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. 2020 Jul 3:11:1642.
doi: 10.3389/fimmu.2020.01642. eCollection 2020.

Establishing a Unified COVID-19 "Immunome": Integrating Coronavirus Pathogenesis and Host Immunopathology

Els Wauters  1 , Karin Thevissen  2 , Carine Wouters  3   4 , Francesca Maria Bosisio  5 , Frederik De Smet  6 , Jan Gunst  7 , Stephanie Humblet-Baron  8 , Diether Lambrechts  9 , Adrian Liston  10 , Patrick Matthys  11 , Johan Neyts  12 , Paul Proost  13 , Birgit Weynand  14 , Joost Wauters  15 , Sabine Tejpar  16 , Abhishek D Garg  17
Affiliations
Free PMC article

Establishing a Unified COVID-19 "Immunome": Integrating Coronavirus Pathogenesis and Host Immunopathology

Els Wauters et al. Front Immunol. .
Free PMC article
No abstract available

Keywords: B-cells; SARS coronavirus; T-cell exhaustion; biomarkers; cytokine storm; interferons (IFNs); macrophages; neutrophils.

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Figures

Figure 1
Figure 1
A unified COVID-19 “immunome” model integrating lung-associated pathophysiology with systemic immunopathology, together accounting for the SARS-CoV-2/COVID19 immunological paradigm. SARS-CoV-2 exhibits increased (direct) tropism toward ACE2+ epithelial cells within the lungs and upper-airways that, due to viral replication, ultimately results in epithelial cell death and epithelium disruption. This is paralleled by disruption of type I interferon (IFN) responses within infected cells, possibly due to direct interference by SARS-CoV-2 derived anti-IFN modules. This is accompanied by release of damage-associated molecular patterns (DAMPs; coming from dying/dead epithelial cells) as well as pathogen-associated molecular patterns (PAMPs; coming from viral genetic material and immunogenic proteins). These events, together with the above viral pathogenic events, fuel dysregulated myeloid hyperinflammation. In addition, through as-yet-unclear mechanisms, SARS-CoV-2 may also exert direct or indirect cytopathic effects on myeloid immune cells, thereby further facilitating immune dysregulation. These events together characterize the COVID-19-associated ARDS phenotype. This ARDS can: (I) on one hand, facilitate systemic cytokine-driven hyperinflammation; yet (II) on the other hand, stress the lymphoid organs by demanding increased recruitment of immune cells for resolution of inflammation. Such prolonged immunological stress accompanied by cytokine-based inflammation facilitates lymphopenia, typically observed in COVID-19 patients (and may also cause lymphoid organ failure if this stressful situation prolongs, as seen in some critically ill patients). Herein, there is some evidence that SARS-CoV-2 may exert (in)direct cytopathic effects against lymphocytes thereby further fuelling lymphopenia. Together these processes define the overall immunological phenotypes or inclusive phenome (i.e., “immunome”) of COVID-19.
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