Human immune responses upon SARS-CoV-2 infection- inflammation and cytokine storm

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in December 2019 in the city of Wuhan, China, causing the COVID-19 pandemic of acute respiratory disease. Since its emergence, SARS-CoV-2 has infected over 639 million people and caused more than 6 million deaths worldwide, highlighting the urgent need to develop effective antiviral therapeutics and prevention strategies. SARS-CoV-2 is an enveloped virus belonging to the genus Betacoronavirus, with a large positive-sense single-stranded RNA (+ssRNA) genome of about 30 kilobases (kb) in length. The viral genome encodes a set of structural proteins (spike glycoprotein, membrane protein, nucleocapsid protein, and envelope protein), non-structural proteins (NSPs), and accessory proteins, which participate in host recognition and entry, genome replication and transcription, viral assembly, and release, as well as in host immune surveillance evasion. The effective host immune response against SARS-CoV-2 is mounted by both the innate and adaptive arms of immunity, and is essential for controlling and resolving the viral infection. However, multiple studies have shown that SARS-CoV-2 suppresses normal antiviral immune responses, leading to an impaired immune system and uncontrolled inflammatory responses in patients with severe COVID-19. Severe COVID-19 is associated with hyperactivation of innate immune cells, overproduction and uncontrolled release of proinflammatory cytokines, a condition known as “cytokine storm”, dysregulated interferon (IFN) responses, reduced T cell numbers, lymphocyte exhaustion as well as exacerbated antibody responses. Based on the current scientific knowledge, this review focuses on host immune responses against SARS-CoV-2 infection, including the contribution of a dysfunctional immune system to disease progression and mortality. An improved understanding of the mechanisms underlying immune abnormalities in severe COVID-19 cases may increase our ability to treat and prevent coronavirus (CoV) infections in this pandemic and beyond.