Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

PLoS One. 2021 Jun 4;16(6):e0252799. doi: 10.1371/journal.pone.0252799. eCollection 2021.

Abstract

Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19.

Methods and results: This analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4-2.3 (P < 0.0001). Plasma ACE2 was significantly higher in COVID-19 patients with hypertension compared with patients without hypertension (P = 0.0045). Circulating ACE2 was also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively).

Conclusion: This study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angiotensin-Converting Enzyme 2 / blood*
  • COVID-19* / blood
  • COVID-19* / mortality
  • COVID-19* / therapy
  • Comorbidity
  • Female
  • Heart Diseases* / blood
  • Heart Diseases* / mortality
  • Heart Diseases* / therapy
  • Hospitalization*
  • Humans
  • Kidney Diseases* / blood
  • Kidney Diseases* / mortality
  • Kidney Diseases* / therapy
  • Male
  • Middle Aged
  • SARS-CoV-2 / metabolism*
  • Severity of Illness Index

Substances

  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

American Lung Association COVID-19 Action Initiative award (MBG). Independent Research Fund Denmark clinician scientist award (9039-00015B, TWK). Olink Proteomics financed and performed the proteomics assays presented in this work as part of the collaboration with Massachusetts General Hospital (MGH and the Broad Institute on the MGH Emergency Department COVID-19 Cohort. Olink Proteomics provided support in the form of salaries for IG, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of all authors are articulated in the ‘author contributions’ section.