Nasopharyngeal Angiotensin Converting Enzyme 2 (ACE2) Expression as a Risk-Factor for SARS-CoV-2 Transmission in Concurrent Hospital Associated Outbreaks

Abstract

AbstractBackgroundWidespread human-to-human transmission of the severe acute respiratory syndrome coronavirus two (SARS-CoV-2) stems from a strong affinity for the cellular receptor angiotensin converting enzyme two (ACE2). We investigate the relationship between a patient’s nasopharyngealACE2transcription and secondary transmission within a series of concurrent hospital associated SARS-CoV-2 outbreaks in British Columbia, Canada.MethodsEpidemiological case data from the outbreak investigations was merged with public health laboratory records and viral lineage calls, from whole genome sequencing, to reconstruct the concurrent outbreaks using infection tracing transmission network analysis.ACE2transcription and RNA viral load were measured by quantitative real-time polymerase chain reaction. The transmission network was resolved to calculate the number of potential secondary cases. Bivariate and multivariable analyses using Poisson and Negative Binomial regression models was performed to estimate the association betweenACE2transcription the number of SARS-CoV-2 secondary cases.ResultsThe infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. Bivariate comparisons found that on averageACE2transcription did not differ between patients and healthcare workers (P = 0.86). HighACE2transcription was observed in 98.6% of transmission events, either the primary or secondary case had above averageACE2. Multivariable analysis found that the association betweenACE2transcription and the number of secondary transmission events differs between patients and healthcare workers. In health care workers Negative Binomial regression estimated that a one unit change inACE2transcription decreases the number of secondary cases (B = −0.132 (95%CI: −0.255 to −0.0181) adjusting for RNA viral load. Conversely, in patients a one unit change inACE2transcription increases the number of secondary cases (B = 0.187 (95% CI: 0.0101 to 0.370) adjusting for RNA viral load. Sensitivity analysis found no significant relationship betweenACE2and secondary transmission in health care workers and confirmed the positive association among patients.ConclusionOur study suggests thatACE2transcription has a positive association with SARS-CoV-2 secondary transmission in admitted inpatients, but not health care workers in concurrent hospital associated outbreaks, and it should be further investigated as a risk-factor for viral transmission.