Genetics of Long COVID: Exploring the Molecular Drivers of Persistent Pulmonary Vascular Disease Symptoms

Background/ Objectives: Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) are symptoms that manifest despite passing the acute infection phase. These manifestations encompass a wide range of symptoms, the most common being fatigue, shortness of breath, and cognitive dysfunction. Genetic predisposition is clearly involved in the susceptibility of individuals to developing these persistent symptoms and the variation in the severity and forms. This review summarizes the role of genetic factors and gene polymorphisms in the development of major pulmonary vascular disorders associated with long COVID. Methods: A comprehensive review of current literature was conducted to examine the genetic contributions to pulmonary complications following SARS-CoV-2 infection. Studies investigating genetic polymorphisms linked to pulmonary hypertension, pulmonary thromboembolism, and pulmonary vascular endothelialitis were reviewed and summarized. Results: Findings show that specific genetic variants contribute to increased susceptibility to pulmonary vascular complications in long COVID patients. Variants associated with endothelial dysfunction, coagulation pathways, and inflammatory responses have been implicated in the development of pulmonary hypertension and thromboembolic events. Genetic predispositions influencing vascular integrity and immune responses appear to influence disease severity and progression. Conclusions: Understanding these mechanisms and genetic predispositions could pave the way for targeted therapeutic interventions to alleviate the burden on patients experiencing long COVID.