Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology

Abstract

Human coronaviruses (hCoVs) can be divided into low pathogenic and highly pathogenic coronaviruses. The low pathogenic CoVs infect the upper respiratory tract and cause mild, cold-like respiratory illness. In contrast, highly pathogenic hCoVs such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) predominantly infect lower airways and cause fatal pneumonia. Severe pneumonia caused by pathogenic hCoVs is often associated with rapid virus replication, massive inflammatory cell infiltration and elevated pro-inflammatory cytokine/chemokine responses resulting in acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Recent studies in experimentally infected animal strongly suggest a crucial role for virus-induced immunopathological events in causing fatal pneumonia after hCoV infections. Here we review the current understanding of how a dysregulated immune response may cause lung immunopathology leading to deleterious clinical manifestations after pathogenic hCoV infections.

Coronavirus 2019-nCoV: A brief perspective from the front line

“…2 , 5 Previous studies indicated that viral evasion of host maladjusted immune responses are believed to play critical roles in acute lung injury (ALI), in addition to CoVs-induced direct cytopathic effects. 5 Indeed, changes of some immune index have been detected in the CoVs infection patients, such as lymphopenia, monocytosis and elevated cytokine levels. 2 , 5 , 25 The treatment of corticosteroids may reduce the risk of lung inflammation but also delay CoVs clearance in addition to other side effects.…”

Middle East respiratory syndrome

“…MERS-CoV pathogenesis reflects a balance between coronavirus-induced protective and pathogenic host immune responses and direct cytotoxic effects of the virus. 52 According to studies of patients infected with SARS-CoV and of mice and other animals infected experimentally with MERS-CoV, successful resolution of MERS and long-term protection from re-infection likely requires well coordinated innate and adaptive B-cell and T-cell responses. In patients with SARS, innate immune responses characterised by an extended period of cytokine secretion (eg, IFNα and IFNβ) was correlated with delayed antibody responses and poor management outcomes; this prolonged innate response has not yet been shown in patients infected with MERS-CoV.…”

MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract

“…According to the statistics provided by the World Health Organization (WHO) on June 10, 2019, a total of 2428 laboratory-confirmed cases of human MERS-CoV infection have been reported, with an estimated 838 deaths in 27 countries. The accumulated evidence suggested that MERS-CoV infections are characterized by high levels of systemic inflammatory cytokines/chemokines as well as immunopathology [4][5][6][7][8][9][10][11]. High inflammatory cytokines and chemokines levels have been strongly correlated with poor disease outcomes, immunopathology and massive infiltration of the immune inflammatory cells into the lungs [10,12].…”

“…High inflammatory cytokines and chemokines levels have been strongly correlated with poor disease outcomes, immunopathology and massive infiltration of the immune inflammatory cells into the lungs [10,12]. Moreover, the stimulation of various cytokines, chemokines and innate immune cells has been associated with the appearance of cytokine storms, which occur during infections with pathogenic coronavirus (CoV) and influenza virus [6,13,14]. In addition, increased IL-8 (CXCL8) levels play a key role in acute SARS https://doi.org/10.1016/j.cyto.2019.154895 Received 10 June 2019; Received in revised form 14 October 2019; Accepted 17 October 2019 infection, viral bronchiolitis pathogenesis, severe immunopathology, and disease enhancement during respiratory syncytial virus (HRSV) infection [10,12,[15][16][17].…”