% (95% confidence interval: 21%-45%). 3 Hospitalized COVID-19 patients taking supplemental zinc in addition to standard therapy were reported to have lower death rates, 4 and patients with lower zinc levels on admission had higher mortality. 5 We recently reported that four outpatient COVID-19 patients taking high dose oral zinc appear to recover shortly after initiation of zinc. 6 We retrospectively reviewed consecutive cases of laboratory confirmed COVID-19 (26 cases), or CDC case definition (two cases), who were started on zinc gluconate/citrate lozenges (23 mg of elemental zinc, 21 patients) or zinc acetate lozenges (15 mg of elemental zinc, seven patients), at a total dosage of 2-2.5 mg/kg/day.

Patients were instructed to place one lozenge on their tongue q2-4 h while awake, for a minimum of 10 days. Depending on weight, patients took between 6 and 12 lozenges daily. Written or verbal consent was obtained before treatment. The median number of days between symptom onset and initiation of zinc was 4 days, ranging from 1 to 21 days after onset of symptoms. The mean age was 40: 17 female, 11 male, 3 Hispanic, 3 Asian, 1 African-American, and 21 Caucasian. Patients were contacted daily for symptom evaluation, and for side effects. Cough, nausea/vomiting, diarrhea, sore throat, headache, muscle/body aches, fatigue and loss of smell/taste were also assessed. The clinical course of Case 18 is seen in Figure 1 . After 2 days of zinc symptoms began to improve. The mechanisms by which zinc may help COVID-19 patients are unknown, but include direct inhibition of viral replication, improvement of mucociliar clearance of SARS-Cov-2, reduction of secondary bacterial infection, improvement of lung and kidney tissue healing after ischemia, modulation of T and B lymphocytes, and restoration of interferon-alpha production. 8, 9 Zinc supplementation reduces the incidence of pneumonia, 10 and improves outcomes in diarrhea. 11 In addition, mild zinc deficiency is often present in those groups at highest risk from COVID-19; namely, the elderly, diabetic, obese, and hypertensive. 8 In mild cases of COVID-19 about 80% of patients begin improving after Day 10; 20% worsen the second week. Zinc treated patients began improvement after 1.6 days on average. Patients older than 40 began recovery slightly later than under 40; however, the clinical outcome at 7 days was the same, and this is not the typical COVID-19 course.

A recent report 12 by the CDC showed that among symptomatic adult COVID-19 outpatients, 35% were still symptomatic 2-3 weeks after testing positive. For those with SOB, one-third experienced these symptoms weeks later. By contrast, all nine of our patients who were SOB began improving after 2 days, and none were SOB after 7 days. Except for fatigue, all 28 patients were symptom free after 3 weeks.

This study has limitations intrinsic to any retrospective review:

absence of blinding and a control group. However, given the low toxicity and cost of oral zinc, it would seem prudent to begin testing of zinc in a controlled trial.

PDTC inhibits picornavirus polyprotein processing and RNA replication by transporting zinc ions into cells

+ ) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture

Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage

Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients Medrxiv

COVID-19: poor outcomes in patients with zinc deficiency

Treatment of SARS-CoV-2 with high dose oral zinc salts: a report on four patients

Zinc lozenges as cure for the common cold-a review and hypothesis

The potential impact of zinc supplementation on Covid-19 pathogenesis

Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress

Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial

Lower-dose zinc for childhood diarrhea-a randomized, multicenter trial

Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network-United States