SARS-CoV-2, Inflammatory Apoptosis, and Cytokine Storm Syndrome

Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), a novel and currently intensively studied beta coronavirus, is the causing agent of COVID-19 (Coronavirus Disease 2019), a highly contagious and devastating disease that has killed more than 2 million human beings since December 2019. Building on what has already been understood from studying SARS-CoV, a closely related single-strand RNA virus that set off SARS in 2002 and 2003, researchers began to learn how SARS-CoV-2 operates its vicious effects on the host cells. In essence, COVID-19 patients display hyperinflammatory and dysregulated cell death phenotypes that give a spectrum of symptoms ranging from mild to moderate upper-respiratory tract illnesses. However, SARS-CoV-2 can elicit serious pathologies, such as acute respiratory distress syndrome, sepsis-like multi-organ failure and even death, depending on the individual and their pre-existing condition(s). As viruses cannot reproduce independently, they hijack the machinery within the host cells and enslave them for the purpose of propagation. SARS-CoV-2 RNA genome harbors the genes that produce the protein products for manipulating host cell, viral replication, and repeating the vicious viral cycle. For counteracting the viral invasion, human cells have developed layers of defense mechanisms, such as restriction factors, Regulated Cell Death (RCD) pathways, interferon production, inflammatory response, and innate and adaptive immunity that are used to recognize and thwart viral infection. Unfortunately, some coronavirus encoded proteins are capable of attacking the host anti-viral system to achieve parasitic advantages. We reviewed the proteins of SARS-CoV and SARS-CoV-2 that possess manipulating effects on the host cell and cause tissue damage, immune cascade, cytokine production and release. We also discuss the means to restore the homeostatic balance between inflammatory response and RCD pathways and the potential targeted interventions that can be used to treat and/or prevent COVID-19.