New study may shed light on the adaptive immune response to COVID-19

New research funded by the National Cancer Institute (NCI) aims to boost understanding of how the immune system responds to COVID-19, from the start of infection to recovery.

Two projects totaling over $2.6 million are led by Case Western Reserve University and Cleveland Clinic researchers as part of the NCI's Serological Sciences Network (SeroNet), which awarded just 13 grants nationally.

The network aims to combat the pandemic by improving the ability to test for infection, especially among diverse populations, and speed the development of treatments and vaccines.

Case Western Reserve is a leader in emerging infections, immune response and clinical cancer investigation. This funding from the National Cancer Institute allows us to pivot existing knowledge and resources to accelerate our understanding of COVID-19 infections to optimize our protections and response to this clinically devastating infection."

Stan Gerson, MD, Interim Dean, School of Medicine and Director, Case Comprehensive Cancer Center and Director, National Center for Regenerative Medicine

From the time a person is exposed to SARS-CoV-2, the virus that causes COVID-19, the immune system is hard at work performing early immunological events. Doctors and researchers have been unable to fully understand the immune response to CoV2 and why certain people show symptoms and others remain asymptomatic.

A team of investigators including Adam Burgener, PhD, Mark Cameron, PhD, David Canaday, MD, Jeff Jacobson, MD, Jon Karn, PhD, Christopher L. King, MD, PhD, and Curtis Tatsuoka, PhD at Case Western Reserve School of Medicine, acknowledges that a major gap exists in understanding antibody resistance to CoV2 and the series of immunological events that take place after exposure.

The team is focused on discerning how the earliest innate immune responses to CoV2 either positively or negatively affect development of humoral immunity.

Their research involves following household contacts of clinical cases of CoV2 to determine innate and adaptive immune events associated with this early viral exposure over a 28-day period. They will track how this impacts the durability of immunity to CoV2 over several years.

"By characterizing the early immune response prior to onset of symptoms we hope to identify features that will predict symptomatic versus asymptomatic cases, disease severity and long-term immunity," said King, who is helping to coordinate the team's effort.

Recovery from COVID-19 can put extreme pressure on the immune system, especially for patients with pre-existing complications. Certain individuals, including those with impaired immune function and those with heart disease, appear to be at a higher risk for contracting COVID-19.

David Zidar, MD, an associate professor at the School of Medicine and an interventional cardiologist at Louis Stokes Cleveland VA Medical Center, and Timothy A. Chan, MD, PhD, director of the Center for Immunotherapy and Precision Immuno-Oncology at Cleveland Clinic and co-director of the National Center for Regenerative Medicine at Case Western Reserve, are investigating differences in immunologic function and risk factors for heart disease, and how these relate to COVID-19.

They will also compare which patients develop heart involvement in response to COVID-19 versus those who do not, identifying ways the virus may directly or indirectly attack distant organs such as the heart.

The team's research could have an impact for all COVID-19 patients with pre-existing conditions, not just those with heart disease.

"We are trying to understand the intrinsic mechanisms that explain why some develop life-threatening disease whereas others are minimally affected," said Zidar. "We hope to develop strategies to identify and prevent severe illness from developing in those with COVID."