Going Beyond Viral Detection: COVID-19 Diagnostics – TriCon 2021

David Parker, PhD

Senior Vice President, Diagnostics Solutions

The emergence of the COVID-19 pandemic spurred the development of nearly 300 diagnostics aimed at detecting exposure to the SARS-CoV-2 virus. 1 Many of these tests are available for use in multiple settings of care to identify the presence of virus, assess viral load, and determine whether a patient has been infected. As we near the end of the acute epidemiology phase of COVID-19 diagnostics, the next generation of diagnostics will address COVID-19 as an endemic disease.

With the emergence of viral variants and disease etiologies ranging from asymptomatic disease to rapid death, it has become clear that COVID-19 will be an ongoing concern long after the public health emergency comes to an end.

To effectively manage the systemic illness resulting from SARS-CoV-2 infection, appropriate diagnostic tools will be required. In his presentation, Dr. Parker explored the analytes and technologies driving this next phase of COVID-19 research and development.

The Search for Relevant Biomarkers

"The first challenge is assessing the efficacy of future vaccines or therapeutics,"

"The second is identifying and preventing clinical complications, and the third is stratifying patients for appropriate treatments."

Said Parker.
Table 1. Emerging Biomarkers for Predicting COVID-19 Severity2-4

Interleukin-6 (IL-6), an inflammatory biomarker, is prominently featured in many research programs. In June 2020, the Roche Elecsys® IL-6 test received Emergency Use Authorization for identifying patients with confirmed COVID-19 who are at high risk of severe inflammatory response.5 A number of novel cytokines are being examined as well. LIGHT, a cytokine encoded by the TNFS14 gene, has been shown to play a key role in regulating COVID-19 responses in the lung, gut, and skin and may be involved in cytokine storm. Currently, there are also a number of studies-including research in Precision for Medicine's own laboratories-looking at immune cell responses to the disease.

Parker shared an example of a biomarker study measuring trends in C-reactive protein levels as a predictor of COVID-19 respiratory decline. This retrospective cohort study found that trending CRP outperforms respiratory oxygen rate in predicting respiratory deterioration and that CRP levels correlated with IL-6 levels and physiological measures of hypoxemic respiratory failure.6

"This is a promising study for the use of a well-established biomarker in predicting disease,"

"But it should be noted that non-specific inflammatory biomarkers have limited utility and CRP can be elevated for many reasons, including co-morbidities associated with severe COVID-19 disease and the infection itself."

Commented Parker.

The Need for Advanced Bioinformatics

Future COVID-19 diagnostics will likely leverage multiple biomarkers and algorithms to associate disease severity. Researchers are applying advanced bioinformatics methods to large data streams encompassing proteomic, immunomic, and genomic analysis to identify not just biomarkers, but biomarker signatures that are prognostic and predictive for COVID-19 disease. Precision for Medicine is supporting the development of one such multi-biomarker assay, Inflammatix's CoVerity™. CoVerity™ is a 5-mRNA classifier test that has demonstrated superiority to clinical biomarkers, including IL-6, in predicting the risk of severe respiratory failure in COVID-19.7

Parker also spoke about MeMed's multianalyte machine learning algorithm for analyzing immune responses to COVID-19, which may have utility in stratifying patients for more aggressive treatment with corticosteroids.8

Next-Generation COVID-19 Diagnostics

The emerging diagnostic clinical need lies in disease management, with a focus on immune system function and activity. Multiple companies have developed cytokine, chemokine, and protein assays as research tools for investigating the COVID-19 disease process and supporting the development of next-generation diagnostics (see Table 2).

Table 2. Molecular Tools for COVID-19 Research

Parker made mention of Fluidigm's immune profiling assay, Luminex's cytokine storm-related biomarker panels, and Adaptive Biotechnologies' quantitative map of T-cell receptors and SARS-CoV-2 antigens.

"Future COVID-19 disease diagnostics will leverage biomarker signatures, proteomics, AI, and machine learning algorithms,"

"Molecular, immunological, clinical, and imaging biomarkers will be integrated into unified signatures that will, in turn, stratify patients for treatment, identify the likely course of disease, and, ultimately, mitigate the clinical effects of COVID-19 disease."

Said Parker.

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