Abstract: ORIGINAL RESEARCH published: 24 January 2022 doi: 10.3389/fimmu.2021.745713 Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19? Federica Saponaro 1*, Maria Franzini 2, Chukwuma Okoye 3, Rachele Antognoli 3, Beatrice Campi 1, Marco Scalese 4, Tommaso Neri 1, Laura Carrozzi 1, Fabio Monzani 3, Riccardo Zucchi 1, Alessandro Celi 1, Aldo Paolicchi 2 and Alessandro Saba 1† on behalf of Pisa COVID-19 Study Group† 1 Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy, 3 Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, 4 Institute of Clinical Physiology, National Council of Research, Pisa, Italy 2 Edited by: Deirdre R. Coombe, Curtin University, Australia Reviewed by: Roi Gazit, Ben Gurion University of the Negev, Israel Peter Ramutis Kvietys, Alfaisal University, Saudi Arabia *Correspondence: Federica Saponaro federica.saponaro@unipi.it † Members are listed in the Acknowledgments section Specialty section: This article was submitted to Inflammation, a section of the journal Frontiers in Immunology Received: 13 August 2021 Accepted: 21 December 2021 Published: 24 January 2022 Citation: Saponaro F, Franzini M, Okoye C, Antognoli R, Campi B, Scalese M, Neri T, Carrozzi L, Monzani F, Zucchi R, Celi A, Paolicchi A and Saba A (2022) Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19? Front. Immunol. 12:745713. doi: 10.3389/fimmu.2021.745713 Background: Hypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection. Methods: The aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available. Results: Sixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9–45.6) vs. 12.9 (8.7–21.1) pg/ml, p = 0.02], CRP [10.7 (4.2–19.2) vs. 5.9 (1.6–8.1) mg/dl, p = 0.003], TNF-a [8.9 (6.0–14.8) vs. 4.4 (1.5–10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25–0.72) vs. 0.22 (0.17–0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8–6.9) vs. 2.3 (0.5–5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p < 0.001), and 25OHD levels were lower in nonsurvivor patients. Conclusions: The relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated. Keywords: COVID-19, SARS-CoV-2, hypovitaminosis D, vitamin D, cytokine storm Frontiers in Immunology |..