Host Metabolic Reprogram (HMR)

Post-acute sequelae of

PASC, also known as the ‘long COVID’, has emerged as a novel clinical condition in COVID-19 survivors with lingering symptoms (or develop new ones) who fail to return to their baseline health. Based on the duration of persistent clinical manifestations, PASC has been further categorized: i) post-acute COVID with symptoms and abnormalities that persist 4-12 weeks; and ii) chronic COVID with symptoms and abnormalities that persist >12 weeks and not attributable to alternative diagnoses. The PASC pathology is a cumulative outcome of several viral-mediated HMR at cellular level such as: i) SARS-CoV-2 infection-induced tissue damage, ii) hyperinflammation-mediated multiorgan impairment, iii) immune exhaustion/dysregulation, iv) hormonal disturbances from maladaptation of ACE2-related pathways, v) coagulopathies due to endothelial damage/microvascular injury, iv) post-viral autoimmunity, vi) microbial dysbiosis, vii) critical care-associated sequelae or a combination of all above. The burden of individual PASC sequelae vary by demography (age, race, and sex) but consistently higher among patients with existing metabolic syndromes and in survivors from severe acute infection. The five most long-term clinical manifestations of PASC include: