First-pass extracted concept

ACE2 degradation hypothesis of COVID-19 severity

Candidate: concept label1 source documents4 linked claims

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Extracted Explainers

What the tool is doing

This concept links ACE2 loss or degradation to amplified inflammatory signaling and more severe COVID-19 outcomes.

Source 1DOI

What problem it solves

It aims to reconcile apparently contradictory observations about ACE2 abundance and age-dependent COVID-19 severity.

Source 1DOI

What it does not solve

The abstract does not show direct experimental proof that SARS-CoV-2 causes ACE2 degradation in human tissues.

Source 1DOI

Evidence Snippets

Here we propose that ACE2 contributes essentially to reverse this inflammatory state ... and that failure to do this, possibly induced by the degradation of ACE2 by SARS-COV-2, may underlie both severe CoViD-19 infection and its many post-infection manifestations, including the multi-inflammatory syndrome of children (MIS-C).

Evidence 1Source 1DOIprovenance

Supporting Sources

Source 1primary paper2022Frontiers in Drug DiscoveryDOI

1 evidence snippet 4 linked claims Claim 1 Claim 2 Claim 3

Linked Claims

Claim 1age expression relationshipsupports2022Source 1DOI

ACE2 level is not monotonically related to age, but instead reaches a maximum at a young age and then decreases in a cell-type-dependent manner.

Claim 2disease mechanism hypothesissupports2022Source 1DOI

Failure of ACE2 to reverse the pro-inflammatory angiotensin-bradykinin state, possibly induced by SARS-CoV-2-mediated ACE2 degradation, may underlie severe COVID-19 and post-infection manifestations including MIS-C.

Claim 3mechanistic relationshipsupports2022Source 1DOI

Age-associated increase in TACE/ADAM17 is proposed to drive ACE2 shedding from the cell membrane to serum, causing ACE2 cell protein to decline earlier and more steeply than ACE2 mRNA.

Claim 4mechanistic relationshipsupports2022Source 1DOI

Higher viral receptor abundance does not necessarily favor virus propagation and can even slow it down according to a mathematical model discussed by the authors.