Work

Megakaryocytes and afucosylated IgG in post-acute COVID-19: Bridging immune dysregulation and vascular pathology — A narrative review

Year: 2026

Type: review

Abstract: Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as long COVID, encompasses a constellation of persistent symptoms lasting for at least three months after acute SARS-CoV-2 infection and not explained by alternative diagnoses. The multifactorial pathophysiology underlying PASC remains incompletely understood, limiting the development of effective management strategies. Increasing evidence suggests that both immune dysregulation and hemostatic imbalance play central roles in post-COVID-19 complications. Megakaryocytes, key regulators of platelet production and coagulation, have emerged as potential contributors to sustained thrombo-inflammatory processes following SARS-CoV-2 infection. In parallel, afucosylated IgG antibodies have been strongly implicated in exaggerated immune activation and hyperinflammatory responses during acute COVID-19. The persistence of such antibody glycosylation patterns beyond the acute phase raises the possibility that they may also contribute to chronic immune and vascular alterations observed in PASC. This narrative review explores the potential interplay between megakaryocyte dysfunction and afucosylated IgG antibodies in the pathogenesis of PASC. By examining mechanisms identified during acute SARS-CoV-2 infection, we discuss how prolonged immune–hemostatic crosstalk may promote persistent inflammation, endothelial dysfunction, and microvascular abnormalities. Understanding these interconnected pathways may provide mechanistic insight into the heterogeneity of PASC manifestations and help identify novel therapeutic targets for long-term post-COVID-19 sequelae. • Megakaryocyte dysregulation contributes to persistent thromboinflammation in PASC. • Afucosylated IgG enhances FcγR-mediated immune and platelet activation after COVID-19. • Immune–hemostatic crosstalk drives endothelial and microvascular dysfunction. • Pulmonary and bone marrow megakaryocytes have distinct roles in long COVID. • Targeting FcγR and platelet pathways offers therapeutic opportunities in PASC.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2026.119049