Deciphering SARS-CoV-2 Virologic and Immunologic Features

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 and its associated pathology, COVID-19, have been of particular concerns these last months due to the worldwide burden they represent. The number of cases requiring intensive care being the critical point in this epidemic, a better understanding of the pathophysiology leading to these severe cases is urgently needed. Tissue lesions can be caused by the pathogen or can be driven by an overwhelmed immune response. Focusing on SARS-CoV-2, we and others have observed that this virus can trigger indeed an immune response that can be dysregulated in severe patients and leading to further injury to multiple organs. The purpose of the review is to bring to light the current knowledge about SARS-CoV-2 virologic and immunologic features. Thus, we address virus biology, life cycle, tropism for many organs and how ultimately it will affect several host biological and physiological functions, notably the immune response. Given that therapeutic avenues are now highly warranted, we also discuss the immunotherapies available to manage the infection and the clinical outcomes.

Keywords: COVID-19; SARS-CoV-2; immunopathology; immunotherapy; virus biology.

Figure 1

SARS-CoV-2 supposed life cycle. (A) Entry of SARS-CoV-2 in target cell expressing ACE2 (or another receptor, CD147 have been evoked but need to be confirmed). (B) Uncoating and releasing SARS-CoV-2 single stranded positive RNA genome. (C) Translation of replicase–transcriptase complex directly from RNA genome. (D) RNA genome replication due to a negative template. (E) Nested production of subgenomic RNA encoding for structural proteins. (F) Translation of viral S, E and M inserted in endoplasmic reticulum. (G) Nucleocapsid coupled to the genome, forming nucleoprotein, combine to S, E and M to form a mature virion (H). (I) Exocytosis of SARS-CoV-2.

Figure 2

The two evoked routes of entry for SARS-CoV-2 to date. Angiotensin-converting-enzyme 2 (ACE2), which has been described as an interferon-stimulated gene (ISG), is a route of entry for SARS-CoV-2. Additionally, CD147 is evoked as a potential second route of entry. Based on a previous study with SARS-CoV, an interaction with Cyclophilin A is possible. The blue background corresponds to cells expressing ACE2, whereas the red background is representing cells expressing CD147. Solid arrows correspond to a direct activity involving ACE2, dotted arrows correspond to an indirect promoting activity.

Figure 3

Tropism and multiple organ injuries in SARS-CoV-2 infection. SARS-CoV-2 infection has been associated with multiple organ injuries due to viral tropism. Among injured organs (and targeted cell) we can find: lung (type II pneumocyte), heart (cardiomyocyte), liver (cholangiocyte), spleen and lymph nodes (macrophage), kidney and brain.

Figure 4

Mild versus severe immune response during SARS-CoV-2 infection. In regards to cytokine signature during SARS-CoV-2, mild and moderate cases showed a controlled response with higher expression of IL-1β, IL-1RA, IL-2RA, IL-6, IL-7, IL-8, IL-9, IL-10, basic FGF, G-CSF, GM-CSF, HGF, IFNγ, IP-10, MCP-1, MIP-1a, MIP-1b, PDGF, TNF-α and VEGF. While, a cytokine-induced immunopathological mechanism has been observed with an increase of IL-2, IL-7, IL-17, IL-10, MCP-1, MIP-1a and TNF-α in severe cases, leading to a bystander effect.

Figure 5

Viral sensing, innate antiviral response and immune evasion. Potential mechanisms of SARS-CoV-2 immune evasion based on previous studies on MERS-CoV (brown) and SARS-CoV (blue). Some mechanisms are inhibiting viral sensing, whereas others are directed against the innate antiviral response. Solid arrows correspond to a direct promoting activity, dotted arrows correspond to an indirect promoting activity and T-bars correspond to a direct inhibitory activity.