Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the "gut-lung axis." Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19
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