Respiratory Virus Detection via ISG Transcript Analysis
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Solution Overview
Problem
Current diagnostic methods, such as PCR tests, struggle to distinguish between replicating and non-replicating respiratory viruses, particularly in asymptomatic or mildly symptomatic individuals, making it difficult to determine the contagiousness of a subject and leading to unnecessary quarantine measures.
Innovation Solution
A method involving the determination of transcript levels of specific interferon-stimulated genes (ISGs) in oral or nasal samples to assess the presence of a replicating respiratory virus, using markers like IFI27, IFI44L, IFIT1, RSAD2, and SIGLEC1, and comparing these levels to reference thresholds to conclude the infectious status.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PCR tests are used to detect viral DNA or RNA, then the presence of virus can be detected, but it cannot distinguish between replicating and non-replicating viruses
Solution Approach 1:
The invention segments the viral detection process into two independent assessments: (1) viral presence detection via PCR for DNA/RNA, and (2) replication activity assessment via ISG transcript level measurement. This segmentation allows each method to perform its specialized function while combining them to provide comprehensive diagnostic information including contagiousness determination.
Solution Approach 2:
The invention introduces interferon-stimulated gene (ISG) transcript levels as an intermediary biomarker that indirectly indicates viral replication activity. Instead of directly measuring replication, the method uses the host's immune response (ISG expression) as a mediator to infer whether the virus is actively replicating, thereby preserving contagiousness information without requiring direct observation of viral replication.
2Reliability
If PCR tests detect viral fragments, then virus presence can be identified, but false positives occur for non-active viruses
Solution Approach 1:
The invention introduces a dynamic assessment by measuring ISG transcript levels that change in response to active viral replication. Unlike static PCR detection of viral fragments, the ISG measurement dynamically reflects the current state of viral activity and host immune response, enabling discrimination between active and inactive infections based on the dynamic interaction between virus and host.
Solution Approach 2:
The method utilizes the host's immune feedback response (ISG expression) as a indicator of active viral replication. When virus is actively replicating, it triggers an immune response that upregulates ISG transcripts; measuring this feedback signal provides information about current replication status, allowing the system to distinguish active from inactive infections.
3Object-affected harmful factors
If quarantine measures are applied to all PCR-positive cases, then transmission risk is reduced, but unnecessary restrictions are imposed on non-replicating cases
Solution Approach 1:
The invention applies local quality differentiation by assessing contagiousness at the individual patient level through ISG transcript measurement. Instead of applying uniform quarantine measures to all PCR-positive cases, the method enables tailored decisions: high ISG levels indicate active replication requiring quarantine, while low ISG levels suggest inactive virus allowing normal activities, thereby optimizing public health responses to local patient characteristics.
Solution Approach 2:
The invention changes the diagnostic parameter from binary viral presence (PCR positive/negative) to a continuous assessment combining viral load with ISG transcript levels. This parameter change enables gradient-based decision-making for quarantine measures, where the combination of PCR and ISG results provides a spectrum of contagiousness risk that informs nuanced public health decisions rather than blanket restrictions.
Data Source
AI summary
A method for determining, in vitro or ex vivo, the presence in a patient of an infection by a replicating respiratory virus, including a step i) of determining, in a test sample taken from the mouth or nose of said patient, the level of transcripts of at least one marker gene selected from the interferon-stimulated genes, referred to as ISGs; and associated kits.