Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients.

Tue W Kragstrup,Arnav Mehta,Marcia B Goldberg,Felice Rivellese,Bo Martin Bibby,Per Qvist,Michael R Filbin,Ida Grundberg,Ane Langkilde-Lauesen Nielsen,Helene Søgaard Singh,Michael Bader

doi:10.1371/journal.pone.0252799

Abstract

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. 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). 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.

Highlights

Since December 2019, a previously undiscovered virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a devastating global pandemic
In models correcting for age, body mass index, hypertension, and preexisting heart conditions, kidney disease, lung disease, diabetes, and immunosuppressive conditions, significant associations were still observed between plasma angiotensin converting enzyme 2 (ACE2) at day 0 and Acuity max (Table 1)
We analyzed the association between plasma ACE2 at day 0 and Acuity max after correcting for C-reactive protein (CRP), absolute neutrophil count, and D-dimer to evaluate whether plasma ACE2 adds to the information already achieved by these laboratory test results

Summary

Introduction

Since December 2019, a previously undiscovered virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a devastating global pandemic. The ACE2-receptor is distributed in different tissues including vascular endothelial cells, smooth muscle cells, nasal and oral mucosa, enterocytes within the intestines, and is especially abundant in the kidneys [9, 10] and type II alveolar pneumocytes in the lungs [11, 12]. This distribution explains possible entry routes for the virus, and why target cells such as the pneumocytes are highly vulnerable to viral infection [12]

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Discussion

Conclusion