Abstract
Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection of host cells occurs predominantly via binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor.1 Hypertension and pre-existing cardiovascular disease are risk factors for morbidity from COVID-19,2 and it remains uncertain whether the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) impacts infection and disease. Here, we aim to shed light on this question by assessing ACE2 expression in normal and diseased human myocardial samples profiled by bulk and single nucleus RNA-seq.
Competing Interest Statement
Drs. Papangeli, Akkad, Hayat and Stegmann are employees of Bayer US LLC (a subsidiary of Bayer AG), and may own stock in Bayer AG. Dr. Ellinor is supported by a grant from Bayer AG to the Broad Institute focused on the genetics and therapeutics of cardiovascular diseases. Dr. Ellinor has also served on advisory boards or consulted for Bayer AG, Quest Diagnostics, MyoKardia and Novartis. Dr. Margulies has research grant funding from Sanofi-Aventis, USA and has also served on advisory boards for MyoKardia and Pfizer. Dr. Regev is a founder of and equity holder in Celsius Therapeutics, an equity holder in Immunitas Therapeutics, and a scientific advisory board (SAB) member of Syros Pharmaceuticals, ThermoFisher Scientific, Asimov, and NeoGene Therapeutics.
Funding Statement
The Precision Cardiology Laboratory is a joint effort between the Broad Institute and Bayer AG. This work was supported by the Fondation Leducq (14CVD01), and by grants from the National Institutes of Health to Dr. Ellinor (1RO1HL092577, R01HL128914, K24HL105780), Dr. Tucker (5K01HL140187) and Dr. Margulies (1R01HL105993), as well as the Klarman Cell Observatory and the Manton Foundation (to Dr. Regev). This work was also supported by a grant from the American Heart Association Strategically Focused Research Networks to Dr. Ellinor (18SFRN34110082).
Author Declarations
All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.
Yes
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Footnotes
↵+ Members of the Human Cell Atlas Lung Biological Network at provided in the Supplementary Materials
Data Availability
Given the urgent nature of the current pandemic, this analysis was confined to the genes known to interact with COVID-19 as described above. The cell subtype expression levels for each of the genes described in this analysis will be available on the Single Cell Portal at the Broad Institute (https://singlecell.broadinstitute.org/single_cell) upon publication. The description of the expression changes observed between dilated cardiomyopathy, hypertrophic cardiomyopathy and non-failing controls will be the basis of a distinct analysis, and the full snRNAseq dataset from these samples will be released upon publication of that manuscript.