Fig. 5.
Schematic representation of a simplified narrative scenario model of uncontrolled dysregulated, DAMP-promoted pathways in light of the exposome and AOP concepts. The figure illustrates the sequelae of key events proposed to leading to ARDS and SIRS, reflecting the adverse outcome in COVID-19. The promoted dysregulated pathways leading to COVID-19 starts with the sequelae of events (MIE → KE4→n) as described for the controlled pathway (Fig. 3). However, instead of proceeding to homeostatic events, the DAMP-induced pathways now provoke “pathogenic” KEs key events resulting in ARDS and/or SIRS/sepsis. The triggering “aberrant” event is the fifth KE that refers to pulmonary hyperinflammation, as characterized by intrapulmonary emission of DAMPs in excessive, which may spread out systemically. The adverse outcomes refer to ARDS and/or SIRS/sepsis. AO adverse outcome, ARDS acute respiratory distress syndrome, DAMPs damage-associated molecular patterns, KE key event, KER key event relationship, MAMPs microbe-associated molecular patterns, MIE molecular initiating event, PRMs pattern recognition molecules, SIRS systemic inflammatory response syndrome.
Source: Land (2018)