Expression values were obtained from the Genotype-Tissue Expression (GTEx) Project (https://gtexportal.org).  Data are reported in transcripts per million (TPM) which is a normalized metric for comparing RNA sequencings.  * indicates a tissue that is associated with common COVID-19 symptoms.

- TMPRSS2 is expressed more in the lungs than ACE2
- both ACE2 and TMPRSS2 are expressed in the gastrointestinal (GI) system which could contribute to the GI symptoms that COVID-19 patients experience
- ACE2 was most expressed in the testes
- TMPRSS2 was most expressed in the prostate

Comparing TMPRSS2 and ACE2 Expression in Different Tissues

Expression values were obtained from the Genotype-Tissue Expression (GTEx) Project (https://gtexportal.org). Data are reported in transcripts per million (TPM) which is a normalized metric for comparing RNA sequencings.  These tissues are among those with the highest TMPRSS2 and ACE2 expression levels.

- only ACE2 expression in subcutaneous adipose tissue significantly differed by sex
- no significant different was observed in lung tissue despite the fact that COVID-19 morbidity and mortality has a male dominance

TMPRSS2 and ACE2 Expression are Similar Across Sexes

It was hypothesized that IBD patients would be at a higher risk for developing severe COVID-19 because of their overactive immune responses and chronic gut inflammation which would result in increased ACE2 expression.  However, a recent study shows that neither inflammation nor medication related to IBD increase ACE2 and TMPRSS2 expression in the gut.  While soluble ACE2 expression may increase, which actually has a protective effect against SARS-CoV-2 infections, full length ACE2 that acts as the cellular receptor for the virus does not.  

Gut ACE2 and TMPRSS2 Expression in IBD Pathology Does Not Increase the Risk for Developing COVID-19

Coexpression of TMPRSS2 and ACE2

- comparing expression levels in different tissues
- comparing expression levels by sex
- coexpression of TMPRSS2 and ACE2 

Michigan State University

State University of New York at Stony Brook

- tissue expression
- comparing expression to ACE2

TMPRSS2 Expression

- subcellular expression
- tissue and organ expression
- mediators that influence expression
- comparing to TMPRSS2 expression
- circulating expression
- expression in embryonic development

ACE2 Expression

Comparing TMPRSS2 and ACE2 Expression

Data from primary manuscripts and microscopy screenings were used to assign a confidence level to the likelihood of different subcellular locations expressing ACE2.  This study showed that the extracellular space and plasma membrane are the most likely places to express ACE2 (confidence = 5), and the Golgi apparatus is the least likely (confidence = 1) out of these listed locations.  

Subcellular Expression of ACE2

- drug mediators
- non-drug mediators
- genetic mediators
- disease states

Mediators that Infleunce ACE2 Expression

- Increased Concentrations of Circulating ACE2 is Associated with Mild COVID-19 Symptoms 
- Circulating ACE2 expression compared to circulating ACE

Expression of Circulating ACE2 and COVID-19

Pregnant mice were used to assess the expression levels of the following genes associated with SARS-CoV-2, inflammation, and other viral diseases:

- ACE2: cellular receptor for the SARS-CoV-2 virus
- TMPRSS2: serine protease involved in cellular entry of the SARS-CoV-2 virus
- St3gal4: related to the influenza virus
- St6gal1: related to the influenza virus
- Ifngr1: related to inflammation
- Tnfrsf1a: related to inflammation

Mice were sacrificed at the following timepoints:

- E12.5: embryonic day 12 (gravid females are sacrificed)
- E14.5: embryonic day 14 (gravid females are sacrificed)
- P1: day pups are born (pups are sacrificed)

Epithelium (Epi) and mesenchyme (Mes) tissue were collected from the soft pallets (SP) and tongues (T) of the different developmental stages.  Notably, ACE2 expression was only observed in large quantities in P1 mice, and TMPRSS2 expression increased throughout the developmental process.  FPKM: fragments per kilobase million reads

ACE2 and Other SARS-CoV-2 Related Gene Expression in Mouse Development

- cancer tissue
- human airway epithelium tissue
- human brain expression
- protein and mRNA expression
- relationship to COVID-19

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