RNase P RNA Biomarker for COVID-19 Severity Assessment
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Solution Overview
Problem
Current methods for diagnosing and monitoring the severity of COVID-19 and predicting acute pulmonary failure and systemic damage lack effective biomarkers, as circulating endogenous RNA is considered fragile and unstable for monitoring purposes.
Innovation Solution
Measuring the level of circulating RNA of RNase P in blood, plasma, or serum samples using droplet-based digital PCR, which correlates with the severity of COVID-19 and predicts the risk of disease aggravation and treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If circulating endogenous RNA is used as a biomarker for monitoring COVID-19 severity, then the monitoring capability is improved, but the reliability is worsened due to RNA fragility and instability
Solution Approach 1:
The patent employs circulating endogenous RNA, a naturally occurring and abundant short-lived molecular entity, as a disposable biomarker that reflects real-time cellular damage. Despite RNA's inherent fragility, its transient nature makes it an ideal indicator of acute cellular injury, with each RNA molecule serving as a single-use signal of tissue damage that can be detected before degradation occurs
Solution Approach 2:
The patent transforms the measurement parameter from viral load (SARS-CoV-2 RNA) to host cellular response (endogenous RNA from damaged cells). This parameter change shifts the focus from tracking the pathogen to monitoring the host's physiological state, using RNA stability and concentration as dynamic indicators of disease progression and treatment response
2Loss of information
If conventional RT-PCR is used to detect SARS-CoV-2 RNA, then the diagnostic capability is improved, but the ability to predict disease severity and outcome is worsened
Solution Approach 1:
The patent extracts the prognostic signal from the background of viral detection by specifically isolating and measuring endogenous RNA molecules released from damaged host cells. This extraction separates the host response information from the viral presence information, allowing independent assessment of tissue injury and disease severity that complements conventional viral load measurement
Solution Approach 2:
Endogenous RNA serves as an intermediary biomarker that translates cellular damage into a detectable molecular signal. Rather than directly measuring cellular injury or organ dysfunction, the patent uses RNA concentration and stability as a mediator that reflects the underlying pathophysiological state, bridging the gap between cellular events and clinical assessment
3Loss of time
If early detection of severe cases is pursued, then the treatment efficacy is improved, but the current biomarker availability is worsened due to lack of effective markers
Solution Approach 1:
The patent enables preliminary identification of patients at risk of severe disease progression by detecting elevated endogenous RNA levels early in the clinical course. This preliminary action allows clinicians to initiate intensive monitoring and preemptive treatment strategies before irreversible organ damage occurs, shifting intervention timing upstream in the disease trajectory
Solution Approach 2:
The patent establishes a feedback mechanism for monitoring disease progression and treatment response through serial measurement of endogenous RNA levels. Rising RNA concentrations provide feedback of ongoing cellular damage requiring treatment escalation, while declining levels provide feedback of effective therapy, enabling dynamic adjustment of clinical management based on molecular biomarker trends
Data Source
AI summary
The invention relates to methods for determining the severity of a disease caused by a coronavirus infection, comprising quantifying the level of cellular RNA of RNase P in a blood sample of a subject.