Dysregulation of the immune system as a driver of the critical course of novel coronavirus disease 2019

Abstract

Novel coronavirus disease 2019 (COVID-19) is a highly contagious, respiratory disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given that inflammatory immune cells may induce severe lung injury, the involvement of immunological factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses have developed mechanisms of immune evasion, making themselves invisible to the immune system at an early stage of infection. The mechanism relies on inhibiting the antiviral response of type I interferons, which enhances uncontrolled viral replication in epithelial cells. There has been a growing body of evidence showing that fatal hyperinflammation (cytokine storm) responsible for the severe course of COVID-19 is a consequence of massive SARS-CoV-2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, the suppressed antiviral innate immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminant systemic inflammation. The occurrence of virus transmission even in asymptomatic individuals infected with SARS-CoV-2 clearly strengthens the evidence for the key role played by the sufficient immune control of viral replication in a subset of cases (eg, in children, a population with a highly effective innate immune response). Although administration of immunomodulatory drugs is recommended under certain conditions by the guidelines for COVID-19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS-CoV-2 still exist. Extending clinicians' knowledge on the dysregulated immune response, which is a driver of the COVID-19 outcome, may improve both therapeutic strategies and the prognosis of patients infected with SARS-CoV-2.