Nutritional Immunity, Zinc Sufficiency, and COVID-19 Mortality in Socially Similar European Populations
Samer Singh, Amita Diwaker, Brijesh P Singh, Rakesh K Singh
Frontiers in Immunology, doi:10.3389/fimmu.2021.699389
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, pvalue < 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.
ETHICS STATEMENT Ethical review and approval were not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
AUTHOR CONTRIBUTIONS SS conceived the idea, collected the data, and wrote the manuscript. AD, BPS and RKS provided the necessary inputs and helped in data analysis and writing. All authors contributed to the article and approved the submitted version.
SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2021.
699389/full#supplementary-material Supplementary Table 1 | COVID-19 incidences and mortality in socially similar European populations up to 26 August 2020.
Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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'abstract': '<jats:p>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 &gt;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 &gt;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 [<jats:italic>r</jats:italic> (23): 0.7893–0.6849, p-value &lt; '
'0.0003] as well as incidence [<jats:italic>r</jats:italic> (23):0.8084–0.5658; p-value '
'&lt; 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.</jats:p>',
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