Abstract: ORIGINAL RESEARCH published: 04 June 2021 doi: 10.3389/fnut.2021.689419 Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity Nikola Kotur 1 , Anita Skakic 1 , Kristel Klaassen 1 , Vladimir Gasic 1 , Branka Zukic 1 , Vesna Skodric-Trifunovic 2,3 , Mihailo Stjepanovic 2,3 , Zorica Zivkovic 4,5 , Olivera Ostojic 4 , Goran Stevanovic 3,6 , Lidija Lavadinovic 6 , Sonja Pavlovic 1 and Biljana Stankovic 1* 1 Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia, 2 Clinic of Pulmonology, Clinical Center of Serbia, Belgrade, Serbia, 3 Medical Faculty, University of Belgrade, Belgrade, Serbia, 4 Children’s Hospital for Lung Diseases and Tbc, MC Dr Dragisa Misovic, Belgrade, Serbia, 5 Faculty of Pharmacy Novi Sad, Business Academy, Novi Sad, Serbia, 6 Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia Edited by: Manja Zec, University of Arizona, United States Reviewed by: Matina Kouvari, Harokopio University, Greece Janaina Donadio, University of São Paulo, Brazil *Correspondence: Biljana Stankovic biljana.stankovic@imgge.bg.ac.rs Specialty section: This article was submitted to Nutrigenomics, a section of the journal Frontiers in Nutrition Received: 31 March 2021 Accepted: 11 May 2021 Published: 04 June 2021 Citation: Kotur N, Skakic A, Klaassen K, Gasic V, Zukic B, Skodric-Trifunovic V, Stjepanovic M, Zivkovic Z, Ostojic O, Stevanovic G, Lavadinovic L, Pavlovic S and Stankovic B (2021) Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity. Front. Nutr. 8:689419. doi: 10.3389/fnut.2021.689419 Frontiers in Nutrition | www.frontiersin.org Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the..