The Comparative Immunological Characteristics of SARS-CoV, MERS-CoV, and SARS-CoV-2 Coronavirus Infections

Abstract

Immune dysfunction and aberrant cytokine storms often lead to rapid exacerbation of the disease during late infection stages in SARS-CoV and MERS-CoV patients. However, the underlying immunopathology mechanisms are not fully understood, and there has been little progress in research regarding the development of vaccines, anti-viral drugs, and immunotherapy. The newly discovered SARS-CoV-2 (2019-nCoV) is responsible for the third coronavirus pandemic in the human population, and this virus exhibits enhanced pathogenicity and transmissibility. SARS-CoV-2 is highly genetically homologous to SARS-CoV, and infection may result in a similar clinical disease (COVID-19). In this review, we provide detailed knowledge of the pathogenesis and immunological characteristics of SARS and MERS, and we present recent findings regarding the clinical features and potential immunopathogenesis of COVID-19. Host immunological characteristics of these three infections are summarised and compared. We aim to provide insights and scientific evidence regarding the pathogenesis of COVID-19 and therapeutic strategies targeting this disease.

Keywords: MERS-CoV; SARS-CoV; SARS-CoV-2; immunology; novel coronavirus.

Figure 1

Potential immunopathogenesis in SARS-CoV-2 infection. This figure shows the potential immunopathogenesis during SARS-CoV-2 infection, inferred from previous SARS-CoV and MERS-CoV studies. Coloured boxes labelled the potential strategies or deleterious events involved in SARS-CoV-2 pathogenesis. Words below each box indicate the pathological consequences. Dashed arrows indicate causal relations between target cell and cell mediators. (A) Initially host-viral entry was found at alveoli epithelial. The virus invades host defences via binding with ACE2 by S-protein RBD. Abortive infection was observed in PBMC and haematopoietic cells—a process that induces expression of pro-inflammatory mediators rather than effective viral production. Another potential viral entry strategy relies on the presence of specific antibodies that form bridges between viral-host and facilitate viral entry rather than expressing ADCC effect. SARS-CoV-2 might have evolved to encode specific proteins to counteract the host anti-viral response and optimise viral entry. Strategies such as interferon antagonism (not shown on the figure) allow viral evasion and prolonged viral shedding. (B) Regarding the host immune response, increased viral loads, and chemokines from abortive infection further enhance infiltration of IMM, an intense release of inflammatory cytokines that results in lung tissue injuries. Delayed viral clearance, aberrant cytokine production, and altered interferon levels hinder the proper functioning of the immune system, such as shifting of functional phenotype in macrophages and lymphocytes which would result in the impaired wound-healing function T cell apoptosis, pathogenic T cell response, functional exhaustion, dysregulated cytokine storm (i.e., MAS/HLH) and impaired viral clearance. Cascades activation of cytokine and chemokine ultimately led to systemic cytokine storm, manifested as sepsis, DIC, haemorrhage, and shock. RBD, receptor binding-domain; ADCC, antibody-dependent cell-mediated cytotoxicity; ACE2, Angiotensin-converting enzyme 2; pDC, Plasmacytoid dendritic cell; IMM, Inflammatory monocyte/macrophage; MAS, macrophage activation syndrome; HLH, Hemophagocytic lymphohistiocytosis; DIC, Disseminated intravascular coagulation.