Zinc Deficiency And sTNF-RII Are Associated With Worse COVID-19 Outcomes

Christian Mouchati; Jared C Durieux; Sokratis N Zisis; Heather Tribout; Sarah Scott; Beth Smith; Danielle Labbato; Grace A McComsey

doi:10.1016/j.tjnut.2023.11.026

Zinc Deficiency And sTNF-RII Are Associated With Worse COVID-19 Outcomes

J Nutr. 2023 Dec 2:S0022-3166(23)72747-8. doi: 10.1016/j.tjnut.2023.11.026. Online ahead of print.

Authors

Christian Mouchati¹, Jared C Durieux², Sokratis N Zisis¹, Heather Tribout², Sarah Scott², Beth Smith², Danielle Labbato², Grace A McComsey³

Affiliations

¹ School of Medicine, Case Western Reserve University, Cleveland, OH, United States.
² Center for Clinical Research, University Hospitals Cleveland Medical Center, Cleveland, OH, United States.
³ School of Medicine, Case Western Reserve University, Cleveland, OH, United States; Center for Clinical Research, University Hospitals Cleveland Medical Center, Cleveland, OH, United States. Electronic address: gam9@case.edu.

PMID: 38043624
DOI: 10.1016/j.tjnut.2023.11.026

Abstract

Background: Zinc (Zn) is known for its substantial involvement in the immune response as an antioxidant and anti-inflammatory agent. Zn plasma levels' clinical significance in coronavirus disease (COVID) diagnosis is not yet fully established.

Objective: We assessed the association between Zn deficiency, gut integrity, inflammation, and COVID-19 outcomes.

Methods: A prospective observational cohort in which plasma Zn, soluble tumor necrosis factor alpha receptor II (sTNF-RII) intestinal fatty-acid binding protein (IFABP; marker of intestinal integrity), and zonulin levels (intestinal permeability) were collected from participants during the acute phase of a confirmed COVID-19 diagnosis. Zn was modeled as continuous and binary, categorized as Zn deficiency (Zn < 75 μg/dL) and Zn sufficiency (Zn ≥ 75 μg/dL). COVID-19 outcomes were classified according to the World Health Organization clinical progression scale. We used cumulative probit regression to assess if suboptimal Zn levels, gut, and inflammatory markers increase the likelihood of worse COVID-19 outcomes.

Results: Zn deficiency was independently associated with 63% higher predicted odds of worse COVID outcomes. Increases in sTNF-RII {unadjusted odds ratio (uOR): 3.43 [95% confidence interval (CI): 2.02, 5.82]} and zonulin [uOR: 1.83 (95% CI: 1.21, 2.76)] levels were associated with greater odds of worse COVID outcomes. IFABP was not associated with worse COVID outcomes [uOR: 1.12 (95% CI: 0.82, 1.53)] or acute Zn deficiency [uOR: 1.35 (95% CI: 0.79, 2.35)]. The adjusted predicted odds of worse COVID outcomes are 3-fold higher (P = 0.04) for every one-unit decrease in Zn and is more than 2 times greater odds of COVID severity (P = 0.01) for every 1-unit increase in sTNF-RII.

Conclusion: Zn deficiency and inflammation were independently associated with greater odds of worse COVID outcomes.

Keywords: COVID outcomes; COVID-19; inflammatory markers; sTNF-RII; zinc.