Numerous faculty members in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University have actively assisted or transformed their research focus to help battle against the global Covid-19 pandemic.
Professor Scott Hollister’s lab (Center for 3D Medical Fabrication) joined with Dr. Ian Wong, Dr. Jenny Han, Dr. Greg Martin and Dr. Colin Swenson with Emory’s Pulmonary/Critical Care service at Grady Memorial Hospital to 3D print multiple replacement parts for a BPAP breathing circuit for Covid-19 respiratory care. These parts were re-designed to accommodate multiple use, re-sanitizing, and adaptability to the BPAP breathing circuit—they are being evaluated for clinical use.
Susan Margulies, professor and chair of the Coulter Department, assisted with the creation of a simple, low-cost ventilator based on the resuscitation bags carried in ambulances – and widely available in hospitals. A small batch of the devices were assembled for bench testing and shared with Georgia hospitals for evaluation.
Krishnendu Roy, professor and Robert A. Milton Chair in the Coulter Department, and his research team received NIH funding to screen and evaluate certain molecules known as adjuvants that may improve the ability of coronavirus vaccines to stimulate the immune system and generate appropriate responses necessary to protect the general population against the virus.
“The adjuvants that we are studying, known as pathogen-associated molecular patterns (PAMPs), are molecules often found in viruses and bacteria, and can efficiently stimulate our immune system,” explained Roy. “Most viruses have several of these molecules in them, and we are trying to mimic that multi-adjuvant structure.”
Adjuvants are used with some vaccines to help them create stronger protective immune responses in people receiving the vaccine. His research team will screen a library of various adjuvant combinations to quickly identify those that may be most useful to enhance the effects of both protein- and RNA-based coronavirus vaccines under development.
Cheng Zhu, Regents’ Professor who also holds the J. Erskine Love Jr. Endowed Chair in Engineering, is studying the interactions of the spike (S) protein on the SARS-COV-2 surface with ACE2, the cell surface receptor the coronavirus targets for viral entry into host cells. His lab is performing biophysical measurements to characterize the in situ binding kinetics and affinity on the cell surface. He is collaborating with a team of Emory researchers led by Dr. Guido Silvestri, a Georgia Research Alliance Eminent Scholar, who is providing reagents for the experiments.
Professor Philip Santangelo is leading a team that includes James Dahlman, an assistant professor in the Coulter Department. Together, this Coulter biomedical engineering team with a strong background in DNA and RNA research, is developing RNA-based drugs with the goal of treating Covid-19.
Edward Botchwey, associate professor, is conducting research that will contribute to the critical science of infectious disease prevention. One aspect of his study will visualize virus and bacteria structural changes on aligned carbon nano tube (CNT) surface(s), verifying the ability of the surface to render pathogens inactive. Another aspect in his research will be the first study of silver (Ag) nanoparticles grafted on aligned CNT forests as a passive contact virucidal. His research will contribute to efforts to understand the synergistic effect of combining mechanical antiviral mechanism(s) of aligned CNT arrays and the role of CNTs enhancing the surface area and dispersion of Ag nanoparticles to optimize the effectiveness.
Manu Platt, associate professor, is exploring the Covid-19 virus at the cellular level. According to Platt, “there are many remaining questions about how the virus enters cells. It actually uses enzymes called proteases produced by human cells that are able to cut the spike protein on the virus surface, once it is cut, the virus is then able to fuse with human cells.”
While investigators are targeting a few known enzymes capable of doing this activation step, the Platt lab is taking an unbiased approach to identify multiple other proteases that are able to activate this viral spike protein using bioinformatics analyses based on the protein sequence, and then will validate those predictions experimentally. “Many of these enzymes are also overexpressed in diseases that are preconditions such as cardiovascular disease and diabetes, that increase the risk of Covid-19 death, so this work will also provide clues as to why these patients are especially vulnerable,” said Platt. “This research effort has involved undergraduates, graduate students, and postdocs in our lab.”
Annabelle Singer, assistant professor, is testing whether her lab’s recently developed innovative approach to manipulate brain cytokines reduces neuroinflammation from systemic infections including in animal models of Covid-19.
“About ten percent of Covid-19 patients have severe neurological complications, like seizure or stroke, which can lead to death or long-lasting disability, and these neurological problems are hypothesized to result from cytokines in the nervous system,” said Singer.
The first therapeutics for Covid-19, such as antiviral or immune suppression therapies, are unlikely to cross the blood brain barrier to treat neurological effects of Covid-19 (e.g. Remdesivir or Tocilizumab). Thus, there is an unmet need to treat the effects of Covid-19 infection in the nervous system. Her research has previously shown that specific patterns of sensory stimulation rapidly activate or suppress cytokines in the brain and her team will determine if this approach is useful to treat neurological complications of Covid-19.
