As of the 7th of July 2024, 775,754,322 confirmed cases of COVID-19, including 7,053,902 deaths worldwide, had been reported to the WHO (World Health Organization). Nevertheless, untill the 15th of July 2024, a total of 13,578,710,228 vaccine doses had been administered, with almost no country spared from COVID-19 attacks. The pathophysiology of this virus is complicated, and several symptoms require a deep understanding of the actual mechanisms. It is unclear why some patients develop severe symptoms while others do not, although literature suggests a role for vitamin D. Vitamin D plays a crucial role in the infection or in ameliorating the severity of symptoms. The mechanism of action of vitamin D and vitamin D deficiency (VDD) is well understood. VDD is associated with increased hospitalization of severely ill patients and increased levels of COVID-19-caused mortality. Recent studies suggest that vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene significantly impact the severity and outcomes of COVID-19, especially in the infections caused by Delta and Omicron variants. Furthermore, VDD causes immune system dysregulation upon infection with SARS-CoV-2, indicating that vitamin D sufficiency is crucial in fighting against COVID-19 infection. The therapeutic effect of vitamin D raises interest in its potential role as a prophylactic and treatment adjunct. We evaluate the immunomodulatory effects of vitamin D and its ability to enhance the efficacy of new antiviral drugs like molnupiravir and paxlovid against SARS-CoV-2. This review discusses the role of vitamin D sufficiency and VDD in COVID-19 initiation and progression, emphasizing the molecular mechanisms by which vitamin D exerts its actions as a proactive step for the next pandemic. However, there is still no clear evidence of vitamin D's impact on prevention and treatment, leading to contradictory findings. Therefore, large-scale randomized trials are required to reach a definitive conclusion. A bibliometric analysis of publications related to vitamin D, immunity, and COVID-19 revealed a significant increase in research activity in this area, particularly in 2020-2024, underscoring the growing recognition of vitamin D's potential role in the context of the pandemic.

Al Ryada University for Science and Technology ElMehwar ElMarkazy 2 Cairo Alex desert RD K92 Sadat City 16504 Egypt

Department of Clinical Pharmacy Faculty of Pharmacy Ahram Canadian University 6th of October City Giza 12566 Egypt

Department of Clinical Pharmacy Faculty of Pharmacy University of Sadat City Sadat City 32897 Egypt

Department of Environmental Biotechnology College of Biotechnology Misr University for Science and Technology P O Box 77 Giza Egypt

Department of Internal Medicine School of Medicine University of California Irvine Irvine CA USA

Department of Medical Biotechnology College of Biotechnology Misr University for Science and Technology P O Box 77 Giza Egypt

Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Ke Karlovu 2 128 08 Praha 2 Czech Republic

Department of Pharmaceutics and Pharmaceutical Technology Faculty of Pharmacy Ahram Canadian University Giza Egypt

Department of PharmD Faculty of Pharmacy Jadara University Irbid 21110 Jordan

Faculty of Science Mansoura University Mansoura Egypt

Molecular Biology Department Genetic Engineering and Biotechnology Research Institute University of Sadat City Sadat City Egypt

Pharmacology and Toxicology Department Faculty of Pharmacy Menoufia University Shebin El Koum Egypt

Scientific Office Egyptian Society of Pharmacogenomics and Personalized Medicine Cairo Egypt

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Inflammopharmacology. 2025 Apr 12. doi: 10.1007/s10787-025-01725-x. PubMed

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