Nasopharyngeal angiotensin converting enzyme 2 (ACE2) expression as a risk-factor for SARS-CoV-2 transmission in concurrent hospital associated outbreaks.

Publication date: Feb 26, 2024

Widespread 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 nasopharyngeal ACE2 transcription and secondary transmission within a series of concurrent hospital associated SARS-CoV-2 outbreaks in British Columbia, Canada. Epidemiological 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. ACE2 transcription 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 between ACE2 transcription the number of SARS-CoV-2 secondary cases. The infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. Bivariate comparisons found that on average ACE2 transcription did not differ between patients and healthcare workers (P = 0. 86). High ACE2 transcription was observed in 98. 6% of transmission events, either the primary or secondary case had above average ACE2. Multivariable analysis found that the association between ACE2 transcription (log fold-change) 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 in ACE2 transcription decreases the number of secondary cases (β = -0. 132 (95%CI: -0. 255 to -0. 0181) adjusting for RNA viral load. Conversely, in patients a one-unit change in ACE2 transcription increases the number of secondary cases (β = 0. 187 (95% CI: 0. 0101 to 0. 370) adjusting for RNA viral load. Sensitivity analysis found no significant relationship between ACE2 and secondary transmission in health care workers and confirmed the positive association among patients. Our study suggests that ACE2 transcription 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.

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Concepts Keywords
Canada ACE2
Coronavirus Infection tracing
Inpatients Multivariable analysis
Polymerase Negative binomial regression
Outbreak investigation
Poisson regression model
Transmission network


Type Source Name
drug DRUGBANK Angiotensin II
disease VO Canada
disease MESH infection
disease VO time
disease MESH Infectious Diseases
disease MESH COVID 19
disease MESH emergencies
disease MESH severe acute respiratory syndrome
disease MESH Middle East respiratory syndrome
disease VO organization
disease VO vaccination
disease MESH re infection
disease VO Viruses
disease IDO host
drug DRUGBANK Serine
pathway KEGG Endocytosis
disease IDO infectivity
disease IDO innate immune response
disease IDO cell
disease IDO replication
disease MESH viral infection
disease MESH viral shedding
disease IDO site
disease VO biological sex
drug DRUGBANK Cysteamine
disease IDO facility
disease VO volume
disease IDO assay
drug DRUGBANK Methionine
disease VO storage
drug DRUGBANK Tretamine
drug DRUGBANK Water
disease VO viral gene
disease VO age
disease IDO symptom
drug DRUGBANK L-Valine
drug DRUGBANK Ribostamycin
drug DRUGBANK Pentaerythritol tetranitrate

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