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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized for inducing severe respiratory symptoms like cough, and shortness of breathing. Although symptom severity varies, some individuals remain asymptomatic. This virus has sparked a global pandemic, imposing a substantial rate of mortality or morbidity, with extended periods of illness reported. People with underlying medical issues and the elderly are more likely to experience adverse results. The virus's frequent mutations pose challenges for medical professionals, necessitating adaptable therapeutic and preventive strategies. Vitamin D, a versatile regulatory molecule, not only influences physiological processes such as serum calcium regulation but also exhibits immunomodulatory functions. Calcium ions play a crucial role as secondary signal transduction molecules, impacting diverse cellular functions and maintaining homeostasis through ion channel regulation. Parathormone, another key regulator of serum calcium, often acts antagonistically to vitamin D. This review delves into the interplay of vitamin D, calcium, and parathormone, exploring their possible influence on the progression of COVID-19. The intricate signaling involving these elements contributes to adverse prognosis, emphasizing the need for comprehensive understanding. Monitoring and controlling these physiological factors and associated pathways have shown the potential to alter disease outcomes, underscoring the importance of a holistic approach., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests, (Copyright © 2024 Elsevier Ltd. All rights reserved.)