Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.06.09.21258271; this version posted July 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 2 3 Title Plasma zinc status and hyperinflammatory syndrome in hospitalized COVID-19 patients: an observational study 4 5 6 7 Authors: Gil Verschelden , Maxim Noeparast , Maryam Noparast , Maïlis 1* 2,3* 4 Lauwers , Charlotte Michel , Frédéric Cotton , Cleo Goyvaerts , Maya Hites . 5 6 7 7 1 * Shared first authors 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 1. Clinic of Infectious Diseases, Cliniques Universitaires de Bruxelles (CUB), Erasme Hospital, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium 2. Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University, 35043 Marburg, Germany 3. Fonds Wetenschappelijk Onderzoek (FWO) – Vlaanderen 4. Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. 5. Department of Clinical Chemistry, Laboratoire Hospitalier Universitaire de Bruxelles (LHUB-ULB), Université Libre de Bruxelles (ULB), Brussels, Belgium 6. Department of Microbiology, Laboratoire Hospitalier Universitaire de Bruxelles (LHUB-ULB), Brussels, Belgium 7. Department of Clinical Chemistry, Laboratoire Hospitalier Universitaire de Bruxelles (LHUB-ULB), Université Libre de Bruxelles (ULB), Brussels, Belgium 8. Laboratory for Molecular and Cellular Therapy (LMCT), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium 26 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.06.09.21258271; this version posted July 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 27 28 Corresponding authors: Gil.Verschelden@erasme.ulb.ac.be, Maxim.Noeparast@staff.uni-marburg.de, and Maya.Hites@erasme.ulb.ac.be 29 30 31 32 33 Abstract Deficiency of the element zinc is associated with cytokine releasing syndrome (CRS) and the related acute respiratory distress syndrome as well as impaired antiviral response. Similar complications associate with severe SARS-CoV-2. 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 We conducted a prospective, single-center, observational study in a tertiary university hospital (CUB-Hopital Erasme, Brussels) to address the zinc status, the association between the plasma zinc concentration, development of CRS, and the clinical outcomes in PCR-confirmed and hospitalized COVID-19 patients. One hundred and thirty-nine eligible patients were included between May 2020 and November 2020 (median age of 65 years [IQR, 54 to 77]). Our cohort's mean plasma zinc concentration was 56.2 µg/dL (standard deviation [SD], 14.8) compared to 75.7 µg/dL (SD = 18.9 µg/dL) in the retrospective nonCOVID-19 control group (N = 1513; P <.001). Markedly, the absolute majority of patients (96%) were zinc deficient (<80 µg/dL). The mean zinc concentration was lower in patients with CRS compared to..