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By Meg Bryant
As doctors and public health officials brace for a possible fall coronavirus surge, one of the challenges continues to be predicting who will have a mild, moderate or severe case of COVID-19. Risk for severe COVID increases with age, disability and underlying medical conditions, but not all patients who fit into those categories become severely ill, while others with no apparent risk factors get sick and even die. Now, a quick and easy blood test from Ampel Biosolutions LLC could identify patients likely to develop a severe course of COVID, leading to early intervention and fewer deaths.
The test, called Covgene, measures a person’s inflammatory response to the virus by measuring expressed genes, known as RNAs, in immune cells in a person’s blood.
Founded in 2013, the Charlottesville, Va.-based precision medicine company began developing Covgene in April 2020, at the start of the pandemic, using an existing RNA analytics platform technology and machine learning algorithms. The goal was to provide clinicians with decision support for early and effective treatment and control the virus before it causes lung damage, other major complications or death.
“We used RNA that was obtained from COVID patient blood, bronchoalveolar … from intubated patients or from lung tissue from deceased patients, and we published a paper in Nature Scientific Reports showing that the Covgene blood test could assay and predict what was going on in the lungs of patients,” Amrie Grammer, Ampel’s co-founder, president and chief scientific officer, told BioWorld.
A 90% accuracy rate
The company then collaborated with physicians in the Division of Pulmonary and Critical Care Medicine at the University of Virginia Medical Center to validate the test and build real-world evidence that a blood sample could predict disease severity before it happened. That longitudinal study – involving two dozen patients at UVA, plus 100 samples from Harvard and Duke – was published this month in Frontiers in Immunology.
The study analyzed blood samples from patients with confirmed SARS-CoV-2 infection who were admitted to the intensive care unit for acute hypoxic respiratory failure, as well as other ICU patients with or without AHRF and matched up gene expression analysis with clinical signs and symptoms. Researchers then compared the results with a second dataset of COVID-19 patients divided by disease stage and severity. Transcriptomic analysis showed that while all COVID-19 patients had enriched plasma cells, only those requiring hospitalization had enriched signatures for interferon and neutrophil.
According to the results, Covgene accurately predicted disease severity 90% of the time. Moreover, the test measures a person’s immune system independent of what SARS-CoV-2 variant the patient has – underscoring its potential for long-term use.
The test could lead to more aggressive treatment of patients at risk of worse outcomes before they become seriously ill. “In particular, drugs that target type 1 interferons, cytokines, such as IL6 or TNF, or myeloid chemokines such as IP-10 or MCP1 could be effective treatments for these individuals,” the study’s authors write.
May predict long COVID
Amrie Grammar, president and CSO, Ampel Biosolutions
Covgene also holds promise for predicting patients at risk of developing long COVID symptoms, and Ampel is seeking a validation partner to that hypothesis.
There’s preliminary work by a variety of groups suggesting long COVID happens when a patient’s immune system “is sort of having a groundhog day,” even though the virus has cleared, Grammer said. Since Covgene examines aspects of the immune system correlated with more severe disease, “similar and even additional aspects of inflammation in the immune system may be predictive not only of the occurrence of long COVID but could provide decision support for physicians of drugs that would address those abnormal pathways.”
Commercialization, pipeline
Ampel’s hope is to make Covgene available to anyone who has recently tested positive for COVID-19, suggesting a substantial market. The company is actively looking for a partner – an existing COVID diagnostic company (Covgene is a PCR test with the same quick turnaround) or a pharma company marketing one of the antivirals used to treat SARs-Cov-2 – to commercialize the test. Given the potential for widespread use outside the U.S., “Ampel is very open to global partners as well, Grammer said.
Covgene was developed in accordance with laboratory-developed test guidelines and could qualify for FDA 510(k) clearance, she said, adding the company will determine the specific pathway with its commercial partner.
“Covgene is ready to come to market now,” Grammer said. “The publication of the validation study with three independent data sets means that Covgene is ready to go and could qualify under [FDA] emergency use authorization to come to the market as early as this winter.”
Ampel, whose focus is on inflammation and autoimmune disorders, has about 10 products in its platform technology-based pipeline. Its first product, Lugene, a CLIA-certified blood test for Lupus, is slated for commercial launch in the U.S. in the fourth quarter of this year.
The company is currently validating a skin biopsy test for Lupus skin disease, psoriasis, scleroderma and atopic dermatitis. “We published that paper in Science Advances in May and showed that, even from non-lesional skin that appeared normal in patients with these diseases, a prediction could be made of a flair, and also medication options,” Grammer said.