The relationship between zinc use and COVID-19 clinical outcomes

Background: Zinc is an essential trace element that plays an important role in the immune system and protein synthesis. It has been shown to help fight viral infections, and a beneficial use for SARS-CoV-2 treatment has been postulated in multiple papers.[i][ii][iii]Previous work has also shown correlations between zinc deficiency and poor outcomes in COVID-19 patients.[iv] Little is known, however, about the use of zinc supplementation and its potential benefits in COVID-19 positive individuals. We sought to determine the association between the use of zinc and clinical outcomes in patients with COVID-19.

Hypothesis: Zinc administration within 1 week prior to, or 48 hours after, hospital admission will result in lower 28-day mortality, ARDS, ICU admission, and need for mechanical ventilation.

Methods:COVID-19 patient data between March 2020 and April 2021 was abstracted from the multicenter collaborative CRUSH COVID registry. Zinc use was defined as at least one dose one week prior to hospital admission or within 48 hours of admission. A multivariate regression analysis was used controlling for the following confounders: month of admission, gender, ethnicity, qSOFA at hospital admission, hydroxychloroquine, azithromycin, tocilizumab, remdesivir, and dexamethasone.

Results: Out of 1781 COVID-19 positive subjects, 794 (44.6%) were administered zinc one week prior to, or within 48 hours of, hospital admission while 987 (55.4%) did not receive zinc. Among patients that received zinc, the odds to meet the primary outcome of 28-day mortality was 0.654 (CI 95%, 0.456—0.938, P = .021) compared to the non-zinc group with OR = .021 (95% CI, 1.07—2.19, P = .021). Odds of mechanical ventilation, ICU admission, or progression to ARDS in the zinc group were individually 3.06 (95% CI, 2.23—4.18, P < .001), 3.17 (95% CI, 2.37—4.24, P < .001), and 6.01 (95% CI, 3.91—9.23).

Conclusions: Zinc use was associated with increased need for ICU admission, mechanical ventilation, and progression to ARDS. Curiously, the risk of mortality was reduced by nearly 40%. These pathophysiologically contradictory results may be a depiction of several unaccounted-for confounders including the balance of patients associated between different hospital systems. Further directions of this study include narrowing down the patient population to subjects from one hospital system. We plan to further analyze these data while accounting for critical confounders to obtain a more accurate description of the potential benefits of zinc for the treatment of COVID-19.

[i] Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The Role of Zinc in Antiviral Immunity. Adv Nutr. 2019;10(4):696-710. doi:10.1093/advances/nmz013

[ii] Wessels I, Rolles B, Rink L. The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis. Front Immunol. 2020;11:1712. Published 2020 Jul 10. doi:10.3389/fimmu.2020.01712

[iii] Kumar A, Kubota Y, Chernov M, Kasuya H. Potential role of zinc supplementation in prophylaxis and treatment of COVID-19. Med Hypotheses. 2020;144:109848. doi:10.1016/j.mehy.2020.109848

[iv]Jothimani D, Kailasam E, Danielraj S, et al. COVID-19: Poor outcomes in patients with zinc deficiency. Int J Infect Dis. 2020;100:343-349