Elsevier

Medical Hypotheses

Volume 143, October 2020, 110117
Medical Hypotheses

Kawasaki-like disease in children with COVID-19: A hypothesis

https://doi.org/10.1016/j.mehy.2020.110117Get rights and content

Abstract

With rapid spread of severe acute respiratory syndrome- corona virus-2 (SARS-COV-2) globally, some new aspects of the disease have been reported. Recently, it has been reported the incidence of Kawasaki-like disease among children with COVID-19. Since, children had been known to be less severely affected by the virus in part due to the higher concentration of Angiotensin converting enzyme (ACE)-2 receptor, this presentation has emerged concerns regarding the infection of children with SARS-COV2. ACE2 has anti-inflammatory, anti-fibrotic and anti-proliferative characteristics through converting angiotensin (Ag)-II to Ang (1–7). ACE2 receptor is downregulated by the SARS-COV through the spike protein of SARS-CoV (SARS-S) via a process that is tightly coupled with Tumor necrosis factor (TNF)-α production. TNF-α plays a key role in aneurysmal formation of coronary arteries in Kawasaki disease (KD). Affected children by COVID-19 with genetically-susceptible to KD might have genetically under-expression of ACE2 receptor that might further decrease the expression of ACE2 due to the downregulation of the receptor by the virus in these patients. It appears that TNF- α might be the cause and the consequence of the ACE2 receptor downregulation which results in arterial walls aneurysm. Conclusion: Genetically under-expression of ACE2 receptor in children with genetically-susceptible to KD who are infected with SARS-CoV-2 possibly further downregulates the ACE2 expression by TNF-α and leads to surge of inflammation including TNF-α and progression to Kawasaki-like disease.

Abbreviations

COVID-19
coronavirus disease-2019
SARS-CoV-2
severe acute respiratory syndrome- corona virus-2
MAS
macrophage activation syndrome
KD
Kawasaki disease
HCOV-NH
human corona virus-new haven
TNF- α
tumor necrosis factor-α
MMP
matrix metalloproteinase
ECM
extra cellular matrix
INF
interferon
IL
interleukin
TGF
tumor growth factor
CCL
chemokine ligand
CXCL
C-X-C motif chemokine ligand
ACE2
angiotensin converting enzyme2
RAS
renin angiotensin system
Ag II
angiotensin-II
AT1
angiotensin receptor type 1
Ang (1–7)
angiotensin (1–7)

Keywords

Kawasaki disease
Kawasaki-like disease
SARS-CoV2
ACE2 receptor
TNF- α
Downregulation

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