Overview and Pathophysiology of Long COVID

Long COVID is the disease entity triggered and potentially driven by SARS-CoV-2 infection. It is an heterogeneous condition characterized by dozens of different symptoms, signs and sequelae, which can affect all organs and body systems and evolve over the disease course. Clinical manifestations of Long COVID can vary from individual to individual and across the broader patient population. Pathology can range from asymptomatic and subclinical manifestations to fatal outcomes. Over 400 million people worldwide are estimated to suffer, or have suffered, from Long COVID, making the sequelae of SARS-CoV-2 infection one of the greatest public health challenges of the 21st century. This article provides an updated overview of epidemiology, definitions, main concepts and terminology for Long COVID. It also summarizes key evidence of pathology and disease mechanisms in major organs and body systems, such as the immune system, cardiovascular system, endothelium, heart, lungs, central nervous system, peripheral nervous system, gastrointestinal system, hapatobiliary system, pancreas and kidney. Heterogeneity in manifestations, potential risk of death and the degree of disability in several disease subsets call for timely diagnosis of each Long COVID types and a fuller understanding of their pathophysiological underpinnings. Further research is recommended to better understand pathobiology, develop effective clinical trials, and identify treatments and scalable biomarkers.