Transcriptomic Profiles Reveal Downregulation of Low-Density Lipoprotein Particle Receptor Pathway Activity in Patients Surviving Severe COVID-19

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.

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

“…On the other hand, the relevance of lipid metabolism for the pathogenesis of COVID-19 is stressed by many researchers [41][42][43]. The recently revealed downregulation of the lowdensity lipoprotein (LDL) metabolism in peripheral blood mononuclear cells of patients who survived severe COVID-19 [42] might be especially important, thus complementing our preliminary findings that have shown a correlation between the level of autoantibodies again oxidized LDL and 4-HNE protein adducts in the blood of COVID-19 patients who did not survive the disease [16]. This is not surprising because 4-HNE-modified epitopes dominate in the oxidized LDL [44].…”

Systems biology models to identify the influence of SARS-CoV-2 infections to the progression of human autoimmune diseases

“… [ 61 ] ITGAV 16 0.42241379 0.05534754 Expressed in downregulated level in surviving patients with COVID-19; Identified more vulnerable to invading lung cells than other cells of the respiratory tracts and nasopharynx. [ 62 , 63 ] TGFB3 15 0.37984496 0.04488816 Redirected to adopt Bacille CalmetteGuérin vaccination in a tuberculosis pathway enrichment test. [ 64 ] …”

“…Again, from the analysis of peripheral blood immune cells in COVID-19 patients [ 61 ], it was unearthed that the CD3G hub gene had a downregulated expression level in the cluster of blood immune cells known as CD 4 + and CD 8 +, both cells are also associated with COVID-19 patients with gastric cancer [ 47 ] and AD disease activities [ 50 ]. Following low-density lipoprotein particle receptor pathway activity in transcriptome study, ITGAV gene expression was found downregulated in COVID-19 patients [ 62 ]. ITGAV is integrins and integrins signals related gene; ITGAV was unpredictably expressed at a very high level in the lungs, signifying that it was more vulnerable to assaulting lung cells than other cells of the respiratory tracts and nasopharynx, according to an analysis of the transcriptome of COVID-19 patients with nasopharyngeal samples and other SARS-CoV-2 infections [ 99 ].…”

Bioinformatics approach to identify the influences of SARS-COV2 infections on atherosclerosis

“…VSIG4 may be involved in lung injury through induction of phagocytosis (22). VSIG4 activate macrophages, through induction of chemokines, promote the migration of inflammatory cells to the lesion area, and participate in the pathogenesis of arteriosclerosis STAB1 encodes an unusual type of multifunctional scavenger receptor that causes increased lipid uptake and transient lipid depletion in virus-infected areas and is associated with poor prognosis for COVID-19 (30). STAB1 expression may contribute to foam cell formation, monocyte adhesion/migration, and regulation of inflammation in atherosclerotic lesions (31).…”

“…STAB1 encodes an unusual type of multifunctional scavenger receptor that causes increased lipid uptake and transient lipid depletion in virus-infected areas and is associated with poor prognosis for COVID-19 ( 30 ). STAB1 expression may contribute to foam cell formation, monocyte adhesion/migration, and regulation of inflammation in atherosclerotic lesions ( 31 ).…”