Blog Series – Covid-19: Stories, Insights and Perspectives Robertson Lab & OID

By Corrinne Fahl

Can We Detect SARS-Cov-2 More Efficiently and Effectively in the Near Future?

In the midst of this pandemic, Penn Medicine continues its history of innovation by leading the way in finding solutions to  fight COVID-19. The Office of Inclusion and Diversity had the opportunity to learn more about one new approach to detect SARS-Cov-2.

Respiratory infections are a major cause of human disease, responsible for some of the world’s most devasting pandemics over the last 100 years. Furthermore, both influenza and corona viruses have been associated with some of the deadliest pandemics. Specifically, to date, the previous outbreaks of respiratory infections include the 1918 Flu responsible for approximately 33 million deaths,  the H1NI outbreak in 2009 which was associated with about 284K deaths,  and the 1957 and 1968 Flu outbreaks, responsible for approximately 2 million and 1 million deaths, respectively. The coronaviruses SARS was responsible for 774 deaths, MERS was associated with 858 deaths, and more recently SARS-Cov-2 with over 2.1 million infected and over 147 thousand deaths to date.

Presently, SARS-Cov-2 has been declared a global pandemic from a possible zoonotic transmission with bats and pangolins, although this is yet to be clearly determined. This virus continues to be an increased health risk for individuals that are elderly (over 65 years), immunocompromised, and have comorbidities. Yet, as we’ve seen, SARS-Cov-2 can negatively impact any individual. Transmission occurs by droplets, freely dispersed from respiratory fluids and by fomite. Of note, this virus can also be shed from individuals who show no symptoms, and so increasing its transmissibility. Current tests for SARS-CoV-2 infection can be accomplished with multiple approaches including: (1) Chest CT, elevated LDH and Leukopenia, (2) Molecular PCR (CDC, Quest and LabCorp) which takes a 3-4 days turnaround, sometimes as long as 8 days, (3) Rapid test by GeneXpert Cepheid (45min) or Abbott (15 min), (4) Serological testing (for point of care), but may not be sufficiently clinically validated, and (5) Viral culture, however, current multiplex respiratory panel test will not detect SARS-CoV-2. Therefore, testing currently remains a challenge in the United States.

Dr. Erle Robertson, Harry P. Schenk Endowed Chair Professor, Vice Chair for Research for the Department of Otolaryngology and Professor of Microbiology and his lab developed a PathoChIP that can enable detection and identification of RNA and DNA pathogens in a single assay and has the sensitivity to detect 1 target sequence in a background of 100,000 copies of host genome. Greater sensitivity and less cumbersome analysis are two potential advantages of this test as compared to other testing modalities.  The specificity is also potentially greater considering there are multiple probes across the genomes, so even if one or two fails, there is also the capacity to detect other regions, reducing false negatives. 

More specifically, the Robertson Lab has developed a “PathoChIP”, which is a metagenomics assay for parallel DNA and RNA detection of all known viruses, and a comprehensive group of human pathogens which include bacteria, fungi, protozoa, helminths. The design has been developed starting from genomic sequences of the infectious agents concatenated into synthetic chromosomes in silico. Importantly, the viral sequences include both unique and common regions that are present in the families of viral agents. This allows for detection of agents that belong to a specific viral family but may not be previously identified. As noted, the PathoChIP can enable detection and identification of RNA and DNA pathogens in a single assay and has the sensitivity to detect 1 target sequence in a background of 100,000 copies of host genome. It includes probes for all known respiratory pathogens (viruses, bacteria, fungi and protozoans), and more recently the identified SARS-CoV-2. The samples and human genome reference DNA are labeled and hybridized on arrays on glass slides, and the information extracted to allow for detection of the positive hits in analysis. The analysis pipeline developed by the Robertson Lab allows to discriminate positive and negative signals, and to identify the pathogen based on combination of positive probes. This technology also allows the possibility to perform regular updates of targeted organisms, such as SARS-Cov-2 in a dynamic fashion. Lastly, since the design includes both conserved and unique probes, the assay has the ability to detect both known and novel viral pathogens which belongs to any family of viruses due to the specificity and conserved nature of the probe design.

The PathoChIP has been developed to quickly detect SARS-Cov-2 at the Perelman School of Medicine and will be used to screen patient samples for obtaining an emergency use authorization from the Federal Drug Administration.  This research holds promise at a time when it seems the world is seeking tests to screen for this novel virus.

Office of Inclusion and Diversity on the Robertson Lab