Long COVID, characterized by persistent symptoms following SARS-CoV-2 infection, remains an enigmatic clinical entity with debilitating consequences for millions globally. While much focus has been on the viral aspects and pulmonary sequelae, a growing body of evidence suggests that cardio-pulmonary microvascular dysfunction might be a central, yet under-recognized, driver of multi-organ damage in Long COVID. This review explores the current understanding of Long COVID's pathophysiology, focusing on the potential role of microvascular dysfunction. It reviews clinical evidence supporting this hypothesis, including persistent exercise intolerance, dyspnea, cognitive impairment, and fatigue. Further, it delves into the complexities of multidisciplinary management in Long COVID, emphasizing the need for a holistic approach that addresses microvascular dysfunction alongside other contributing factors. Cardio-pulmonary microvascular dysfunction (CMD and PMD) has emerged as a significant factor in various cardiovascular and pulmonary conditions. The role of microvascular dysfunction in heart failure with preserved ejection fraction (HFpEF), coronary microvascular disease, and its link to left ventricular remodeling and clinical outcomes in patients with chronic kidney impairment is discussed. The review also addresses the potential implications of CMD and PMD in the context of endothelial dysfunction and progressive disease. The findings presented in this article underscore the importance of recognizing and targeting microvascular dysfunction in the management of cardio-pulmonary conditions.

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Keywords: Long COVID, Microvascular Dysfunction, Cardio-Pulmonary, Multi-Organ Damage.