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Involvement of nasopharyngeal angiotensin converting enzyme 2 in severe acute respiratory coronavirus 2 infection and transmission Nikiforuk, Aidan McKerrell


Introduction: The angiotensin converting enzyme two (ACE2) protein serves as the host receptor for the severe acute respiratory syndrome coronavirus two (SARS-CoV-2). We aim to understand if transcription of ACE2 can be reliably detected in diagnostic specimens collected by nasopharyngeal swab and if a relationship exists between availability of ACE2 in the upper human respiratory tract, SARS-CoV-2 viral load, and secondary transmission. Methods: Measurements of ACE2 transcription and SARS-CoV-2 viral load were taken by targeted ribonucleic acid sequencing (RNA-Seq) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Alternative measures of ACE2 transcription were compared using bivariate statistical analysis to quantify instrument bias. Viral load was only measured by RT-qPCR. A cross-sectional study of n = 424 people who tested positive (n = 212) or negative (n = 212) for SARS-CoV-2 was performed to observe the association between ACE2 transcription and SARS-CoV-2 viral load. Statistical analysis involved bivariate testing and multivariable linear regression. To assess involvement of ACE2 in transmission of SARS-CoV-2, nasopharyngeal ACE2 transcription was measured in confirmed cases from hospital associated outbreaks. An infection tracing transmission network and multivariable Poisson/Negative Binomial regression was used for analysis. Results: No instrument bias was detected. In COVID-19 negative participants nasopharyngeal ACE2 transcription had no relationship with biological sex (P = 0.832) or age (P = 0.092), in adults over the age of 18. Regardless, nasopharyngeal ACE2 transcription varied greatly between SARS-CoV-2 negative participants indicating inter-individual heterogeneity. In COVID-19 positive participants the association between ACE2 transcription and SARS-CoV-2 viral load differed by isoform. Transmembrane ACE2 transcription positively correlated (β = 0.89, 95%CI: [0.59 to 1.18]) while the putative soluble transcript had a negative association (β = -0.099, 95%CI: [-0.18 to -0.022]). The infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. High ACE2 transcription was observed in 98.6% of transmission events. In patients, ACE2 transcription was associated with an increased in the number of secondary cases (β = 0.187 (95% CI: 0.0101 to 0.370) adjusting for viral load. Conclusion: ACE2 expression in the upper respiratory tract may differentiate an individual’s risk of SARS-CoV-2 infection and likelihood of transmission.

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