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Relationship: 2358

Title

A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream). More help

SARS-CoV-2 production leads to Diminished Protective Response to ROS

Upstream event
The causing Key Event (KE) in a Key Event Relationship (KER). More help
SARS-CoV-2 production
Downstream event
The responding Key Event (KE) in a Key Event Relationship (KER). More help
Diminished Protective Response to ROS

Key Event Relationship Overview

The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE. More help

AOPs Referencing Relationship

AOP Name Adjacency Weight of Evidence Quantitative Understanding Point of Contact Author Status OECD Status
Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation adjacent Moderate Not Specified Arthur Author (send email) Under development: Not open for comment. Do not cite Under Development
SARS-CoV-2 infection leading to hyperinflammation adjacent Arthur Author (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER.  More help
Term Scientific Term Evidence Link
human Homo sapiens Moderate NCBI

Sex Applicability

An indication of the the relevant sex for this KER. More help
Sex Evidence
Unspecific Moderate

Life Stage Applicability

An indication of the the relevant life stage(s) for this KER.  More help
Term Evidence
All life stages Moderate

Key Event Relationship Description

Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves. More help

ROS is generated upon the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19), and induces oxidative stress (Janardhan VV and Kalousek V, 2020). SARS-CoV-2 infection induces cytokine storm (Frisoni P et al., 2021, Kaidashev I et al., 2021). Cytokine storm includes ROS-induced oxidative stress and immune cell dysregulation. Glutathione S-transferase genes, which have functions in the elimination of ROS, involves the morbidity and mortality from COVID-19 (Kaidashev I et al., 2021). The heme oxygenase-1 (HO-1) induction may be involved in the inflammation-induced coagulation in COVID-19 (Kaidashev I et al., 2021). ROS quenching by vitamin C, E, beta-carotene and polyphenols has been suggested in COVID-19 in the point of view of the nutrient, since oxidative stress causes inflammation (Iddir M et al., 2020). Potential roles of omega-3 fatty acids accompanied by antioxidants have been suggested in the cytokine storm due to SARS-CoV-2 infection (Rogero MM, 2020).

Evidence Collection Strategy

Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings.  Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible. More help

References were selected based on the knowledge. The evidence was collected with literature search with key words including "reactive oxygen species" and "SARS-CoV-2" and NRF2. Some of the content of the literature has been summarized in Editorial (Tanabe S, 2021).

Evidence Map 2.0

ID Experimental Design Species Upstream Observation Downstream Observation Citation (first author, year) Notes

Evidence Map

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help
Title First Author
Biological Plausibility
Dose Concordance
Temporal Concordance
Incidence Concordance
Biological Plausibility
Dose Concordance Evidence
Temporal Concordance Evidence
Incidence Concordance Evidence
Uncertainties and Inconsistencies
Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance. More help

The transient up-regulation of ROS may serve as an inhibitory factor of pathogen (Zhu et al., 2021).

Known modulating factors

This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references.  More help
Modulating Factor (MF) MF Specification Effect(s) on the KER Reference(s)
Selenium      
Vitamin D      

Domain of Applicability

A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms. More help

The KER applies to species including Homo sapiens which have ACE2 receptors to bind to SARS-CoV-2 and protective responsive system to ROS, as ROS scavenging system. The KER has relatively broad applicability among Homo sapiens.