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Granulocytes, including neutrophils, eosinophils, and basophils, are critical components of the innate immune system that play dual roles in protection and pathogenesis during infection. In this review, we examine the multifaceted roles of granulocytes in COVID-19 and their impact on disease severity through excessive inflammation, cytokine storm, and tissue damage. Neutrophil extracellular traps (NETs) and the overactivation of neutrophil subtypes contribute to the development of thrombosis and acute respiratory distress syndrome. In contrast, eosinophils and basophils modulate T helper 2-type and allergic responses that may influence recovery or disease progression. We further summarize the therapeutic strategies targeting granulocyte activation and signaling pathways, including IL-1, IL-6, IL-17, IL-5 receptor, granulocyte-macrophage colony-stimulating factor inhibitors, and antihistamines, emphasizing their clinical outcomes, approval status, and the global regions in which they are studied. Understanding the regulatory mechanisms of granulocyte activation and inhibition provides new insights into COVID-19 immunopathology and opens pathways for targeted immunomodulatory therapy. 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