Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

SARS-CoV-2???infected individuals may suffer a multi???organ system disorder known as ???long COVID??? or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype. Acute COVID-19 correlates with biomarkers of systemic inflammation, hypercoagulability, and comorbidities that are less prominent in PASC. Macrovessel thrombosis, a hallmark of acute COVID-19, is less frequent in PASC. Female sex at birth is associated with reduced risk for acute COVID-19 progression, but with increased risk of PASC. Persistent microvascular endotheliopathy associated with cryptic SARS-CoV-2 tissue reservoirs has been implicated in PASC pathology. Autoantibodies, localized inflammation, and reactivation of latent pathogens may also be involved, potentially leading to microvascular thrombosis, as documented in multiple PASC tissues. Diagnostic assays illuminating possible therapeutic targets are discussed.

Automated summary

SARS-CoV-2 infected individuals may suffer from a multi-organ disorder known as "long COVID" or post-acute sequelae of SARS-CoV-2 infection (PASC). The pathophysiology is unknown and there are no standard treatments available. Acute COVID-19 and PASC have different clinical characteristics, with acute COVID-19 being associated with systemic inflammation, hypercoagulability, and comorbidities, while these features are less prominent in PASC. The involvement of microvascular endotheliopathy and autoimmune responses in PASC is suggested, along with the reactivation of latent pathogens and microvascular thrombosis.