Nanotechnology-based approaches to testing for COVID-19 infections in high-risk individuals

(Nanowerk Spotlight) In the absence of vaccines, many scientists argue that the best approach to control the spread of the Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) would be fast, cheap, reliable, and portable means of diagnosing COVID-19 infection (the name of disease caused by SARS-CoV-2).
A recent review paper (ACS Nano, "Diagnosing COVID-19: The Disease and Tools for Detection") describes current diagnostic methods (e.g., nucleic acid and computed tomography testing) and possible new approaches (e.g., protein and point-of-care testing) based on nanotechnologies. It encourages researchers to advance their technologies beyond conception. While tremendously helpful for the ongoing pandemic, developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics as well.
Morteza Mahmoudi, an Assistant Professor in the Precision Health Program at Michigan State University writes in a Perspective in Molecular Pharmaceutics ("Emerging Biomolecular Testing to Assess Risk of Mortality from COVID-19 Infection") that among patients for whom COVID-19 is deadly are those with pre-existing co-morbidities.
He argues that the identification of patients with the highest risk of COVID-19 mortality (i.e. those with co-morbidities such as cardiovascular disorders or massive alveolar damage and progressive respiratory failure) could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives.
"In addition to detection of COVID-19 infection, we need a complementary approach for early identification of infected patients at high risk of death," Mahmoudi tells Nanowerk. "Assessment of risk before the progression of disease is of crucial importance to protect limited healthcare resources and to lower death rates. However, it is not possible to classify individuals as having a high-risk life-threatening condition or being asymptomatic carriers other than clinical observation; faster, more reliable strategies are needed."
Mahmoudi describes two main areas for possible point-of-care diagnosis of COVID-19 patients at high risk of mortality: biomolecular corona and magnetic levitation.

Biomolecular corona

When nanoparticles enter a biological environment – e.g. human blood – they come into immediate contact with various biomolecules, such as proteins. These biomolecules form a coating layer on the nanoparticle surface – the so-called biomolecular corona – thereby imparting a unique biological identity to the nanoparticle, which could be very different from the pristine nanoparticle surface (read more in our previous Nanowerk Spotlight: "Exploring the crucial role of biomolecular coronas for nanoparticle-cell interactions" and "Personalized protein coronas result in different therapeutic or toxic impacts of identical nanoparticles").
Researchers also have demonstrated that disease-specific protein corona, in combination with advanced classifiers, can be used for early detection and discrimination of cancers (read more: "A quick and simple blood test to detect early-stage cancer" and "Early cancer detection with sensory protein corona 'fingerprints'").
"A similar approach could be used for accurate discrimination between fatal and non-fatal COVID-19 infection, as we previously demonstrated that common cold can change the profile of protein corona at the surface of silica and polystyrene nanoparticles" Mahmoudi points out. "Protein corona sensor array technology may help us in defining the plasma protein/biomolecule patterns that indicate fatal COVID-19 infection at very early stages. It is noteworthy that although the lion share of biomolecular corona is occupied by proteins, other type of biomolecules (e.g., lipids, metabolomes, and nucleic acids) that may have diagnostic capacities are available in the corona composition."
With regard to quick point-of-care or at home testing, he adds that the use of biological fluids that can be collected non-invasively – tears, saliva and urine – may also be considered in the protein corona sensor array approach as they carry disease-related protein markers.
"Compared to human plasma, which requires a blood sample to be taken, the use of simple-to-gather biological fluids in such a discrimination platform is the goal of creating a point-of-care device that does not require an expert healthcare provider to be present," says Mahmoudi. "The main disadvantage of non-plasma biological fluids over human plasma is that tears, saliva, and urine contain a dramatically smaller range of biomolecules which may reduce their sensitivity, specificity and prediction accuracy."

Magnetic levitation (MagLev)

The MagLev technique may provide useful insights into the measurement of the density of proteins in solution for better understanding the physicochemical properties of proteins. Recent research suggests that levitation patterns of human plasma proteins using the MagLev technique may provide useful information about the health spectrum of individual donors (read more: "Detecting diseases with magnetically levitated plasma proteins").
Since different diseases produce substantial variations in the plasma proteome, the levitation progress and patterns of plasma proteins may hold some information on an individual's health conditions.
"More specifically, we found that MagLev optic images of levitated proteins, subjected to machine-learning analysis, offer valuable information on the individual's health status," Mahmoudi explains. "In addition, the levitated ellipsoidal patterns of proteins can be separated and analyzed with proteomic approaches to learn more about the role of important proteins in disease development."
Based on these results, he believes that the MagLev platform may have the capacity for rapid discrimination of patients at risk of fatal COVID-19 progressive disease (e.g., by exacerbating cardiovascular diseases) and also accelerate the development of biomarker(s) to identify such patients.
Mahmoudi cautions that the central disadvantage of both the biomolecular corona and the MagLev approaches is the fact that, unlike conventional assays, we do not have specific biomarkers or nucleic acid to detect. "Therefore, the very first step for developing such assays for identification of populations at highest risk of COVID-19 mortality is to collect human plasma and other non-plasma biological fluids from a considerable numbers of COVID-19 infected patients at fatal and non-fatal stages; the collected biological fluids will then need to examined by MagLev and protein corona sensor array platforms and analyzed by omics techniques and machine learning to define the library of biomolecular patterns that have high association with highest risk of COVID-19 mortality."
On the plus side, the main advantage of these approaches, compared to the conventional diagnostic tests, is their capacity of biomolecular pattern recognition among various types of biomolecules. Such pattern recognition is essential for fast and accurate diagnosis of COVID-19 infections that likely to be fatal; this is mainly because many of the biomolecules may be associated to the personalized plasma variation and/or co-morbidity.
"The proposed approaches may eventually yield a sensitive, easy-to-use optical system to accurately identify COVID19-infected patients at high risk of death," Mahmoudi concludes. "This could significantly improve both the management of health care resources (e.g., avoiding overwhelming hospitals) and improve our control of possible future pandemics without incurring such a large social and economic burden."
Michael Berger By – Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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