The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in approximately 778 million reported cases and over 7 million deaths worldwide as of August 2025 (WHO COVID-19 Dashboard), predominantly due to variable acute and chronic lung infections accompanied by inflammatory responses within the pulmonary tract and vasculature. Despite ongoing research, no definitive cure has been identified. Preventive measures, including vaccines and monoclonal antibody-based interventions, have been developed to protect vulnerable populations, and hundreds of therapeutic candidates have been evaluated worldwide. Complementing these strategies, vitamin D and zinc (Zn) supplementation have emerged as promising, accessible adjunctive strategies due to their immunomodulatory and anti-inflammatory properties. This review synthesizes current experimental, clinical, and epidemiological evidence on the roles of vitamin D and Zn in modulating immune responses relevant to SARS-CoV-2 infection. Available data suggest that adequate vitamin D and Zn status may support immune function, reduce excessive inflammation, and potentially mitigate disease severity, particularly in deficient individuals. However, clinical trial outcomes remain heterogeneous. Overall, vitamin D and Zn supplementation may be considered supportive, adjunctive preventive measures. Further well-designed randomized controlled trials are required to define their optimal use in COVID-19 prevention and management.
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