Transcriptomics Curation of SARS-CoV-2 Related Host Genes in Mice With COVID-19 Comorbidity: A Pilot Study

Abstract

The pandemic of coronavirus disease 2019 (COVID-19), a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2, is causing substantial morbidity and mortality. Along with the respiratory symptoms, underlying diseases in senior patients, such as diabetes, hypertension, and coronary heart disease, are the most common comorbidities, which cause more severe outcomes and even death. During cellular attachment and entry of severe acute respiratory syndrome coronavirus-2, the key protein involved is the angiotensin I converting enzyme 2 (ACE2), which is located on the membrane of host cells. Here, we aim to curate an expression profile of Ace2 and other COVID-19 related genes across the available diabetes murine strains. Based on strictly manual curation and bioinformatics analysis of the publicly deposited expression datasets, Ace2 and other potentially involved genes such as Furin, Tmprss2, Ang, and Ang2 were examined. We found that Ace2 expression is rather ubiquitous in three selected diabetes prone strains (db/db, ob/ob and diet-induced obese). With the most abundant datasets present, the liver shows a medium Ace2 expression level compared with the lungs, pancreatic islets, brain and even T cells. Age is a more critical factor for Ace2 expression in db/db compared with the other two strains. Besides Ace2, the other four host genes showed varied levels of correlation to each other. To accelerate research on the interaction between COVID-19 and underlying diseases, the Murine4Covid transcriptomics database (www.geneureka.org/Murine4Covid) will facilitate the design of research on COVID-19 and comorbidities.

Keywords: ACE2; COVID-19; SARS-CoV-2; diabetes; murine model.

Figure 1

Pipeline to retrieve the most important diabetes murine strains.

Figure 2

Summary of Ace2 expression in mouse tissues based on publicly available transcriptomics datasets. Different sizes of circles represent normalized expression levels of Ace2, and scaled colors of circles represent number of samples curated in certain tissues of strains. A consistent expression in the lungs, pancreatic islets, liver, adipose tissue, heart, aortas, brain, kidney, gall bladder, muscle, and T cells was observed across all datasets. Blank in situ represents no qualified dataset available. Intensity is normalized and shown as /(10³ intensity of geometric mean of Gapdh and Actb). Ace2: angiotensin I converting enzyme 2.

Figure 3

Ace2 expression changes in age, strains, and organs. Ace2 expression changes according to conditions of different strains, age, tissues, and diets. All data are from a single dataset. Ace2: angiotensin I converting enzyme 2.

Figure 4

Correlation of five reported COVID-19 related targets. Correlation is displayed according to the diagonal order of Ace2, Furin, Tmprss22, Ang, and Ang2. The top half shows graphical demonstration and the bottom half shows the corresponding correlation coefficient. Scaled color is shown in the legend bar. Ace2: angiotensin I converting enzyme 2; COVID-19: coronavirus disease 2019.