Cancer clinicians and scientists transition their talents to tackle the COVID-19 pandemic

The spread of COVID-19 has challenged physicians and scientists across the globe to come together and use their expertise to tackle the pandemic. The researchers of the University of Chicago Medicine Comprehensive Cancer Center are leading large-scale efforts to diagnose and treat this disease, not only to protect their patients, but to protect and improve the health of everyone. Goals critical to fighting COVID-19 are improving diagnosis to treat infected patients and to efficiently monitor the spread of infection, characterizing responses to determine why it is severe in some patients, and developing treatments to minimize the need for intensive care and prevent death.

Detecting and diagnosing COVID-19

Developing computer-aided imaging methods to outsmart COVID-19

Maryellen Giger, PhD, an expert in computer-aided imaging of lung and breast cancers, is spearheading the development of artificial intelligence (AI) to detect, diagnose and guide treatment for COVID-19.

“Over the decades, my lab has been investigating and developing AI for cancer images with the goal of improving the detection, diagnosis and assessment of response to therapy,” Giger said. “We are now applying that knowledge as we develop AI methods to help interpret lung images of COVID-19.”

Giger, with Samuel G. Armato, PhD, and UChicago Medicine colleagues are collaborating with researchers from Argonne National Laboratory to develop AI to analyze x-rays and CT scans from COVID-19 patients in order to identify, characterize stage of infection and guide treatment decisions.

This computer vision system for COVID-19 is developed by “training” the system with a pre-existing dataset of cases with various lung diseases, then building on that dataset through “transfer learning” with COVID-19 cases from UChicago Medicine. Giger’s innovative technology can apply models from other lung conditions, such as cancer, to characterize COVID-19 cases. In addition to helping individual patients, these algorithms may eventually be used to track current and previous infection, providing critical data for public health.

Optimizing molecular biology techniques to detect COVID-19

A molecular biology technique called PCR (polymerase chain reaction) has been widely used to detect the genetic material of the SARS-CoV-2 virus in order to determine if a patient is COVID-19-positive. In general, this type of test is fairly quick and reliable, but sample collection by swabbing the nasal passages requires a healthcare professional, which is an extra hurdle. Also, the supplies needed for the test are expensive, limiting widespread use.

A team of Comprehensive Cancer Center researchers, led by Jeremy Segal, MD, PhD, Nishant Agrawal, MD, are comparing two different PCR tests: an optimized quantitative (q)PCR versus droplet digital (dd)PCR to see if they can reliably detect the COVID-19 virus in saliva as well as in nasal swabs. They will also optimize an automated high-throughput lab test to decrease the processing time and reduce the use of expensive reagents, or chemical ingredients, without losing accuracy.

Izumchenko commented, “the goal of this study is to develop a less invasive and more sensitive method and to reduce risk of exposure for healthcare workers.”

This work could lead to home testing for COVID-19 with only a saliva sample and without the need for expensive reagents, making testing much more affordable and convenient for widespread use.

Differences in severity of COVID-19

Why is the response to SARS-CoV-2 infection so varied?

Thomas F. Gajewski, MD, PhD, is leading a study to track and characterize the immune response of patients enrolled in COVID-19 drug trials. Gajewski and colleagues are using samples collected from patients to examine their levels of cytokines—the molecules that trigger inflammation—and characterize their immune cells to see how these factors relate to a patient’s ability to fight the virus and respond to therapies.

“This translational research study is an outstanding example of the team science capabilities at UChicago Medicine, involving dozens of investigators,” Gajewski commented.

In addition to immune profiling of patients, this in-depth study will determine how other factors correlate with disease severity. The levels of virus-attacking antibodies and T cells will be measured. Gene expression analysis will be performed on patient immune cells to further characterize individual responses. Also, genetic tests will uncover differences in patient DNA that impact response. Each of these components will provide insight as to why patients have widely variable susceptibility to the severity of COVID-19.

Environmental factors will be taken into account, as well. Because there is evidence that the bacteria in the normal lung can be beneficial or detrimental to the development of severe lung pathology, the microbiota in the airways and lungs will be analyzed. This extensive data will provide evidence as to whether interventions that alter the lung microbiome might improve outcomes.

Treating COVID-19: Examining all approaches

Antibodies: keys to treatment and vaccine discovery

Patrick Wilson, PhD, is an expert in B cell biology and antibodies. Since early in the pandemic, he has been analyzing blood samples from recovered patients provided by collaborators across the country. Wilson isolates B cells (immune cells which produce antibodies) from these samples, then sequences the DNA to use in the production of antibodies that may have anti-viral function. Antibodies created from this patient DNA are being tested against viral proteins to see which ones can bind.

Wilson is collaborating with Argonne scientists to use the powerful X-ray imager, Advanced Photon Source, to visualize the protein-antibody interactions to determine which antibodies best bind to viral particles and may be effective against the virus. Effective antibodies may be tested to directly treat patients and offer clues to develop effective vaccines. Also, it is possible to use this method to determine if people have immunity to the virus, which is important for modeling community spread.

Tocilizumab inhibits severe inflammatory responses

High levels of the inflammatory cytokine interleukin (IL)-6, can trigger cytokine release syndrome (CRS), a deadly inflammatory response. The IL-6 receptor-targeting monoclonal antibody, tocilizumab, is an existing drug that successfully blocks IL-6 activity and is currently used to treat cancer patients with hyperinflammation following CAR T-cell therapy. It is a promising treatment of lung inflammation caused by COVID-19.

Mark J. Ratain, MD, and Gajewski are co-investigators on a clinical trial testing the efficacy of tocilizumab in COVID-19 patients. The trial is led by UChicago Medicine clinician Pankti Reid, MD, MPH, from the section of rheumatology. In addition to using tocilizumab to reduce COVID-19 symptoms, this trial will improve understanding of the role of IL-6 and the inflammatory response in COVID-19 disease.

Does hydroxychloroquine work against COVID-19?

Hydroxychloroquine inhibits production of inflammatory cytokines by immune cells, and overall immune cell activity, in a non-specific, non-targeted fashion. It is currently used to treat lupus and rheumatoid arthritis, both auto-immune diseases. Hydroxychloroquine is thought to function by reducing activation of the immune system and may have direct anti-viral function.

Ratain and Gajewski are co-investigators of a clinical trial led by Reem Jan, MD, testing hydroxychloroquine in COVID-19 patients. This study will provide evidence of whether hydroxychloroquine is effective against COVID-19.

Cancer clinicians and researchers are creating solutions

Cancer clinicians and researchers are dedicated to maintaining and improving the health and well-being of their patients. Usually, this means screening, diagnosing, treating and developing new therapies to help patients beat cancer. In this time of the COVID-19 pandemic, these scientists leapt to the frontline, fighting this deadly virus to protect not only cancer patients, but all patients.

“UChicago Medicine and Comprehensive Cancer Center investigators rapidly deployed their research talents towards beating this pandemic,” Ratain said. “We have banded together with other physicians and scientists across disciplines and institutions, to develop and test tools for detection, diagnosis, treatment and tracking of COVID-19. This work is critical to allowing the return to a focus on defeating all forms of cancer, and improving health for everyone.”