Immunopathogenesis of Pneumonia in COVID-19

Coronavirus disease 2019 (COVID-19), caused by a member of the Coronaviridae family (SARS-CoV-2), was initially reported in Wuhan, China in late December and spread rapidly around the world, reaching a pandemic level (1). This disease has been diagnosed in almost 4.44 million people globally, resulting in more than 302,000 deaths until 15 May, 2020 (2). In Iran, a total of 115,000 confirmed cases of COVID-19 were reported until May 2020, with a fatality rate of 5.118%. Coronaviruses are enveloped positive-stranded RNA viruses with an approximate size of 80-120 nm. They contain the longest viral RNA genomes of all RNA virus families (3). The whole genome sequence of this novel virus contains 29,903 nucleotides. SARS-CoV-2 is closely related to bat-derived SARS-like coronaviruses, sharing 79% nucleotide identity with SARS-CoV (4, 5). Also, viral capsid proteins, including spike glycoprotein (S protein), play an important role in the cell entry and tropism in patients with COVID-19 (6). Overall, coronaviruses use a variety of receptors to enter the cells. Recent evidence shows high homology between SARS-CoV and SARS-CoV-2, as SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as its receptor, similar to SARS-CoV (7). ACE2 is an enzyme, involved in the renin–angiotensin–aldosterone system (RAAS) (8). A positive relationship has been documented between the ACE2 expression pattern and SARS-CoV-2 pathogenicity (9). Therefore, the pattern of ACE2 expression in different tissues can determine the tropism, susceptibility, symptoms, and outcomes of SARS-CoV-2 infection (10). On the other hand, targeting ACE2 may be effective in controlling the initial COVID-19 infection. About 80% of COVID-19 cases are asymptomatic or show mild symptoms, whereas a low percentage experience severe organ failure (11). In the first stage of the disease, that is, one to two days after the infection, the virus may infect epithelial cells in the nasal cavity and initiate replication. Over the next few days, the upper and conducting airways become infected, and the virus is detectable in nasal swabs or sputum samples (12). At this time, patients show clinical manifestations, and the innate immune response is triggered. The infected epithelial cells become the major source of interferons (IFN), and CXCL10 is produced in response to IFN production. CXCL10 is an important immune factor in SARS and influenza and is considered as a disease marker in SARS (13).