Assistant professor Aniruddh Sarkar stated, “current worldwide challenges in scaling Covid-19 diagnosis underscore the need for developing inexpensive point-of-care diagnostic tools for infectious diseases. The heterogeneity of the disease – a large number of mild or asymptomatic cases coupled with the relatively rapid degradation in symptoms in some patients – pose a challenge for the healthcare system and emphasize the need for developing predictive biomarkers of disease severity.”
The Sarkar lab is harnessing microscale technology to solve these challenges by developing devices for high-throughput discovery and inexpensive electronic detection of biomarkers for Covid-19. His research work is being done with collaborators at Emory University and at the University of Pittsburgh Medical Center.
Rapid Acceleration of Diagnostics (RADx) program
In April, it was announced that Children’s Healthcare of Atlanta, the Emory University School of Medicine Department of Pediatrics, and the Georgia Institute of Technology were selected to lead the national effort in Covid-19 testing validation through the Atlanta Center for Microsystems Engineered Point-of-Care Technologies (ACME POCT). All are participants in the Rapid Acceleration of Diagnostics (RADx) program. RADx is a federal initiative designed to rapidly transform early, innovative technologies into widely accessible Covid-19 diagnostic testing.
ACME POCT will use a $31 million supplement provided to the three institutions from the National Institutes of Health to lead testing validation and work closely with partners across the country. The goal of the project is to make millions of accurate and easy-to-use tests per week available by the end of summer 2020 and in time for flu season. Wilbur Lam, M.D. and associate professor in the Coulter Department, is one of the three principal investigators leading ACME POCT. Lam and his team will lead testing validation for the NIH as they urgently solicit SARS-CoV-2 diagnostic tests that will assist the public’s safe return to normal activities.
Covid-19 BME Seed Grant Awardees
The Coulter Biomedical Engineering Department also awarded four seed grants in April for BME faculty doing COVID-related research to help advance their efforts: Gabe Kwong, Shuichi Takayama, Cassie Mitchell, and Frank Hammond.
Kwong, an associate professor, is pursuing paper tests for rapid SARS-CoV-2 detection. According to Kwong, “the lack of rapid testing for SARS-CoV-2 has significantly impeded efforts to track the virus and contain its spread.” Currently, a diagnosis is performed by collecting a patient sample followed by quantitative PCR analysis at a certified CLIA laboratory. (Polymerase chain reaction (PCR) is a technique used to "amplify" small segments of DNA. The Clinical Laboratory Improvement Amendments (CLIA) establishes quality standards for laboratory testing).
Kwong said, “the PCR process can take several days to return results, which remains a challenge as 40-50% of cases may be attributable to spread by presymptomatic people.” His lab is developing a rapid antigen test where CoV-2 signals are amplified without the need for PCR, and test results are read using a paper test strip similar to a home pregnancy test within one hour. If successful, his approach will provide a low-cost and scalable paper test to markedly increase current abilities to test large segments of the population for SARS-CoV-2.
Takayama, a professor, believes the quickest path to an anti-Covid-19 drug is using an existing FDA-approved therapy. His lab is working to narrow the pool to a few promising candidates for clinical trials, and says we need rapid, high-throughput screening in cell culture models that replicate conditions in infected lung tissue. “Our high throughout, 96-well lung model helps screen therapeutics that interrupt mechanisms of inflammation and disease that contribute to Covid-19 morbidity and mortality,” said Takayama. His project is still in its early phases and is a collaboration with Emory School of Medicine and other Emory University researchers.
Mitchell, an assistant professor, runs the Laboratory for Pathology Dynamics at Georgia Tech, which is using its novel and nationally recognized machine learning platforms to text mine millions of peer-reviewed scientific articles with the goal of identifying hidden patterns relevant to Covid-19. “Information and relationships mined from articles are constructed into a ‘knowledge graph’ or network that links symptoms, drugs, antecedent diseases, genes, proteins, and much more, to Covid-19 or similar coronaviruses,” said Mitchell. “Relationships with coronavirus are quantitatively ranked to find the most promising research avenues, with the intent of expediting successful translational research.” Her current project phase focuses on ranking the most promising repurposed drugs for Covid-19 and identifying a list of collective factors that best define patient Covid-19 risk categories.
Assistant Professor Hammond’s Covid-related project is titled “Soft Pneumatic Vest for Trans-Thoracic Manipulation of Ventilation/Perfusion (VQ).” The objective of his project is to develop a wearable, low-cost device for the treatment of acute respiratory distress syndromes (ARDS) caused by Covid-19.
The proposed vest works by applying localized pressures to the chest and back to simulate "proning" – a process used in pulmonary function assessments, where ARDS patients are flipped onto their chests to redistribute blood to uninflamed regions of the lungs where oxygen is more efficiently uptaken, increasing their ventilation and potentially improving patient outcomes. The simulated proning enabled by this device will eliminate hours of clinical staff effort normally required for conventional proning while reducing the risk of adverse cardiac events induced by the physical stress.
Researchers across the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University will continue to explore solutions to battle the Covid-19 pandemic and are making every effort to keep their research teams operating efficiently and safely.
Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology