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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (log2 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 (ß = -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 (ß = 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. CONCLUSION: 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.

Risk factors associated with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission, outbreak duration, and mortality in acute-care settings.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute-care settings affects patients, healthcare workers, and the healthcare system. We conducted an analysis of risk factors associated with outbreak severity to inform prevention strategies. METHODS: This cross-sectional analysis of COVID-19 outbreaks was conducted at Fraser Health acute-care sites between March 2020 and March 2021. Outbreak severity measures included COVID-19 attack rate, outbreak duration, and 30-day case mortality. Generalized linear models with generalized estimating equations were used for all outcome measures. A P value of 0.05 indicated statistical significance. Analyses were performed using SAS version 3.8 software, R version 4.1.0 software, and Stata version 16.0 software. RESULTS: Between March 2020 and March 2021, 54 COVID-19 outbreaks were declared in Fraser Health acute-care sites. Overall, a 10% increase in the hand hygiene rate during the outbreak resulted in an 18% decrease in the attack rate (P < .01), 1 fewer death (P = .03), and shorter outbreaks (P < .01). A 10-year increase in unit age was associated with 2.2 additional days of outbreak (P < 0.01) and increases in the attack rate (P < .05) and the number of deaths (P < .01). DISCUSSION: We observed an inverse relationship between increased hand hygiene compliance during outbreaks and all 3 severity measures. Increased unit age was also associated with increases in each of the severity measures. CONCLUSION: This study highlights the importance of hand hygiene practices during an outbreak and the difficulties faced by older facilities, many of which have infrastructural challenges. The latter reinforces the need to incorporate infection control standards into healthcare planning and construction.