Long COVID: Molecular Mechanisms and Detection Techniques

Abstract

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction.

Keywords: SARS-CoV-2; gene expression; immunity; inflammation; sequencing.

Figure 1

Cellular and molecular mechanisms involved in Long COVID (abbreviations: APOE, apolipoprotein E; IBA1, ionized calcium-binding adapter molecule 1; GFAP, glial fibrillary acidic protein; FGF2, Fibroblast Growth Factor 2; TGF-β, Transforming growth factor-β; IL-6, Interleukin 6; and TNF-α, Tumor Necrosis Factor α). (Figure designed using BioRender).

Figure 2

Possible mechanisms involved in the pro-thrombotic state in long COVID. Different mechanisms are currently being explored to understand thrombogenicity in long COVID, many of which have previously been confirmed to play a role in acute COVID-19. These include platelet and neutrophil hyperactivity, increased thrombin generation, decreased fibrinolysis, the presence of microclots, persistent endotheliopathy, and an increase in the VWF:ADAMTS13 ratio. (Figure designed using BioRender).