Abstract
To assess the biology of the lethal endpoint in patients with SARS-CoV-2 infection, we compared the transcriptional response to the virus in patients who survived or died during severe COVID-19. We applied gene expression profiling to generate transcriptional signatures for peripheral blood mononuclear cells (PBMCs) from patients with SARS-CoV-2 infection at the time when they were placed in the Intensive Care Unit of the Pavlov First State Medical University of St. Petersburg (Russia). Three different bioinformatics approaches to RNA-seq analysis identified a downregulation of three common pathways in survivors compared with nonsurvivors among patients with severe COVID-19, namely, low-density lipoprotein (LDL) particle receptor activity (GO:0005041), important for maintaining cholesterol homeostasis, leukocyte differentiation (GO:0002521), and cargo receptor activity (GO:0038024). Specifically, PBMCs from surviving patients were characterized by reduced expression of PPARG, CD36, STAB1, ITGAV, and ANXA2. Taken together, our findings suggest that LDL particle receptor pathway activity in patients with COVID-19 infection is associated with poor disease prognosis.
Highlights
Coronavirus disease (COVID-19) is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the HCoV family of coronaviruses [1].The first cases of this disease were described in China in the province of Wuhan, but by the end of January 2020, COVID-19 had been diagnosed in almost 12,000 people from27 countries, and 259 patients had died
After applying a statistical filter (FDR < 0.05 and absolute fold change (FC) > 1.5), we identified a total of 1038 differentially expressed genes (DEGs) (6.9% of the total expressed 15793; 448 upregulated and 550 downregulated genes) using Pipeline 1; 866 DEGs (5.1% of the total expressed 16,991; 399 upregulated and 467 downregulated genes) using Pipeline 2; and 516 DEGs
We report for the first time to our knowledge, downregulation of low-density lipoprotein (LDL) particle receptor pathway activity in patients of Intensive Care Unit (ICU) surviving from severe COVID-19 infection
Summary
Coronavirus disease (COVID-19) is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the HCoV family of coronaviruses [1].The first cases of this disease were described in China in the province of Wuhan, but by the end of January 2020, COVID-19 had been diagnosed in almost 12,000 people from27 countries, and 259 patients had died. Coronavirus disease (COVID-19) is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the HCoV family of coronaviruses [1]. On 11 March 2020, the World Health Organization announced the COVID-19 pandemic—by this time the disease had been detected in 126 countries worldwide in more than 125,000 people [2]. Angiotensin-converting enzyme 2, known as the ACE2 receptor protein, serves as a target or entry point for SARS-CoV-2 [4,5,6]. The binding of the virus spike protein S1 to this receptor leads to rapid internalization of the virus by ACE2-expressing cells, primarily epithelial cells of the upper respiratory tract, alveolocytes, and enterocytes of the small intestine [7]. As ACE2 plays the role of a negative regulator of the activity of the entire renin–angiotensin–aldosterone system (RAAS), the partial dysfunction of ACE2 caused by the interaction with the viral protein S1 can lead to damage to various organs and tissues; from the lungs as the primary target of damage to the nervous tissue [9]
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