Transcriptomic Profiles Reveal Downregulation of Low-Density Lipoprotein Particle Receptor Pathway Activity in Patients Surviving Severe COVID-19.
Ivan Vlasov, Alexandra Panteleeva, Tatiana Usenko, Mikhael Nikolaev, Artem Izumchenko, Elena Gavrilova, Irina Shlyk, Valentina Miroshnikova, Maria Shadrina, Yurii Polushin, Sofya Pchelina, Petr Slonimsky
Author Information
Ivan Vlasov: Institute of Molecular Genetics of National Research Center "Kurchatov Institute", 123182 Moscow, Russia. ORCID
Alexandra Panteleeva: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia.
Tatiana Usenko: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia.
Mikhael Nikolaev: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia. ORCID
Artem Izumchenko: Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center "Kurchatov Institute", 188300 Saint-Petersburg, Russia. ORCID
Elena Gavrilova: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia.
Irina Shlyk: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia.
Valentina Miroshnikova: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia.
Maria Shadrina: Institute of Molecular Genetics of National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
Yurii Polushin: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia.
Sofya Pchelina: Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia.
Petr Slonimsky: Institute of Molecular Genetics of National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
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.
