Abstract
The impact of zinc (Zn) sufficiency/supplementation on COVID-19-associated mortality and incidence (SARS-CoV-2 infections) remains unknown. During an infection, the levels of free Zn are reduced as part of “nutritional immunity” to limit the growth and replication of pathogen and the ensuing inflammatory damage. Considering its key role in immune competency and frequently recorded deficiency in large sections of different populations, Zn has been prescribed for both prophylactic and therapeutic purposes in COVID-19 without any corroborating evidence for its protective role. Multiple trials are underway evaluating the effect of Zn supplementation on COVID-19 outcome in patients getting standard of care treatment. However, the trial designs presumably lack the power to identify negative effects of Zn supplementation, especially in the vulnerable groups of elderly and patients with comorbidities (contributing 9 out of 10 deaths; up to >8,000-fold higher mortality). In this study, we have analyzed COVID-19 mortality and incidence (case) data from 23 socially similar European populations with comparable confounders (population: 522.47 million; experiencing up to >150-fold difference in death rates) and at the matching stage of the pandemic (March 12 to June 26, 2020; first wave of COVID-19 incidence and mortality). Our results suggest a positive correlation between populations’ Zn-sufficiency status and COVID-19 mortality [r (23): 0.7893–0.6849, p-value < 0.0003] as well as incidence [r (23):0.8084–0.5658; p-value < 0.005]. The observed association is contrary to what would be expected if Zn sufficiency was protective in COVID-19. Thus, controlled trials or retrospective analyses of the adverse event patients’ data should be undertaken to correctly guide the practice of Zn supplementation in COVID-19.
Highlights
Zinc (Zn) is a redox-neutral key micronutrient that plays an important role in immune competence and wellbeing [1,2,3]
As the wave of SARS-CoV-2 infections spread to other parts of the world by August 26, 2020, the relative contribution of the selected countries changed to 8.85% of cases and 21.78% of total global COVID-19 deaths
The observations made are briefly summarized below: 1. Globally COVID-19 mortality rates positively correlate with zinc sufficiency levels: Zn sufficiency/deficiency levels vary across the globe (Supplementary Figure 1)
Summary
Zinc (Zn) is a redox-neutral key micronutrient that plays an important role in immune competence and wellbeing [1,2,3]. The explicit and implicit general recommendations for immune augmentation of the supposed “Zn-deficient” population components and COVID-19 patients by healthy diet or Zn supplementation are in place. A surge in the number of articles advocating a role of Zn supplementation in COVID-19 treatment/management has been observed. Speculative benefit from Zn supplementation in COVID-19 has fueled its widespread prescription and over-the-counter purchases. This practice has gained momentum due to incorrect interpretation and implementation of CDC’s guidelines, inability to accurately assay Zn deficiency, and mild to no side effects of Zn overdose in healthy individuals. The clinical evidence supporting any beneficial effect of Zn supplementation or the ecological association studies supporting the potential positive impact of Zn sufficiency of the population/individuals on COVID-19 disease is nonexistent. Its deficiency in populations is widely associated with vulnerability to infectious diseases, chronic immune system disorders, and other medical conditions [3,4,5, 7, 14, 15]
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