Association Between Serum Zinc Concentration Levels And Severity Of Coronavirus Disease 2019 (Covid-19) In Japanese Inpatients

Naomi Matsumoto,1,2 Hirohide Yokokawa,1 Hirotake Mori,1 Makoto Hiki,2,3 Yoko Tabe,4,5 Kazuhisa Takahashi,5,6 Toshio Naito1,5 1Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 2Department of Emergency and Disaster Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 3Department of Cardiovascular Biology and Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 4Department of Clinical Laboratory Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 5Department of Research Support Utilizing Bioresource Bank, Juntendo University Graduate School of Medicine, Tokyo, Japan; 6Department of Respiratory Medicine Juntendo University Faculty of Medicine, Tokyo, JapanCorrespondence: Hirohide Yokokawa, Department of General Medicine, Juntendo University Faculty of Medicine, 2-1-1 hongo, Bunkyo-ku, Tokyo, 113-8421, Japan, Tel/Fax +81-3-5802-1190, Email [email protected]: It has been reported that zinc deficiency is related to severe inflammatory conditions especially those of respiratory diseases. However, studies that have examined the association between the serum zinc concentration and the severity of coronavirus disease 2019 (COVID-19) are still limited. The aim of this study was to assess that association in Japanese inpatients with COVID-19.Methods: This cross-sectional study, conducted from April 2020 to August 2021, included 467 eligible adult inpatients with COVID-19 whose serum zinc concentration was measured. Serum zinc concentration categories were defined as deficiency (< 60 μg/dL), marginal deficiency (≥ 60 to < 80 μg/dL), and normal (≥ 80 μg/dL). Multivariate logistic regression was used to assess the association between serum zinc deficiency and severe COVID-19. Serum zinc concentration levels were compared between mild and other severities of COVID-19 by Dunnett’s method. The P for trend was estimated using the Jonckheere-Terpstra test.Results: The proportions of subjects with serum zinc deficiency (< 60 μg/dL) and marginal zinc deficiency (≥ 60 to < 80 μg/dL) were 39.5% and 54.3% in women, and 36.4% and 57.0% in men, respectively. Serum zinc deficiency was significantly associated with severe COVID-19 compared to marginal deficiency and normal (odds ratio = 3.60, 95% confidence interval = 1.60– 8.13, P < 0.01) after adjusting for confounders. An increase in severity of COVID-19 was inversely related to increases in serum zinc concentration levels (P < 0.01 for trend). Each serum zinc concentration of moderate and severe cases was also significantly lower compared with mild cases (P < 0.01).Conclusion: The severity of COVID-19 was significantly related to serum zinc concentration levels. These results suggest the importance of considering the serum zinc concentration when treating patients with COVID-19.Keywords: COVID-19, Zinc, severity, nutrition, epidemiology