The Immune Response and Immunopathology of COVID-19

Abstract

Coronaviruses were first discovered in the 1960s and are named due to their crown-like shape. Sometimes, but not often, a coronavirus can infect both animals and humans. An acute respiratory disease, caused by a novel coronavirus (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 previously known as 2019-nCoV) was identified as the cause of coronavirus disease 2019 (COVID-19) as it spread throughout China and subsequently across the globe. As of 14th July 2020, a total of 13.1 million confirmed cases globally and 572,426 deaths had been reported by the World Health Organization (WHO). SARS-CoV-2 belongs to the β-coronavirus family and shares extensive genomic identity with bat coronavirus suggesting that bats are the natural host. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as that for SARS-CoV, the coronavirus associated with the SARS outbreak in 2003. It mainly spreads through the respiratory tract with lymphopenia and cytokine storms occuring in the blood of subjects with severe disease. This suggests the existence of immunological dysregulation as an accompanying event during severe illness caused by this virus. The early recognition of this immunological phenotype could assist prompt recognition of patients who will progress to severe disease. Here we review the data of the immune response during COVID-19 infection. The current review summarizes our understanding of how immune dysregulation and altered cytokine networks contribute to the pathophysiology of COVID-19 patients.

Keywords: IL-6; SARS-CoV; SARS-CoV-2; coronavirus; cytokines storm; pathogenesis.

FIGURE 1

Schematic immune responses to CoVs. (A) When the SARS-CoV-2 virus invades the host, it is first recognized by the angiotensin converting enzyme (ACE) 2 receptor present on respiratory epithelial cells allowing viral entry. Following viral replication within the cells, the virus is released where it is met by the host’s innate immune system. T lymphocytes and dendritic cells are activated through pattern recognition receptors (PRRs) including C-type lectin-like receptors, Toll-like receptor (TLR), NOD-like receptor (NLR), and RIG-I-like receptor (RLR). The virus induces the expression of numerous inflammatory factors, maturation of dendritic cells, and the synthesis of type I interferons (IFNs) which limits the viral spread and accelerates macrophage phagocytosis of viral antigens resulting in clinical recovery. However, the N protein of SARS-CoV can help the virus escape from the immune responses and overreaction of the immune system generates high levels of inflammatory mediators and free radicals. These induce severe local damage to the lungs and other organs, and, in the worst scenario, multi-organ failure and even death. (B) The adaptive immune response joins the fight against the virus. T lymphocytes including CD4 + and CD8 + T cells play an important role in this defense. CD4 + T cells stimulate B cells to produce virus-specific antibodies whilst CD8 + T cells are able to directly kill virus-infected cells. T helper cells produce pro-inflammatory cytokines to help the defending cells. However, SARS-CoV-2 can inhibit T cells by inducing programmed cell death (apoptosis). (C) Humoral immunity including complement factors such as C3a and C5a and specific B cell-derived antibodies are also essential in combating SARS-CoV-2 infection.