Study Confirms Inflammasome Activation Linked to T-Cell Dysregulation & Poor Outcomes in Comorbid COVID-19 Patients

Study Confirms Inflammasome Activation Linked to T-Cell Dysregulation & Poor Outcomes in Comorbid COVID-19 Patients

MedStar Georgetown Transplant Institute (MGT) led an important study discovering that inflammation, resulting from heightened inflammasome activity, leads to immune dysregulation and ultimately severe disease for comorbid patients with COVID-19. With results published in the Journal of Hepatology, early publicized risk profiles associated with COVID-19 warned patients with inflammatory comorbidities, such as obesity, diabetes, hypertension and cardiovascular disease, were at greater risk of morbidity and death due to SARS-CoV-2. This study reinforces that this risk list, including patients with liver disease and liver transplant recipients, those who are likely to have a co-occurrence of comorbid illness. Put another way, the MedStar led study team produced data explaining why COVID-19 patients with clinical recognized predisposing factors (e.g. obesity, liver, kidney and heart diseases) have a more severe and dangerous form of the disease.

Transplant Patients Vulnerable to COVID-19

Dr. Alexander Kroemer, a transplant surgeon and MGTI scientific director as well as the study’s lead author, along with Dr. Khalid Khan, medical director of the Islet Cell Transplant Program, and Dr. Thomas Fishbein, executive director of MedStar Georgetown Transplant Institute, recognized early on that COVID-19 represented a significant risk to transplant candidates. They sought to better understand how to provide specialized care and treatment given these risks.

What is the Inflammasome?

This is an intracellular protein complex that monitors and mediates the body’s inflammatory responses to injury or illness. Upon activation it can induce a form of highly inflammatory cell death called pyroptosis, which has two implications, including (1) triggers the release of pro-inflammatory cytokines which could possibly contribute to the deadly so-called cytokine storm that have been reported in severe COVID-19 cases, and (2) drive immune dysfunction via T-cell and lymphocyte depletion, which prevents the adaptive immune system from mounting an effective antiviral response.

The Hypothesis

A virus such as SARS-CoV-2 (COVID-19) can further activate the inflammasome, and hence exacerbate and accelerate this detrimental immune response in patients who already have chronic activation. This places the patient in far greater danger.

The Study

A collaborative effort, this study was led by MGTI and included Amerimmune, a CLIA-certified laboratory, and SUNY Downstate Medical Center. The research team investigated the possibly critical role of the inflammasome in COVID-19 patient outcomes.

The study team focused on eight COVID-19 liver patients from the MedStar Georgetown Transplant Institute (MGTI) and eight matched COVID-19 non-liver patient controls from SUNY Downstate Medical Center (SUNY). The eight control patients from SUNY were matched based on age, gender, race, comorbidities and COVID-19 outcome during the same time period.

Summary of Findings

The study team reports that based on the preliminary data, they did find a link between immune dysfunction and inflammatory comorbidities, reported Dr. Kroemer. He emphasized additionally that this link associating the SARS-CoV-2 virus and “inflammasome and resulting inflammatory cell death” potentially triggering or influencing low lymphocyte and T-cell counts is also observable in other viruses such as HIV.

MedStar Georgetown University Hospital

MedStar Georgetown University Hospital is a not-for-profit, acute-care teaching and research hospital licensed for 609 beds located in Northwest Washington, D.C. Founded in the Jesuit principle of cura personalis, caring for the whole person, MedStar Georgetown is committed to offering a variety of innovative diagnostic and treatment options within a trusting and compassionate environment.  MedStar Georgetown’s centers of excellence include neurosciences, transplant, cancer and gastroenterology. Along with Magnet® nurses, internationally recognized physicians, advanced research and cutting-edge technologies, MedStar Georgetown’s healthcare professionals have a reputation for medical excellence and leadership.

Lead Research/investigators (MedStar)

Dr. Alexander Kroemer, a transplant surgeon and MGTI scientific director as well as the study’s lead author

Dr. Khalid Khan, medical director of the Islet Cell Transplant Program

Dr. Thomas Fishbein, executive director of MedStar Georgetown Transplant Institute, recognized early on that COVID-19 represented a significant risk to transplant candidates. They sought to better understand how to provide specialized care and treatment given these risks.