Related Experiment Video
Updated: Aug 5, 2026
05:23
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
RNAemia and Severe COVID-19: Candidate Treatment Targets Identified Through Transcriptomics
Sultanah Alharthi1,2, Nusrat J Epsi2,3, David A Lindholm4,5
1Vanderbilt University Medical Center, Nashville, TN, USA.
The Journal of Infectious Diseases
|July 29, 2026
Summary
SARS-CoV-2 RNA in blood (RNAemia) predicts severe COVID-19. Host gene expression changes, particularly involving OLAH, PCSK9, and ADAMTS2, are more strongly linked to severe outcomes and may offer new treatment targets.
Area of Science:
- Infectious Diseases
- Genomics
- Molecular Biology
Background:
- SARS-CoV-2 RNA in blood (RNAemia) is a potential marker for severe COVID-19.
- The role of RNAemia in disease progression and associated host gene expression changes remain unclear.
Purpose of the Study:
- To investigate the association between RNAemia, host gene expression, and COVID-19 severity.
- To identify potential therapeutic targets for severe COVID-19 based on RNAemia-associated gene expression patterns.
Main Methods:
- Analysis of 202 hospitalized COVID-19 patients using digital droplet PCR (ddPCR) for SARS-CoV-2 RNA quantification in plasma.
- Host RNA sequencing of peripheral blood and differential gene expression (DGE) logistic regression modeling.
Main Results:
- RNAemia was detected in 39.1% of participants and was significantly associated with severe COVID-19.
- Independent predictors of severity included RNAemia and host genes ADAMTS2, OLAH, and PCSK9.
- Host gene expression changes showed stronger statistical association with severe outcomes than RNAemia itself.
Conclusions:
- RNAemia is an independent predictor of COVID-19 severity.
- Host genes OLAH, PCSK9, and ADAMTS2 are significantly associated with severe COVID-19 outcomes.
- PCSK9 represents a potential, intervenable therapeutic target for severe COVID-19.
Related Concept Videos
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
02:28Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
01:29Viruses with RNA Genomes
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
01:29Coronavirus
Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...