ACE2 Expression Is Increased in the Lungs of Patients With Comorbidities Associated With Severe COVID-19

J Infect Dis. 2020 Jul 23;222(4):556-563. doi: 10.1093/infdis/jiaa332.


Patients who died from COVID-19 often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. Although angiotensin-converting enzyme 2 (ACE2) is crucial for SARS-CoV-2 to bind and enter host cells, no study has systematically assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples from patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. Our systems biology approach offers a possible explanation for increased COVID-19 severity in patients with certain comorbidities.

Keywords: COVID-19; KDM5B; SARS-CoV-2; angiotensin converting enzyme 2.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • COVID-19
  • Case-Control Studies
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / genetics
  • Comorbidity
  • Coronary Disease / epidemiology
  • Coronary Disease / genetics
  • Coronavirus Infections / enzymology
  • Coronavirus Infections / epidemiology*
  • Coronavirus Infections / genetics
  • Diabetes Complications / epidemiology
  • Diabetes Complications / genetics
  • Epigenomics
  • Female
  • Humans
  • Hypertension / epidemiology
  • Hypertension / genetics
  • Lung / enzymology*
  • Male
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / enzymology
  • Pneumonia, Viral / epidemiology*
  • Pneumonia, Viral / genetics
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Severity of Illness Index
  • Systems Biology
  • Transcriptome


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2