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Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1 Mustafa Sait Gonen^ 1 , Merve Alaylioglu^ 2 , Emre Durcan^ 1 , Yusuf Ozdemir^ 3 , Serdar Sahin^ 1 , Dildar Konukoglu^ 4 , Okan Kadir Nohut^ 5 , Seval Urkmez^ 6 , Berna Kucukece^ 7 , Ilker Inanc Balkan^ 3 , H Volkan Kara^ 8 , Sermin Borekci^ 9 , Hande Ozkaya^ 1 , Zekayi Kutlubay^ 10 , Yalim Dikmen^ 6 , Yilmaz Keskindemirci^ 11 12 , Spyridon N Karras^ 13 , Cedric Annweiler^ 14 15 , Duygu Gezen-Ak^ 2 , Erdinc Dursun^ 2 16 Affiliations Expand Affiliations * ^1 Endocrinology and Metabolism Unit, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^2 Brain and Neurodegenerative Disorders Research Laboratories, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^3 Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^4 Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^5 Fikert Biyal Biochemistry Laboratory, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^6 Department of Anesthesiology and Reanimation, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^7 Cerrahpasa Hospital Pharmacy Unit, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^8 Department of Thoracic Surgery, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^9 Department of Pulmonary Diseases, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^10 Dermatology and Venerology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^11 General Directorate of Hospitals, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^12 Department of Medical Services and Techniques, Health Services Vocational School, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^13 National Scholarship Foundation, 55535 Thessaloniki, Greece. * ^14 Division of Geriatric Medicine, Department of Neuroscience, Angers University Hospital, 49035 Angers, France. * ^15 Department of Medical Biophysics, Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada. * ^16 Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * PMID: 34836309 * PMCID: PMC8618389 * DOI: 10.3390/nu13114047 Free PMC article Item in Clipboard Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1 Mustafa Sait Gonen et al. Nutrients. 2021. Free PMC article Show details Display options Display options Format [Abstract] Nutrients Actions * Search in PubMed * Search in NLM Catalog * Add to Search . 2021 Nov 12;13(11):4047. doi: 10.3390/nu13114047. Authors Mustafa Sait Gonen^ 1 , Merve Alaylioglu^ 2 , Emre Durcan^ 1 , Yusuf Ozdemir^ 3 , Serdar Sahin^ 1 , Dildar Konukoglu^ 4 , Okan Kadir Nohut^ 5 , Seval Urkmez^ 6 , Berna Kucukece^ 7 , Ilker Inanc Balkan^ 3 , H Volkan Kara^ 8 , Sermin Borekci^ 9 , Hande Ozkaya^ 1 , Zekayi Kutlubay^ 10 , Yalim Dikmen^ 6 , Yilmaz Keskindemirci^ 11 12 , Spyridon N Karras^ 13 , Cedric Annweiler^ 14 15 , Duygu Gezen-Ak^ 2 , Erdinc Dursun^ 2 16 Affiliations * ^1 Endocrinology and Metabolism Unit, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^2 Brain and Neurodegenerative Disorders Research Laboratories, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^3 Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^4 Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^5 Fikert Biyal Biochemistry Laboratory, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^6 Department of Anesthesiology and Reanimation, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^7 Cerrahpasa Hospital Pharmacy Unit, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^8 Department of Thoracic Surgery, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^9 Department of Pulmonary Diseases, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^10 Dermatology and Venerology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^11 General Directorate of Hospitals, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^12 Department of Medical Services and Techniques, Health Services Vocational School, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * ^13 National Scholarship Foundation, 55535 Thessaloniki, Greece. * ^14 Division of Geriatric Medicine, Department of Neuroscience, Angers University Hospital, 49035 Angers, France. * ^15 Department of Medical Biophysics, Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada. * ^16 Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey. * PMID: 34836309 * PMCID: PMC8618389 * DOI: 10.3390/nu13114047 Item in Clipboard Full text links Cite Display options Display options Format [Abstract] Abstract Background: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. Methods: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. Results: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. Conclusions: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment. Keywords: COVID-19; SARS-CoV-2; acute respiratory failure; cathelicidin-LL37; cytokine; vitamin D. Conflict of interest statement All authors declare that they have no conflict of interest. Figures Figure 1 Figure 1 The study design and patient... Figure 1 The study design and patient groups. Figure 1 The study design and patient groups. See this image and copyright information in PMC References 1. 1. Wan S., Yi Q., Fan S., Lv J., Zhang X., Guo L., Lang C., Xiao Q., Xiao K., Yi Z., et al. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br. J. Haematol. 2020;189:428-437. doi: 10.1111/bjh.16659. - DOI - PMC - PubMed 2. 1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., et al. Clinical features of patients infected with 2019 novel coronavirus in wuhan, china. Lancet. 2020;395:497-506. doi: 10.1016/S0140-6736(20)30183-5. - DOI - PMC - PubMed 3. 1. Cao W., Li T. COVID-19: Towards understanding of pathogenesis. Cell Res. 2020;30:367-369. doi: 10.1038/ s41422-020-0327-4. - DOI - PMC - PubMed 4. 1. Dos Santos W.G. Natural history of COVID-19 and current knowledge on treatment therapeutic options. Biomed. Pharmacother. 2020;129:110493. doi: 10.1016/ j.biopha.2020.110493. - DOI - PMC - PubMed 5. 1. Dursun E., Alaylioglu M., Bilgic B., Hanagasi H., Lohmann E., Atasoy I.L., Candas E., Araz O.S., Onal B., Gurvit H., et al. Vitamin d deficiency might pose a greater risk for apo-evarepsilon4 non-carrier alzheimer's disease patients. Neurol. Sci. 2016;37:1633-1643. doi: 10.1007/ s10072-016-2647-1. - DOI - PubMed Show all 62 references Grant support * TSG-2020-34998/Istanbul University Cerrahpasa LinkOut - more resources * Full Text Sources + Multidisciplinary Digital Publishing Institute (MDPI) + PubMed Central * Miscellaneous + NCI CPTAC Assay Portal Full text links [x] full text provider logo Multidisciplinary Digital Publishing Institute (MDPI) Free PMC article [x] Cite Copy Download .nbib Format: [NLM] Send To * Clipboard * Email * Save * My Bibliography * Collections * Citation Manager [x] NCBI Literature Resources MeSH PMC Bookshelf Disclaimer Follow NCBI Connect with NLM * * * National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA Help Accessibility Careers * NLM * NIH * HHS * USA.gov