Background
Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) binds to angiotensin converting enzyme 2 (
ACE2 HGNC) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (
COVID-19 MESHD).
COVID-19 MESHD is a disease with a very broad spectrum of clinical manifestations, ranging from asymptomatic and subclinical infection to severe
hyperinflammatory syndrome MESHD and
death MESHD. Methods This study used data from a large longitudinal study of 306
COVID-19 MESHD positive patients and 78
COVID-19 MESHD negative patients (MGH Emergency Department
COVID-19 MESHD Cohort with Olink Proteomics). Comprehensive clinical data were collected on this cohort, including 28-day outcomes classified according to the World Health Organization (WHO)
COVID-19 MESHD outcomes scale. The samples were run on the Olink Explore 1536 platform which includes measurement of the
ACE2 HGNC protein. Findings High baseline levels of
ACE2 HGNC in plasma from
COVID-19 MESHD patients were associated with worse WHOmax category at 28 days with OR=0.56, 95%-CI: 0.44-0.71 (P < 0.0001). This association was significant in regression models with correction for baseline characteristics, pre-existing medical conditions, and laboratory test results. High levels of
ACE2 HGNC in plasma from
COVID-19 MESHD patients were also significantly associated with worse WHO category at the time of blood sampling at both day 0, day 3, and day 7 (P = 0.0004, P < 0.0001, and P < 0.0001, respectively). The levels of
ACE2 HGNC in plasma from
COVID-19 MESHD patients with
hypertension MESHD were significantly higher compared to patients without
hypertension MESHD (P = 0.0045). The plasma
ACE2 HGNC levels were also significantly higher in
COVID-19 MESHD patients with pre-existing heart conditions and
kidney disease MESHD compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). There was no difference in plasma
ACE2 HGNC levels comparing patients with or without pre-existing
lung disease MESHD,
diabetes MESHD, or immunosuppressive conditions (P = 0.953, P = 0.291, and P = 0.237, respectively). The associations between high plasma levels of
ACE2 HGNC and worse WHOmax category during 28 days were more pronounced in
COVID-19 MESHD positive patients compared with
COVID-19 MESHD negative patients but the difference was not significant in the two-way ANOVA analysis. Interpretation This study suggests that measuring
ACE2 HGNC is potentially valuable in predicting
COVID-19 MESHD outcomes. Further,
ACE2 HGNC levels could be a link between severe
COVID-19 MESHD disease and its risk factors, namely
hypertension MESHD, pre-existing
heart disease MESHD and pre-existing
kidney disease MESHD. The design of the data analysis using the Olink platform does not allow assessment of quantitative differences. However, previous studies have described a positive correlation between plasma
ACE2 HGNC and
ACE1 HGNC activity. This is interesting because
ACE1 HGNC (serum
ACE HGNC) analysis is a standardized test in most hospital laboratories. Therefore, our study encourages quantitative investigations of both plasma ACE 1 and 2 in
COVID-19 MESHD.