The contrasting role of nasopharyngeal angiotensin converting enzyme 2 (ACE2) transcription in SARS-CoV-2 infection: A cross-sectional study of people tested for COVID-19 in British Columbia, Canada.
EBioMedicine
; 66: 103316, 2021 Apr.
Article
in English
| MEDLINE | ID: covidwho-1163668
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
BACKGROUND:
Angiotensin converting enzyme 2 (ACE2) protein serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 transcription in people tested for COVID-19 and the relationship between ACE2 transcription and SARS-CoV-2 viral load, while adjusting for expression of (i) the complementary protease, Transmembrane serine protease 2 (TMPRSS2), (ii) soluble ACE2, (iii) age, and (iv) biological sex. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts.METHODS:
A cross-sectional study of n = 424 "participants" aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Patients who tested positive for COVID-19 were matched by age and biological sex to patients who tested negative. Viral load and host gene expression were assessed by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection.FINDINGS:
Analysis showed no association between age and nasopharyngeal ACE2 transcription in those who tested negative for COVID-19 (P = 0â¢092). Mean relative transcription of transmembrane (P = 0â¢00012) and soluble (P<0â¢0001) ACE2 isoforms, as well as TMPRSS2 (P<0â¢0001) was higher in COVID-19-negative participants than COVID--19 positive ones, yielding a negative correlation between targeted host gene expression and positive COVID-19 diagnosis. In bivariate analysis of COVID-19-positive participants, transcription of transmembrane ACE2 positively correlated with SARS-CoV-2 viral RNA load (B = 0â¢49, R2=0â¢14, P<0â¢0001), transcription of soluble ACE2 negatively correlated (B= -0â¢85, R2= 0â¢26, P<0â¢0001), and no correlation was found with TMPRSS2 transcription (B= -0â¢042, R2=<0â¢10, P = 0â¢69). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 transcription (Β= 0â¢89, 95%CI [0â¢59 to 1â¢18]), while transcription of the soluble isoform appears to protect against high viral RNA load in the upper respiratory tract (Β= -0â¢099, 95%CI [-0â¢18 to -0â¢022]).INTERPRETATION:
Nasopharyngeal ACE2 transcription plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transcription of the transmembrane ACE2 isoform positively correlates, while transcription of the soluble isoform negatively correlates with viral RNA load after adjusting for age, biological sex, and transcription of TMPRSS2.FUNDING:
This project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Nasopharynx
/
Angiotensin-Converting Enzyme 2
/
COVID-19 Testing
/
COVID-19
Type of study:
Diagnostic study
/
Observational study
/
Randomized controlled trials
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
North America
Language:
English
Journal:
EBioMedicine
Year:
2021
Document Type:
Article
Affiliation country:
J.ebiom.2021.103316
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