Pivoting Critical Care Research to Help With the COVID-19 Pandemic

Illustration courtesy of Michigan Medicine - University of Michigan

In response to the COVID-19 pandemic, members of the Michigan Center for Integrative Research in Critical Care (MCIRCC) have rapidly adapted research and lessons learned from other critical illnesses to develop COVID-specific diagnostic, protective and therapeutic solutions.

“Across the board, health care workers caring for COVID-19 patients identify two critical needs: personal protective equipment (PPE) and an expansion of our critical care resources,” says Robert Dickson, M.D., an assistant professor of pulmonary and critical care at Michigan Medicine and an associate director of MCIRCC.

“Without adequate PPE, we risk losing our most valuable weapon against COVID: a healthy health care workforce. Without expansion of our critical care capacity, we risk turning a survivable illness into a lethal one due to lack of life-saving equipment and personnel.”

With more than 20 projects already underway – many of which were initially created to serve another area of critical care – MCIRCC teams are developing new innovations and leveraging existing research projects to assist with caring for those impacted by the pandemic.

“Innovation through team science is one of our greatest weapons to combat threats like COVID-19,” says Kevin Ward, M.D., a professor of emergency medicine and executive director of MCIRCC.

“MCIRCC’s existing integration platform has made it possible to rapidly and meaningfully respond to this pandemic through the strategic adaptation of many of its existing efforts, as well as the ability to develop new approaches - including several with industry partners.”

Research projects from the MCIRCC team focus on finding improved ways to protect health care workers, diagnosing and stratifying patients, managing care and understanding the underlying biology of the virus.

Protecting those on the frontlines
Depleting supplies of PPE, such as N95 face masks, and reduced numbers of negative pressure rooms and ventilators have been a concern for health care systems treating patients affected by COVID-19. Current MCIRCC projects protecting patients and health care workers on the frontlines include:

Portable helmet system: Researchers have developed a new, portable and mass-producible helmet system that can potentially transform any hospital bed into a negative pressure room, while protecting caregivers, and sparing ventilators for the most critical cases. Built largely from commercially available parts, the innovation’s compact design effectively isolates COVID-19 positive patients and allows for more liberal use of aggressive respiratory treatments, while decreasing the risk of potential exposure to the virus to health care providers. The idea for the device was cultivated by a team of engineers and clinicians, led by Ward and Sridhar Kota, Ph.D., a professor of mechanical engineering at U-M, as well as MCIRCC members, Ben Bassin, M.D., and Nathan Haas, M.D.

PPE: Investigators are researching ways of managing PPE, spanning from building an in-house PPE assembly line to establishing sterilization protocols that could allow for the safe reuse of equipment. Multiple teams, comprised of experts from Michigan Medicine and the U-M College of Engineering (see the full list of team members on the MCIRCC website), are working on these new initiatives. “Right now, we don’t need great solutions that take six months,” says Jesse Capecelatro, Ph.D., an assistant professor mechanical engineering at U-M. “We need good solutions that take 48 hours. It’s been incredible to see the various groups moving forward.”

Diagnosing COVID-19 quickly and easily to guide therapies
With COVID-19 rapidly spreading, the efficient detection of the virus is pivotal to identify and isolate infected individuals as early as possible, support them as needed and determine the appropriate therapy.

Portable computed tomography (CT) scanners: Better detection methods are being examined by many of MCIRCC’s members, including Craig Galban, Ph.D., from the Michigan Medicine Department of Radiology, and Meilan Han, M.D., Michael Sjoding, M.D., and Dickson, from the Michigan Medicine Division of Pulmonary and Critical Care, who propose utilizing portable CT scanners to both diagnosis COVID-positive patients and better determine the severity of the disease and lung condition. Present CT scanning is time consuming due to required decontamination of the machine and room between patients, and it currently requires transporting patients from an intensive care unit to radiology care areas, posing an increased risk of exposure. Providing portable bedside scanning could alleviate these risks and expedite the management of patients. Dickson is currently engaging local imaging companies to develop a solution.

Quantifying patient risk: Early detection of patient deterioration has been found to lead to reduced mortality risk, reduced length-of-stay in the hospital and decreased hospital costs. Yet, identifying COVID-19 patients at greatest risk for life-threatening deterioration is a challenge for clinicians. In response, MCIRCC researchers, including Chris Gillies, Ph.D., Sardar Ansari, Ph.D., Fred Korley, M.D., Ph.D., Kayvan Najarian, Ph.D., and Rodney Daniels, M.D., and others, are developing a system that quantifies patient risk. The project, led by Sjoding, leverages three analytical approaches developed by MCIRCC data scientists: (1) using commonly available labs and vital sign data from the electronic health record (EHR) for clinical surveillance; (2) using heart rate variability (HRV) data for prediction and diagnosis; and (3) using chest X-ray image analysis to enhance prognostication. Combining these three analytics into a powerful diagnostic and surveillance platform could help to conserve resources and treat patients sooner and more effectively.

