Abstract
BackgroundThe coronavirus disease 2019 (COVID-19) has spread rapidly around the world. In addition to common respiratory symptoms such as cough and fever, some patients also have cardiac injury, however, the mechanism of cardiac injury is not clear. In this study, we analyzed the RNA expression atlases of angiotensin-converting enzyme 2(ACE2), cathepsin B (CTSB) and cathepsin L (CTSL) in the human embryonic heart at single-cell resolution.ResultsThe results showed that ACE2 was preferentially enriched in cardiomyocytes. Interestingly, serine protease transmembrane serine protease 2 (TMPRSS2) had less expression in cardiomyocytes, but CTSB and CTSL, which belonged to cell protease, could be found to be enriched in cardiomyocytes. The results of enrichment analysis showed that differentially expressed genes (DEGs) in ACE2-positive cardiomyocytes were mainly enriched in the processes of cardiac muscle contraction, regulation of cardiac conduction, mitochondrial respiratory chain, ion channel binding, adrenergic signaling in cardiomyocytes and viral transcription.ConclusionsOur study suggests that both atrial and ventricular cardiomyocytes are potentially susceptible to severe acute respiratory syndrome coronavirus-2(SARS-CoV-2), and SARS-CoV-2 may enter ventricular cardiomyocytes using CTSB/CTSL for S protein priming. This may be the partial cellular mechanism of cardiac injury in patients with COVID-19.
Highlights
IntroductionIn addition to common respiratory symptoms such as cough and fever, some patients have cardiac injury, the mechanism of cardiac injury is not clear
The coronavirus disease 2019 (COVID-19) has spread rapidly around the world
Serine protein Serine protease transmembrane serine protease 2 (TMPRSS2) had less expression in cardiomyocytes, but cathepsin B (CTSB) and cathepsin L (CTSL), which belonged to cell protease, could be found to be enriched in cardiomyocytes
Summary
In addition to common respiratory symptoms such as cough and fever, some patients have cardiac injury, the mechanism of cardiac injury is not clear. The World Health Organization announced that this new epidemic disease caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) is the coronavirus disease 2019 (COVID-19) [2]. A recent study showed that 19.7% of patients with COVID19 had cardiac injury, which was associated with higher risk of in-hospital mortality [5].the mechanism of cardiac injury is not clear. COVID-19 is caused by SARS-CoV-2, which belongs to Betacoronavirus and is an enveloped and positive-sense single-stranded RNA (+ssRNA) virus [6].SARS-CoV-2 mainly uses angiotensinconverting enzyme 2(ACE2) as the entry receptor [7], and it employs the cellular serine protease transmembrane serine protease 2(TMPRSS2) for spike(S) protein priming [8]. SARS-CoV-2 could use cathepsin B (CTSB) or cathepsin L (CTSL) entering TMPRSS2-negative
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