Abstract: www.nature.com/scientificreports OPEN Association of ApaI rs7975232 and BsmI rs1544410 in clinical outcomes of COVID‑19 patients according to different SARS‑CoV‑2 variants Ayad Naji Radha Al‑Gharrawi 1, Enayat Anvari 2* & Abolfazl Fateh 3,4* A growing body of research has shown how important vitamin D is in the prognosis of coronavirus disease 19 (COVID-19). The vitamin D receptor is necessary for vitamin D to perform its effects, and its polymorphisms can help in this regard. Therefore, we aimed to evaluate whether the association of ApaI rs7975232 and BsmI rs1544410 polymorphisms in different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were influential in the outcomes of COVID-19. The polymerase chain reaction-restriction fragment length polymorphism method was utilized to determine the different genotypes of ApaI rs7975232 and BsmI rs1544410 in 1734 and 1450 patients who had recovered and deceased, respectively. Our finding revealed that the ApaI rs7975232 AA genotype in the Delta and Omicron BA.5 and the CA genotype in the Delta and Alpha variants were associated with higher mortality rate. Also, the BsmI rs1544410 GG genotype in the Delta and Omicron BA.5 and the GA genotype in the Delta and Alpha variants were related to a higher mortality rate. The A-G haplotype was linked with COVID-19 mortality in both the Alpha and Delta variants. The A-A haplotype for the Omicron BA.5 variants was statistically significant. In conclusion, our research revealed a connection between SARS-CoV-2 variants and the impacts of ApaI rs7975232 and BsmI rs1544410 polymorphisms. However, more research is still needed to substantiate our findings. The World Health Organization (WHO) reports demonstrate that severe acute respiratory syndrome associated with coronavirus-2 (SARS-CoV-2) has caused Coronavirus disease 2019 (COVID-19), a worldwide pandemic, in millions of people since December 2019. The symptoms of the COVID-19 can range from mild to moderate and severe to critical, necessitating hospitalization and intensive care unit (ICU) admissions for some p ­ atients1. It is appropriate to shift our focus from preventive to therapeutic measures in light of the development of effective vaccines against COVID-19, whose efficacies are unusually high but not absolute, and in light of the prospect that new viral variations may limit its efficacy. Additionally, there are still a significant number of unvaccinated ­people2. Vitamin D deficiency has increased the severity of viral illnesses such as ­influenza3. According to recent research, vitamin D can influence SARS-CoV-2 gene expression and reduce infection rate when it binds to the vitamin D response e­ lement4. The angiotensin-converting enzyme 2 (ACE2) mediates the SARS-CoV-2 infection and its receptor, which vitamin D. Additionally regulates, vitamin D is known to increase the generation of antimicrobial proteins, modulate innate and adaptive immune responses, and possibly operate as an antiinflammatory ­agent5–7. Vitamin D exerprimarily biological effects through vitamin D receptors (VDRs) are mostly found in the gastrointestinal tract, bones, lungs, and most immune cells. Even though the VDR is abundantly expressed in the lung tissue, it is yet unclear how vitamin D-VDR signaling may contribute to pulmonary i­ mmunopathology8. Regarding the related mechanisms, single nucleotide polymorphisms (SNPs) in the gene encoding the VDR could alter the protective efficacy of vitamin..