Cykotine detection platform: One of the health characteristics of patients who are very sick with COVID-19 is called cytokine release syndrome, which is a strong activation of the immune system. Information about which cytokines are elevated, and when, might help clinicians make decisions about how best to treat patients who are critically ill. However, current tests take several days to return. Using an ultra-rapid, ultra-sensitive cytokine detection platform, MCIRCC members Katsuo Kurabayashi, Ph.D., from U-M mechanical engineering, and Benjamin Singer, M.D., and Ted Standiford, M.D., from Michigan Medicine’s Division of Pulmonary and Critical Care, are conducting a clinical study. The study will perform cytokine measurements in near real time and return the results to clinicians on the same day (in this case to guide the use of Tocilizumab, an anti-IL6 cytokine therapy used to treat arthritis). In addition, the team is also developing simple, low cost technology for performing and reading the testing – which would normally require equipment costing thousands of dollars. This platform would be able to be widely deployed near the patient, rather than in a laboratory, making it cost effective and able to bring precision medicine to patients in a wide variety of conditions and in future pandemics.

Meeting the challenges of patient care
MCIRCC members are developing potential solutions to patient care issues taking place during the pandemic, such as limited patient access to ventilators and adopting enhanced safety protocols for procedures.

Airway management of patients: Airway management of COVID-19 patients poses significant risks to health care workers due to aerosolization, or production of airborne particles and tiny liquid droplets of the virus. Cindy Hsu, M.D., Ph.D., Bassin and Brendan Munzer, M.D., from the Michigan Medicine Department of Emergency Medicine, have combined best practices from health systems around the world into a modified airway management algorithm and protocol that is already being used around the United States, including as far away as rural Alaska. With help from the MCIRCC marketing team, the protocol has also been paired with infographics.

Understanding the underlying biology
COVID-19 doesn’t appear to equally affect every individual that is infected with the virus. Understanding the biological basis for how the virus affects patient populations differently could lead to new protective strategies.

Portable breath analyzers: The rapid community transmission of COVID-19 has led to significant incidence of acute hypoxic respiratory failure around the world. Many patients then develop, and can die from, acute respiratory distress syndrome (ARDS) and require intubation and mechanical ventilation. It’s critical to identify the onset of ARDS early and monitor its progress over time to help stratify patients, guide therapies and better allocate resources. Over the past three years, Sherman Fan, Ph.D., from U-M biomedical engineering, along with Ward and their team, have been working with the Michigan Medicine Department of Emergency Medicine and Michigan Medicine intensive care units to use breath analysis to diagnose and monitor ARDS. Using existing breathomic biomarkers, the team is constructing portable breath analyzers that attach to ventilation machines and can predict the onset and trajectory of ARDS earlier than the existing clinical method. For a patient on a ventilator, the device provides breath analysis every 30 minutes. In addition, during the recovery stage and subsequent rehabilitation stage, the device can be used to monitor the patients’ response to treatment and any potential relapse. The team was just awarded a grant from the U.S. Intelligence Advanced Research Projects Activity (IARPA) to understand if breath signatures from COVID-19 patients are similar.

Antibody testing: Fan is also working on a project to rapidly detect and quantify multiple coronavirus biomarkers using blood from a patient’s fingertip. The current gold standard method to diagnose coronavirus infection is based on the detection of viral RNA – snippets of the virus’ genetic material – from swabs taken from individuals’ noses and throats and amplifying them with a DNA copying technique. This approach, however, requires a complicated nucleic acid extraction process that is time consuming and can significantly limit clinical diagnoses. Fan’s team is developing an automated and highly portable device that can rapidly detect multiple types of coronavirus-related antibodies in only 15 minutes using fingertip blood. According to Fan, recent studies have shown that these antibodies can be detected in serum as early as seven days after viral infection. In addition, the device generates sensitive and quantitative measurements of antibodies so that clinicians can monitor the patients’ response to infection and treatment, as well as vaccination.

“MCIRCC and its members from across U-M are using every available resource to continue research that could help protect our health care workers and expand our capacity to provide critical care,” Dickson says. “MCIRCC is fully engaged in both our immediate response to COVID-19, as well as in advancing our fundamental understanding of critical illness, which will be crucial to preventing and providing care for the next pandemic.”

Source: Michigan Medicine - University of Michigan

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