Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.
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