Understanding the immunopathology of SARS-CoV-2 infection - the key to successful COVID-19 therapy

Abstract

In December 2019, an outbreak of pneumonia cases was reported in Wuhan, China. The new virus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) ̶ a highly pathogenic strain of coronaviruses ̶ was isolated on 7 January 2020 and identified as the cause of the outbreak. The SARS-CoV-2 virus rapidly spread across China and many other countries and lead to an unprecedented public health crisis worldwide. While 80% of infected individuals remain asymptomatic or develop only mild symptoms, the remaining 20% experience a rapid progression of the disease and severe/critical clinical condition. In patients with severe/critical stage of COVID-19, the SARS-CoV-2 virus has been shown to disrupt the normal immune response, leading to dysregulation of the immune system function and development of uncontrolled hyperinflammatory processes. Several studies highlight relevant changes occurring both in innate and adaptive immune system. Recent data indicate that a hyperinflammatory syndrome induced by SARS-CoV-2 contributes to the disease severity and mortality. It was demonstrated that patients with severe/critical phase of COVID-19 exhibit lymphopenia, a decrease in number of NK cells, eosinophils and basophils, an increase in inflammatory monocytes and neutrophils, an impaired interferon-α production and activity, no detectable circulating interferon-β, and massive production of proinflammatory cytokines, commonly known as cytokine storm. Many reports suggest that acute respiratory depression syndrome, cardiac dysfunction, hepatic impairment, acute kidney injury, coagulopathies, and multi-organ failure, that are characteristic of severe/critical COVID-19, are not due to direct effects of SARS -CoV-2, but result from the exaggerated cytokine release in response to viral infection. A better understanding of the pathophysiology and immune system dysregulation associated with cytokine storm and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and to develop effective vaccines and drugs. In addition, the knowledge on the processes induced by SARS-CoV-2 infection opens a door for development and introduction of predictive diagnostic tests that enable the prognosis of the course and severity of the disease.

Keywords

• cytokines
• infection
• innate immune response
• covid-19
• sars-cov-2
• cytokine storm
• adaptive immune response