Serum alkaline phosphatase in ankylosing spondylitis.

Abstract

<h3>Summary</h3> <h3>Background</h3> Angiotensin converting enzyme 2 (<i>ACE2</i>) 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 <i>ACE2</i> expression in people tested for COVID-19 and the relationship between <i>ACE2</i> expression and SARS-CoV-2 viral RNA load, while adjusting for expression of the complementary protease, Transmembrane serine protease 2 (<i>TMPRSS2)</i>, soluble <i>ACE2</i>, age, and biological sex. <h3>Methods</h3> 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 <i>ACE2</i> expression in SARS-CoV-2 infection. The <i>ACE2</i> gene was targeted to measure expression of transmembrane and soluble transcripts. <h3>Findings</h3> Analysis shows no association between age and nasopharyngeal <i>ACE2</i> expression in those who tested negative for COVID-19 (P=0·092). Mean expression of transmembrane (P=1·2e-4), soluble <i>ACE2</i> (P&lt;0·0001) and <i>TMPRSS2</i> (P&lt;0·0001) differed between COVID-19-negative and -positive groups. In bivariate analysis of COVID-19-positive participants, expression of transmembrane <i>ACE2</i> positively correlated with SARS-CoV-2 RNA viral load (P&lt;0·0001), expression of soluble <i>ACE2</i> negatively correlated (P&lt;0·0001), and no correlation was found with <i>TMPRSS2 (P=</i>0·694<i>)</i>. Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane <i>ACE2</i> expression (<i>B</i>=0·886, 95%CI:[0·596 to 1·18]), while expression of soluble <i>ACE2</i> may protect against high viral RNA load in the upper respiratory tract (<i>B</i>= −0·0990, 95%CI:[−0·176 to −0·0224]). <h3>Interpretation</h3> Nasopharyngeal <i>ACE2</i> expression plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transmembrane <i>ACE2</i> positively correlates, while soluble <i>ACE2</i> negatively correlates with viral RNA load after adjusting for age, biological sex and expression of TMPRSS2. <h3>Funding</h3> This project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.