From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

Abstract

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.

Keywords: COVID-19; PASC; SARS-CoV-2; angiotensin-converting enzyme 2; cell dysfunction; coronavirus; cytokine storm; cytopathy; long COVID; sequelae.

Figure 1

Summary of some of the cytopathic effects that occur following SARS-CoV-2 infection in specific cell types. Cytopathic effects predicted from the virus–host interactome are highlighted in purple and bold. Note that not all occur simultaneously in the infected cell, as these alterations depend on the cell phenotype.

Figure 2

Compilation of some of the cytopathic effects of SARS-CoV-2 in various tissues, as well as some of its indirect consequences. Note that not all of these phenomena occur simultaneously in all patients.