Abstract: healthcare Article Effectiveness of Vitamin D Supplements among Patients Hospitalized for COVID-19: Results from a Monocentric Matched-Cohort Study Vito Fiore 1, * , Andrea De Vito 1 , Paola Bagella 1 , Elija Princic 1 , Anna Antonella Mariani 1 , Lucia Denti 1 , Alessandro Giuseppe Fois 2 , Giordano Madeddu 1 , Sergio Babudieri 1 and Ivana Maida 1 1 2 * Infectious and Tropical Diseases Clinic, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy; andreadevitoaho@gmail.com (A.D.V.); paola.bagella@tiscali.it (P.B.); princic_e@hotmail.com (E.P.); annaanto82@gmail.com (A.A.M.); dentilucia@outlook.it (L.D.); giordano@uniss.it (G.M.); babuder@uniss.it (S.B.); imaida@uniss.it (I.M.) Unit of Respiratory Diseases, University Hospital Sassari (AOU), 07100 Sassari, Italy; agfois@uniss.it Correspondence: vitofiore30010516@gmail.com Academic Editor: Marina Sartini Abstract: Objectives: Our study aimed to evaluate the usefulness of Vitamin D3 (VitD3) among patients hospitalized for COVID-19. The primary endpoint was to evaluate the difference in survival rates between patients receiving and not VitD3. The secondary endpoints were to evaluate clinical outcomes, such as needing non-invasive ventilation (NIV), ICU transfer, and laboratory findings (inflammatory parameters). Methods: We conducted a retrospective, monocentric matched-cohort study, including patients attending our ward for COVID-19. Patients were divided into two groups depending on VitD3 administration (Group A) or not (Group B) among patients with low VitD levels (defined as blood levels < 30 ng/mL), which depended on physicians’ judgment. Our internal protocol provides VitD3 100,000 UI/daily for two days. Findings: 58 patients were included in Group A, and 58 in Group B. Patients were matched for age, sex, comorbidities, COVID-19-related symptoms, PaO2/FiO2 ratio, blood exams, and medical treatments. Regarding the principal endpoint, there was a statistically significant difference between the two groups in survival rates [Group A vs. Group B = 3 vs. 11 (p = 0.042)]. When considering secondary endpoints, Group A patients were less likely to undergo NIV [Group A vs. Group B = 12 vs. 23 (p = 0.026)] and showed an improvement in almost all inflammatory parameters. Conclusions: The link between VitD3 deficiency and the clinical course of COVID-19 during hospitalization suggests that VitD3 level is a useful prognostic marker. Considering the safety of supplementation and the low cost, VitD3 replacement should be considered among SARS-CoV-2 infected patients needing hospitalization. Received: 28 April 2022 Keywords: COVID-19; vitamin D3 supplement; SARS-CoV-2; matched cohort Citation: Fiore, V.; De Vito, A.; Bagella, P.; Princic, E.; Mariani, A.A.; Denti, L.; Fois, A.G.; Madeddu, G.; Babudieri, S.; Maida, I. Effectiveness of Vitamin D Supplements among Patients Hospitalized for COVID-19: Results from a Monocentric Matched-Cohort Study. Healthcare 2022, 10, 956. https://doi.org/ 10.3390/healthcare10050956 Accepted: 19 May 2022 Published: 22 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in