The deciphering of the immune cells and marker signature in COVID-19 pathogenesis: An update

Abstract

The precise interaction between the immune system and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in deciphering the pathogenesis of coronavirus disease 2019 (COVID-19) and is also vital for developing novel therapeutic tools, including monoclonal antibodies, antivirals drugs, and vaccines. Viral infections need innate and adaptive immune reactions since the various immune components, such as neutrophils, macrophages, CD4⁺ T, CD8⁺ T, and B lymphocytes, play different roles in various infections. Consequently, the characterization of innate and adaptive immune reactions toward SARS-CoV-2 is crucial for defining the pathogenicity of COVID-19. In this study, we explain what is currently understood concerning the conventional immune reactions to SARS-CoV-2 infection to shed light on the protective and pathogenic role of immune response in this case. Also, in particular, we investigate the in-depth roles of other immune mediators, including neutrophil elastase, serum amyloid A, and syndecan, in the immunopathogenesis of COVID-19.

Keywords: COVID-19; adaptive immunity; innate immunity; neutrophil elastase; pathogenesis; syndecan.

Figure 1

. The schematic representation of SARS‐CoV‐2 pathophysiology. (A) SARS‐CoV‐2 enters the body primarily through cells in the nasal cavity and the upper and lower respiratory tracts. (B) Several PRRs that identify foreign RNA, such as endosomal TLR3 and TLR7, and cytoplasmic RIG‐I and MDA5, are thought to be involved in recognizing SARS‐CoV‐2. Results from genetic research, functional and clinical findings, interaction modeling, and CRISPR screens are used to estimate downstream signaling occurrences. Direct communication among viral or host proteins and interplay among SARS‐CoV‐2‐derived proteins and cellular mechanisms as defined by interaction mapping derived information. ORF3b was found to be functionally active in the suppression of type I IFN, but no specific target was recognized. CRISPR, clustered regularly interspaced short palindromic repeat; IFN, interferon; MDA5, melanoma differentiation‐associated protein 5; ORF, open reading frame; PRR, pattern recognition receptor; TLR, Toll‐like receptor; RIG‐I, retinoic acid‐inducible gene I; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.

Figure 2

The schematic representation of the immune reaction against SARS‐CoV‐2. When SARS‐CoV‐2 infects the epithelium, cells may undergo lysis and significant injury to the epithelial cell during virus replication. The viral antigens were presented to CD8⁺ T cells by the epithelial cell. CD8⁺ T cells and NK cells could cytolyze the endothelial cells infected by SARS‐CoV‐2 with their perforin and granzymes, causing programmed cell death (apoptosis). DC in subepithelial recognize SARS‐CoV‐2 antigens and then the processed antigens presented to the T CD4⁺, causing these T cells to differentiate toward memory Th1, Th17, and memory TFH. TFH supports the development of B cells into PC and the development of specific antibodies against SARS‐CoV‐2 (IgA, IgM, and IgG). Moreover, SARS‐CoV‐2 antigens were presented to the T CD4⁺ cells by DCs and tissue MΦ. DC, dendritic cell; Ig, immunoglobulin; MΦ, macrophage; NK, natural killer; PC, plasma cells; TFH, T follicular helper cells; Th, helper T cell; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.