Project Title: IFN signature response and cytokine profiling of samples from hospitalized patients with respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19)
NIAID Principal Investigator: Raphaela Goldbach-Mansky M.D., M.H.S.
Chief, Translational Autoinflammatory Disease Studies Unit, LCIM
How does the IFN response and an inflammatory cytokine profile change over the course of COVID-19 infection?
Early research on COVID-19 suggests that some patients may undergo cytokine storm, a process in which the immune system releases too many cytokines, causing too much inflammation that is not only damaging to the virus, but also causes severe damage to the host, including the lungs in patients with COVID-19. The full extent of the cytokine profile in COVID-19 patients, especially a longitudinal view of how that profile changes over time, and how it differs in patients with poor outcomes compared to those who recover, is not understood. The Translational Autoinflammatory Disease Studies Unit of the Laboratory of Clinical Immunology and Microbiology (LCIM) will harness the power of Nanostring and RNA-Seq to measure and characterize the pro-inflammatory cytokine signature of COVID-19. Drawing upon their expertise in interferon (IFN)-mediated and inflammasome-mediated autoinflammatory diseases, they also hope to probe the role of IFNs including the Type I IFNs (IFN-α and IFN-β) and IFN-γ as well as the role of inflammasomes in determining the course of disease. In collaboration with John Tsang, Ph.D. (NIAID), expression profiles will be analyzed for contribution of myeloid cells (monocytes and neutrophils) to the cytokine storm. The results of their studies will be used to provide important diagnostic markers for monitoring disease progression and assist with the development of new therapeutic approaches to minimize tissue damage. In collaboration with Doug Kuhns, Ph.D. (NCI), Scott Canna, M.D. (University of Pittsburgh) and Mihalis Lionakis, M.D, Sc.D. (NIAID), the lab will examine the in vivo inflammatory signature of COVID-19 by comprehensively assessing cytokines in serum. Results from both sets of experiments will be correlated to clinical features and compared to patients with IFN- and inflammasome-mediated autoinflammatory diseases. This work will help to uncover important clinical markers of COVID-19 and offer insight on therapeutic approaches to treat the disease.
Frederick National Laboratory for Cancer Research
University of Pittsburgh
- Scott Canna, M.D., NIAID special volunteer
One PAX gene tube (2.5 mL of blood in 16x100 mm tube). Longitudinal sampling in patients is highly desired, if possible, but not a requirement. BAL cell pellets and aspirates are highly desirable if available. Ideally, samples would be taken 1) upon hospital admission, 2) during hospitalization, 3) at discharge, and 4) after discharge.
For serological studies (cytokine/chemokine levels), 0.5 mL of serum or plasma is required. Ideally, samples would be taken 1) upon hospital admission, 2) during hospitalization, 3) at discharge, and 4) after discharge.