Pathological sequelae of long-haul COVID

Abstract

The world continues to contend with successive waves of coronavirus disease 2019 (COVID-19), fueled by the emergence of viral variants. At the same time, persistent, prolonged and often debilitating sequelae are increasingly recognized in convalescent individuals, named 'post-COVID-19 syndrome' or 'long-haul COVID'. Clinical symptomatology includes fatigue, malaise, dyspnea, defects in memory and concentration and a variety of neuropsychiatric syndromes as the major manifestations, and several organ systems can be involved. The underlying pathophysiological mechanisms are poorly understood at present. This Review details organ-specific sequelae of post-COVID-19 syndromes and examines the underlying pathophysiological mechanisms available so far, elaborating on persistent inflammation, induced autoimmunity and putative viral reservoirs. Finally, we propose diagnostic strategies to better understand this heterogeneous disorder that continues to afflict millions of people worldwide.

Fig. 1 ∣. Putative mechanisms and diagnostic strategies for patients with post-COVID-19 syndromes.

Delayed resolution of inflammation, autoimmunity and viral persistence represents overlapping mechanisms that may contribute to the pathogenesis of post-COVID-19 syndromes. Strategies to better characterize patients with post-COVID-19 syndromes are indicated. ITP, idiopathic thrombocytopenic purpura; OXPHOS, oxidative phosphorylation; PDCs, plasmacytoid dendritic cells; ROS, reactive oxygen species; TGF-β, transforming growth factor-β.