Dr. Sean Monaghan, a trauma and critical care surgeon with Brown Surgical Associates, is the principal investigator on a nearly $2 million research project on sepsis at Rhode Island Hospital.
Funded by a five-year grant from the hospital, Monaghan is working with Dr. Mitchell Levy, director of critical care for Lifespan Corp., to perform research that they hope will lead to better methods to diagnose sepsis and more effective treatments. Both Monaghan and Levy are known as experts in sepsis research.
PBN: Please describe some of the work that you plan to do with the grant, and is the research already underway?
MONAGHAN: With this grant we will enroll 75 patients in the intensive care unit with sepsis and 75 patients in the ICU without sepsis. The 75 patients without sepsis will act as controls who are sick but do not have an infection.
From these 150 patients, we will obtain informed consent then collect blood samples on day zero, one, three, seven while in the ICU. This blood will be collected in tubes that stabilize the RNA in the blood. RNA is known to degrade much faster than DNA, so special tubes are needed.
The blood will then be sent for RNA sequencing where every piece of RNA is identified in the sample and the results are sent to us. We then use powerful computers to analyze the data, which will be over 100 million pieces of data per patient.
This research is currently obtaining samples from patients in the ICU. In addition, we are currently working on a small project where we collected blood from 15 patients with COVID-19 in the ICU.
PBN: How is sepsis usually diagnosed now, and are there specific parts of that process that you are hoping to improve upon?
MONAGHAN: Sepsis is usually diagnosed through clinical parameters and blood tests. Patients with sepsis usually have a change in their mental status, trouble breathing and low blood pressure. Patients could also have a fever or high heart rate. In terms of blood tests, clinicians often use a white blood cell count, lactate and other specific tests that can identify the pathogen (bacteria, virus) that is causing the infection.
The immune system is known to play a role in the organ dysfunction that happens in sepsis. With the RNA sequencing data, we hope to look at markers of the immune system, markers of RNA biology and potentially identify the pathogen, all with this single vial of blood.
PBN: What other sepsis-related projects have you done, and do you plan to build on any of that work with this new research?
MONAGHAN: My previous research focused on the disease acute respiratory distress syndrome, which at times is a consequence of sepsis. In studying that disease, we were able to learn how to collect RNA and analyze it with computational biology. We will be applying those techniques to sepsis, which impacts many more people.
PBN: Is there any data that you can share on COVID-19 and sepsis? What are the chances of survival once a person with the virus has developed sepsis?
MONAGHAN: Many patients who have COVID-19 and end up in the ICU have sepsis. Sepsis is defined as organ dysfunction due to an infection. The infection in the case of COVID-19 is due to the SARS-CoV-2 virus. In patients in the ICU with COVID-19, those patients typically have dysfunction of the lungs, heart, kidney and blood clotting system. In terms of survival from COVID-19 once sepsis develops, as we learn more, the chances of survival keep improving.
PBN: Whether they have COVID-19 or not, does a patient’s age play any role in whether they are more likely to develop sepsis after an infection?
MONAGHAN: Sepsis is known to impact patients at the extremes of age. That is, people who are old or very young children. This idea speaks to the role the immune system plays in the development of sepsis.
Elizabeth Graham is a PBN contributing writer.
