The Contrasting Role of Nasopharyngeal Angiotensin Converting Enzyme 2 ( <i>ACE2</i> ) Expression in SARS-CoV-2 Infection: A Cross-Sectional Study of People Tested for COVID-19 in British Columbia
Bibliographic record
Abstract
Summary Background Angiotensin converting enzyme 2 ( ACE2 ) 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 expression in people tested for COVID-19 and the relationship between ACE2 expression and SARS-CoV-2 viral RNA load, while adjusting for expression of the complementary protease, Transmembrane serine protease 2 ( TMPRSS2) , soluble ACE2 , age, and biological sex. Methods A cross-sectional study of n=424 participants aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Participants who tested negative or positive for COVID-19 were matched by age and biological sex. Viral and host gene expression was measured 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. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. Findings Analysis shows no association between age and nasopharyngeal ACE2 expression in those who tested negative for COVID-19 (P=0·092). Mean expression of transmembrane (P=1·2e-4), soluble ACE2 (P<0·0001) and TMPRSS2 (P<0·0001) differed between COVID-19-negative and -positive groups. In bivariate analysis of COVID-19-positive participants, expression of transmembrane ACE2 positively correlated with SARS-CoV-2 RNA viral load (P<0·0001), expression of soluble ACE2 negatively correlated (P<0·0001), and no correlation was found with TMPRSS2 (P= 0·694 ) . Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 expression ( B =0·886, 95%CI:[0·596 to 1·18]), while expression of soluble ACE2 may protect against high viral RNA load in the upper respiratory tract ( B = −0·0990, 95%CI:[−0·176 to −0·0224]). Interpretation Nasopharyngeal ACE2 expression plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transmembrane ACE2 positively correlates, while soluble ACE2 negatively correlates with viral RNA load after adjusting for age, biological sex and expression of TMPRSS2. Funding This project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".