Kevin Hrusovsky, CEO and president of Quanterix, founder of Powering Precision Health analyses findings in a recent study showing advancements in COVID-19 research and testing through biomarkers.
Despite the rapid proliferation of COVID-19 testing, the global community continues to struggle to overcome critical challenges with the accuracy, cost and availability of diagnostic tests, and access to research tools that could help enable a highly tailored approach to COVID-19 patient care. While vaccine deployment continues at an aggressive pace, COVID-19 testing and clinical research tools will remain a global priority in the months to come.
While current PCR-based testing remains the gold standard for COVID-19 detection, false-negative PCR results have presented significant challenges during the pandemic, particularly for patients who are pre-symptomatic. According to data published in the Annals of Internal Medicine, on day five of infection – the median time for symptom onset and the peak of viral transmission – molecular tests show a 38% probability of producing a false negative result. Moreover, PCR-based supply chains have been strained by increased testing demands, requiring the need to evaluate new testing paradigms.
Shifting to a new era of COVID-19 testing
Measuring biomarkers through blood or salvia could provide a more precise, sensitive testing results, reducing the risk of receiving a false negative during the pre-symptomatic window. It could also provide a deeper understanding of COVID-19. Highly sensitive measurements of viral antigen and the adaptive immune response from sample types suitable for collection at point-of-care settings and at home have the potential to facilitate global public health efforts, ultimately curtailing viral spread and accelerating therapy development across clinical research programs.
A recent research study published in Nature Communications confirms the promise of antigen testing. In that study, Quanterix’ highly sensitive Simoa technology was used to detect N-protein present early in blood and saliva during asymptomatic and symptomatic COVID-19 infection. The study found that Simoa SARS-CoV-2 N-protein assay effectively detected COVID-19 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at-home and point-of-care sample collection. Improving the reliability of results while also offering testing options that are less invasive and can be taken remotely could not only help defeat COVID-19, but also have long-term ramifications for the future of healthcare. It could create a foundation for monitoring and diagnosing all manner of diseases pre-symptomatically through a simple, routine, at-home blood test.
Increasing testing accuracy with higher sensitivity
Harnessing the capabilities of the Simoa HD-X Analyzer to quantitate both the SARS-CoV-2 nucleocapsid protein and the anti-SARS-CoV-2 spike IgG directly in the various sample matrices in this research test, the research team observed a more than 90% positive percentage agreement (PPA) of COVID-19 positive patients. The team also reported a more than 98% negative percent agreement (NPA) in all matrices within seven days of a positive PCR test using sample cohorts with asymptomatic and symptomatic patients. The research also demonstrates an inverse correlation between nucleocapsid protein clearance and an increase in SARS-CoV-2 anti-spike IgG in all matrices. This suggests that an early and robust IgG response alleviates severe disease outcomes, even when high levels of viral nucleocapsid protein are initially present.
The research offers further evidence that non-invasive antigen detection in blood or saliva samples, including from asymptomatic and pre-symptomatic individuals, can serve as an important complement to testing of nasal and nasopharyngeal swab samples. In addition to the benefits of detecting COVID-19 during the pre-symptomatic window – when transmissibility is known to be highest – measuring viral load in blood may be particularly relevant in the context of clinical studies, as an indicator of disease severity or progression, and potentially of therapeutic efficacy. These studies will remain critical in understanding who is at highest risk of developing “long COVID” symptoms and learning how to best treat patients with lingering symptoms.
Creating a new treatment paradigm through reliable testing
The impact of the COVID-19 pandemic will continue to reverberate globally in the months and years ahead. Deploying technologies with higher sensitivity that can measure the concentration of viral proteins in blood and saliva samples obtained non-invasively, we can create new pathways to expand access to accurate and reliable testing and extend our understanding of COVID-19 biology. When combined with more widespread use of technology that can measure biomarkers of inflammation and neurodegeneration, we can further unravel the mysteries of COVID-19 infection, including the estimated 30% of infections that create long-term health implications and accelerate development of effective treatment paradigms.
